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Montessori education has existed for more than 100 years and counts almost 16,000 schools worldwide (Debs et al., 2022). Still, little is known about the implementation and fidelity of Montessori principles. Measuring implementations holds significant importance as it provides insight into current Montessori practices and because it is assumed that implementation might influence its effectiveness. In the Netherlands, it is especially important to measure fidelity because of the country's history of flexible implementation of Montessori principles. No instruments currently exist that are specifically designed to measure Montessori implementation in the Dutch context. This study aims to validate a translated version of the Teacher Questionnaire for Montessori Practices, developed by Murray et al. (2019), within the Dutch early childhood education context. Additionally, it seeks to investigate the extent to which Montessori principles are implemented in Dutch early childhood schools. Data were collected from 131 early childhood Montessori teachers. Confirmatory factor analysis revealed that the Dutch dataset did not align with the factor structure proposed by Murray et al. (2019). Subsequent exploratory factor analysis led to the identification of a 3-factor solution, encompassing dimensions related to Children's Freedom, Teacher Guidance, and Curriculum, which shows some similarities with Murray et al.'s (2019) factors. Implementation levels in the Netherlands varied, with the highest level of implementation observed in Children's Freedom and the lowest in Curriculum.

The purpose of this study is to synthesize Montessori's writings on citizenship education to support the implementation of a Montessorian view. This synthesis demonstrates that Montessori was of the explicit conviction that a better world can be achieved through citizenship education, as it strives for a peaceful and harmonious society. We approach this topic through the Dutch context. Although schools in the Netherlands are required by law to promote active citizenship and social cohesion, this law does not stipulate which of the many different views on citizenship education schools must adhere to. Schools have the liberty to devise their own citizenship curricula if they can substantiate their views and choices. For Montessori schools, this requires insight into Montessori's view on citizenship education. Although Montessori's views are still largely appropriate in our time, an ongoing dialogue about citizenship education is required, as Montessori lived and worked in a specific geopolitical context. Based on our analysis, we have identified seven themes that characterize Montessori's view on citizenship education: one common citizenship goal; preparation for independent thinking and action; image of the future citizen; adapted and critical citizens; humanity for harmony; knowledge as prerequisite, personality development as goal; and an ever-expanding worldview. The results of this study provide valuable insights for designing and teaching citizenship education through a Montessorian lens.

Abstract Objective To assess common gastrointestinal symptoms in healthy Brazilian infants receiving goat milk-based formula (GMF) compared to cow’s milk-based formula (CMF). Methods We performed a 24-weeks double-blind, randomized, controlled study in Brazil, enrolling healthy infants from 3 to 12 months of age. Primary outcome were the gastrointestinal (GI) symptoms stool consistency, regurgitation frequency and crying duration. Secondary outcomes were growth trajectories and hemoglobin levels. Repeated mixed models were used to compare outcomes variables between GMF and CMF groups, while adjusting for age at baseline. Results Fifty-six infants were recruited and randomly allocated in the GMF (n = 26) and the CMF (n = 30) group. Scores on all measured GI symptoms were low and similar among the groups throughout intervention period and improved over time. Average age- and sex-adjusted WHO z-scores of weight, length, head circumference, and weight-for-length were all within +/-1 SD and similar between groups, indicating adequate growth. Serum hemoglobin was 11.1 (SD 0.7) g/dL in infants fed GMF and 11.0 (SD 0.8) g/dL in infants fed CMF after the intervention and was similar between groups. Conclusion GMF was well tolerated, safe and supported adequate growth in infants. This was shown by the low occurrence of GI symptoms, adequate blood hemoglobin levels and adequate growth within WHO standards. Trial registration The clinical trial was approved by the ethics committee of the Federal University of Bahia under number CAAE06923319.5.0000.5577. The study was retrospectively registered in clinicaltrials.gov on 02/05/2024 under identifier NCT06395571.

Abstract Background Asthma, a complex respiratory disease, presents with inflammatory symptoms in the lungs, blood, and other tissues. We investigated the relationship between DNA methylation and 35 clinical markers of asthma. Methods The Illumina Infinium EPIC v1 methylation array was used to evaluate 742,442 CpGs in whole blood from 319 participants from 94 families. They were part of the Netherlands Twin Register from families with at least one member suffering from severe asthma. Repeat blood samples were taken after 10 years from 182 individuals. Principal component analysis on the clinical asthma markers yielded ten principal components (PCs) that explained 92.8% of the total variance. We performed epigenome-wide association studies (EWAS) for each of the ten PCs correcting for familial structure and other covariates. Results 221 unique CpGs reached genome-wide significance at timepoint 1 after Bonferroni correction. PC7, which correlated with loadings of eosinophil counts and immunoglobulin levels, accounted for the majority of associations (204). Enrichment analysis via the EWAS Atlas identified 190 of these CpGs to be previously identified in EWASs of asthma and asthma-related traits. Proximity assessment to previously identified SNPs associated with asthma identified 17 unique SNPs within 1 MB of two of the 221 CpGs. EWAS in 182 individuals with epigenetic data at a second timepoint identified 49 significant CpGs. EWAS Atlas enrichment analysis indicated that 4 of the 49 were previously associated with asthma or asthma-related traits. Comparing the estimates of all the significant associations identified across the two time points yielded a correlation of 0.81. Conclusion We identified 270 unique CpGs that were associated with PC scores generated from 35 clinical markers of asthma, either cross-sectionally or 10 years later. A strong correlation was present between effect sizes at the 2 timepoints. Most associations were identified for PC7, which captured blood eosinophil counts and immunoglobulin levels and many of these CpGs have previous associations in earlier studies of asthma and asthma-related traits. The results point to a robust DNA methylation profile as a new, stable biomarker for asthma.

Thermally activated delayed fluorescence (TADF) emitters potentially can provide organic light‐emitting diodes with 100% internal quantum efficiency by harvesting triplet excitons. Generally, TADF emitters are small molecules that are not applicable for solution processability. The addition of tert‐butyl groups to the periphery of TADF emitters has proven to improve their solubility in various organic solvents, reduce aggregation‐induced quenching, and enhance the photoluminescence quantum yield (PLQY). This article studies the photophysical influence of the tert‐butyl group attached to an emitter with a carbazole acceptor and a triazine donor. The resulting t3CzTrz‐F is a blue–green TADF emitter, in which the addition of a tert‐butyl group increases the rate of reverse intersystem crossing (rISC), while simultaneously decreasing the nonradiative decay rate substantially. In addition, dilution of t3CzTrz‐F in a host matrix in film results in an enhanced PLQY, which is associated with a decrease in the nonradiative decay constant, while there is no change in the rISC rate. Through a solid‐state NMR study, the change in rISC and nonradiative rate upon tert‐butylation by enlarged intermolecular spacing and reduced vibrational and rotational freedom is rationalized, resulting in improved photophysical performance.

This study generates new insights into the disintegration phenomena that take place upon blending different classes of biodegradable polymers. Polymer blending is found to be an effective method to tailor the disintegration rate of these polymers in soil. It is shown that the biodegradation of poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) can be accelerated by blending with poly(butylene succinate-co-adipate) (PBSA) and polycaprolactone (PCL). The observed high rate of disintegration of poly(butylene succinate) (PBS) in soil (severe deterioration in 4 weeks, and fragmentation in 4 months) does not fully align with its current reputation in the market as a polymer that is non-biodegradable in soil. Disintegration trials executed in soil media with different inoculants demonstrate that the biodegradation rate of PBS in soil is highly dependent on the specific soil conditions. Moreover, it is shown that the biodegradation of PBS can be substantially accelerated by blending it with PBSA (fragmentation in 8 weeks). Finally, it is shown that the disintegration of poly(lactic acid) (PLA) in soil can be enhanced by blending it with PCL. Experiments that monitor the CO2 evolution of these blends, both in soil and in home composting environments, demonstrate that not just the disintegration, but also the overall biodegradation of PLA is enhanced by blending with PCL (39 % conversion to CO2 in 12 months incubation in soil; 89 % conversion to CO2 in 6 months incubation in home composting conditions). This opens up possibilities for targeted blending strategies to reduce potential accumulation of PLA-based plastics in soil environments.

This study aimed to examine acute effects of exposure to ambient air pollution on COVID-19 hospital admissions and mortality in the Netherlands. We hypothesized that exposure to increased air pollution in the preceding week might trigger an exacerbation of health of infected individuals.Associations between daily concentrations of particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) and ≤10 µm (PM10), nitrogen dioxide (NO2), ozone (O3) and risk of hospital admissions and mortality due to COVID-19 from February to December 2020 was analyzed across all 352 Dutch municipalities grouped into 12 provinces. Time-series models were used to fit province-specific estimates, followed by meta-analyses to produce national estimates. Analyses were based on daily averages of PM2.5, PM10, NO2, and maximum 8-hour running average of O3 on a 1×1 km grid and averaged on municipality level by population weight. Models were adjusted for spatiotemporal confounders, including government policies in response to the number of COVID-19 infections. Since there were only few COVID-19 cases during the summertime when O3 levels were highest, associations between O3 and COVID-19 health outcomes were not further explored.We found associations between exposure to air pollution in the preceding week (average of lag 0-7 days) and COVID-19 hospital admissions and mortality. On a national level, an interquartile range increase in PM2.5, PM10 and NO2 exposure was associated with 11-12% increased mortality risk; the risk for hospital admissions was higher: 19-25%. Observed associations were more robust for PM than NO2 in two-pollutant models.Our results suggest that short-term exposure to PM2.5 and PM10 may increase the risk of COVID-19 mortality and hospital admission. This indicates that, consistent with previous studies on air pollution and respiratory infections, the population at risk of being hospitalized or dying of COVID-19 is extra vulnerable to the adverse effects of short-term air pollution exposure.

Abstract Background To date, no disease modifying therapies are available for Parkinson’s disease (PD). Since PD is the second most prevalent neurodegenerative disorder, there is a high demand for such therapies. Both environmental and genetic risk factors play an important role in the etiology and progression of PD. The most common genetic risk factor for PD is a mutation in the GBA1(GBA)-gene, encoding the lysosomal enzyme glucocerebrosidase (GCase). The mucolytic ambroxol is a repurposed drug, which has shown the property to upregulate GCase activity in-vitro and in-vivo. Ambroxol therefore has the potency to become a disease modifying therapy in PD, which was the reason to design this randomized controlled trial with ambroxol in PD patients. Methods This trial is a single-center, double-blind, randomized, placebo-controlled study, including 80 PD patients with a GBA mutation, receiving either ambroxol 1800 mg/day or placebo for 48 weeks. The primary outcome measure is the Unified Parkinson’s Disease Rating Scale motor subscore (part III) of the Movement Disorder Society (MDS-UPDRSIII) in the practically defined off-state at 60 weeks (after a 12-week washout period). Secondary outcomes include a 3,4-dihydroxy-6-18F-fluoro-I-phenylalanine ([18F]FDOPA) PET-scan of the brain, Magnetic Resonance Imaging (with resting state f-MRI and Diffusion Tensor Imaging), GCase activity, both intra- and extracellularly, sphingolipid profiles in plasma, Montreal Cognitive Assessment (MoCA), quality of life (QoL) measured by the Parkinson’s Disease Questionnaire (PDQ-39) and the Non-Motor Symptom Scale (NMSS) questionnaire. Discussion Ambroxol up to 1200 mg/day has shown effects on human cerebrospinal fluid endpoints, which supports at least passage of the blood-brain-barrier. The dose titration in this trial up to 1800 mg/day will reveal if this dose level is safe and also effective in modifying the course of the disease. Trial registration NCT05830396. Registration date: March 20, 2023.

Abstract Background Severe asthma (SA) encompasses several clinical phenotypes with a heterogeneous airway microbiome. We determined the phenotypes associated with a low α‐diversity microbiome. Methods Metagenomic sequencing was performed on sputum samples from SA participants. A threshold of 2 standard deviations below the mean of α‐diversity of mild‐moderate asthma and healthy control subjects was used to define those with an abnormal abundance threshold as relative dominant species (RDS). Findings Fifty‐one out of 97 SA samples were classified as RDSs with Haemophilus influenzae RDS being most common (n = 16), followed by Actinobacillus unclassified (n = 10), Veillonella unclassified (n = 9), Haemophilus aegyptius (n = 9), Streptococcus pseudopneumoniae (n = 7), Propionibacterium acnes (n = 5), Moraxella catarrhalis (n = 5) and Tropheryma whipplei (n = 5). Haemophilus influenzae RDS had the highest duration of disease, more exacerbations in previous year and greatest number on daily oral corticosteroids. Hierarchical clustering of RDSs revealed a C2 cluster (n = 9) of highest relative abundance of exclusively Haemophilus influenzae RDSs with longer duration of disease and higher sputum neutrophil counts associated with enrichment pathways of MAPK, NF‐κB, TNF, mTOR and necroptosis, compared to the only other cluster, C1, which consisted of 7 Haemophilus influenzae RDSs out of 42. Sputum transcriptomics of C2 cluster compared to C1 RDSs revealed higher expression of neutrophil extracellular trap pathway (NETosis), IL6‐transignalling signature and neutrophil activation. Conclusion We describe a Haemophilus influenzae cluster of the highest relative abundance associated with neutrophilic inflammation and NETosis indicating a host response to the bacteria. This phenotype of severe asthma may respond to specific antibiotics.

Abstract Hypercholesterolemia is characterized by elevated low‐density lipoprotein (LDL)‐cholesterol levels and an increased risk of cardiovascular disease. The adipokine chemerin is an additional risk factor. Here we investigated whether cholesterol‐lowering with statins or proprotein convertase subtilisin‐kexin type 9 inhibitors (PCSK9i) affects chemerin. Both statins and PCKS9i lowered plasma LDL‐cholesterol, triglycerides and total cholesterol in hypercholesterolemic patients, and increased high‐density lipoprotein (HDL)‐cholesterol. Yet, only statins additionally reduced chemerin and high‐sensitivity C‐reactive protein (hsCRP). Applying PCSK9i on top of statins did not further reduce chemerin. Around 20% of chemerin occurred in the HDL2/HDL3 fractions, while >75% was free. Statins lowered both HDL‐bound and free chemerin. Pull‐down assays revealed that chemerin binds to the HDL‐component Apolipoprotein A‐I (ApoA‐I). The statins, but not PCSK9i, diminished chemerin secretion from HepG2 cells by upregulating LDL receptor mRNA. Furthermore, chemerin inhibited HDL‐mediated cholesterol efflux via its chemerin chemokine‐like receptor 1 in differentiated macrophages. In conclusion, statins, but not PCSK9i, lower circulating chemerin by directly affecting its release from hepatocytes. Chemerin binds to ApoA‐I and inhibits HDL‐mediated cholesterol efflux. Statins prevent this by lowering HDL‐bound chemerin. Combined with their anti‐inflammatory effect evidenced by hsCRP suppression, this represents a novel cardiovascular protective function of statins that distinguishes them from PCSK9i.

Background: Healthcare is responsible for 4% to 10% of carbon emissions worldwide, of which 22% is related to transport. Telemedicine emerged as a potential solution to reduce the footprint, for example, by reducing travel. However, a need to understand which variables to include in carbon footprint estimations in telemedicine limits our understanding of the beneficial impact telemedicine might have on our environment. This paper aims to systematically assess the reported carbon footprint and include variables assessed by the literature, comparing telemedicine with usual care. Methods: The systematic review followed the PRISMA guidelines in PubMed, Medline, Embase and Scopus. A quality assessment was performed using a transparency checklist for carbon footprint calculators. Carbon emissions were evaluated based on four categories, including patient travel, and streamlined life cycle assessment (LCA) for assessing included variables relevant to telemedicine. Results: We included 33 articles from 1117 records for analysis. The average transparency score was 38% (range 18%-68%). The median roundtrip travel distance for each patient was 131 km (interquartile range [IQR]: 60.8-351), or 25.6 kgCO 2 (IQR: 10.6-105.6) emissions. There is high variance among included variables. Saved emissions are structurally underestimated by not including external factors such as a streamlined LCA. Conclusions: Telemedicine aids in reducing emissions, with travel distance being the most significant contributor. Additionally, we recommend accounting for the LCA since it highlights important nuances. This review furthers the debate on assessing carbon footprint savings due to telemedicine.

Cardiovascular diseases (CVDs) are a global burden that requires attention. For the detection and diagnosis of CVDs, the 12-lead ECG is a key tool. With technological advancements, ECG devices are becoming smaller and available for home use. Most of these devices contain a limited number of leads and are aimed to detect atrial fibrillation (AF). To investigate whether a four-electrode arrangement could provide enough information to diagnose other CVDs, further research is necessary. At the University Medical Center Utrecht in a multidisciplinary team, we developed the miniECG, a four-electrode ECG handheld system for scientific research in clinical environments (TRL6). This paper describes the process followed during the development of the miniECG. From assembling a multidisciplinary team, which includes engineers, cardiologists, and clinical physicians to the contribution of team members in the design input, design, and testing for safety and functionality of the device. Finally, we detail how the development process was composed by iterative design steps based on user input and intended use evolution. The miniECG is a device compliant for scientific research with patients within Dutch Medical Centers. We believe that hospital-based development led to a streamlined process, which could be applied for the design and development of other technologies used for scientific research in clinical environments.

Whole-body vibration (WBV) therapy is a way of passive exercise in which subjects are exposed to mild and well-controlled mechanical vibrations through a vibrating platform. For a long time, studies have focused on the effects and applications of WBV to enhance musculoskeletal performance in athletes and patients suffering from musculoskeletal disorders. Recent evidence points toward the positive effect of WBV on the brain and its therapeutic potential in brain disorders. Research being done in the field gradually reveals cellular and molecular mechanisms underlying WBV affecting the body and brain. Particularly, the influence of WBV on immune and brain function is a growing field that warrants an up-to-date and integrated review. Immune function is closely intertwined with brain functioning and plays a significant role in various brain disorders. Dysregulation of the immune response is linked to conditions such as neuroinflammation, neurodegenerative diseases, and mood disorders, highlighting the crucial connection between the immune system and the brain. This review aims to explore the impact of WBV on the cellular and molecular pathways involved in immune and brain functions. Understanding the effects of WBV at a cellular and molecular level will aid in optimizing WBV protocols to improve its therapeutic potential for brain disorders.

Abstract Background Clustering approaches using single omics platforms are increasingly used to characterise molecular phenotypes of eosinophilic and neutrophilic asthma. Effective integration of multi‐omics platforms should lead towards greater refinement of asthma endotypes across molecular dimensions and indicate key targets for intervention or biomarker development. Objectives To determine whether multi‐omics integration of sputum leads to improved granularity of the molecular classification of severe asthma. Methods We analyzed six ‐omics data blocks–microarray transcriptomics, gene set variation analysis of microarray transcriptomics, SomaSCAN proteomics assay, shotgun proteomics, 16S microbiome sequencing, and shotgun metagenomic sequencing–from induced sputum samples of 57 severe asthma patients, 15 mild‐moderate asthma patients, and 13 healthy volunteers in the U‐BIOPRED European cohort. We used Monti consensus clustering algorithm for aggregation of clustering results and Similarity Network Fusion to integrate the 6 multi‐omics datasets of the 72 asthmatics. Results Five stable omics‐associated clusters were identified (OACs). OAC1 had the best lung function with the least number of severe asthmatics with sputum paucigranulocytic inflammation. OAC5 also had fewer severe asthma patients but the highest incidence of atopy and allergic rhinitis, with paucigranulocytic inflammation. OAC3 comprised only severe asthmatics with the highest sputum eosinophilia. OAC2 had the highest sputum neutrophilia followed by OAC4 with both clusters consisting of mostly severe asthma but with more ex/current smokers in OAC4. Compared to OAC4, there was higher incidence of nasal polyps, allergic rhinitis, and eczema in OAC2. OAC2 had microbial dysbiosis with abundant Moraxella catarrhalis and Haemophilus influenzae. OAC4 was associated with pathways linked to IL‐22 cytokine activation, with the prediction of therapeutic response to anti‐IL22 antibody therapy. Conclusion Multi‐omics analysis of sputum in asthma has defined with greater granularity the asthma endotypes linked to neutrophilic and eosinophilic inflammation. Modelling diverse types of high‐dimensional interactions will contribute to a more comprehensive understanding of complex endotypes. Key Points Unsupervised clustering on sputum multi‐omics of asthma subjects identified 3 out of 5 clusters with predominantly severe asthma. One severe asthma cluster was linked to type 2 inflammation and sputum eosinophilia while the other 2 clusters to sputum neutrophilia. One severe neutrophilic asthma cluster was linked to Moraxella catarrhalis and to a lesser extent Haemophilus influenzae while the second cluster to activation of IL‐22.

Background Four months after SARS-CoV-2 infection, 22%–50% of COVID-19 patients still experience complaints. Long COVID is a heterogeneous disease and finding subtypes could aid in optimising and developing treatment for the individual patient.Methods Data were collected from 95 patients in the P4O2 COVID-19 cohort at 3–6 months after infection. Unsupervised hierarchical clustering was performed on patient characteristics, characteristics from acute SARS-CoV-2 infection, long COVID symptom data, lung function and questionnaires describing the impact and severity of long COVID. To assess robustness, partitioning around medoids was used as alternative clustering.Results Three distinct clusters of patients with long COVID were revealed. Cluster 1 (44%) represented predominantly female patients (93%) with pre-existing asthma and suffered from a median of four symptom categories, including fatigue and respiratory and neurological symptoms. They showed a milder SARS-CoV-2 infection. Cluster 2 (38%) consisted of predominantly male patients (83%) with cardiovascular disease (CVD) and suffered from a median of three symptom categories, most commonly respiratory and neurological symptoms. This cluster also showed a significantly lower forced expiratory volume within 1 s and diffusion capacity of the lung for carbon monoxide. Cluster 3 (18%) was predominantly male (88%) with pre-existing CVD and diabetes. This cluster showed the mildest long COVID, and suffered from symptoms in a median of one symptom category.Conclusions Long COVID patients can be clustered into three distinct phenotypes based on their clinical presentation and easily obtainable information. These clusters show distinction in patient characteristics, lung function, long COVID severity and acute SARS-CoV-2 infection severity. This clustering can help in selecting the most beneficial monitoring and/or treatment strategies for patients suffering from long COVID. Follow-up research is needed to reveal the underlying molecular mechanisms implicated in the different phenotypes and determine the efficacy of treatment.

Introduction: A peculiar spongy appearance of the perianal skin was observed in a patient who underwent wide excision surgery for inguinal and gluteal hidradenitis suppurativa (HS). Case Presentation: This peculiar appearance was observed in a 62-year-old male patient. It included multiple orifices and cavities forming the spongy aspect of the perianal skin with multiple cysts and giant comedones. The perianal lesions were asymptomatic and the patient had never received any perianal treatment for the comedones or cysts. Histopathology was performed and demonstrated dilated hair follicles with flaky keratin and loose hair shafts in the center. The spongy appearance was most likely the result of spontaneous shedding of the cystic contents. Conclusion: We suspect that the “cystic sponge anus” might be associated with HS, smoking, the male gender, and may yet be another expression of an occlusive follicular disease. Future studies will be needed to clarify the prevalence and comorbidities of the “cystic sponge anus.”