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Taylor dispersion analysis of micellization (TDAM) reveals distinct assembly and dissociation pathways of α-, β-, and κ-casein micelles
No full textCasein micelles are essential protein structures in milk and are crucial for its stability and nutritional properties. Understanding their self-assembly and dissociation dynamics is vital for applications in food science, biotechnology, and pharmaceuticals. In this study, we introduce Taylor Dispersion Analysis of Micellization (TDAM), a microcapillary-based technique combining intrinsic and extrinsic fluorescence detection to investigate the Ca2+-dependent colloidal stability, viscosity, and association/dissociation kinetics of α-, β-, and κ-casein (αCN, βCN, κCN) micelles. Our results reveal distinctly different behaviors between the types of caseins: αCN micelles exhibit the lowest stability, rapidly dissociating in the absence of Ca2+ and pronounced sensitivity to Ca2+-induced size changes. βCN forms concentration-dependent micellar species, with complex dissociation patterns, while κCN micelles remain highly stable under all investigated conditions. TDAM, complemented by dynamic light scattering (DLS) and finite element modeling, uncovers the critical influence of Ca2+ on micelle association, viscosity, and dissociation kinetics. Although excessive Ca2+ can induce aggregation and thereby reduce the colloidal stability of casein micelles, Ca2+ also promotes the formation of micellar aggregates that are more resistant to dissociation upon dilution under flow conditions and exhibit reduced monomer exchange rates, particularly for κCN. This study provides fundamental insights into casein micellization mechanisms, advancing the understanding of their structural and functional properties. The TDAM methodology offers a powerful tool for characterizing protein self-assembly in complex matrices, with broad implications for dairy science, biomaterials, and protein engineering.</p
Immunogenicity of SARS-CoV-2 primary vaccination and boosters in patients with immune-mediated inflammatory diseases:Impact of immunosuppressive therapy
No full textINTRODUCTION: Patients with immune-mediated inflammatory diseases (IMID) are at increased risk of severe COVID-19 infection. Their immunosuppressive treatment may lead to attenuated vaccine responses. In this study, we assessed the impact of specific immunosuppressive treatments on the immunogenicity of primary SARS-CoV-2 vaccination as well as booster vaccinations in IMID patients.MATERIAL AND METHODS: We included participants with IMID from the Danish ENFORCE cohort with baseline sampling prior to SARS-CoV-2 vaccination. Participants were followed for two years, with scheduled visits prior to vaccine dose 2, day 90, 180, 365 and 730 as well as before and after each booster dose. At all visits, seroconversion rates and quantitative SARS-CoV-2 Spike IgG antibody levels were assessed. Vaccine hyporesponsiveness, defined as <2log10 increase in SARS-CoV-2 Spike IgG levels from baseline, was evaluated at day 90 and again after the first booster.RESULTS: We included 282 patients with IMID and 482 immunocompetent controls. At day 90, patients with IMID treated with anti-CD20 antibodies or fingolimod exhibited markedly reduced seroconversion rates (27 % and 60 %, respectively, vs 100 % for controls), significantly lower antibody levels (2251 AU/mL [95 % CI: 888-5703] and 1743 AU/mL [95 % CI:784-3873] vs 186,308 AU/mL [95 % CI, 171366-202,552]) and higher odds of vaccine hyporesponsiveness (odds ratio (OR) = 67.5 [95 % CI, 25.4-179.7] and 82.5 [95 % CI, 29.6-196.3]). This impaired response persisted throughout the follow-up period, and anti-CD20 antibodies and fingolimod treated patients never reached antibody titers comparable to day 90 titers in controls, despite repeated booster vaccinations.CONCLUSION: Anti-CD20 antibody treatment and fingolimod severely impair humoral vaccine responses in IMID patients. In contrast, IMID patients treated with Methotrexate, TNF-alpha inhibitors, or other immunosuppressants mounted efficient vaccine responses. These findings support that tailored vaccine schedules with early and frequent boosters are crucial to protect this high-risk population.CLINICAL TRIAL REGISTRATION: EudraCT no, 2020-006003-42, NVK no. 1-10-72-337-20.</p
"Monkey influencers":conservation culturomics of human-macaque (<i>Macaca fascicularis</i>) interactions
No full textConservation culturomics can offer insights into the online presence of threatened primate species, such as the long-tailed macaque (Macaca fascicularis). The long-tailed macaque is the most commercially traded primate and increasingly exploited in the digital realm. By filtering content accessed via Application Programming Interfaces (APIs), we identified and analyzed 1366 posts and links involving long-tailed macaques across three major platforms: YouTube (611 posts; 44.73 %), Flickr (201 posts; 14.71 %), and Google (554 links; 40.56 %). More than two thirds (66.62 %) of the content was categorized as 'wildlife trade', of which 51 % pertained to "Pet Trade", 20 % to "Medical Trade", 9 % to "Entertainment Trade", and 21 % to "Other" content. The majority of the content analysed originated from Southeast Asian range countries, such as Indonesia and Thailand, where long-tailed macaques were frequently featured as part of unethical or exploitative content. Based on IP-addresses, most content originated from Indonesia, while the USA accounted for most viewers. In light of our findings, we emphasize the need to promote responsible online engagement to prevent negative consequences such as the normalization of some human-macaque interactions (e.g., in the pet trade) that may affect long-tailed macaque conservation and welfare. By leveraging digital methodologies, this paper contributes to the broader field of primate conservation, offering insights into future conservation measures employing machine learning
Mental health, coping and related risk factors during the first 2 years of the COVID-19 pandemic in children:Nationally representative, multi-wave, cross-sectional results from 12 countries from the global COH-FIT study
No full textFew multinational studies have assessed risk factors and coping strategies associated with the impact of the COVID-19 pandemic on children’s mental health over time. The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is the largest transcontinental, multi-wave, cross-sectional survey collecting multi-nation data on well-being and psychopathology during the pandemic. We analyzed country-specific, general-population-based, representative COH-FIT data of 6067 children aged 6–13 years from 12 countries across repeated cross-sectional waves over a period of >2 years (Apr/2020–May/2022), addressing through current and retrospective assessment pre- to intra-pandemic changes in well-being (WHO-5) and general psychopathology scores (Pc) (0–100) in relation to COVID-related deaths, stringency index, eight a priori risk factors, and 16 coping strategies in different responders at each wave. From pre- to intra-pandemic, WHO-5 scores decreased (−4.59, 95 %CI=−6.18 to −2.99, p < 0.001), while PC-scores increased (+6.68, 95 %CI=4.48–8.88, p < 0.001) significantly, following distinct time patterns but both returning to near pre-pandemic levels. Changes in both scores varied by country. WHO-5 scores correlated strongly with PC and subdomain scores. Both score changes were significantly but minimally associated to COVID-19 deaths/stringency index. The proportion of children screening positive for depression increased from 3.9 % to 8.3 % (χ²=145.70, p < 0.001) and for major depression from 0.6 % to 2.2 % (χ²=68.64, p < 0.001) intrapandemic. WHO-5 and PC-score changes were significantly associated with female gender, school closure, and pre-existing physical and mental conditions, with cumulative effects. The five most frequently endorsed coping strategies were family contact (85.2 %), friends (67.3 %), outdoor play (54.0 %), pet interaction (51.5 %), and internet use (50.9 %). Identified risk groups and coping strategies can inform targeted interventions and global public health policy. Trial Registration: ClinicalTrials.gov;</p
Plasma growth differentiation factor-15 is associated with cardiovascular events in patients hospitalized for acute exacerbation of COPD
No full textPatients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are at increased risk of major adverse cardiovascular events (MACE) and death. Growth differentiation factor-15 (GDF-15), a marker of cellular stress and inflammation, and Syndecan-1, a marker of endothelial dysfunction, have been suggested as prognostic biomarkers in plasma for MACE. We aimed to assess their association with a combined outcome of MACE or all-cause mortality over a 5-year period. This sub-study was embedded within the randomized controlled trial CORTICOsteroid reduction in COPD (CORTICO-COP), which investigated the effects of eosinophil-guided corticosteroid therapy in patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A total of 299 patients hospitalized with AECOPD were included in this analysis. Baseline plasma concentrations of growth differentiation factor 15 (GDF-15) and Syndecan-1 were measured and stored in a biobank for later analysis. The primary outcome was MACE or all-cause mortality, secondary outcomes included heart failure, re-AECOPD, and all-cause mortality. Hazard ratios (HRs) between low and high biomarker levels were adjusted for age, smoking, sex, GOLD class, and kidney insufficiency. The area under the receiver operating curve (AUC) was reported for each model after 6 months and two years respectively. Among the 299 hospitalized AECOPD patients included in this sub-study of the randomized controlled trial CORTICOsteroid reduction in COPD (CORTICO-COP), higher baseline concentrations of GDF-15 were associated with an increased risk of the combined outcome of MACE or all-cause mortality (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.16-2.44, p = 0.007), as well as all-cause mortality alone (HR 1.5, 95% CI 1.07-2.19, p = 0.02). GDF-15 showed moderate discriminative ability for survival, with an AUC of 64% at 6 months and 60% at 2 years. No significant associations were observed between GDF-15 and heart failure or hospital re-admission due to respiratory disease. Syndecan-1 concentrations were not associated with the combined endpoint or any of the secondary outcomes. GDF-15 may identify AECOPD patients at risk of MACE and all-cause mortality. Syndecan-1 has no predictive value in AECOPD patients.</p