The human umbilical cord (hUC) is the lifeline that connects the fetus to the mother. Hypercoiling of the hUC is associated with pre- and perinatal morbidity and mortality. We investigated the... Show moreThe human umbilical cord (hUC) is the lifeline that connects the fetus to the mother. Hypercoiling of the hUC is associated with pre- and perinatal morbidity and mortality. We investigated the origin of hUC hypercoiling using state-of-the-art imaging and omics approaches. Macroscopic inspection of the hUC revealed the helices to originate from the arteries rather than other components of the hUC. Digital reconstruction of the hUC arteries showed the dynamic alignment of two layers of muscle fibers in the tunica media aligning in opposing directions. We observed that genetically identical twins can be discordant for hUC coiling, excluding genetic, many environmental, and parental origins of hUC coiling. Comparing the transcriptomic and DNA methylation profile of the hUC arteries of four twin pairs with discordant cord coiling, we detected 28 differentially expressed genes, but no differentially methylated CpGs. These genes play a role in vascular development, cell–cell interaction, and axis formation and may account for the increased number of hUC helices. When combined, our results provide a novel framework to understand the origin of hUC helices in fetal development. Show less
Morwani-Mangnani, J.; Rodriguez-Girondo, M.; Singh-Povel, C.; Verlaan, S.; Beekman, M.; Slagboom, P.E. 2024
Background: Aging triggers intricate physiological changes, particularly in whole-body fat-free mass (FFM) and handgrip strength, affecting overall health and independence. Despite existing... Show moreBackground: Aging triggers intricate physiological changes, particularly in whole-body fat-free mass (FFM) and handgrip strength, affecting overall health and independence. Despite existing research, the broader significance of how muscle health is affected by the intricate interplay of lifestyle factors simultaneously during aging needs more exploration. This study aims to examine how nutrition, physical activity, and sleep impact on FFM and handgrip strength in middle-aged men and women, facilitating future personalized recommendations for preserving muscle health. Methods: The cross-sectional analysis of the UK Biobank involved 45,984 individuals (54 % women) aged 40–70 years with a complete dataset. Multiple linear regression explored determinants of FFM and handgrip strength, considering traditional, socio-demographics, medication use and smoking as covariates, with sex and age (younger and older than 55 years) stratifications. Results: In older men and women, higher physical activity beneficially affect both FFM (respectively В = 3.36 × 10− 3 , p-value = 1.66 × 10− 3 ; В = 2.52 × 10− 3 , p-value = 3.57 × 10− 4 ) and handgrip strength (В = 6.05 × 10− 3 , p-value = 7.99 × 10− 5 , В = 8.98 × 10− 3 , p-value = 2.95 × 10− 15). Similar results were found in fiber intake for FFM in older men and women (respectively B = 3.00 × 10− 2 , p-value = 2.76 × 10− 5 ; B = 2.68 × 10− 2 , p-value = 1.78 × 10− 9 ) and handgrip strength (В = 3.27 × 10− 2 , p-value = 1.40 × 10− 3 ; В = 3.12 × 10− 2 , p-value = 1.34 × 10− 5 ). Other lifestyle factors influence FFM and handgrip strength differently. Key determinants influencing handgrip strength included higher protein intake, lower water intake, higher alcohol intake, and extended sleep duration whereas mainly higher water intake is associated with higher FFM. Conclusions: In both men and women, the main factors associated with FFM and handgrip strength are physical activity and fiber intake, which may underlie a connection between gut and muscle health. Given the observed complexity of muscle health in the age and sex strata, further longitudinal research is needed to provide personalized lifestyle recommendations. Show less
Background: Travellers visiting rabies-endemic countries are at risk of rabies infection. Assessing travellers’ knowledge and risk perception of rabies and risk behaviour during travel can help... Show moreBackground: Travellers visiting rabies-endemic countries are at risk of rabies infection. Assessing travellers’ knowledge and risk perception of rabies and risk behaviour during travel can help identify knowledge gaps and improve pre-travel risk education. Methods: Cohort study in Dutch adult travellers, using two surveys: one before travel to assess knowledge and perception of rabies, and one after return to identify risk behaviour during travel. Results: The pre-travel and post-travel survey were completed by 301 and 276 participants, respectively. 222 participants had travelled to a high-risk rabies-endemic country. 21.6 % of the participants scored their rabies knowledge as poor. Some participants were unaware cats or bats can transmit rabies (26.6 % and 13.6 %, respectively), or that post-exposure prophylaxis (PEP) is required for certain exposures such as skin abrasions without bleeding or licks on damaged skin (35.5 % and 18.9 %, respectively), while 27.9 % of participants did not know PEP needs to be administered within one day. 115 participants (51.8 %) reported any form of contact with any animal during travel. Two participants reported animal exposure, of which one took adequate PEP measures. Risk factors for animal contact abroad were regularly touching cats or dogs at home or abroad, longer travel duration, having pets during childhood and being an animal lover. Conclusions: Pre-travel rabies risk education currently does not meet travellers’ needs, which is reflected in knowledge gaps and engagement in risk behaviour during travel. During pre-travel health advice, avoiding animal contact abroad should be emphasized, and additional education is required about indications for PEP. Show less
Objectives: The study aimed to investigate the added value of blood glucose monitoring in high-risk individuals (HRIs) participating in pancreatic cancer surveillance. Materials and Methods: High... Show moreObjectives: The study aimed to investigate the added value of blood glucose monitoring in high-risk individuals (HRIs) participating in pancreatic cancer surveillance. Materials and Methods: High-risk individuals with a CDKN2A/p16 germline pathogenic variant participating in pancreatic cancer surveillance were included in this study. Multivariable logistic regression was performed to assess the relationship between new-onset diabetes (NOD) and pancreatic ductal adenocarcinoma (PDAC). To quantify the diagnostic performance of NOD as a marker for PDAC, receiver operating characteristic curve with area under the curve was computed. Results: In total, 220 HRIs were included between 2000 and 2019. Median age was 61 (interquartile range. 53–71) years and 62.7% of participants were female. During the study period, 26 (11.8%) HRIs developed NOD, of whom 5 (19.2%) later developed PDAC. The other 23 (82.1%) PDAC cases remained NOD-free. Multivariable analysis showed no statistically significant relationship between NOD and PDAC (odds ratio, 1.21; 95% confidence interval, 0.39–3.78) and 4 of 5 PDAC cases seemed to have NOD within 3 months before diagnosis. Furthermore, NOD did not differentiate between HRIs with and without PDAC (area under the curve, 0.54; 95% confidence interval, 0.46–0.61). Conclusions: In this study, we found no added value for longitudinal glucose monitoring in CDKN2A pathogenic variant carriers participating in an imaging-based pancreatic cancer surveillance program. Show less
The environmental impact of traded plastic waste hinges on how it is treated. Existing studies often use domestic or scenario-based recycling rates for imported plastic waste, which is problematic... Show moreThe environmental impact of traded plastic waste hinges on how it is treated. Existing studies often use domestic or scenario-based recycling rates for imported plastic waste, which is problematic due to differences in recyclability and the fact that importers pay for it. We estimate the minimum required recycling rate (RRR) needed to break even financially by analysing import prices, recycling costs, and the value of recycled plastics across 22 leading importing countries and four plastic waste types during 2013–2022. Here we show that at least 63% of imported plastic waste must be recycled, surpassing the average domestic recycling rate of 23% by 40 percentage points. This discrepancy suggests that recycled plastics volumes from the global North-to-South trade may be underestimated. The country-specific RRR provided could enhance research and policy efforts to better quantify and mitigate the environmental impact of plastic waste trade. Show less
As cousins, we discovered a treasure trove of family papers, revealing the intricate relationship between precarity and privilege of our family from Salonica navigating the post-Ottoman transition.... Show moreAs cousins, we discovered a treasure trove of family papers, revealing the intricate relationship between precarity and privilege of our family from Salonica navigating the post-Ottoman transition. Recognising the potential of family history to provide a more intimate and complex historiography, this article offers our initial study of these family papers. By highlighting the challenges posed by the scarcity of such documents in Middle Eastern studies, emphasising women’s roles in preserving family memory and focussing on the interplay between personal and political domains, we identify the preparation of a family tree as a gendered and socioeconomic project of preserving the past and shaping the present. By tracing our family's origins, including unsettling discoveries, we address matters of identity and memory before embarking on our analysis. By reconstructing the biographies of two generations, we characterise the family’s socioeconomic struggle to sustain their precarious privilege amid shifting frontiers and along their journey from Ottoman Salonica to Kemalist Turkey. Ultimately, this article underscores the significance of family history as a transnational, intergenerational, intersectional and social history that enriches our understanding of the post-Ottoman transition through the lives of ordinary (and some extraordinary) Ottomans. Show less
The goal of the study was to describe the population pharmacokinetics of trimethoprim, sulfamethoxazole, and N-acetyl sulfamethoxazole in hospitalized patients. Furthermore, this study used the... Show moreThe goal of the study was to describe the population pharmacokinetics of trimethoprim, sulfamethoxazole, and N-acetyl sulfamethoxazole in hospitalized patients. Furthermore, this study used the model to optimize dosing regimens of cotrimoxazole for Pneumocystis jirovecii pneumonia and in patients with renal insufficiency or with continuous renal replacement therapy (CRRT). This was a retrospective multicenter observational cohort study based on therapeutic drug monitoring (TDM) data from hospitalized patients treated with cotrimoxazole. We developed two population pharmacokinetic (POPPK) models: a model of trimethoprim and an integrated model with both sulfamethoxazole and N-acetyl sulfamethoxazole concentrations. Monte Carlo simulations were performed to determine the optimal dosing regimen. A total of 348 measurements from 168 patients were available. The estimated glomerular filtration rate (eGFR) and CRRT were included as covariates on the clearance of all three compounds. Cotrimoxazole TID 1,920 mg and b.i.d. 2,400 mg led to sufficient exposure for infections with P. jirovecii in patients without renal insufficiency. To reach equivalent exposure, a dose reduction of 33.3% is needed in patients with an eGFR of 10 mL/minute/1.73 m2 and of 16.7% for an eGFR of 30 mL/minute/1.73 m2. N-acetyl sulfamethoxazole accumulates in patients with a reduced eGFR. CRRT increased the clearance of sulfamethoxazole, but not trimethoprim or N-acetyl sulfamethoxazole, compared with the median clearance in the population. Doubling the sulfamethoxazole dose is needed for patients on CRRT to reach equivalent exposure. Show less
Wastewater-based epidemiological surveillance at municipal wastewater treatment plants has proven to play an important role in COVID-19 surveillance. Considering international passenger hubs... Show moreWastewater-based epidemiological surveillance at municipal wastewater treatment plants has proven to play an important role in COVID-19 surveillance. Considering international passenger hubs contribute extensively to global transmission of viruses, wastewater surveillance at this type of location may be of added value as well. The aim of this study is to explore the potential of long-term wastewater surveillance at a large passenger hub as an additional tool for public health surveillance during different stages of a pandemic. Here, we present an analysis of SARS-CoV-2 viral loads in airport wastewater by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) from the beginning of the COVID-19 pandemic in Feb 2020, and an analysis of SARS-CoV-2 variants by whole-genome next-generation sequencing from Sep 2020, both until Sep 2022, in the Netherlands. Results are contextualized using (inter)national measures and data sources such as passenger numbers, clinical surveillance data and national wastewater surveillance data. Our findings show that wastewater surveillance was possible throughout the study period, irrespective of measures, as viral loads were detected and quantified in 98.6 % (273/277) of samples. Emergence of SARS-CoV-2 variants, identified in 91.0 % (161/177) of sequenced samples, coincided with increases in viral loads. Furthermore, trends in viral load and variant detection in airport wastewater closely followed, and in some cases preceded, trends in national daily average viral load in wastewater and variants detected in clinical surveillance. Wastewater-based epidemiology at a large international airport is a valuable addition to classical COVID-19 surveillance and the developed expertise can be applied in pandemic preparedness plans for other (emerging) pathogens in the future. Show less
As China’s internet has matured, from its initial web-based origins through innovative ‘2.0’ and ‘3.0’ innovations, so too have the community sentiments that criss-cross the People’s Republic of... Show moreAs China’s internet has matured, from its initial web-based origins through innovative ‘2.0’ and ‘3.0’ innovations, so too have the community sentiments that criss-cross the People’s Republic of China’s networked society. A perennial issue has been the question of how Chinese nationhood has been constructed and reproduced through digital technologies and how the evolving affordances of internet technology have contributed to China’s many nationalisms. This short essay reflects on this history. It discusses how early internet forums and blogs allowed users to coordinate their sense of Chineseness, how these processes later changed when communication moved to widely adopted microblogging platforms and what we can expect of the future, as China’s media environments shift their focus towards short-messaging applications and video-sharing platforms. What will happen to Chinese nationalisms as China’s platformisation enters its next phases? Show less
Tuberculosis (TB) has been and still is a global emergency for centuries. Prevention of disease through vaccination would have a major impact on disease prevalence, but the only available current... Show moreTuberculosis (TB) has been and still is a global emergency for centuries. Prevention of disease through vaccination would have a major impact on disease prevalence, but the only available current vaccine, BCG, has insufficient impact. In this article, a novel subunit vaccine against TB was developed, using the Ag85B-ESAT6-Rv2034 fusion antigen, two adjuvants - CpG and MPLA, and a cationic pH-sensitive liposome as a delivery system, representing a new TB vaccine delivery strategy not previously reported for TB. In vitro in human dendritic cells (DCs), the adjuvanted formulation induced a significant increase in the production of (innate) cytokines and chemokines compared to the liposome without additional adjuvants. In vivo, the new vaccine administrated subcutaneously significantly reduced Mycobacterium tuberculosis (Mtb) bacterial load in the lungs and spleens of mice, significantly outperforming results from mice vaccinated with the antigen mixed with adjuvants without liposomes. In-depth analysis underpinned the vaccine's effectiveness in terms of its capacity to induce polyfunctional CD4+ and CD8+ T-cell responses, both considered essential for controlling Mtb infection. Also noteworthy was the differential abundance of various CD69+ B-cell subpopulations, which included IL17-A-producing B cells. The vaccine stimulated robust antigen-specific antibody titers, further extending its potential as a novel protective agent against TB. Show less
Tan, N.H.; Lafeber, M.; Sablerolles, R.S.G.; Roders, I.V.; Hoef, A. van de; Grafhorst, K. van; ... ; Kuy, P.H.M. van der 2024
Background Electronic informed consent (eConsent) usage has expanded in recent years in Europe, especially during the pandemic. Slow recruitment rate and limitations in participant outreach are the... Show moreBackground Electronic informed consent (eConsent) usage has expanded in recent years in Europe, especially during the pandemic. Slow recruitment rate and limitations in participant outreach are the challenges often faced in clinical research. Given the benefts of eConsent and group counselling reported in the literature, group eConsent was implemented in recruitment for the SWITCH-ON study. We aim to explore the experience of participants who attended group eConsent for the SWITCH-ON study and evaluate its potential for future use. Methods SWITCH-ON study aims to analyse the immunogenicity of a healthy population following bivalent COVID19 booster vaccination. Four hundred thirty-four healthcare workers aged 18–65 were successfully recruited and sent a questionnaire about their experience with group eConsent. Out of 399 completed questionnaires (response rate 92%), 39 participants did not join group eConsent. The remaining 360 responses were included in the fnal analysis. Quantitative and qualitative data were reported using descriptive statistical analysis and thematic analysis respectively. Results Participants found that group eConsent was an efcient method that it allowed them to hear each other’s questions and concerns and created a sense of togetherness. However, limited privacy, barriers to asking questions in a group, and peer pressure can limit the use of group eConsent. One hundred sixty-fve (46%) participants thought that group eConsent was suitable to recruit participants with diseases or conditions, while 87 (24%) reported limitations with this method. The remaining participants suggested that applicability of group eConsent depended on the diseases or conditions of the study population, and one-to-one conversation should always be available. Participants who had experienced both one-to-one and group eConsent shared diferent preferred consent formats for future studies. Conclusion Group eConsent was positively evaluated by the participants of a low-risk vaccination study. Participants advised using webinars to provide general information about the study, followed by an individual session for each participant, would retain the benefts of group eConsent and minimise the limitations it posed. This proposed setting addresses privacy questions and makes group eConsent easier to implement. Show less
Caenegem, W. van; Boeken, M.; Dees, A.J.; Lubbers, M.; Moereels, L.; Schilthuizen, M.; ... ; Haelewaters, D. 2024
Twenty-three species of Laboulbeniales (Fungi, Ascomycota) are reported for the first time from the Netherlands. These are Appendiculina scaptomyzae, Autoicomyces aquatilis, Cantharomyces...Show moreTwenty-three species of Laboulbeniales (Fungi, Ascomycota) are reported for the first time from the Netherlands. These are Appendiculina scaptomyzae, Autoicomyces aquatilis, Cantharomyces denigratus, Chitonomyces hydropori, Eusynaptomyces hydrobii, Hesperomyces coccinelloides, Hydrophilomyces atroseptatus, Laboulbenia expectata sp. nov., L. hyalopoda, L. murmanica, L. ophoni, L. thaxteri, Rhachomyces lavagnei, Rhadinomyces cristatus, Rhynchophoromyces anacaenae, Stigmatomyces crassicollis, S. divergatus, S. ephydrae, S. geomyzae, S. ptilomyiae,S. purpureus, Tavaresiella hebri, and Thripomyces tessinensis. Laboulbenia expectata sp. nov. is uniquely associated with Pterostichus vernalis and is also reported from Belgium, Czechia, Denmark, Germany, Poland, and Spain. Morphological characteristics and a four-locus phylogenetic reconstruction recognized it as a new species in the L. flagellata species complex. New host species for the Netherlands are reported for Chitonomyces bidessarius, Hydraeomyces halipli, and Zodimyces vorticoellarius. Show less
