Eczema in early childhood increases the risk of allergic multimorbidity.

BACKGROUND: Eczema in early childhood is associated with the development of subsequent allergic diseases, including food allergy (FA), asthma and hay fever. However, eczema has a heterogenous presentation regarding onset age and persistence, which may lead to different allergic outcomes during childhood/adolescence. Recently, sub-phenotypes of eczema have been suggested as predictors of allergic multimorbidity. Thus, we aimed to identify associations of eczema phenotypes with FA, asthma and hay fever during childhood/adolescence. Additionally, we described the trajectories of eczema, asthma and hay fever stratified by FA presence. METHODS: TRACKER (Trajectories of Allergy in Children in Real Life Databases) is a population-based cohort study of 6852 children/adolescents from the Lifelines cohort. We investigated the associations of seven eczema phenotypes, based on onset age and persistence, with FA, asthma and hay fever using logistic regression, adjusted for appropriate covariates. Disease trajectories were determined by calculating prevalence at different ages. RESULTS: Participants who suffered from eczema throughout childhood showed higher risks of developing FA, hay fever and asthma. "Very early onset-persistent" eczema showed the strongest associations with FA, asthma and hay fever. The prevalence of eczema, asthma and hay fever at all ages was significantly higher in participants with FA, compared to those without. CONCLUSION: One of the largest cohort studies on this topic to date shows that (very) early onset and persistent eczema increases the risk of allergic multimorbidity. Identification of infants at risk for developing (very) early onset eczema is of utmost importance to prevent allergic multimorbidity.

Species specific responses to stressors hamper Trichoptera recovery.

Worldwide, aquatic biodiversity is severely threatened as a result of anthropogenic pressures such as pollution, habitat destruction and climate change. Widescale legislation resulted in reduced nutrient- and pesticide loads, and restoration measures allowed modest recovery of freshwater biodiversity. However, from 2010 onwards, recovery in the otherwise unrestored aquatic habitats stagnated. The aim of the present study was therefore to reveal long-term trends in aquatic biodiversity in an anthropogenic landscape and to explain the observed patterns. To this end, over 40 years of biomonitoring data of the indicative taxa group Trichoptera (caddisflies), with an exceptionally high spatial and temporal resolution, was employed. Periods of recovery, stagnation, and decline were delineated using linear and non-linear modelling approaches. Subsequently, species were grouped based on abundance patterns over time and this grouping was used to ascertain species-specific responses to anthropogenic stressors using a trait-based approach. Richness and abundance of all Trichoptera jointly, as well as of the five most abundant and the remaining 136 species, significantly increased from 1980 to significant breakpoints from 2010 onwards, after which these metrics, except the abundances of the 5 most abundant, declined significantly. Trend-based species groupings were not significantly explained by biological traits or ecological preferences. However, Trichoptera species increasing in abundance were less sensitive to climate change and poor water quality, or concerned sensitive species which benefited from restoration measures. Species with stable or declining abundances showed higher sensitivity to climate change. The Trichoptera declining in abundance indicated that conditions in non-protected or restored habitats did not improve due to climate change on top of the other anthropogenic pressures. These observations reinforce the need for increased efforts to improve the only moderately restored water- and habitat quality in anthropogenic landscapes to halt further aquatic ecosystem degradation and to turn biodiversity losses again into recoveries.

Food webs in isolation: The food-web structure of a freshwater reservoir with armoured shores in a former coastal bay area.

Many shallow coastal bays have been closed off from the sea to mitigate the risk of flooding, resulting in coastal reservoir lakes with artificial armoured shorelines. Often these enclosed ecosystems show a persistent decline in biodiversity and ecosystem services, which is likely reflected in their food-web structure. We therefore hypothesize that the food webs of coastal reservoir lakes with armoured shorelines (1) consist of relatively few species with a low food-web connectance and short food chains, and (2) are mainly fuelled by autochthonous organic matter produced in the pelagic zone. To investigate these two hypotheses, we used stable-isotope analysis to determine the food-web structure of lake Markermeer (The Netherlands), a large reservoir lake with armoured shorelines in a former coastal bay area. Contrary to expectation, connectance of the food web in lake Markermeer was comparable to other lakes, while food-chain length was in the higher range. However, the trophic links revealed that numerous macroinvertebrates and fish species in this constructed lake exhibited omnivorous feeding behaviour. Furthermore, in line with our second hypothesis, primary consumers heavily relied on pelagically derived organic matter, while benthic primary production exerted only a minor and seasonal influence on higher trophic levels. Stable-isotope values and the C:N ratio of sediment organic matter in the lake also aligned more closely with phytoplankton than with benthic primary producers. Moreover, terrestrial subsidies of organic matter were virtually absent in lake Markermeer. These findings support the notion that isolation of the lake through shore armouring and the lack of littoral habitats in combination with persistent resuspension of sediments have affected the food web. We argue that restoration initiatives should prioritize the establishment of land-water transition zones, thereby enhancing habitat diversity, benthic primary production, and the inflow of external organic matter while preserving pelagic primary production.

Scale of Emotional Development - Short: reliability and validity in adults with intellectual disability.

BACKGROUND: Intellectual disability (ID) is often associated with delays in emotional development (ED). The Scale of Emotional Development - Short (SED-S) was developed to assess the level of ED and to adapt treatment and care accordingly. METHODS: In a sample of 724 adults from five study sites in three countries, a confirmatory factor analysis with a one-factor model was conducted on the entire dataset as well as in different subgroups. Furthermore, internal consistency was investigated using Cronbach's alpha. RESULTS: The confirmatory factor analysis indicated that a single-factor model fits the SED-S data well. The subgroup analyses revealed good model fit, regardless of the severity of ID and irrespective of sex or the presence of autism spectrum disorder or psychiatric disorders. Internal consistency was excellent for the entire sample (Cronbach's alpha = 0.93) and various subgroups (0.869-0.938). CONCLUSION: The results of this study suggest that the SED-S is psychometrically sound and can be used to assess the level of ED in adults with ID.

Research Priorities for the Environmental Risk Assessment of Per- and Polyfluorinated Substances.

Per- and polyfluorinated substances (PFAS) are a group of thousands of ubiquitously applied persistent industrial chemicals. The field of PFAS environmental research is developing rapidly, but suffers from substantial biases toward specific compounds, environmental compartments, and organisms. The aim of our study was therefore to highlight current developments and to identify knowledge gaps and subsequent research needs that would contribute to a comprehensive environmental risk assessment for PFAS. To this end, we consulted the open literature and databases and found that knowledge of the environmental fate of PFAS is based on the analysis of <1% of the compounds categorized as PFAS. Moreover, soils and suspended particulate matter remain largely understudied. The bioavailability, bioaccumulation, and food web transfer studies of PFAS also focus on a very limited number of compounds and are biased toward aquatic biota, predominantly fish, and less frequently aquatic invertebrates and macrophytes. The available ecotoxicity data revealed that only a few PFAS have been well studied for their environmental hazards, and that PFAS ecotoxicity data are also strongly biased toward aquatic organisms. Ecotoxicity studies in the terrestrial environment are needed, as well as chronic, multigenerational, and community ecotoxicity research, in light of the persistency and bioaccumulation of PFAS. Finally, we identified an urgent need to unravel the relationships among sorption, bioaccumulation, and ecotoxicity on the one hand and molecular descriptors of PFAS chemical structures and physicochemical properties on the other, to allow predictions of exposure, bioaccumulation, and toxicity. Environ Toxicol Chem 2023;42:2302-2316. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Social individuation: Extending the scale of emotional development - Short (SED-S) for adolescent reference ages.

BACKGROUND: The SED-S is a standardized diagnostic instrument for assessing emotional development (ED) in people with a disorder of intellectual development. The SED-S defines five ED stages covering emotional reference ages up to 12 years in eight domains (5 items per domain). Stage 6 will extend the scale for early adolescent reference ages. AIMS: The aim of this study is to define the SED-S items for stage 6 ('Social Individuation'). METHODS AND PROCEDURES: Experts in developmental psychology phrased 56 items (7 items/domain) describing typical behaviors for emotional reference ages 13th-18th year (145th-216th month) in English, German and Dutch. Twenty-eight independent experts assessed the items' content validity and observability on a Likert scale (0 = good to 3 = unacceptable). Two items/domain with the lowest ratings were excluded to finally select 5 items/domain for SED-S stage 6. OUTCOMES AND RESULTS: The ratings were good with results ranging from 0.06 to 0.78 for validity and 0.06-1.78 for observability. After exclusion of the 2 lowest ranking items/domain, a set of 40 items was selected. CONCLUSIONS AND IMPLICATIONS: The SED-S is extended to allow the assessment of emotional reference ages up to 18 years. Further research should evaluate the scale's psychometric properties. WHAT THIS PAPER ADDS?: The current version of the SED-S covers emotional reference ages up to 12 years (144 months). Extending the SED-S for emotional reference ages up to 18 years (145th-216th months of life) in Dutch, German and English allows better differentiation in the higher ED range and expands the applicability of the scale. Specifically, it makes it possible to apply the SED-S in people with borderline intellectual functioning. Accounting for the level of ED may provide valuable information about the behaviors and needs of individuals with higher reference ages and may support targeted treatment options in a population highly vulnerable to behavioral or mental disorders.

Multispectral optoacoustic tomography for in vivo detection of lymph node metastases in oral cancer patients using an EGFR-targeted contrast agent and intrinsic tissue contrast: A proof-of-concept study.

Oral cancer patients undergo diagnostic surgeries to detect occult lymph node metastases missed by preoperative structural imaging techniques. Reducing these invasive procedures that are associated with considerable morbidity, requires better preoperative detection. Multispectral optoacoustic tomography (MSOT) is a rapidly evolving imaging technique that may improve preoperative detection of (early-stage) lymph node metastases, enabling the identification of molecular changes that often precede structural changes in tumorigenesis. Here, we characterize the optoacoustic properties of cetuximab-800CW, a tumor-specific fluorescent tracer showing several photophysical properties that benefit optoacoustic signal generation. In this first clinical proof-of-concept study, we explore its use as optoacoustic to differentiate between malignant and benign lymph nodes. We characterize the appearance of malignant lymph nodes and show differences in the distribution of intrinsic chromophores compared to benign lymph nodes. In addition, we suggest several approaches to improve the efficiency of follow-up studies.

Differential linguistic features of verbal fluency in behavioral variant frontotemporal dementia and primary progressive aphasia.

Frontotemporal dementia (FTD) is an early-onset neurodegenerative disorder with a heterogeneous clinical presentation. Verbal fluency is regularly used as a sensitive measure of language ability, semantic memory, and executive functioning, but qualitative changes in verbal fluency in FTD are currently overlooked. This retrospective study examined qualitative, linguistic features of verbal fluency in 137 patients with behavioral variant (bv)FTD (n = 50), or primary progressive aphasia (PPA) [25 non-fluent variant (nfvPPA), 27 semantic variant (svPPA), and 34 logopenic variant (lvPPA)] and 25 control participants. Between-group differences in clustering, switching, lexical frequency (LF), age of acquisition (AoA), neighborhood density (ND), and word length (WL) were examined in the category and letter fluency with analysis of variance adjusted for age, sex, and the total number of words. Associations with other cognitive functions were explored with linear regression analysis. The results showed that the verbal fluency performance of patients with svPPA could be distinguished from controls and other patient groups by fewer and smaller clusters, more switches, higher LF, and lower AoA (all p < 0.05). Patients with lvPPA specifically produced words with higher ND than the other patient groups (p < 0.05). Patients with bvFTD produced longer words than the PPA groups (p < 0.05). Clustering, switching, LF, AoA, and ND-but not WL-were differentially predicted by measures of language, memory, and executive functioning (range standardized regression coefficient 0.25-0.41). In addition to the total number of words, qualitative linguistic features differ between subtypes of FTD. These features provide additional information on lexical processing and semantic memory that may aid the differential diagnosis of FTD.

Fluorescence grid analysis for the evaluation of piecemeal surgery in sinonasal inverted papilloma: a proof-of-concept study.

PURPOSE: Local recurrence occurs in ~ 19% of sinonasal inverted papilloma (SNIP) surgeries and is strongly associated with incomplete resection. During surgery, it is technically challenging to visualize and resect all SNIP tissue in this anatomically complex area. Proteins that are overexpressed in SNIP, such as vascular endothelial growth factor (VEGF), may serve as a target for fluorescence molecular imaging to guide surgical removal of SNIP. A proof-of-concept study was performed to investigate if the VEGF-targeted near-infrared fluorescent tracer bevacizumab-800CW specifically localizes in SNIP and whether it could be used as a clinical tool to guide SNIP surgery. METHODS: In five patients diagnosed with SNIP, 10 mg of bevacizumab-800CW was intravenously administered 3 days prior to surgery. Fluorescence molecular imaging was performed in vivo during surgery and ex vivo during the processing of the surgical specimen. Fluorescence signals were correlated with final histopathology and VEGF-A immunohistochemistry. We introduced a fluorescence grid analysis to assess the fluorescence signal in individual tissue fragments, due to the nature of the surgical procedure (i.e., piecemeal resection) allowing the detection of small SNIP residues and location of the tracer ex vivo. RESULTS: In all patients, fluorescence signal was detected in vivo during endoscopic SNIP surgery. Using ex vivo fluorescence grid analysis, we were able to correlate bevacizumab-800CW fluorescence of individual tissue fragments with final histopathology. Fluorescence grid analysis showed substantial variability in mean fluorescence intensity (FImean), with SNIP tissue showing a median FImean of 77.54 (IQR 50.47-112.30) compared to 35.99 (IQR 21.48-57.81) in uninvolved tissue (p < 0.0001), although the diagnostic ability was limited with an area under the curve of 0.78. CONCLUSIONS: A fluorescence grid analysis could serve as a valid method to evaluate fluorescence molecular imaging in piecemeal surgeries. As such, although substantial differences were observed in fluorescence intensities, VEGF-A may not be the ideal target for SNIP surgery. TRIAL REGISTRATION: NCT03925285.

Responsivity and Reproducibility of Sputum Inflammatory Biomarkers During COPD Exacerbation and Stable Phases - A Pilot Study.

INTRODUCTION: There is a great interest to identify airway biomarkers to evaluate the potential and efficacy of anti-inflammatory therapeutic interventions. In this pilot study, we compared cytokine mRNA and protein levels of IL-6, IL-8, CCL2, CCL4, and TNF-α, as well as LTB-4 expression regarding their reproducibility and responsivity in induced sputum in COPD patients. METHODS: We recruited a cohort of 17 patients with a moderate COPD exacerbation, necessitating antibiotics and/or oral corticosteroids. Patients were followed for two consecutive stable phase visits. Cytokine mRNA and protein levels were measured in induced sputum samples. RESULTS: IL-6 and CCL4 protein levels decreased from exacerbation to stable phase, whereas their mRNA expression showed the same trend (not statistically significant). Coefficients of variation were overall lower (ie, more favorable for responsiveness) at protein levels compared to mRNA levels. No significant differences were observed in the reproducibility between cytokine mRNA expression and protein measurements. IL-6, IL-8, CCL2, and TNF-α gene expression levels yielded moderate to high intraclass correlation coefficients and/or Spearman correlation coefficients between both stable phase samples in contrast to their protein levels. CONCLUSION: Our findings suggest that several protein levels yield better responsivity with lower noise-to-signal ratios compared to their respective mRNA levels. In contrast, cytokine mRNA expression was more reproducible as it varied less in a stable state than proteins. Future studies are needed with a larger sample size to further evaluate the differences of responsivity and reproducibility between cytokine mRNA and protein measurements, not only during exacerbations.

Eutrophication induces shifts in the trophic position of invertebrates in aquatic food webs.

Changes in the ecological stoichiometry of primary producers may have considerable implications for energy and matter transfer in food webs. We hypothesized that nutrient enrichment shifts the trophic position of omnivores towards herbivory, as the nutritional quality of primary producers increases. This hypothesis was tested by analyzing the ecological stoichiometry and stable isotope signature of primary producers and a wide range of aquatic macroinvertebrates, including primary consumers (herbivores) and secondary consumers (both potential omnivores and strict carnivores), along a eutrophication gradient in an agricultural landscape. Our results showed (1) that carbon : nutrient ratios of primary producers decreased along the eutrophication gradient, while the elemental composition of consumers remained homeostatic, and (2) that the trophic position of several omnivores and the generalist predator Notonecta decreased, while the trophic position of most other consumers remained constant. These findings suggest that shifts in the diets of aquatic invertebrates induced by increasing eutrophication may affect species interactions and food web structure in aquatic ecosystems.

Scale of emotional development-short: Reliability and validity in two samples of children with an intellectual disability.

BACKGROUND: Intellectual disability (ID) is often accompanied by more significant delays in emotional development than in cognitive development. Diagnostic assessment can provide insight into emotional functioning. However, few standardized assessment instruments are available. AIMS: Examine the reliability and validity of the Scale of Emotional Development-Short (SED-S) in children with ID. METHODS AND PROCEDURES: This methodological instrument validation study was conducted in the Netherlands and Switzerland with children (N = 118) older than 3 and younger than 18 years with ID ranging from profound to mild. Measures included: demographic and medical data, SED-S, and the Vineland. Coherence and reliability of the SED-S were determined using Cronbach's alpha, and validity was examined using Goodman and Kruskal's γ, Kruskal-Wallis H, and Mann-Whitney U tests. OUTCOMES AND RESULTS: The reliability of the SED-S was high, the convergent validity was good, and divergent validity was indicated in relation to autism spectrum disorder (ASD), visual and/or auditory impairment, and adaptive functioning. FURTHER RESEARCH: Research is needed to better understand the implications of ASD and visual and/or auditory impairment on emotional development and their association with (normal) intelligence. Children with ID may also benefit from (more) detailed guidelines for imbalanced profiles on the SED-S.

Herbicide Exposure and Toxicity to Aquatic Primary Producers.

The aim of the present review was to give an overview of the current state of science concerning herbicide exposure and toxicity to aquatic primary producers. To this end we assessed the open literature, revealing the widespread presence of (mixtures of) herbicides, inevitably leading to the exposure of non-target primary producers. Yet, herbicide concentrations show strong temporal and spatial variations. Concerning herbicide toxicity, it was concluded that the most sensitive as well as the least sensitive species differed per herbicide and that the observed effect concentrations for some herbicides were rather independent from the exposure time. More extensive ecotoxicity testing is required, especially considering macrophytes and marine herbicide toxicity. Hence, it was concluded that the largest knowledge gap concerns the effects of sediment-associated herbicides on primary producers in the marine/estuarine environment. Generally, there is no actual risk of waterborne herbicides to aquatic primary producers. Still, median concentrations of atrazine and especially of diuron measured in China, the USA and Europe represented moderate risks for primary producers. Maximum concentrations due to misuse and accidents may even cause the exceedance of almost 60% of the effect concentrations plotted in SSDs. Using bioassays to determine the effect of contaminated water and sediment and to identify the herbicides of concern is a promising addition to chemical analysis, especially for the photosynthesis-inhibiting herbicides using photosynthesis as endpoint in the bioassays. This review concluded that to come to a reliable herbicide hazard and risk assessment, an extensive catch-up must be made concerning macrophytes, the marine environment and especially sediment as overlooked and understudied environmental compartments.

Colistin dry powder inhalation with the Twincer™: An effective and more patient friendly alternative to nebulization.

BACKGROUND: Nebulization of antimicrobial drugs such as tobramycin and colistin is a cornerstone in the treatment of patients with cystic fibrosis (CF) infected with Pseudomonas aeruginosa. However, nebulization has a high treatment burden. The Twincer™ is a dry powder inhaler specifically developed for the inhalation of antibiotics such as colistin. The aim of this study was to compare patient outcomes and experience with colistin dry powder by the Twincer with nebulization of colistin or tobramycin in adult CF patients in a real-life setting. METHODS: This was a retrospective study from 01-01-2015 until 01-07-2018. Effectiveness was evaluated by comparing FEV1 decline and exacerbation rate during a mean of 4.1 years of nebulization therapy prior to the initiation of the Twincer against the same values during a mean of 1.7 years of treatment with the Twincer. RESULTS: Twenty-one patients were evaluated, of whom twelve could be included in the effectiveness analysis, with a total of twenty patient years. Of all patients 71.4% preferred therapy with the Twincer over nebulization. Twincer use resulted in high treatment adherence with an average adherence rate of 92.5%. There was no significant difference in annual decline in FEV1%pred prior to and after start changing from nebulization to the use of the Twincer powder inhaler (median decline -1.56 [-5.57-5.31] and 1.35 [-8.45-6.36]) respectively, p = 0.45 (linear mixed effect model)). No significant difference was found in the number of intravenous or combined total intravenous and oral antibiotic courses during Twincer therapy compared to when using nebulization (1.68 and 2.49 courses during Twincer therapy versus 1.51 and 2.94 courses during nebulization, p = 0.88 and p = 0.63). CONCLUSION: Colistin dry powder inhalation with the Twincer is a more patient friendly alternative to nebulization, and we did not observe significant differences in the clinical outcome, regarding lung function and exacerbation rates.

Determinants of SARS-CoV-2 receptor gene expression in upper and lower airways.

The recent outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has led to a worldwide pandemic. One week after initial symptoms develop, a subset of patients progresses to severe disease, with high mortality and limited treatment options. To design novel interventions aimed at preventing spread of the virus and reducing progression to severe disease, detailed knowledge of the cell types and regulating factors driving cellular entry is urgently needed. Here we assess the expression patterns in genes required for COVID-19 entry into cells and replication, and their regulation by genetic, epigenetic and environmental factors, throughout the respiratory tract using samples collected from the upper (nasal) and lower airways (bronchi). Matched samples from the upper and lower airways show a clear increased expression of these genes in the nose compared to the bronchi and parenchyma. Cellular deconvolution indicates a clear association of these genes with the proportion of secretory epithelial cells. Smoking status was found to increase the majority of COVID-19 related genes including ACE2 and TMPRSS2 but only in the lower airways, which was associated with a significant increase in the predicted proportion of goblet cells in bronchial samples of current smokers. Both acute and second hand smoke were found to increase ACE2 expression in the bronchus. Inhaled corticosteroids decrease ACE2 expression in the lower airways. No significant effect of genetics on ACE2 expression was observed, but a strong association of DNA- methylation with ACE2 and TMPRSS2- mRNA expression was identified in the bronchus.