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Background: Social media have become integral in adolescents’ lives, presenting both opportunities and risks, especially concerning psychiatric issues like eating disorders, prevalent in this vulnerable age group. Methods: This qualitative study employed semi-structured interviews with seven adolescent girls (aged 15–17) diagnosed with eating disorders. Interviews covered seven predefined topics, recorded and transcribed for thematic analysis. Results: Participants identified four key themes: exposure to selective content, biased interpretation, behavioural adaptation, and evolving perspectives during recovery. They highlighted social media’s role in exacerbating body dissatisfaction and altering behaviours related to eating disorders. Conclusions: This research underscores the critical need for awareness and guidance in adolescents’ social media use to mitigate negative impacts, emphasizing the potential link between exposure to specific content and cognitive-behavioural changes in those with eating disorders. Further investigation is warranted to deepen our comprehension of these dynamics.

The major focus of this research is the level of awareness among Dutch parents of general patient rights in relation to minors’ patient rights. Moreover, this study is intended to highlight the most effective strategies to increase the awareness of general and minor patient rights in the Netherlands. A survey was conducted among 1010 Dutch parents aged between 35 and 55 years who had at least one child. In this study, we described the relationship between the knowledge among parents of general patient rights and their understanding of the patient rights of minors. A significant connection was found between the knowledge levels of general patient rights and the knowledge levels of the patient rights of minors (p < 0.05 [95% CI: 0.019–0.183]). While age and sex (male/female) did not appear to be significant confounders in this association, the educational background of the participants may have played a role. This study provides comprehensive insights into the association between the knowledge of general patient rights and the patient rights of minors among Dutch parents. Furthermore, this study points out that there is a need for focused educational interventions to address specific areas of misunderstanding or uncertainty.

Abstract Red blood cell (RBC) hitchhiking has great potential in enhancing drug therapy, by improving targeting and reducing rapid clearance of nanoparticles (NPs). However, to improve the potential for clinical translation of RBC hitchhiking, a more thorough understanding of the RBC-NP interface is needed. Here, we evaluate the effects of NP surface parameters on the success and biocompatibility of NP adsorption to extracted RBCs from various species. Major differences in RBC characteristics between rabbit, mouse and human were proven to significantly impact NP adsorption outcomes. Additionally, the effects of NP design parameters, including NP hydrophobicity, zeta potential, surfactant concentration and drug encapsulation, on RBC hitchhiking are investigated. Our studies demonstrate the importance of electrostatic interactions in balancing NP adsorption success and biocompatibility. We further investigated the effect of varying the anti-coagulant used for blood storage. The results presented here offer new insights into the parameters that impact NP adsorption on RBCs that will assist researchers in experimental design choices for using RBC hitchhiking as drug delivery strategy.

Abstract The mammalian pulmonary vasculature consists of functionally and morphologically heterogeneous compartments. When comparing sets of lungs, for example, in disease models or therapeutic interventions, local changes may be masked by the overall heterogeneity of the organ structure. Therefore, alterations taking place only in a sub‐compartment may not be detectable by global analysis. In the monopodial lung, the characterization of distinct vessel groups is difficult, due to the asymmetrical branching pattern. In this pilot study, a previously established method to classify segments of the monopodial pulmonary arterial tree into homogeneous groups was employed. To test its suitability for experimental settings, the method was applied to a hyperoxia (HYX, ≥95% oxygen) rabbit model of bronchopulmonary dysplasia and a normoxic control group (NOX, 21% oxygen). The method allowed the identification of morphological differences between the HYX and the NOX groups. Globally visible differences in lumen diameter were pinpointed to specific lung regions. Furthermore, local changes of wall dimension and cell layers in single compartments, that would not have been identifiable in an unfocused analysis of the whole dataset, were found. In conclusion, the described method achieves a higher precision in morphological studies of lung disease models, compared to a common, global analysis approach.

Thanks to its non-invasive nature and high-resolution imaging capabilities, magnetic resonance imaging (MRI) is a valuable diagnostic tool for pediatric patients. However, the fear and anxiety experienced by young children during MRI scans often result in suboptimal image quality and the need for sedation/anesthesia. This study aimed to evaluate the effect of a smartphone application called COSMO@home to prepare children for MRI scans to reduce the need for sedation or general anesthesia. The COSMO@home app was developed incorporating mini-games and an engaging storyline to prepare children for learning goals related to the MRI procedure. A multicenter study was conducted involving four hospitals in Belgium. Eligible children aged 4–10 years were prepared with the COSMO@home app at home. Baseline, pre-scan, and post-scan questionnaires measured anxiety evolution in two age groups (4–6 years and 7–10 years). Eighty-two children participated in the study, with 95% obtaining high-quality MRI images. The app was well-received by children and parents, with minimal technical difficulties reported. In the 4–6-year-old group (N = 33), there was a significant difference between baseline and pre-scan parent-reported anxiety scores, indicating an increase in anxiety levels prior to the scan. In the 7–10-year-old group (N = 49), no significant differences were observed between baseline and pre-scan parent-reported anxiety scores. Overall, the COSMO@home app proved to be useful in preparing children for MRI scans, with high satisfaction rates and successful image outcomes across different hospitals. The app, combined with minimal face-to-face guidance on the day of the scan, showed the potential to replace or assist traditional face-to-face training methods. This innovative approach has the potential to reduce the need for sedation or general anesthesia during pediatric MRI scans and its associated risks and improve patient experience.

BackgroundPrompt appropriate treatment reduces mortality of severe febrile illness in sub-Saharan Africa. We studied the health itinerary of children under-five admitted to the hospital with severe febrile illness in a setting endemic for Plasmodium falciparum (Pf) malaria and invasive non-typhoidal Salmonella infections, identified delaying factors and assessed their associations with in-hospital death.MethodologyHealth itinerary data of this cohort study were collected during 6 months by interviewing caretakers of children (>28 days - Principal findingsFrom 784 enrolled children, 36.1% were admitted >3 days after fever onset. This long health itinerary was more frequent in children with bacterial bloodstream infection (52.9% (63/119)) than in children with severe Pf malaria (31.0% (97/313)). Long health itinerary was associated with in-hospital death (OR = 2.1, p = 0.007) and two thirds of deaths occurred during the first 3 days of admission. Case fatality was higher in bloodstream infection (22.8% (26/114)) compared to severe Pf malaria (2.6%, 8/309). Bloodstream infections were mainly (74.8% (89/119)) caused by non-typhoidal Salmonella. Bloodstream infections occurred in 20/43 children who died in-hospital before possible enrolment and non-typhoidal Salmonella caused 16 out of these 20 bloodstream infections. Delaying factors associated with in-hospital death were consulting traditional, private and/or multiple providers, rural residence, prehospital intravenous therapy, and prehospital overnight stays. Use of antibiotics reserved for hospital use, intravenous therapy and prehospital overnight stays were most frequent in the private sector.ConclusionsLong health itineraries delayed appropriate treatment of bloodstream infections in children under-five and were associated with increased in-hospital mortality. Non-typhoidal Salmonella were the main cause of bloodstream infection and had high case fatality.Trial registrationNCT04289688.

The PinPoint Case Platform (PPCP) offers independent online case-based CME. To align with personal learning needs, a functionality of needs assessments (“QuickScan”) was developed, directing users to follow personalised case journeys. A randomised study was conducted, comparing its effectiveness, time efficiency and user experience with a format of non-individualised case-based learning. Forty-two residents in urology from five European countries were randomly assigned to follow non-individualised case-based learning (control group) or a needs assessment plus personalised case journeys on different topics in prostate cancer. After performing a pre- and post-assessment, both groups showed a similar increase in test scores (Mann-Whitney U = 247; p = .113), but the time needed for completing the learning exercise was significantly lower in the group with the personalised approach (median: 45 vs 90 minutes; Mann-Whitney U = 97.5; p = .0141). The quality of the two learning methods was similarly well received by both groups. In conclusion, learners who followed personalised case journeys learned similarly effective but more time efficient than non-individualised case-based learners. Future studies should determine if these findings can be extrapolated to board-certified physicians following CME activities.

Child abuse and neglect is a common, underreported, and worldwide problem. Health care providers play an important role in detecting and reporting this problem. This study examined the knowledge on the clinical signs and mimickers of child abuse among Belgian trainees in family medicine and pediatrics. Participants filled out an anonymous online survey of 15 fictional but realistic cases with either suspicious or non-suspicious signs of abuse or neglect in the context of primary or emergency care. The overall score on all cases, the number of correct answers per case, and the median score were calculated, and the association of the participant’s demographic characteristics with their score was examined using regression analysis. A total of 70 participants completed the survey. The overall median score was 73.3% (IQR 20.0%). The suspicious cases were solved more correctly than the non-suspicious cases (median: 85.7% versus 62.5%, p < 0.001). Regression analysis could not reveal a significant association of type and level of education with the performance on the survey. Knowledge of the clinical signs of child maltreatment among pediatricians and general practitioners in training is good, but there is still room for improvement.

Registration of histological serial sections is a challenging task. Serial sections exhibit distortions and damage from sectioning. Missing information on how the tissue looked before cutting makes a realistic validation of 2D registrations extremely difficult. This work proposes methods for ground-truth-based evaluation of registrations. Firstly, we present a methodology to generate test data for registrations. We distort an innately registered image stack in the manner similar to the cutting distortion of serial sections. Test cases are generated from existing 3D data sets, thus the ground truth is known. Secondly, our test case generation premises evaluation of the registrations with known ground truths. Our methodology for such an evaluation technique distinguishes this work from other approaches. Both under- and over-registration become evident in our evaluations. We also survey existing validation efforts. We present a full-series evaluation across six different registration methods applied to our distorted 3D data sets of animal lungs. Our distorted and ground truth data sets are made publicly available.

The data presented in this article provide one of the first large-scale insights on adult preferences for confidentiality and consent with regards to medical decision-making for minors. We collected data on these preferences through 12 hypothetical scenario's that were presented, for which each participant had to indicate if they would (not) follow the minor's preferences. Data regarding family communication, relationship quality, and sociodemographic characteristics were also collected. The data were collected through an online survey in September and October 2020, which yielded responses from 1000 Belgian and 1000 Dutch participants between 35 and 55 years of age. We selected this age range because it increased the chances that they had a child near the age of the fictional minor in the hypothetical cases. These data can be of interest for family researchers and/or health workers who want to explore adults’ perceptions regarding confidentiality and consent among minors.

Abstract Background Although recruiting newborns is ethically challenging, clinical trials remain essential to improve neonatal care. There is a lack of empirical data on the parental perspectives following participation of their neonate in a clinical trial, especially at long term. The objective of this study is to assess experiences and emotions of parents, long term after trial participation in an interventional drug trial. Methods Parents of former participants of five neonatal interventional drug trials were surveyed at long term (3–13 years ago) after participation. The survey assessed parental contentment with trial participation, perceived influence of the trial on care and health, emotional consequences of participation, and awareness of typical clinical trial characteristics on 6-point Likert scales. Results Complete responses were received from 123 parents (52% of involved families). Twenty percent of parents did not remember participation. Those who remembered participation reported high contentment with overall trial participation (median 5.00), but not with follow-up (median 3.00). Most parents did not perceive any influence of the trial on care (median 2.00) and health (median 2.43). Almost all parents reported satisfaction and pride (median 4.40), while a minority of parents reported anxiety and stress (median 1.44) or guilt (median 1.33) related to trial participation. A relevant minority was unaware of typical trial characteristics (median 4.20; 27% being unaware). Conclusions Overall, parents reported positive experiences and little emotional distress long term after participation. Future efforts to improve the practice of neonatal clinical trials should focus on ensuring effective communication about the concept and characteristics of a clinical trial during consent discussions and on the follow-up after the trial.

Abstract Background Non-typhoidal Salmonella (NTS) are a frequent cause of invasive infections in sub-Saharan Africa. They are frequently multidrug resistant (co-resistant to ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol), and resistance to third-generation cephalosporin and fluoroquinolone non-susceptibility have been reported. Third-generation cephalosporins and fluoroquinolones are often used to treat invasive NTS infections, but azithromycin might be an alternative. However, data on antibiotic treatment efficacy in invasive NTS infections are lacking. In this study, we aimed to assess the spatiotemporal distribution of antimicrobial resistance in invasive NTS infections in sub-Saharan Africa and to describe the available evidence and recommendations on antimicrobial treatment. Methods We conducted a systematic review of all available literature on antimicrobial resistance and treatment in invasive NTS infections. We performed a random effects meta-analysis to assess the temporal distribution of multidrug resistance, third-generation cephalosporin resistance, and fluoroquinolone non-susceptibility. We mapped these data to assess the spatial distribution. We provided a narrative synthesis of the available evidence and recommendations on antimicrobial treatment. Results Since 2001, multidrug resistance was observed in 75% of NTS isolates from all sub-Saharan African regions (95% confidence interval, 70–80% and 65–84%). Third-generation cephalosporin resistance emerged in all sub-Saharan African regions and was present in 5% (95% confidence interval, 1–10%) after 2010. Fluoroquinolone non-susceptibility emerged in all sub-Saharan African regions but did not increase over time. Azithromycin resistance was reported in DR Congo. There were no reports on carbapenem resistance. We did not find high-quality evidence on the efficacy of antimicrobial treatment. There were no supranational guidelines. The “Access group” antibiotics ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol and “Watch group” antibiotics ceftriaxone, cefotaxime, and ciprofloxacin were recommended as the first-choice antibiotics in national guidelines or reviews. These also recommended (a switch to) oral fluoroquinolones or azithromycin. Conclusions In addition to the widespread multidrug resistance in invasive NTS infections in sub-Saharan Africa, resistance to third-generation cephalosporins and fluoroquinolone non-susceptibility was present in all regions. There was a lack of data on the efficacy of antimicrobial treatment in these infections, and supranational evidence-based guidelines were absent.

Abstract Background Bronchopulmonary dysplasia continues to cause important respiratory morbidity throughout life, and new therapies are needed. The common denominator of all BPD cases is preterm birth, however most preclinical research in this area focusses on the effect of hyperoxia or mechanical ventilation. In this study we investigated if and how prematurity affects lung structure and function in neonatal rabbits. Methods Pups were delivered on either day 28 or day 31. For each gestational age a group of pups was harvested immediately after birth for lung morphometry and surfactant protein B and C quantification. All other pups were hand raised and harvested on day 4 for the term pups and day 7 for the preterm pups (same corrected age) for lung morphometry, lung function testing and qPCR. A subset of pups underwent microCT and dark field imaging on day 0, 2 and 4 for terms and on day 0, 3, 5 and 7 for preterms. Results Preterm pups assessed at birth depicted a more rudimentary lung structure (larger alveoli and thicker septations) and a lower expression of surfactant proteins in comparison to term pups. MicroCT and dark field imaging revealed delayed lung aeration in preterm pups, in comparison to term pups. Preterm birth led to smaller pups, with smaller lungs with a lower alveolar surface area on day 7/day 4. Furthermore, preterm birth affected lung function with increased tissue damping, tissue elastance and resistance and decreased dynamic compliance. Expression of vascular endothelial growth factor (VEGFA) was significantly decreased in preterm pups, however in the absence of structural vascular differences. Conclusions Preterm birth affects lung structure and function at birth, but also has persistent effects on the developing lung. This supports the use of a preterm animal model, such as the preterm rabbit, for preclinical research on BPD. Future research that focuses on the identification of pathways that are involved in in-utero lung development and disrupted by pre-term birth, could lead to novel therapeutic strategies for BPD.

About one in seven accidents involving children occurs at school. Roughly 70% of these accidents involve children under the age of 12 years. Thus, primary school teachers may be confronted with accidents where first aid could improve the outcome. Despite the importance of first-aid knowledge among teachers, little is known about this topic. To fill this gap, we conducted case-based survey research on the objective and subjective first-aid knowledge of primary school and kindergarten teachers in Flanders, Belgium. An online survey was distributed to primary school and kindergarten teachers. It included 14 hypothetical first-aid scenarios in a primary school context to assess objective knowledge, along with one item to assess subjective knowledge. A total of 361 primary school and kindergarten teachers completed the questionnaire. The participants achieved an average knowledge score of 66%. Those who had completed a first-aid course had significantly higher scores. Knowledge regarding child CPR was amongst the lowest, with only 40% correct answers. Structural equation modeling showed that only previous first-aid training, recent experience with first aid, and subjective first-aid knowledge were linked to teachers’ objective first-aid knowledge—particularly for basic first aid. This study shows that completing a first-aid course and completing a refresher course can predict objective first-aid knowledge. We therefore recommend that first-aid training and regular refresher courses should be mandatory in teacher training, given that a large share of teachers may need to apply first aid to a pupil at some point during their career.

Background In Belgium, schools closed during the first lockdown in March 2020, with a partial reopening in May. They fully reopened in September. During the summer, infections started to increase in the general population, speeding up in September. Some measures were taken to limit social contacts but those were insufficient to mitigate the exponential rise of infections in October. Children were still receiving all lessons at school at that time and it was questioned whether this position was tenable. We systematically compared the benefits and harms of closing primary and secondary schools and developed a recommendation.Methods A multidisciplinary panel, including school pupils and teachers, educational experts, clinicians and researchers, produced this recommendation in compliance with the standards for trustworthy rapid guidelines. The recommendation is based on data collected through national surveillance or studies from Belgium, and supported by a rapid literature review.Results Closing schools during the first lockdown probably resulted in a large learning delay and possibly led to more cases of child abuse. We are uncertain about the effect on the infection rate, hospitalisations, transmission rates, mental health of children, teachers and parents. The panel concluded that the balance of benefits and harms of closing schools clearly shifts against closing schools. Detrimental effects are even worse for vulnerable children. This recommendation is affected by the local virus circulation.Conclusion The guideline panel issues a strong recommendation against closing schools when the virus circulation is low to moderate, and a weak recommendation against closing schools when the virus circulation is high. It does not apply when the school system cannot function due to lack of teachers, too many children who are at home or a shortage of support services. As the results of international studies are consistent with Belgian study results, this recommendation may also be relevant internationally.

There is an increasing need for effective anxiety and pain reduction during medical imaging procedures in children, addressed by non-pharmacological or pharmacological approaches. Dexmedetomidine is a fairly recently marketed, selective α2-adrenergic agonist that can be administered intranasally. To develop an evidence-guided clinical protocol, we investigated the (side) effects, preconditions and safety aspects following intranasal dexmedetomidine administration in children (1 month–5 years) for procedural sedation during medical imaging. To this end, a systematic search (PubMed, Embase and CINAHL (12/2021)) was performed to identify studies on intranasal dexmedetomidine for procedural sedation for medical imaging (computer tomography and magnetic resonance imaging). Following screening and quality assessment, eight studies were retained. Nasal nebulization was considered the best administration method, dosing varied between 2 and 4 µg/kg (age-dependent) 30–45 min prior to imaging and contraindications or restrictions with respect to oral intake were somewhat consistent across studies. Valid sedation scores and monitoring of vital signs were routinely used to assess sedation and the need for rescue dosing (different approaches), whereas discharge was generally based on Aldrete score (score ≥ 9). Heart rate, blood pressure and saturation were routinely monitored, with commonly observed bradycardia or hypotension (decrease by 20%). Based on these findings, a roadmap for evidence-guided clinical protocol was generated.

Thiazolidinediones (TZDs) are potent PPARγ agonists that have been shown to attenuate alveolar simplification after prolonged hyperoxia in term rodent models of bronchopulmonary dysplasia. However, the pulmonary outcomes of postnatal TZDs have not been investigated in preterm animal models. Here, we first investigated the PPARγ selectivity, epithelial permeability, and lung tissue binding of three types of TZDs in vitro (rosiglitazone (RGZ), pioglitazone, and DRF-2546), followed by an in vivo study in preterm rabbits exposed to hyperoxia (95% oxygen) to investigate the pharmacokinetics and the pulmonary outcomes of daily RGZ administration. In addition, blood lipids and a comparative lung proteomics analysis were also performed on Day 7. All TZDs showed high epithelial permeability through Caco-2 monolayers and high plasma and lung tissue binding; however, RGZ showed the highest affinity for PPARγ. The pharmacokinetic profiling of RGZ (1 mg/kg) revealed an equivalent biodistribution after either intratracheal or intraperitoneal administration, with detectable levels in lungs and plasma after 24 h. However, daily RGZ doses of 1 mg/kg did not improve lung function in preterm rabbits exposed to hyperoxia, and daily 10 mg/kg doses were even associated with a significant lung function worsening, which could be partially explained by the upregulation of lung inflammation and lipid metabolism pathways revealed by the proteomic analysis. Notably, daily postnatal RGZ produced an aberrant modulation of serum lipids, particularly in rabbit pups treated with the 10 mg/kg dose. In conclusion, daily postnatal RGZ did not improve lung function and caused dyslipidemia in preterm rabbits exposed to hyperoxia.

BackgroundPreterm birth (PTB) and particularly late preterm PTB has become a research focus for obstetricians, perinatologists, neonatologists, pediatricians and policy makers alike. Translational models are useful tools to expedite and guide clinical but presently no model exists that contextualizes the late PTB scenario. Herein we aimed to develop a rabbit model that echo's the clinical neurocognitive phenotypes of early and late PTB.MethodsTime mated rabbit does underwent caesarean delivery at a postconceptional age (PCA) of either 28 (n = 6), 29 (n = 5), 30 (n = 4) or 31 (n = 4) days, term = 31 d. Newborn rabbits were mixed and randomly allocated to be raised by cross fostering and underwent short term neurobehavioral testing on corrected post-natal day 1. Open field (OFT), spontaneous alteration (TMT) and novel object recognition (NORT) tests were subsequently performed at 4 and 8 weeks of age.ResultsPTB was associated with a significant gradient of short-term mortality and morbidity inversely related to the PCA. On postnatal day 1 PTB was associated with a significant sensory deficit in all groups but a clear motor insult was only noted in the PCA 29d and PCA 28d groups. Furthermore, PCA 29d and PCA 28d rabbits had a persistent neurobehavioral deficit with less exploration and hyperanxious state in the OFT, less alternation in TMT and lower discriminatory index in the NORT. While PCA 30d rabbits had some anxiety behavior and lower spontaneous alteration at 4 weeks, however at 8 weeks only mild anxiety driven behavior was observed in some of these rabbits.ConclusionsIn this rabbit model, delivery at PCA 29d and PCA 28d mimics the clinical phenotype of early PTB while delivery at PCA 30d resembles that of late PTB. This could serve as a model to investigate perinatal insults during the early and late preterm period.

ObjectivesHealth care professionals regularly struggle with issues relating to confidentiality and consent for physical and/or mental health issues among adolescents. We investigate late adolescents' own and assumed parental preferences towards health-care related confidentiality and consent.MethodsWe analyzed online survey data of four vignettes from 463 first-year university students at KU Leuven (Flanders, Belgium). We used paired samples t-tests to assess the (in)consistency between attitudes of late adolescents and their assumed parental attitudes, independent samples t-tests to estimate gender differences, and binomial logistic regressions to analyze the association of assumed parental preferences with late adolescents' own preferences.ResultsAttitudinal inconsistencies were present in all vignettes. Late adolescents were significantly more in favor of confidentiality and adolescent consent than what they believed their parents were. Gender differences were limited. Binomial logistic regressions indicated that assumed parental preferences were strongly associated with late adolescents' own preferences.ConclusionsFindings suggest a clear difference between late adolescents' preferences and assumed parental preferences: they believe that their parents are less inclined to favor confidentiality and adolescent consent. We also find that this difference depends on the case, indicating that there is no such thing as general 'confidentiality preferences'. Rather, a decision- and/or context-specific perspective should be adopted.

The hospital can be a stressful environment for a child. To address the increase in demands for pediatric procedural sedation, the PROSA team initiative was started in the Leuven University Hospitals in 2014. In this study, we assessed the efficacy and safety of this project since its initiation. Demographic (age, sex) and clinical (procedure, sedation method) data were prospectively registered by the dedicated PROSA team. Anonymized data (11/2014–6/2021) were extracted to a database for analysis. Data on 5090 procedures were available. The median age was 4.8 years. The sedation was successful in 98% of patients, be it classified as ‘technically difficult’ in 3.3%. Of the 2% of failed procedures, 69% were due to inadequate sedation and 31% to logistic reasons unrelated to sedation (such as puncture problem, suboptimal bowel preparation). The overall adverse event incidence was 2% and occurred predominantly during gastro-coloscopy or bronchoscopy. Pethidine/midazolam was used in 81 cases, nitrous oxide in 10 cases. A saturation decrease with oxygen supply was the documented adverse event in 83 cases. There were no deaths reported. With the current training and implementation, PROSA is effective with a success rate of 98% and an adverse event rate of 2%.

Objective: Digital images might contribute to stigma associated with mental disorders. The aim of this study was to investigate whether these images accurately represent pediatric mental disorders, as well as to explore specific image-related factors that influence perception. Methods: Four hundred pictures were retrieved from three stock photograph websites (‘Shutterstock’, ‘iStock’ and ‘Adobe’) and ‘Google Images’ for mental disorders (ADHD, ASD, and depression) and somatic diseases (asthma, diabetes, and influenza) in childhood. Each picture was scored for gender, age, and emotional load. Data was compared against data from epidemiological studies. Ordinal regression was used to predict emotional load from image-related factors. Results: There was a significant difference in gender representation of ADHD, ASD, depression, diabetes, and influenza. With respect to age, models were significantly younger in pictures of depression but older in pictures of influenza. Pictures of ASD, asthma and diabetes were mostly positive; however, images for ADHD, depression and influenza carried more negative connotations. For mental disorders, a more positive emotional load was associated with images of young and/or male models. iStock gave more positive images. Conclusions: Digital images available in stock databases do not accurately represent pediatric mental and somatic disease. For mental disorders, image-related factors (including age, gender and emotional load) may influence societal perception.

Reproducible and unbiased methods to quantify alveolar structure are important for research on many lung diseases. However, manually estimating alveolar structure through stereology is time consuming and inter-observer variability is high. The objective of this work was to develop and validate a fast, reproducible and accurate (semi-)automatic alternative. A FIJI-macro was designed that automatically segments lung images to binary masks, and counts the number of test points falling on tissue and the number of intersections of the air-tissue interface with a set of test lines. Manual selection remains necessary for the recognition of non-parenchymal tissue and alveolar exudates. Volume density of alveolar septa ([Formula: see text]) and mean linear intercept of the airspaces (Lm) as measured by the macro were compared to theoretical values for 11 artificial test images and to manually counted values for 17 lungs slides using linear regression and Bland-Altman plots. Inter-observer agreement between 3 observers, measuring 8 lungs both manually and automatically, was assessed using intraclass correlation coefficients (ICC). [Formula: see text] and Lm measured by the macro closely approached theoretical values for artificial test images (R2 of 0.9750 and 0.9573 and bias of 0.34% and 8.7%). The macro data in lungs were slightly higher for [Formula: see text] and slightly lower for Lm in comparison to manually counted values (R2 of 0.8262 and 0.8288 and bias of -6.0% and 12.1%). Visually, semi-automatic segmentation was accurate. Most importantly, manually counted [Formula: see text] and Lm had only moderate to good inter-observer agreement (ICC 0.859 and 0.643), but agreements were excellent for semi-automatically counted values (ICC 0.956 and 0.900). This semi-automatic method provides accurate and highly reproducible alveolar morphometry results. Future efforts should focus on refining methods for automatic detection of non-parenchymal tissue or exudates, and for assessment of lung structure on 3D reconstructions of lungs scanned with microCT.

Recent advances in neonatal care have improved the survival rate of those born premature. But prenatal conditions, premature birth and clinical interventions can lead to transient and permanent problems in these fragile patients. Premature birth (

We wanted to investigate the relationship of medical and non-medical factors with the clinical decision-making of pediatricians. We hypothesize that the addition of relevant medical information (either alarming or reassuring) will influence the physician’s decision-making, but that the addition of non-medical information will also play a role. To investigate this, we designed an online questionnaire containing ten clinical case-based scenarios, of which five focused on medical factors and five on non-medical/context factors, each scored on a five-point Likert scale. In total, 113 pediatricians completed the online questionnaire. Both medical and non-medical/context factors were considered relevant to change the initial decision in most cases. Additional information of an alarming nature induces the physician to become more worried, whereas reassuring information decreases this worry. In some cases, with the medical factors, the gender and the age of the pediatrician does have some effect on the clinical decision-making. We conclude that medical decision-making is affected by multiple intrinsic and extrinsic factors that differ between physicians. Our data indicate that these non-medical factors must be considered when making a medical decision, as it is crucial to be aware that they have a substantial influence on that decision-making.

As part of a field study (NCT04473768) in children presenting with severe febrile illness to Kisantu hospital (DR Congo), we retrospectively compiled user experiences (not performance) with handheld diagnostic devices assisting triage: tympanic thermometer, pulse oximeter (measuring heart rate, respiratory rate and oxygen saturation), hemoglobinometer and glucometer. Guidance documents for product selection were generic and scattered. Stock rupture, market withdrawal and unaffordable prices interfered with procurement. Challenges at implementation included environmental temperature, capillary blood sampling (antisepsis, order of multiple tests, filling microcuvettes and glucose strips), calibration (environmental temperature, cold chain) and liability-oriented communication with a manufacturer. Instructions for use were readable and contained symbol keys; two devices had printed French-language instructions. Shortcomings were poor integration of figures with text and distinct procedures for the oximeter and its sensor. Usability interview revealed appreciations for quick results, visibility of the display and memory function (three devices) but also problems of capillary blood sample transfer, cleaning, too long of a time-to-results (respiratory rate) and size, fitting and disposal of thermometer probes. Pictorial error messages were preferred over alphanumeric error codes but interpretation of symbols was poor. Alarm sounds of the oximeter caused unrest in children and caretakers perceived the device as associated with poor prognosis.

To improve the early recognition of danger signs in children with severe febrile illness in low resource settings, WHO promotes automated respiratory rate (RR) counting, but its performance is unknown in this population. Therefore, we prospectively evaluated the field performance of automated point-of-care plethysmography-based RR counting in hospitalized children with severe febrile illness (p > 0.05). Children without fast breathing were mostly correctly classified (negative percent agreement: 98.3%). In conclusion, in the present setting the automated RR counter performed insufficiently to facilitate the early recognition of danger signs in children with severe febrile illness, given wide limits of agreement and a too low positive percent agreement.

BackgroundPulmonary hypoplasia, characterized by incomplete alveolar development, remains a major cause of mortality and morbidity in congenital diaphragmatic hernia. Recently demonstrated to differentiate from a common bipotent progenitor during development, the two cell types that line the alveoli type 1 and type 2 alveolar cells have shown to alter their relative ratio in congenital diaphragmatic hernia lungs.ObjectiveWe used the nitrofen/bisdiamine mouse model to induce congenital diaphragmatic hernia and accurately assess the status of alveolar epithelial cell differentiation in relation to the common bipotent progenitors.Study designPregnant Swiss mice were gavage-fed with nitrofen/bisdiamine or vehicle at embryonic day 8.5. The administered dose was optimized by assessing the survival, congenital diaphragmatic hernia and facial abnormality rates of the exposed mouse pups. NanoCT was performed on embryonic day 11.5 and 16.5 to assess the embryonic and early canalicular stages of lung development. At embryonic day 17.5 corresponding to late canalicular stage, congenital diaphragmatic hernia lungs were characterized by measuring the lung weight/body weight ratio, morphometry, epithelial cell marker gene expression levels and alveolar cell type quantification.ResultsNitrofen/bisdiamine associated congenital diaphragmatic hernia lungs showed delayed development, hypoplasia with morphologic immaturity and thickened alveolar walls. Expression levels of distal epithelial progenitor marker Id2 increased, alveolar type 1 cell markers Pdpn and Hopx decreased, while type 2 cell markers pro-SPC and Muc1 remained constant during the canalicular stage. The number of Pdpn+ type 1 alveolar cells also decreased in congenital diaphragmatic hernia lungs.ConclusionThe mouse nitrofen/bisdiamine model is a potential model allowing the study of congenital diaphragmatic hernia lung development from early stages using a wide array of methods. Based on this model, the alveolar epithelium showed a decrease in the number of alveolar type 1 cell in congenital diaphragmatic hernia lungs while type 2 cell population remains unchanged.

[This corrects the article DOI: 10.1371/journal.pone.0214793.].

Congenital diaphragmatic hernia (CDH) is a malformation leading to pulmonary hypoplasia, which can be treated in utero by fetal tracheal occlusion (TO). However, the changes of gene expression induced by TO remain largely unknown but could be used to further improve the clinically used prenatal treatment of this devastating malformation. Therefore, we aimed to investigate the pulmonary transcriptome changes caused by surgical induction of diaphragmatic hernia (DH) and additional TO in the fetal rabbit model. Induction of DH was associated with 378 upregulated genes compared to controls when allowing a false-discovery rate (FDR) of 0.1 and a fold change (FC) of 2. Those genes were again downregulated by consecutive TO. But DH+TO was associated with an upregulation of 157 genes compared to DH and controls. When being compared to control lungs, 106 genes were downregulated in the DH group and were not changed by TO. Therefore, the overall pattern of gene expression in DH+TO is more similar to the control group than to the DH group. In this study, we further provide a database of gene expression changes induced by surgical creation of DH and consecutive TO in the rabbit model. Future treatment strategies could be developed using this dataset. We also discuss the most relevant genes that are involved in CDH.

Children and adolescents with severe burns require medical and nursing interventions, associated with pain. As immersive virtual reality (VR) gained prominence as non-pharmacological adjuvant analgesia, we conducted a systematic review and meta-analysis on the efficacy of full immersive VR on pain experienced during dressing changes in hospitalized children and adolescents with severe burns. This exercise included quality and risk of bias assessment. The systematic review resulted in eight studies and 142 patients. Due to missing data, four studies were excluded from the meta-analysis. Fixed effects meta-analysis of the four included studies (n = 104) revealed a large effect size (ES) (Standardized Mean Difference = 0.94; 95% Confidence Interval = 0.62, 1.27; Z = 5.70; p < 0.00001) for adjuvant full immersive VR compared to standard care (SC). In conclusion, adjuvant full immersive VR significantly reduces pain experienced during dressing changes in children and adolescents with burns. We therefore recommend implementing full immersive VR as an adjuvant in this specific setting and population. However, this requires further research into the hygienic use of VR appliances in health institutions. Furthermore, due to the high cost of the hardware, a cost–benefit analysis is required. Finally, research should also verify the long term physical and psychological benefits of VR.

The Duchenne and Becker muscular dystrophies are caused by mutation of dystrophin gene and primarily affect skeletal and cardiac muscles. Cardiac involvement in dystrophic GRMD dogs has been demonstrated by electrocardiographic studies with the onset of a progressive cardiomyopathy similar to the cardiac disease in DMD patients. In this respect, GRMD is a useful model to explore cardiac and skeletal muscle pathogenesis and for developing new therapeutic protocols. Here we describe a protocol to convert GRMD canine fibroblasts isolated from heart and skin into induced cardiac-like myocytes (ciCLMs). We used a mix of transcription factors (GATA4, HAND2, TBX5, and MEF2C), known to be able to differentiate mouse and human somatic cells into ciCLMs. Exogenous gene expression was obtained using four lentiviral vectors carrying transcription factor genes and different resistance genes. Our data demonstrate a direct switch from fibroblast into ciCLMs with no activation of early cardiac genes. ciCLMs were unable to contract spontaneously, suggesting, differently from mouse and human cells, an incomplete differentiation process. However, when transplanted in neonatal hearts of SCID/Beige mice, ciCLMs participate in cardiac myogenesis.

Mesenchymal stem cells derived from human amniotic fluid (hAFSCs) are a promising source for cellular therapy, especially for renal disorders, as a subpopulation is derived from the fetal urinary tract. The purpose of this study was to evaluate if hAFSCs with a renal progenitor phenotype demonstrate a nephroprotective effect in acute ischemia reperfusion (I/R) model and prevent late stage fibrosis.A total of 45 male 12-wk-old Wistar rats were divided into three equal groups;: rats subjected to I/R injury and treated with Chang Medium, rats subjected to I/R injury and treated with hAFSCs and sham-operated animals. In the first part of this study, hAFSCs that highly expressed CD24, CD117, SIX2 and PAX2 were isolated and characterized. In the second part, renal I/R injury was induced in male rats and cellular treatment was performed 6 hours later via arterial injection. Functional and histological analyses were performed 24 hours, 48 hours and 2 months after treatment using serum creatinine, urine protein to creatinine ratio, inflammatory and regeneration markers and histomorphometric analysis of the kidney. Statistical analysis was performed by analysis of variance followed by the Tukey's test for multiple comparisons or by nonparametric Kruskal-Wallis followed by Dunn. Statistical significance level was defined as p

The neonatal management of preterm born infants often results in damage to the developing lung and subsequent morbidity, referred to as bronchopulmonary dysplasia (BPD). Animal models may help in understanding the molecular processes involved in this condition and define therapeutic targets. Our goal was to identify molecular pathways using the earlier described preterm rabbit model of hyperoxia induced lung-injury. Transcriptome analysis by mRNA-sequencing was performed on lungs from preterm rabbit pups born at day 28 of gestation (term: 31 days) and kept in hyperoxia (95% O2) for 7 days. Controls were preterm pups kept in normoxia. Transcriptomic data were analyzed using Array Studio and Ingenuity Pathway Analysis (IPA), in order to identify the central molecules responsible for the observed transcriptional changes. We detected 2217 significantly dysregulated transcripts following hyperoxia, of which 90% could be identified. Major pathophysiological dysregulations were found in inflammation, lung development, vascular development and reactive oxygen species (ROS) metabolism. To conclude, amongst the many dysregulated transcripts, major changes were found in the inflammatory, oxidative stress and lung developmental pathways. This information may be used for the generation of new treatment hypotheses for hyperoxia-induced lung injury and BPD.

Cystinosis is a rare disease caused by homozygous mutations of the CTNS gene, encoding a cystine efflux channel in the lysosomal membrane. In Ctns knockout mice, the pathologic intralysosomal accumulation of cystine that drives progressive organ damage can be reversed by infusion of wildtype bone marrow-derived stem cells, but the mechanism involved is unclear since the exogeneous stem cells are rarely integrated into renal tubules. Here we show that human mesenchymal stem cells, from amniotic fluid or bone marrow, reduce pathologic cystine accumulation in co-cultured CTNS mutant fibroblasts or proximal tubular cells from cystinosis patients. This paracrine effect is associated with release into the culture medium of stem cell microvesicles (100-400 nm diameter) containing wildtype cystinosin protein and CTNS mRNA. Isolated stem cell microvesicles reduce target cell cystine accumulation in a dose-dependent, Annexin V-sensitive manner. Microvesicles from stem cells expressing CTNS(Red) transfer tagged CTNS protein to the lysosome/endosome compartment of cystinotic fibroblasts. Our observations suggest that exogenous stem cells may reprogram the biology of mutant tissues by direct microvesicle transfer of membrane-associated wildtype molecules.