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Abstract Background Wastewater can contain a complex mixture of organic micropollutants, with both chemical analysis and effect-based methods needed to identify relevant micropollutants and detect mixture effects. Solid-phase extraction (SPE) is commonly used to enrich micropollutants prior to analysis. While the recovery and stability of individual micropollutants by SPE has been well studied, few studies have optimized SPE for effect-based methods. The aim of the current study was to develop and evaluate two standard operating procedures (SOPs) for the enrichment of micropollutants in preparation for chemical analysis and bioanalysis, one covering a broad range of chemicals and the other selective for estrogenic chemicals. Results Pristine surface water spiked with > 600 micropollutants was used to develop a generic extraction method for micropollutants with a wide range of physiochemical properties, while water spiked with estrogenic chemicals was used to identify a selective extraction method. Three different SPE sorbents were tested, with recoveries of individual chemicals and effect in assays indicative of mutagenicity, estrogenic activity, and fish embryo toxicity assessed. The sorbent HRX at pH 7 was selected for the generic extraction method as it showed the best recovery of both individual chemicals and effect in the bioassays. The sorbent HLB at pH 3 showed optimal recovery of estrogenic chemicals and estrogenic activity. The two optimal SPE methods were applied to spiked and unspiked wastewater effluents, with the concentrations of detected chemicals and observed effects similar to those of previous studies. The long-term storage of both extracts and SPE cartridges for estrogens and estrogenic activity after extraction with the HRX and HLB methods were evaluated, with estrogenic effectiveness close to 100% after 112 days when HLB was used. Conclusions HRX is recommended for generic extraction, while HLB is optimal for the selective extraction of estrogenic micropollutants. However, if a laboratory only wants to use a single SPE sorbent, HLB can be used for both generic and selective extraction as it yielded similar chemical and effect recovery as HRX for a wide range of micropollutants. This paper is supplemented by the final SOP that includes a variant for generic extraction and one for the extraction of estrogenic chemicals.

Growing concerns about the environmental impact of ionic liquids (ILs) have spurred research into their (eco)toxic effects, but studies on their mode of toxic action (MOA) still remain limited. However, understanding the MOA and identifying structural features responsible for enhanced toxicity is crucial for characterising the hazard and designing safer alternatives. Therefore, 45 ILs, with systematically varied chemical structures, were tested for cytotoxicity and two specific endpoints in reporter gene assays targeting the Nrf2-ARE mediated oxidative stress response (AREc32) and aryl hydrocarbon receptor activation (AhR-CALUX). While none of the ILs activated the reporter genes, cytotoxicity was high and markedly different between cell lines. Seven and 25 ILs proved more cytotoxic than predicted by baseline toxicity model in the AREc32 and the AhR-CALUX assays, respectively. The length of the side chain and headgroup structures of ILs altered the MOA of ILs. Cellular metabolism of the ILs, investigated by LC-MS/MS, showed side-chain oxidation of the long-chain quaternary ammonium compounds in AhR-CALUX cells and, to a lower extent, in AREc32 cells, however, this transformation could not explain the high cytotoxicity. Effect data for 72 ILs for ten endpoints retrieved from the Tox21 database identified the inhibition of aromatase activity and of mitochondrial membrane potential as potential MOAs. However, in vitro fluorimetric assays for these endpoints demonstrated that effects were activated in a non-specific manner, probably through cytotoxicity. Although many of the ILs tested induced cytotoxicity at concentrations lower than baseline toxicity, the specific MOAs responsible could not be identified. Alternatively, we suggest that the descriptors currently used may fail to define the affinity of ILs for cells. Testing of the affinity of ILs for a diverse range of biomolecules is needed to accurately describe their interactions with cells.

Monitoring methodologies reflecting the long-term quality and contamination of surface waters are needed to obtain a representative picture of pollution and identify risk drivers. This study sets a baseline for characterizing chemical pollution in the Danube River using an innovative approach, combining continuous three-months use of passive sampling technology with comprehensive chemical (747 chemicals) and bioanalytical (seven in vitro bioassays) assessment during the Joint Danube Survey (JDS4). This is one of the world's largest investigative surface-water monitoring efforts in the longest river in the European Union, which water after riverbank filtration is broadly used for drinking water production. Two types of passive samplers, silicone rubber (SR) sheets for hydrophobic compounds and AttractSPETM HLB disks for hydrophilic compounds, were deployed at nine sites for approximately 100 days. The Danube River pollution was dominated by industrial compounds in SR samplers and by industrial compounds together with pharmaceuticals and personal care products in HLB samplers. Comparison of the Estimated Environmental Concentrations with Predicted No-Effect Concentrations revealed that at the studied sites, at least one (SR) and 4–7 (HLB) compound(s) exceeded the risk quotient of 1. We also detected AhR-mediated activity, oxidative stress response, peroxisome proliferator-activated receptor gamma-mediated activity, estrogenic, androgenic, and anti-androgenic activities using in vitro bioassays. A significant portion of the AhR-mediated and estrogenic activities could be explained by detected analytes at several sites, while for the other bioassays and other sites, much of the activity remained unexplained. The effect-based trigger values for estrogenic and anti-androgenic activities were exceeded at some sites. The identified drivers of mixture in vitro effects deserve further attention in ecotoxicological and environmental pollution research. This novel approach using long-term passive sampling provides a representative benchmark of pollution and effect potentials of chemical mixtures for future water quality monitoring of the Danube River and other large water bodies.

In vitro cell-based bioassays have great potential for applications in the human health risk assessment of chemicals. The quantification of freely dissolved concentrations (Cfree) in in vitro assays is essential to generate reliable data for in vitro-to-in vivo extrapolation. Existing methods for the quantification of Cfree are limited to low-throughput microtiter plates. The present study is a proof of principle for the applicability of a solid-phase microextraction (SPME) method for the determination of Cfree in the peroxisome proliferator-activated receptor gamma (PPARγ) bioassay run in 384-well plates with 80 µL medium per well. The effect concentrations obtained from 384-well plates were compared with those obtained from 96-well plates in a previous study. Nominal effect concentrations obtained using 96- and 384-well plates agreed with each other within a factor of three, and freely dissolved effect concentrations agreed within a factor of 6.5. The good degree of agreement in the results from both plate formats proves the general applicability of the SPME method for the determination of Cfree for bioassays in 384-well plates, making the present study a first step toward exposure assessment in high-throughput bioassays.

Perfluoroalkyl substances (PFAS) are persistent and pose a risk to human health. High throughput screening (HTS) cell-based bioassays may inform risk assessment of PFAS provided that quantitative in vitro to in vivo extrapolation (QIVIVE) can be developed. The QIVIVE ratio is the ratio of nominal (Cnom) or freely dissolved concentration (Cfree) in human blood to Cnom or Cfree in the bioassays. Considering that the concentrations of PFAS in human plasma and in vitro bioassays may vary by orders of magnitude, we tested the hypothesis that anionic PFAS bind to proteins concentration-dependently and therefore the binding differs substantially between human plasma and bioassays, which has an impact on QIVIVE. Solid phase microextraction (SPME) with C18-coated fibers served to quantify the Cfree of four anionic PFAS (perfluorobutanoate (PFBA), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS)) in the presence of proteins and lipid, medium components, cells and human plasma over five orders of magnitude in concentrations. The C18-SPME method was used to quantify the non-linear binding to proteins, human plasma and medium, and the partition constants to cells. These binding parameters were used to predict Cfree of PFAS in cell bioassays and human plasma by a concentration-dependent mass balance model (MBM). The approach was illustrated with a reporter gene assay indicating activation of the peroxisome proliferator-activated receptor gamma (PPARγ-GeneBLAzer). Blood plasma levels were collected from literature for occupational exposure and the general population. The QIVIVEnom ratios were higher than the QIVIVEfree ratios due to the strong affinity to proteins and large differences in protein contents between human blood and bioassays. For human health risk assessment, the QIVIVEfree ratios of many in vitro assays need to be combined to cover all health relevant endpoints. If Cfree cannot be measured, they can be estimated with the MBM and concentration-dependent distribution ratios.

In the present study on endocrine disrupting chemicals (EDCs) in treated wastewater, we used chemical and effect-based tools to analyse 56 wastewater treatment plant (WWTP) effluents from 15 European countries. The main objectives were (i) to compare three different receptor-based estrogenicity assays (ERα-GeneBLAzer, p-YES, ERα-CALUX®), and (ii) to investigate a combined approach of chemical target analysis and receptor-based testing for estrogenicity, glucocorticogenic activity, androgenicity and progestagenic activity (ERα-, GR-, AR- and PR-GeneBLAzer assays, respectively) in treated wastewater. A total of 56 steroids and phenols were detected at concentrations ranging from 25 pg/L (estriol, E3) up to 2.4 μg/L (cortisone). WWTP effluents, which passed an advanced treatment via ozonation or via activated carbon, were found to be less contaminated, in terms of lower or no detection of steroids and phenols, as well as hormone receptor-mediated effects. This result was confirmed by the effect screening, including the three ERα-bioassays. In the GeneBLAzer assays, ERα-activity was detected in 82 %, and GR-activity in 73 % of the samples, while AR- and PR-activity were only measured in 14 % and 21 % of the samples, respectively. 17β-estradiol was confirmed as the estrogen dominating the observed estrogenic mixture effect and triamcinolone acetonide was the dominant driver of glucocorticogenic activity. The comparison of bioanalytical equivalent concentrations (BEQ) predicted from the detected concentrations and the relative effect potency (BEQchem) with measured BEQ (BEQbio) demonstrated good correlations of chemical target analysis and receptor-based testing results with deviations mostly within a factor of 10. Bioassay-specific effect-based trigger values (EBTs) from the literature, but also newly calculated EBTs based on previously proposed derivation options, were applied and allowed a preliminary assessment of the water quality of the tested WWTP effluent samples. Overall, this study demonstrates the high potential of linking chemical with effect-based analysis in water quality assessment with regard to EDC contamination.

Cell-based bioassays are useful tools for the effect assessment of complex mixtures, but so far exposure assessment has not been performed for mixtures of chemicals. In the present study, cytotoxicity and activation of oxidative stress response were measured for three designed chemical mixtures with up to twelve components. The measurements of biological responses were complemented by concentration measurements using solid-phase microextraction to derive the freely dissolved concentrations of the mixtures (Cfree,mix). The tested mixtures showed slightly higher cytotoxic effects than predicted by the concentration addition model. Nominal and freely dissolved effect concentrations of the mixtures were very similar (within a factor of 1.5), but nominal concentrations (Cnom) and Cfree of the individual mixture components were only similar for the hydrophilic chemicals (e.g., caffeine, coumarin, lamotrigine). For hydrophobic (e.g., fluoranthene) and acidic chemicals (e.g., diclofenac, naproxen) Cfree was up to 648 times lower than Cnom. Chemicals were dosed in equipotent nominal concentration ratios and therefore contributed equally to the detected effects. Hydrophilic chemicals with low potency dominated Cnom,mix (up to 95%) and Cfree,mix (up to 99%). Several mixture components (e.g., diclofenac, ibuprofen, naproxen and warfarin) showed increasing free fractions with increasing Cnom,mix and therefore also a concentration-dependent contribution to Cfree,mix. Based on the findings of this study, we concluded that Cnom,mix will be sufficient for evaluating the toxicity of mixtures that contain chemicals with diverse physicochemical properties at low concentration levels. In contrast, for risk assessment purposes and quantitative in vitro to in vivo extrapolations, Cfree,mix is a better parameter because the in vitro responses can be related to freely dissolved concentrations in human plasma.

Bioassays show promise as a complementary approach to chemical analysis to assess the efficacy of wastewater treatment processes as they can detect the mixture effects of all bioactive chemicals in a sample. We investigated the treatment efficacy of ten Australian wastewater treatment plants (WWTPs) covering 42% of the national population over seven consecutive days. Solid-phase extracts of influent and effluent were subjected to an in vitro test battery with six bioassays covering nine endpoints that captured the major modes of action detected in receiving surface waters. WWTP influents and effluents were compared on the basis of population- and flow-normalised effect loads, which provided insights into the biological effects exhibited by the mixture of chemicals before and after treatment. Effect removal efficacy varied between effect endpoints and depended on the treatment process. An ozonation treatment step had the best treatment efficacy, while WWTPs with only primary treatment resulted in poor removal of effects. Effect removal was generally better for estrogenic effects and the peroxisome proliferator-activated receptor than for inhibition of photosynthesis, which is consistent with the persistence of herbicides causing this effect. Cytotoxicity and oxidative stress response provided a sum parameter of all bioactive chemicals including transformation products and removal was poorer than for specific endpoints except for photosynthesis inhibition. Although more than 500 chemicals were analysed, the detected chemicals explained typically less than 10% of the measured biological effect, apart from algal toxicity, where the majority of the effect could be explained by one dominant herbicide, diuron. Overall, the current study demonstrated the utility of applying bioassays alongside chemical analysis to evaluate loads of chemical pollution reaching WWTPs and treatment efficacy.

This data article focuses on the production of monoclonal antibodies (mAb) and their fragments Fab and F(ab′)2. Here, we present the data of an optimization protocol to improve the product yield of a hybridoma cell process using a Design of Experiment (DoE) strategy. Furthermore, the data of the evaluated conditions were used to test feeding strategies in shake flasks. They were verified in controlled 2 L fed-batch bioreactor processes. Supplementing the culture medium with human insulin-like growth factor-I (IGF-I) and Pluronic F-68, as well as a nutrient rich additive for fed-batch, resulted in improved cell growth correlating with a 7 day elongated process time and a 4.5 fold higher product titer. Finally, a rapid Fab generation protocol and the respective data are presented using different papain digestion and a camelid anti-kappa light chain VHH affinity ligand. Keywords: Design of Experiment, Hybridoma, Papain, Production, Fab, F(ab′)2, Bioprocess

Abstract Background Anthocyanin-containing plant extracts and carotenoids, such as astaxanthin, have been well-known for their antiviral and anti-inflammatory activity, respectively. We hypothesised that a mixture of Ribes nigrum L. (Grossulariaceae) (common name black currant (BC)) and Vaccinium myrtillus L. (Ericaceae) (common name bilberry (BL)) extracts (BC/BL) with standardised anthocyanin content as well as single plant extracts interfered with the replication of Measles virus and Herpesviruses in vitro. Methods We treated cell cultures with BC/BL or defined single plant extracts, purified anthocyanins and astaxanthin in different concentrations and subsequently infected the cultures with the Measles virus (wild-type or vaccine strain Edmonston), Herpesvirus 1 or 8, or murine Cytomegalovirus. Then, we analysed the number of infected cells and viral infectivity and compared the data to non-treated controls. Results The BC/BL extract inhibited wild-type Measles virus replication, syncytia formation and cell-to-cell spread. This suppression was dependent on the wild-type virus-receptor-interaction since the Measles vaccine strain was unaffected by BC/BL treatment. Furthermore, the evidence was provided that the delphinidin-3-rutinoside chloride, a component of BC/BL, and purified astaxanthin, were effective anti-Measles virus compounds. Human Herpesvirus 1 and murine Cytomegalovirus replication was inhibited by BC/BL, single bilberry or black currant extracts, and the BC/BL component delphinidin-3-glucoside chloride. Additionally, we observed that BC/BL seemed to act synergistically with aciclovir. Moreover, BC/BL, the single bilberry and black currant extracts, and the BC/BL components delphinidin-3-glucoside chloride, cyanidin-3-glucoside, delphinidin-3-rutinoside chloride, and petunidin-3-galactoside inhibited human Herpesvirus 8 replication. Conclusions Our data indicate that Measles viruses and Herpesviruses are differentially susceptible to a specific BC/BL mixture, single plant extracts, purified anthocyanins and astaxanthin. These compounds might be used in the prevention of viral diseases and in addition to direct-acting antivirals, such as aciclovir.

SARS-CoV-2 variants such as the delta or omicron variants, with higher transmission rates, accelerated the global COVID-19 pandemic. Thus, novel therapeutic strategies need to be deployed. The inhibition of acid sphingomyelinase (ASM), interfering with viral entry by fluoxetine was reported. Here, we described the acid ceramidase as an additional target of fluoxetine. To discover these effects, we synthesized an ASM-independent fluoxetine derivative, AKS466. High-resolution SARS-CoV-2–RNA FISH and RTqPCR analyses demonstrate that AKS466 down-regulates viral gene expression. It is shown that SARS-CoV-2 deacidifies the lysosomal pH using the ORF3 protein. However, treatment with AKS488 or fluoxetine lowers the lysosomal pH. Our biochemical results show that AKS466 localizes to the endo-lysosomal replication compartments of infected cells, and demonstrate the enrichment of the viral genomic, minus-stranded RNA and mRNAs there. Both fluoxetine and AKS466 inhibit the acid ceramidase activity, cause endo-lysosomal ceramide elevation, and interfere with viral replication. Furthermore, Ceranib-2, a specific acid ceramidase inhibitor, reduces SARS-CoV-2 replication and, most importantly, the exogenous supplementation of C6-ceramide interferes with viral replication. These results support the hypotheses that the acid ceramidase is a SARS-CoV-2 host factor.

The transport and Golgi organization 1 (TANGO1) proteins play pivotal roles in the secretory pathway. Full length TANGO1 is a transmembrane protein localised at endoplasmic reticulum (ER) exit sites, where it binds bulky cargo within the ER lumen and recruits membranes from the ER Golgi intermediate compartment to create an exit route for their export. Here we report the first TANGO1-associated syndrome in humans. A synonymous substitution that results in exon eight skipping in most mRNA molecules, ultimately leading to a truncated TANGO1 protein was identified as disease-causing mutation. The four homozygously affected sons of a consanguineous family display severe dentinogenesis imperfecta, short stature, various skeletal abnormalities, insulin-dependent diabetes mellitus, sensorineural hearing loss, and mild intellectual disability. Functional studies in HeLa and U2OS cells revealed that the corresponding truncated TANGO1 protein is dispersed in the ER and its expression in cells with intact endogenous TANGO1 impairs cellular collagen I secretion.

Bacteria of the family Rhodobacteraceae are widespread in marine environments and known to colonize surfaces, such as those of e.g., oysters and shells. The marine bacterium Labrenzia sp. 011 is here investigated and it was found to produce two cyclopropane-containing medium-chain fatty acids (1, 2), which inhibit the growth of a range of bacteria and fungi, most effectively that of a causative agent of Roseovarius oyster disease (ROD), Pseudoroseovarius crassostreae DSM 16950. Additionally, compound 2 acts as a potent partial, β-arrestin-biased agonist at the medium-chain fatty acid-activated orphan G-protein coupled receptor GPR84, which is highly expressed on immune cells. The genome of Labrenzia sp. 011 was sequenced and bioinformatically compared with those of other Labrenzia spp. This analysis revealed several cyclopropane fatty acid synthases (CFAS) conserved in all Labrenzia strains analyzed and a putative gene cluster encoding for two distinct CFASs is proposed as the biosynthetic origin of 1 and 2.

Background. Prevalence of cognitive decline and dementia is rising globally, with more than 10 million new cases every year. These conditions cause a significant burden for individuals, their caregivers, and health care systems. As no causal treatment for dementia exists, prevention of cognitive decline is of utmost importance. Notably, alcohol is among the most significant modifiable risk factors for cognitive decline. Methods. Longitudinal data across 15 years on 6,967 individuals of the Survey of Health, Ageing and Retirement in Europe were used to analyze the effect of alcohol consumption and further modifiable (i.e., smoking, depression, and educational obtainment) and non-modifiable risk factors (sex and age) on cognitive functioning (i.e., memory and verbal fluency). For this, a generalized estimating equation linear model was estimated for every cognitive test domain assessed. Results. Consistent results were revealed in all three regression models: A nonlinear association between alcohol consumption and cognitive decline was found—moderate alcohol intake was associated with overall better global cognitive function than low or elevated alcohol consumption or complete abstinence. Furthermore, female sex and higher educational obtainment were associated with better cognitive function, whereas higher age and depression were associated with a decline in cognitive functioning. No significant association was found for smoking. Conclusion. Our data indicate that alcohol use is a relevant risk factor for cognitive decline in older adults. Furthermore, evidence-based therapeutic concepts to reduce alcohol consumption exist and should be of primary interest in prevention measures considering the aging European population. [ABSTRACT FROM AUTHOR]

Abstract Very low carbohydrate high fat (VLCHF) diet and high-intensity interval training (HIIT) are widely utilized for weight reduction and cardiorespiratory fitness improvement, respectively. To assess the acceptability of these approaches, it is essential to examine mental health-related indicators. This secondary analysis of a randomized controlled trial investigated the isolated and synergistic effects of VLCHF and HIIT on mental health-related indicators in individuals with excessive weight or obesity. Sixty-eight participants (age = 42 ± 10.2; 20–60 years; BMI = 29.8 ± 3.7) were analysed across four groups: HIIT (n = 15, 4 males, 11 females), VLCHF (n = 19, 4 males, 15 females), VLCHF + HIIT (n = 19, 4 males, 15 females), and control (n = 15, 4 males, 11 females). The 12-week intervention, involved VLCHF diet or HIIT sessions, depending on group affiliation and completing online questionnaires via Qualtrics software before and after the intervention. The questionnaires included the 12-item Short Form Survey (SF-12) for mental (MHS) and physical health scores (PHS), the Satisfaction with Life Scale (SWLS), and the Perceived Stress Scale (PSS). Using the Kruskal–Wallis test, we found no significant differences in mental health-related indicators between groups after 12 weeks, except for SWLS (p = 0.031; ES = 0.133; medium), which improved significantly in the VLCHF + HIIT group compared to the HIIT group. Our findings indicate that HIIT and VLCHF, alone or combined, do not significantly affect mental health-related indicators.

Background: Obesity is a global health issue affecting over 2 billion people. Mobile health apps, specifically nutrition apps, have been identified as promising solutions to combat obesity. However, research on adherence to nutrition apps is scarce, especially for publicly available apps without monetary incentives and personal onboarding. Understanding factors associated with adherence is essential to improve the efficacy of these apps. This study aims to identify such factors by analyzing a large dataset of a free and publicly available app (“MySwissFoodPyramid”) that promotes healthy eating through dietary self-monitoring and nutrition literacy delivered via a conversational agent. Methods: A retrospective analysis was conducted on 19,805 users who used the app for at least two days between November 2018 and May 2022. Adherence was defined as completing a food diary by tracking dietary intake over a suggested period of three days. Users who finished multiple diaries were considered long-term adherent. The associations between the day and time of installation, tutorial use, reminder use, and conversational agent choice were examined regarding adherence, long-term adherence, and the number of completed diaries. Results: Overall, 66.8% of included users were adherent, and 8.5% were long-term adherent. Users who started the intervention during the day (5 a.m.–7 p.m.) were more likely to be adherent and completed more diaries. Starting to use the intervention between Sunday and Wednesday was associated with better adherence and a higher number of completed diaries. Users who chose the female conversational agent were more likely to be adherent, long-term adherent, and completed more diaries. Users who skipped the tutorial were less adherent and completed fewer diaries. Users who set a follow-up reminder were more likely to be long-term adherent and completed more diaries. Conclusions: This study demonstrates the potential of digital health interventions to achieve comparably high adherence rates, even without monetary incentives or human-delivered support. It also reveals factors associated with adherence highlighting the importance of app tutorials, customizable reminders, tailored content, and the date and time of user onboarding for improving adherence to mHealth apps. Ultimately, these findings may help improve the effectiveness of digital health interventions in promoting healthy behaviors.

Abstract Background Breastfeeding is important for the healthy growth and development of newborns, and the nutrient composition of human milk can be affected by maternal nutrition and supplementation. In Germany, iodine supplementation is recommended for all lactating mothers, and docosahexaenoic acid (DHA) supplementation is recommended for mothers with inadequate or no fish intake. Vitamin B12 supplementation is required for strict vegans during lactation, and other nutrient supplementation may be necessary depending on the individual's nutritional status. To address the lack of data on dietary supplements used by lactating mothers following a vegetarian or vegan diet, an online survey was conducted in Germany, with a focus on iodine, DHA, and vitamin B12. Methods Study participants were asked to report whether they followed specific dietary patterns (omnivorous [OM], vegetarian [VT], vegan [VN]) as well as their use of dietary supplements. Relationships between diets and supplement use were analyzed using chi-square tests. Results 2054 lactating women were included (1240 OM, 410 VT, and 404 VN) in this analysis. Within OM, VT and VN, at least one dietary supplement was taken by 67.3%, 84.9% and 98.0% respectively (p

BackgroundLiver metastases are common in patients with breast cancer, and determining the factors associated with such metastases may improve both their early detection and treatment. Given that liver function protein level changes in these patients have not been determined, the aim of our study was to investigate liver function protein level changes over time, spanning 6 months before the detection of liver metastasis to 12 months after.MethodsWe retrospectively studied 104 patients with hepatic metastasis from breast cancer who were treated at the Departments of Internal Medicine I and the Department of Obstetrics and Gynecology at the Medical University of Vienna between 1980 and 2019. Data were extracted from patient records.ResultsAspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, lactate dehydrogenase and alkaline phosphatase were significantly elevated when compared to normal range 6 months before the detection of liver metastases (pConclusionLiver function protein levels should be considered as potential indicators when screening for liver metastasis in patients with breast cancer. With the new treatment options available, it could lead to prolonged life.

Abstract Background Prevalence of cognitive decline and dementia is rising globally, with more than 10 million new cases every year. These conditions cause a significant burden for individuals, their caregivers, and health care systems. As no causal treatment for dementia exists, prevention of cognitive decline is of utmost importance. Notably, alcohol is among the most significant modifiable risk factors for cognitive decline. Methods Longitudinal data across 15 years on 6,967 individuals of the Survey of Health, Ageing and Retirement in Europe were used to analyze the effect of alcohol consumption and further modifiable (i.e., smoking, depression, and educational obtainment) and non-modifiable risk factors (sex and age) on cognitive functioning (i.e., memory and verbal fluency). For this, a generalized estimating equation linear model was estimated for every cognitive test domain assessed. Results Consistent results were revealed in all three regression models: A nonlinear association between alcohol consumption and cognitive decline was found—moderate alcohol intake was associated with overall better global cognitive function than low or elevated alcohol consumption or complete abstinence. Furthermore, female sex and higher educational obtainment were associated with better cognitive function, whereas higher age and depression were associated with a decline in cognitive functioning. No significant association was found for smoking. Conclusion Our data indicate that alcohol use is a relevant risk factor for cognitive decline in older adults. Furthermore, evidence-based therapeutic concepts to reduce alcohol consumption exist and should be of primary interest in prevention measures considering the aging European population.

BackgroundNutrition apps are effective in changing eating behavior and diet-related health risk factors. However, while they may curb growing overweight and obesity rates, widespread adoption is yet to be achieved. Hence, profound knowledge regarding factors motivating and hindering (long-term) nutrition app use is crucial for developing design guidelines aimed at supporting uptake and prolonged use of nutrition apps. ObjectiveIn this systematic review, we synthesized the literature on barriers to and facilitators for nutrition app use across disciplines including empirical qualitative and quantitative studies with current users, ex-users, and nonusers of nutrition apps. MethodsA systematic literature search including 6 databases (PubMed, Web of Science, PsychINFO, PSYNDEX, PsycArticles, and SPORTDiscus) as well as backward and forward citation search was conducted. Search strategy, inclusion and exclusion criteria, and the planned data extraction process were preregistered. All empirical qualitative and quantitative studies published in German or English were eligible for inclusion if they examined adolescents (aged 13-18) or adults who were either current users, ex-users, and nonusers of nutrition apps. Based on qualitative content analysis, extracted individual barriers and facilitators were grouped into categories. ResultsA total of 28 publications were identified as eligible. A framework with a 3-level hierarchy was designed which grouped 328 individual barriers and facilitators into 23 subcategories, 12 categories, and 4 clusters that focus on either the individual user (goal setting and goal striving, motivation, routines, lack of awareness of knowledge), different aspects of the app and the smartphone (features, usability of the app or food database, technical issues, data security, accuracy/trustworthiness, costs), positive and negative outcomes of nutrition app use, or interactions between the user and their social environment. ConclusionsThe resulting conceptual framework underlines a pronounced diversity of reasons for (not) using nutrition apps, indicating that there is no “one-size-fits-all” approach for uptake and prolonged use of nutrition apps. Hence, tailoring nutrition apps to needs of specific user groups seems promising for increasing engagement.

Inherited platelet disorders (IPD) form a rare and heterogeneous disease entity that is present in about 8% of patients with non-acquired bleeding diathesis. Identification of the defective cellular pathway is an important criterion for stratifying the patient's individual risk profile and for choosing personalized therapeutic options. While costs of high-throughput sequencing technologies have rapidly declined over the last decade, molecular genetic diagnosis of bleeding and platelet disorders is getting more and more suitable within the diagnostic algorithms. In this study, we developed, verified, and evaluated a targeted, panel-based next-generation sequencing approach comprising 59 genes associated with IPD for a cohort of 38 patients with a history of recurrent bleeding episodes and functionally suspected, but so far genetically undefined IPD. DNA samples from five patients with genetically defined IPD with disease-causing variants in WAS, RBM8A, FERMT3, P2YR12, and MYH9 served as controls during the validation process. In 40% of 35 patients analyzed, we were able to finally detect 15 variants, eight of which were novel, in 11 genes, ACTN1, AP3B1, GFI1B, HPS1, HPS4, HPS6, MPL, MYH9, TBXA2R, TPM4, and TUBB1, and classified them according to current guidelines. Apart from seven variants of uncertain significance in 11% of patients, nine variants were classified as likely pathogenic or pathogenic providing a molecular diagnosis for 26% of patients. This report also emphasizes on potentials and pitfalls of this tool and prospectively proposes its rational implementation within the diagnostic algorithms of IPD.

Studies show that implicit and explicit attitudes influence food choice. However, precursors of food choice often are investigated using tasks offering a very limited number of options despite the comparably complex environment surrounding real life food choice. In the present study we investigated how the assortment impacts the relationship between implicit and explicit attitudes and food choice (confectionery and fruit), assuming that a more complex choice architecture is more taxing on cognitive resources. Specifically, a binary and a multiple option choice task based on the same stimulus set (fake food items) were presented to ninety-seven participants. Path modeling revealed that both explicit and implicit attitudes were associated with relative food choice (confectionery vs. fruit) in both tasks. In the binary option choice task, both explicit and implicit attitudes were significant precursors of food choice, with explicit attitudes having a greater impact. Conversely, in the multiple option choice task, the additive impact of explicit and implicit attitudes was qualified by an interaction indicating that, even if explicit and implicit attitudes towards confectionery were inconsistent, more confectionery was chosen than fruit if either was positive. This compensatory ‘one is sufficient’-effect indicates that the structure of the choice environment modulates the relationship between attitudes and choice. The study highlights that environmental constraints, such as the number of choice options, are an important boundary condition that need to be included when investigating the relationship between psychological precursors and behavior.