Einfluss von n3-PUFA auf den Verlauf des exspiratorischen NO unter niedrig-dosierter Allergenbelastung bei milden allergischen Asthmatikern

Asthma bronchiale bezeichnet eine chronisch entzündliche Erkrankung der Atemwege, wobei die milden Verlaufsformen die höchsten Prävalenzen haben. Außer den antiinflammatorisch wirksamen Substanzgruppen (Glucocorticoide, Leukotrien-Rezeptor-Antagonisten) stellt eine Nahrungsergänzung mit n3-PUFA eine interessante Behandlungsalternative dar. Ziel dieser Studie war es, den Einfluss von n3-PUFA speziell auf die allergische Entzündung von milden Asthmatikern (n=23) zu untersuchen. Als primärer Wirkparameter wurde das eNO, ein spezifischer und sensibler Marker der allergischen Entzündung in den Atemwegen allergischer Asthmatiker untersucht. Die Patienten bekamen fünf Wochen lang entweder n3-PUFA (450 mg EPA und 180 mg DHA pro Tag) oder Plazebo als Nahrungsergänzung. Nach einer dreiwöchigen Aufsättigungsphase wurden die Patienten zwei Wochen lang mit einer niedrigen Dosis Hausstaubmilbenallergen provoziert, an jedem Termin wurde die Konzentration des eNO gemessen. Es war deutlich zu erkennen, das in der n3-PUFA-Gruppe die Entzündung weniger stark ausgeprägt war (Visite 6 Mittelwert Plazebo 153,7±21,1 ppb, n3-PUFA 91,8±16,7 ppb; p= 0,03 und Visite 7 Mittelwert Plazebo 117,4±18,8 ppb, n3-PUFA 68,1±11,4 ppb p=0,03). In der zweiten Provokationswoche kam es in beiden Gruppen zu einem weiteren Anstieg des eNO, in der n3-PUFAGruppe waren dir Werte jedoch durchweg niedriger. In der Studie konnte gezeigt werden, dass auch niedrig dosierte n3-PUFA einen positiven Effekt auf die allergische Entzündung in den Atemwegen allergischer Asthmatiker hat. Die eNO Werte waren in der n3-PUFA-Gruppe Studie durchgehend niedriger als in der Plazebo-Gruppe. Die Einnahme von n3-PUFA könnte bei milden Asthmatikern durchaus einen Therapie-Unterstützenden Effekt aufweisen, so dass unter Therapie mit den gängigen Asthma-Medikamenten, diese durchaus in einem gewissen Maße eingespart werden könnten.We investigated the anti-inflammatory potential of n– 3 polyunsaturated fatty acids (PUFA) on specific bronchial inflammation. Allergic asthmatics were challenged using a low-dose allergen provocation model. Our parallel double-blinded study randomly assigned 23 house dust mite-allergic asthmatics (aged 22–29 years; 13 females, 10 males) to dietary supplementation with either an n–3 PUFA-enriched fat blend (0.69 g/day) or placebo for 5 weeks. After 3 weeks, the patients were challenged daily with low doses of mite allergen for 2 weeks. Primary outcome parameters were effects on lung function (forced expiratory volume in 1 s, FEV 1 ) and exhaled nitric oxide (eNO) as a marker of bronchial inflammation. Even before the bronchial challenge, eNO was significantly lower in the n–3 PUFA group (p = 0.014). Levels of eNO increased during allergen exposure in both groups, but differences in means were significantly lower in the n–3 PUFA group (p = 0.022). During the low-dose allergen challenge, there were no differences between the groups with regard to symptoms, FEV1 or the allergen dose required to induce deterioration of lung function (PD20). Numbers of sputum eosinophils did not differ significantly, while serum eosinophils (10.1 ± 0.1.84 vs. 5.79 ± 0.69%) as well as changes in eosinophilic cationic protein (20.5 ± 9.93 vs. –1.68 ± 4.36 ng/ml) and in vitro cysteinyl leukotriene release (2,889 ± 872 vs. 1,120 ± 173 ng/ml) were significantly lower in the n–3 PUFA group (p < 0.05 each). Our results provide evidence that dietary supplementation with n–3 PUFA is able to reduce bronchial inflammation even after low-dose allergen challenge

Zebra dolomites of the Spessart, Germany: implications for hydrothermal systems of the European Zechstein Basin

Zebra dolomites have a distinctive texture and are a peculiar structural variety of dolostones often encountered in the vicinity of base metal deposits commonly in the Mississippi Valley-Type (MVT). We investigate origin and evolution of the zebra dolomites found in the region of the Spessart, northwestern Bavaria, Germany, through diagenetic and petrogenetic analysis using SEM, CL microscopy, O–C isotopes, and fluid inclusion micro-thermometry. Here, we aim to shed light on the nature of the fluids that altered the zebra dolomite of the Zechstein formation. We distinguish the geochemical signatures of two different fluid flow regimes post-dating texture formation, each characterized by specific homogenization temperatures and oxygen–carbon isotope ratios (Event 1: Th = 120 °C; δ18Ofluids = [0 to 2‰]; Event 2; Th = 300 °C; δ18Ofluids = 18‰). Comparison of these fluids and the associated mineralization with published regional fluid flow data support that the zebra dolomites in the Spessart most likely coincided with the Permian large-scale fluid flow event that occurred throughout the European Zechstein Basin

Enabling the freight traffic controller for collaborative multi-drop urban logistics: practical and theoretical challenges

There is increasing interest in how horizontal collaboration between parcel carriers might help alleviate problems associated with last-mile logistics in congested urban centers. Through a detailed review of the literature on parcel logistics pertaining to collaboration, along with practical insights from carriers operating in the United Kingdom, this paper examines the challenges that will be faced in optimizing multicarrier, multidrop collection, and delivery schedules. A “freight traffic controller” (FTC) concept is proposed. The FTC would be a trusted third party, assigned to equitably manage the work allocation between collaborating carriers and the passage of vehicles over the last mile when joint benefits to the parties could be achieved. Creating this FTC concept required a combinatorial optimization approach for evaluation of the many combinations of hub locations, network configuration, and routing options for vehicle or walking to find the true value of each potential collaboration. At the same time, the traffic, social, and environmental impacts of these activities had to be considered. Cooperative game theory is a way to investigate the formation of collaborations (or coalitions), and the analysis used in this study identified a significant shortfall in current applications of this theory to last-mile parcel logistics. Application of theory to urban freight logistics has, thus far, failed to account for critical concerns including (a) the mismatch of vehicle parking locations relative to actual delivery addresses; (b) the combination of deliveries with collections, requests for the latter often being received in real time during the round; and (c) the variability in travel times and route options attributable to traffic and road network conditions

Psycho-social factors associated with mental resilience in the Corona lockdown.

The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social outcomes, as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. To gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (22 March to 19 April) in a convenience sample of N = 15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience (p < 0.0001). The resilience factor PAS also partly mediated the positive association between perceived social support and resilience, and its association with resilience was in turn partly mediated by the ability to easily recover from stress (both p < 0.0001). In comparison with other resilience factors, good stress response recovery and positive appraisal specifically of the consequences of the Corona crisis were the strongest factors. Preregistered exploratory subgroup analyses (osf.io/thka9) showed that all tested resilience factors generalize across major socio-demographic categories. This research identifies modifiable protective factors that can be targeted by public mental health efforts in this and in future pandemics

GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors

Objective: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and crossvalidated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS metaanalysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. Methods: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. Results: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values &lt;5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. Conclusions: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.</p

GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors

OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. RESULTS: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values \u3c5×10 CONCLUSIONS: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Predicting the next pandemic: VACCELERATE ranking of the World Health Organization's Blueprint for Action to Prevent Epidemics

Introduction: The World Health Organization (WHO)'s Research and Development (R&D) Blueprint for Action to Prevent Epidemics, a plan of action, highlighted several infectious diseases as crucial targets for prevention. These infections were selected based on a thorough assessment of factors such as transmissibility, infectivity, severity, and evolutionary potential. In line with this blueprint, the VACCELERATE Site Network approached infectious disease experts to rank the diseases listed in the WHO R&D Blueprint according to their perceived risk of triggering a pandemic. VACCELERATE is an EU-funded collaborative European network of clinical trial sites, established to respond to emerging pandemics and enhance vaccine development capabilities. Methods: Between February and June 2023, a survey was conducted using an online form to collect data from members of the VACCELERATE Site Network and infectious disease experts worldwide. Participants were asked to rank various pathogens based on their perceived risk of causing a pandemic, including those listed in the WHO R&D Blueprint and additional pathogens. Results: A total of 187 responses were obtained from infectious disease experts representing 57 countries, with Germany, Spain, and Italy providing the highest number of replies. Influenza viruses received the highest rankings among the pathogens, with 79 % of participants including them in their top rankings. Disease X, SARS-CoV-2, SARS-CoV, and Ebola virus were also ranked highly. Hantavirus, Lassa virus, Nipah virus, and henipavirus were among the bottom-ranked pathogens in terms of pandemic potential. Conclusion: Influenza, SARS-CoV, SARS-CoV-2, and Ebola virus were found to be the most concerning pathogens with pandemic potential, characterised by transmissibility through respiratory droplets and a reported history of epidemic or pandemic outbreaks

Resilience and depressive symptoms in inpatients with depression: a cross-lagged panel model

Resilience—the ability to bounce back or quickly recover from stress—has been found to predict treatment outcome in patients with mental disorders such as depression. Yet, there are mixed findings whether resilience itself changes during treatment and whether resilience exclusively predicts changes in depressive symptoms or whether depressive symptoms also predict changes in resilience. Inpatients with depression (N = 2165; average length of stay M = 60 days, SD = 32) completed the Brief Resilience Scale and the Patient Health Questionnaire Depression Scale at admission and discharge. Resilience increased and depressive symptoms decreased from admission to discharge. Cross-sectionally, higher resilience related to lower depressive symptoms at admission and discharge. Prospectively, a cross-lagged panel model revealed that higher resilience at admission predicted stronger decreases in depressive symptoms and that higher depressive symptoms at admission predicted smaller increases in resilience. The current study further supports that resilience is not only related to fewer mental health problems cross-sectionally but is also sensitive to change and a predictor of treatment outcome in patients with mental disorders. Given this pivotal role in mental health, the current findings highlight the importance of prevention and intervention approaches for promoting resilience in the general population and in persons with mental disorders in particular