Common Pediatric Disease Research Articles

Exploring Pediatric Dermatology in Skin of Color: Focus on Dermoscopy

This literature review aims to comprehensively evaluate the clinical and dermoscopic presentations of common pediatric diseases among children with skin of color (SoC) while also addressing potential variations based on racial backgrounds. This review encompasses various conditions, such as nevi subtypes, viral infections, infestations, and inflammatory dermatoses, as well as hair diseases and abnormal vascular formations, occurring in pediatric populations. Overall, we identified 7 studies on nevi subtypes, 24 studies on skin infections, 6 on inflammatory dermatoses, 10 on hair diseases and disorders, and 14 on miscellaneous disorders that also satisfied our SoC- and race-specific criteria. In case of no results, we assumed that dermoscopic findings are similar between SoC adults and children, confirming the hypothesis with our cases of dark-skinned Indian child patients. Inflammatory dermatoses such as psoriasis, eczema, and cutaneous mastocytosis, as well as skin infections like cutaneous leishmaniasis, appear with brownish backgrounds or exhibit dark structures more frequently than the respective dermoscopy images of Caucasian populations. Dermoscopy traits such as erythema in tinea capitis are uncommon or even absent on a dark-colored scalp, while a dark skin tone often obscures many characteristic features, such as dark and yellow dots in alopecia areata and even parts of an intradermal parasite in the case of scabies. Race-specific traits were also observed, such as corkscrew hair in tinea capitis, primarily seen in patients of African origin. Many dermoscopic images are consistent between SoC and non-SoC in various skin lesions, including vascular anomalies, juvenile xanthogranuloma, mastocytoma, and viral skin lesions like molluscum contagiosum, as well as in various hair disorders such as trichotillomania, while tinea capitis displays the most diverse reported dermoscopic features across SoC- and race-specific studies.

Nanomedicine for pediatric healthcare: A review of the current state and future prospectives.

Nanomedicine has emerged as a valuable treatment and diagnosis option, due to its ability not only to address formulation challenges associated with new therapeutic moieties, but also to improve the existing drugs efficacy. Nanomedicine provides appealing advantages such as increased drug payload, enhanced stability, tailored drug release profile, improved bioavailability and targeted drug delivery, etc. Tremendous research and regulatory efforts have been made in the past decades to advance nanomedicine from the benchtop to clinic. Numerous nanotechnology-based formulation approaches have been seen succeeding in commercialization. Despite the progress in nanomedicine use in adults, the advancement in pediatric population has been much slower. Clearly the treatment of disease in children cannot be simplified by dose adjustment based on body weight or surface, due to the significant differences in physiology thus the drug absorption, distribution, metabolism, excretion and transport (ADMET), between children and adults. This inherent variable among others poses much more challenges when developing pediatric-specific nanomedicine or translating adult nanodrug to pediatric indication. This review therefore intends to highlight the physiological differences between children and adult, and the common pediatric diseases which are good candidates for nanomedicine. The formulation approaches utilized in the marketed nanomedicine with pediatric indications, including liposomes, nanocrystals, polymeric nanoparticles and lipid nanoemulsions are elaborated. Finally, the challenges and gaps in pediatric nanomedicine development and commercialization, and the future prospectives are discussed.

The Effect of Metabolic Disease on Language and Swallowing Skills in Children: A Case Report

Objectives: The present research aims to highlight the impact of hyperammonemia, a common pediatric metabolic disease, on children’s language and feeding skills. This research was conducted through a literature review and the presentation of a 2.5-year-old girl diagnosed with hyperammonemia. Case Presentation: The research was conducted on a 2.5-year-old girl who had been diagnosed with a sudden-onset metabolic disorder that resulted in swallowing, speech, and language problems. The child’s receptive and productive language and feeding history were obtained through interviews with her mother. Formal and informal tests were used to assess the child’s language and feeding skills at two different times after the onset of symptoms. Discussion: This study presents a new and unique case of a child with very high levels of ammonia and severe clinical manifestations of cognitive, language, and motor dysfunctions. Although the child did not receive any direct interventions during the study, a secondary assessment revealed slight improvements in some language and oral motor skills, possibly due to maturation and advice provided by rehabilitation team members.

Dihydroxyacetone phosphate is a novel predictor of hepatic fibrosis in Latino adolescents with obesity.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common pediatric liver disease and can progress to liver fibrosis. Latino adolescents have increased MASLD and fibrosis risk. While fibrosis is diagnosed by biopsy or imaging, more accessible, noninvasive, and economical screening methods are needed. We aimed to use plasma metabolomics/lipidomics to identify potential fibrosis biomarkers in Latino adolescents with obesity. Liver stiffness (LS) was measured in 93 Latino adolescents with obesity using magnetic resonance elastography. Metabolites and lipids were extracted from plasma and identified on Compound Discoverer. Associations between metabolites/lipids and fibrosis (LS > 2.73 kPa) were determined using linear regression models after covariate adjustment. False discovery rate (FDR) adjusted Pearson's correlations were performed. Analytes yielding significant FDR-adjusted correlations were examined further by receiver operator curve analysis. Mean (±standard deviation) alanine transaminase (ALT) was 45.7(±65.2) IU/L, hepatic fat fraction was 12.7(±9.1)%, and LS was 2.4(±0.3) kPa. We identified 795 metabolites and 413 lipids in plasma, but only one single metabolite, dihydroxyacetone phosphate (DHAP), a marker of triglyceride synthesis, was significantly associated with fibrosis after FDR adjustment (p < 0.05). In terms of predicting fibrosis, ALT had an area under the curve (AUC) of 0.79, and DHAP had an AUC of 0.79. When combined, ALT + DHAP had an AUC of 0.89. The combination of ALT + DHAP may have the potential as an accurate, noninvasive test for liver fibrosis. Our data is limited to Latino children with obesity, and a larger cohort should be examined to further validate this novel biomarker.

Perspectives and Challenges of Telemedicine and Artificial Intelligence in Pediatric Dermatology.

Pediatric dermatology represents one of the most underserved subspecialties in pediatrics. Artificial intelligence (AI) and telemedicine have become considerable in dermatology, reaching diagnostic accuracy comparable to or exceeding that of in-person visits. This work aims to review the current state of telemedicine and AI in pediatric dermatology, suggesting potential ways to address existing issues and challenges. We conducted a literature review including only articles published in the last 15 years. A total of 458 studies were identified, of which only 76 were included. Most of the studies on telemedicine evaluate accuracy focused on concordance, which ranges from 70% to 89% for the most common pediatric skin diseases. Telemedicine showed the potential to manage chronic dermatological conditions in children, as well as decrease waiting times, and represents the chance for unprivileged populations to overcome barriers limiting access to medical care. The main limitations of telemedicine consist of the language barrier and the need for adequate technologies and acceptable image-quality video, which can be overcome by AI. AI-driven apps and platforms can facilitate remote consultations between pediatric dermatologists and patients or their caregivers. However, the integration of AI into clinical practice faces some challenges ranging from technical to ethical and regulatory. It is crucial to ensure that the development, deployment, and utilization of AI systems conform to the seven fundamental requirements for trustworthy AI. This study supplies a detailed discussion of open challenges with a particular focus on equity and ethical considerations and defining possible concrete directions.

Deregulated Expression of Long Non-coding RNA ZFAS1 as a Predictive Biomarker for Respiratory Failure in Severe Pneumonia Children and Its Impact on Clinical Outcome

Abstract Objective Severe pneumonia is a common pediatric disease, often complicated by respiratory failure (RF). The expression changes of long non-coding RNA zinc finger antisense 1 (ZFAS1) were examined in children with severe pneumonia, as well as their predictive value in the occurrence of RF and poor outcomes. Methods A total of 120 children with severe pneumonia were included, 60 of whom had RF. RT-qPCR was used to detect mRNA levels. Deaths during the follow-up period were recorded through a 28-day follow-up survey. Receiver operating characteristic (ROC) curve and Kaplan Meier (K-M) plot were drawn to display diagnostic and predictive values, with the help of multiple logistic and Cox regression analysis. Results A sharp rise of serum ZFAS1 was tested in severe pneumonia children, providing a area under the receiver operator characteristic curve (AUC-ROC) of 0.920, with a sensitivity of 81.67% and a specificity of 90.00%. Serum ZFAS1 (OR = 5.832, 95% CI = 2.283–14.899) was found to be associated with the occurrence of RF after adjusting other clinical indexes, with an AUC-ROC of 0.843. ZFAS1 (HR = 4.624, 95% CI = 1.318–16.217, P &lt; 0.05) was an independent influence factor for the poor prognosis. Cases with high ZFAS1 levels had worse clinical outcomes. Conclusion Monitoring serum ZFAS1 levels is helpful in assessing severe pneumonia in children, especially for early identification of cases with RF. High serum ZFAS1 levels have a certain predictive value for poor prognosis in patients.

Differential performance regarding the relationship of C3-epi-25(OH)D3 levels and %C3-epi-25(OH)D3 with common pediatric diseases: a case control study

BackgroundRecently, the C3-epimer of 25-hydroxyvitamin D [C3-epi-25(OH)D] has become a topic of interest among 25-hydroxyvitamin D [25(OH)D] metabolites. Although it can lead to an overestimation of vitamin D storage, its relationship with disease occurrence remains controversial, possibly related to the great extent of tracking of 25(OH)D by C3-epi-25(OH)D over time. This study aimed to investigate the differential performance of C3-epi-25(OH)D3 and its percentage [%C3-epi-25(OH)D3] with respect to 20 common paediatric diseases.MethodsThis study involved 805 healthy children and adolescents and 2962 patients with common paediatric diseases. We investigated sex, age, and seasonal differences in C3-epi-25(OH)D3 and %C3-epi-25(OH)D3 levels; their variations on 20 common paediatric diseases; and their degree of correlation with 25(OH)D3 levels and various diseases.ResultsAmong the healthy underage participants, C3-epi-25(OH)D3 and %C3-epi-25(OH)D3 changed similarly, with no sex differences. Moreover, their levels were higher in the infant period than in the other periods (t = 5.329–5.833, t = 4.640–5.711, all Padj < 0.001), and in spring and summer than in autumn and winter (t = 3.495–6.061, t = 3.495–5.658, all Padj < 0.01). Under healthy and disease conditions, C3-epi-25(OH)D3 was positively correlated with 25(OH)D3 (ρ = 0.318 ~ 0.678, all P < 0.017), whereas %C3-epi-25(OH)D3 was not, except in patients with nephrotic syndrome (ρ=-0.393, P = 0.001). Before and after adjusting for 25(OH)D3, the relationship of C3-epi-25(OH)D3 with the diseases was notably different. However, it was almost consistent for %C3-epi-25(OH)D3. Our results indicated that %C3-epi-25(OH)D3 was associated with short stature, nephrotic syndrome, lymphocytic leukaemia, rickets, paediatric malnutrition, and hypovitaminosis D (OR = 0.80 ~ 1.21, all P < 0.05).ConclusionsThe %C3-epi-25(OH)D3 can correct the properties of C3-epi-25(OH)D3 to better track 25(OH)D3 and may be more suitable for exploring its pathological relevance. Further detailed studies of each disease should be conducted.

Febrile young infants and the association with enterovirus infection

BackgroundEnterovirus is a common pediatric infectious disease, but the epidemiological data in young infants were lacking. This study aims to evaluate the role of enterovirus in febrile young infants and identify risk factors for severe infections. MethodsWe enrolled febrile infants younger than 90 days admitted to National Taiwan University Hospital from January 2010 to June 2021. Enterovirus infection was confirmed via viral isolation or pan-enterovirus PCR. Central nervous system involvement was defined by positive culture or PCR in cerebrospinal fluid. Severe complications included sepsis, hepatic failure, myocarditis, shock, encephalitis, acute kidney injury, respiratory failure, and multiorgan failure. ResultsOut of 840 febrile infants, 17.4% (n = 146) had enterovirus infection. Among these, 46% (n = 67) presented with meningitis and/or encephalitis. Early-onset enterovirus infection within the first two weeks of life was significantly linked to increased risks of anemia (hemoglobin <9 g/dL), ICU admission, central nervous system involvement, shock, hepatic failure, and mortality. Multivariable logistic regression identified high-risk serotypes (aOR 17.4, [95% CI 1.58, 191.5], p = 0.019) and hemoglobin <9 g/dL (aOR 44.9, [95% CI 5.6, 357.6], p < 0.001) as significant risk factors for severe complications. ConclusionsEnterovirus accounted for 17.4% of the etiology in febrile young infants and the case-fatality rate was 2%. Febrile young infants who had risk factors of enterovirus infection should consider viral culture or PCR examination for confirmation.

A Case Report on Anomalous Origin of Left Coronary Artery from Pulmonary Artery in a Child

ABSTRACT Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare but fatal congenital cardiovascular disease. In this condition, the left coronary artery originates from the pulmonary artery, which should actually originate from the ascending aorta. This causes left ventricular dysfunction/insufficiency. Many a times it is asymptomatic and is missed during the initial months of life. Incidence is 1 in 300000 live births and comprises about 0.25–0.5% of congenital heart disease. In this article, we present a case of a 4-month-old infant who came with complaints of fever and increased work of breathing. On examination, there were signs of respiratory distress. Systemic examination was normal. Electrocardiogram findings showed inverted T waves in leads 1 and aVL, and in leads V5-V6, elevated ST segments were noted. Patient was suspected to have ALCAPA, and the echocardiogram confirmed the diagnosis. Patient was planned for surgery. ALCAPA is a clinical diagnostic challenge as it presents with similar complaints of common pediatric diseases such as bronchiolitis, failure to thrive, gastroesophageal reflux, and cardiomyopathy. Usually, majority of affected children remain undiagnosed and die within the first year of life. Hence, it is of utmost importance to keep a watch for this condition for early diagnosis and surgical intervention which will help in improving the prognosis.

Influencing factors for pediatric eye disorders and health related quality of life: a cross-sectional study in Shanghai, China.

Myopia, strabismus, and ptosis are common pediatric eye diseases, which have a negative impact on children and adolescents in terms of visual function, mental health, and health-related quality of life (HRQoL). Therefore, this study focused on those pediatric eye diseases by analyzing their risk factors and HRQoL for the comprehensive management of myopia, strabismus, and ptosis. A total of 363 participants (2-18 years old) were included in this study for risk factors analysis of myopia, strabismus, and ptosis. We collected demographic characteristics, lifestyle habits and eye care habits of these children and analyzed them by using univariable and multivariable logistic regression. In addition, we applied the Chinese version of Pediatric Quality of Life Inventory-Version 4.0 (PedsQL 4.0) to assess HRQoL in 256 children with strabismus and ptosis. Univariable and multivariable linear regression models were applied to evaluate potential influencing factors of HRQoL. Of all the participants, 140 had myopia, 127 had strabismus, and 145 had ptosis. Based on the multivariable logistic regression analysis model, we found that the history of parental myopia and daily average near-distance eye usage time were risk factors for myopia, and increased body mass index (BMI) was identified as a risk factor for strabismus and ptosis. Individuals with ptosis possessed decreased HRQoL. The multivariable linear regression model suggested that daily average near-distance eye usage time, light intensity during visual tasks, and daily average sleep duration had potential influences on HRQoL. This is the first study to assess the risk factors and HRQoL of myopia, strabismus, and ptosis together. We identified risk factors for these common pediatric eye diseases to help doctors, parents, and teachers better manage them. Our study discovered that children with eye disorders exhibit a notably diminished HRQoL. Consequently, it emphasizes the necessity for increased social attention and mental health assistance for these children.

Approach to the patient with Childhood Interstitial and Diffuse Lung Disease.

Childhood Interstitial and Diffuse Lung Disease (chILD) encompasses a group of rare, chronic lung disorders in infants and children with overlapping clinical features but diverse etiologies. The clinical presentation of chILD is of chronic or recurring respiratory signs and symptoms, often including increased work of breathing and hypoxia, with diffuse radiographic abnormalities on chest imaging. Recognition can be challenging since some clinical features overlap with those of more common pediatric respiratory diseases including asthma and recurrent viral infections, among others. chILD should be considered as an underlying diagnosis when a patient's respiratory symptoms seem disproportionate to the clinical scenario and/or persist. The diagnostic process involves multiple steps and is tailored to the individual patient. Nearly all children will undergo imaging and pulmonary function testing, many will undergo bronchoscopy with bronchoalveolar lavage, many will receive genetic testing, and some will require lung biopsy. Treatment includes preventive care, evaluation for comorbidities, pharmacotherapy according to diagnosis, and ongoing disease surveillance, including revisiting genetic and histopathologic results as new clinical information becomes available and as our understanding of these rare disorders improves. The purpose of this review is to provide a broad approach to the diagnosis and management of patients with chILD.

Impact of the COVID-19 Pandemic on Inpatient Pediatric Medical Student Education in Hawai'i.

The COVID-19 pandemic has had many effects on medical student education, ranging from safety measures limiting patient exposure to changes in patient diagnoses encountered by medical students in their clerkship experience. This study aimed to identify the impact of the pandemic on the inpatient experiences of third- and fourth-year medical students by assessing patient volumes and diagnoses seen by students. Frequency and types of notes written by medical students on hospital-based pediatric rotations at Kapi'olani Medical Center for Women and Children as well as patient diagnoses and ages were compared between 2 time periods: pre-pandemic (July 2018-February 2020) and pandemic (May 2020-September 2021). On average, the number of patients seen by medical students was significantly reduced in the pandemic period from 112 patients/month to 88 patients/month (P=.041). The proportion of patients with bronchiolitis or pneumonia were also significantly reduced in the pandemic period (P<.001). Bronchiolitis was diagnosed in 1.3% of patients seen by medical students during the pandemic period, compared with 5.9% of patients pre-pandemic. Pneumonia was diagnosed in 1.0% of patients seen by medical students in the pandemic period compared with 4.6% pre-pandemic. There was no significant difference in patient age between the 2 groups (P=.092). During the first 18 months of the COVID-19 pandemic, medical students in this institution had a remarkably different inpatient experience from that of their predecessors. They saw fewer patients, and those patients had fewer common pediatric respiratory diseases. These decreases suggest these students may require supplemental education to compensate for these gaps in direct pediatric clinical experience.

Interventional oncology in children: Where are we now?

Paediatric Interventional Oncology (IO) lags behind adult IO due to a scarcity of specific outcome data. The suboptimal way to evolve this field is relying heavily on adult experiences. The distinct tumour types prevalent in children, such as extracranial germ cell tumours, sarcomas, and neuroblastoma, differ strongly from those found in adults, presenting a completely different biological behaviour. Compounding this challenge, paediatric interventional radiology often employs adapted or off-label techniques, potentially compromising optimal outcomes. This review outlines the present indications for interventional radiology in paediatric cancer, from biopsy to supportive care, including complication management. It emphasises the role of locoregional approaches, and explores the status of common paediatric oncological diseases, highlighting areas where IO has made progress identifying potential opportunities for future advancements in this evolving field.

The first translation on pediatrics: Er Ke Cuo Yao

Er Ke Cuo Yao(The Pediatric Summary) is the first monograph on pediatrics of Western medicine translated and introduced in the late Qing Dynasty. It occupies an important position in the history of the development of modern pediatrics and modern Western medicine in China. Edited by American missionary Mary Hannah Fulton and translated by Chinese Western medicine scholar Yin Duanmo, the book consists of 2 volumes and 14 books, including general discussion of pediatrics, diagnosis of pediatric diseases, and discussion on teething, throat diseases, gastrointestinal diseases, worms, liver diseases, abdominal epimesis, and new infectious diseases, etc. covering the diagnosis, treatment, maintenance and other knowledge of Western medical pediatrics. The source of Er Ke Cuo Yao is not yet available, but it may be a synthesis of various materials, and the translation uses paraphrasing, transliteration, and traditional Chinese medicine terminology, and the language is easy to understand. Er Ke Cuo Yao reflects the level of development of pediatrics in Western medicine in the early modern period, makes up for the lack of pediatrics knowledge of traditional Chinese medicine, and plays an active role in the diagnosis and treatment of common pediatric diseases, epidemiological diseases, surgical diseases, and malnutrition prevention.

RECOGNIZING CHILD PARENTAL ANTIBIOTIC SELFMEDICATION: ORIGINS, TRENDS, AND CONSEQUENCES

Objective: Identifying parental reasons for self-treating children under ten years of age with antibiotics and theirpublic health implications for creating targeted interventions for antibiotic control reports of infectious disease.Study Design: A Cross-sectional StudyPlace and Duration of Study: From 11- January 2023 to 11-July 2023, this research was carried out at thePeoples university of Medical Health Sciences Nawab Shah Department of Pediatrics.Materials and Methods: 100 kids under ten who got antibiotics from their parents without a prescription wereincluded in the study. Parents were questioned using a pre-made, structured questionnaire written in English andtranslated into Urdu. We investigated the factors that affect parents’ understanding of the hazards associated withoverusing antibiotics as well as their decision to self-administer antibiotics to their children.Results: Important information on parental antibiotic self-medication was found in the research. The antibioticsmost often overused were azithromycin, co-amoxiclav, cefixime, and clarithromycin. The most common reasons forself-administration of antibiotics were fever, skin rashes, vomiting, and diarrhoea. Mothers were the primary initiatorsof antibiotic use, closely followed by male children beginning their consumption. These findings highlight the need forfocused initiatives, especially when it comes to treating common pediatric diseases, to raise parental knowledge of theproper use of antibiotics and the possible hazards associated with indiscriminate self-medication.Conclusion: It is exceedingly unusual for parents to give their kids medications on their own, which leads to theexcessive use of antibiotics and the development of antibiotic resistance. The entire public, especially parents, shouldbe made aware of this situation to halt the danger to global health. Policies that prohibit easy access to antibioticsshould be applied with greater efficacy.Keywords: Parental antibiotic self-medication, Children Causes Awareness, Antibiotic resistance

Associations of dietary sugars with liver stiffness in Latino adolescents with obesity differ on PNPLA3 and liver disease severity.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common paediatric liver disease. Latinos have high MASLD risk due to 50% prevalence of GG genotype of PNPLA3. Our primary aim was to evaluate associations between dietary carbohydrates/sugars and liver stiffness in Latino adolescents with obesity. Our secondary aim was to examine effect modification by (a) PNPLA3 genotype or (b) liver disease severity. Data were obtained from 114 Latino adolescents with obesity involved in two prior studies. No associations were seen between dietary carbohydrates/sugars and liver stiffness in the group as a whole. In subjects with GG genotype of PNPLA3, total sugar, fructose, sucrose, and glucose were associated with liver stiffness. Positive relationships between carbohydrate, total sugar, and sucrose and liver stiffness were stronger in those with MASLD and fibrosis compared to those with healthy livers and MASLD without fibrosis.

A rat model of adenoid hypertrophy constructed by using ovalbumin and lipopolysaccharides to induce allergy, chronic inflammation, and chronic intermittent hypoxia.

Adenoid hypertrophy (AH) is a common pediatric disease that significantly impacts the growth and quality of life of children. However, there is no replicable and valid model for AH. An AH rat model was developed via comprehensive allergic sensitization, chronic inflammation induction, and chronic intermittent hypoxia (CIH). The modeling process involved three steps: female Sprague-Dawley rats (aged 4-5 weeks) were used for modeling. Allergen sensitization was induced via intraperitoneal administration and intranasal provocation using ovalbumin (OVA); chronic nasal inflammation was induced through intranasal lipopolysaccharide (LPS) administration for sustained nasal irritation; CIH akin to obstructive sleep apnea/hypopnea syndrome was induced using an animal hypoxia chamber. Postmodel establishment, behaviors, and histological changes in nasopharynx-associated lymphoid tissue (NALT) and nasal mucosa were assessed. Arterial blood gas analysis and quantification of serum and tissue levels of (interleukin) IL-4 and IL-13, OVA-specific immunoglobulin E (sIgE), eosinophil cationic protein (ECP), tumor necrosis factor (TNF-α), IL-17, and transforming growth factor (TGF)-β were conducted for assessment. The treatment group received a combination of mometasone furoate and montelukast sodium for a week and then was evaluated. Rats exhibited notable nasal symptoms and hypoxia after modeling. Histopathological analysis revealed NALT follicle hypertrophy and nasal mucosa inflammatory cell infiltration. Elevated IL-4, IL-13, IL-17, OVA-sIgE, ECP, and TNF-α levels and reduced TGF-β levels were observed in the serum and tissue of model-group rats. After a week of treatment, the treatment group exhibited symptom and inflammatory factor improvement. The model effectively simulates AH symptoms and pathological changes. But it should be further validated for genetic, immunological, and hormonal backgrounds in the currently used and other strains and species.

Stratum corneum and microbial biomarkers precede and characterize childhood atopic dermatitis.

Atopic dermatitis (AD) is the most common paediatric inflammatory skin disease. There are currently no robust biomarkers that could reliably predict its manifestation, and on the molecular level, it is less well characterized than adult AD. This study aimed to extend previous findings and provide evidence for distinct changes of the epidermal proteome and microbiome preceding the onset of AD as well as characterizing early AD. We longitudinally analysed epidermal biomarker levels and microbial profiles in a cohort of 50 neonates at high risk for AD, who had participated in a randomized controlled trial on early emollient use for AD prevention. About 26% of the infants developed AD until month 24 with an average age of 10 month at disease onset. In children with later AD, IL-1Ra, TNFβ, IL-8, IL-18, IL-22, CCL2, TARC, TSLP and VEGFa showed increased levels prior to disease manifestation with levels of IL-1Ra, TNFβ and VEGFa already increased shortly after birth. Further, children with later AD displayed a delayed maturation and differentially composed skin microbiome prior to AD onset. At manifestation, levels of multiple Th2, Th17/22 and Th1-associated biomarkers as well as innate immunity markers were elevated, and abundances of commensal Streptococcus species were reduced in favour of Staphylococcus epidermidis. Our results indicate that elevations of proinflammatory stratum corneum biomarkers and alterations of the skin microbiome precede paediatric AD and characterize the disease at onset.

MR-based Bony 3D models enable radiation-free preoperative patient-specific analysis and 3D printing for SCFE patients.

Slipped capital femoral epiphyses (SCFE) is a common pediatric hip disease with the risk of osteoarthritis and impingement deformities, and 3D models could be useful for patient-specific analysis. Therefore, magnetic resonance imaging (MRI) bone segmentation and feasibility of 3D printing and of 3D ROM simulation using MRI-based 3D models were investigated. A retrospective study involving 22 symptomatic patients (22 hips) with SCFE was performed. All patients underwent preoperative hip MR with pelvic coronal high-resolution images (T1 images). Slice thickness was 0.8-1.2 mm. Mean age was 12 ± 2 years (59% male patients). All patients underwent surgical treatment. Semi-automatic MRI-based bone segmentation with manual corrections and 3D printing of plastic 3D models was performed. Virtual 3D models were tested for computer-assisted 3D ROM simulation of patients with knee images and were compared to asymptomatic contralateral hips with unilateral SCFE (15 hips, control group). MRI-based bone segmentation was feasible (all patients, 100%, in 4.5 h, mean 272 ± 52 min). Three-dimensional printing of plastic 3D models was feasible (all patients, 100%) and was considered helpful for deformity analysis by the treating surgeons for severe and moderate SCFE. Three-dimensional ROM simulation showed significantly (p < 0.001) decreased flexion (48 ± 40°) and IR in 90° of flexion (-14 ± 21°, IRF-90°) for severe SCFE patients with MRI compared to control group (122 ± 9° and 36 ± 11°). Slip angle improved significantly (p < 0.001) from preoperative 54 ± 15° to postoperative 4 ± 2°. MRI-based 3D models were feasible for SCFE patients. Three-dimensional models could be useful for severe SCFE patients for preoperative 3D printing and deformity analysis and for ROM simulation. This could aid for patient-specific diagnosis, treatment decisions, and preoperative planning. MRI-based 3D models are radiation-free and could be used instead of CT-based 3D models in the future.

Human beta defensin 3 knockdown inhibits the proliferation and migration of airway smooth muscle cells through regulating the PI3K/AKT signaling pathway

Asthma, a common pediatric pulmonary disease, significantly affects children’s healthy development. This study aimed to investigate the functions of human β defensin-3 (HBD-3) in asthma progression. For this purpose, blood samples from asthmatic and healthy children were collected. Moreover, the airway smooth muscle cells (ASMCs) were treated with platelet-derived growth factor BB (PDGF-BB) to develop an in vitro asthma model, then evaluated cell viability and migration via CCK-8 and transwell assays. The mRNA levels of interferon γ (INF-γ), interleukin 4 (IL-4), interleukin 10 (IL-10), alpha-smooth muscle actin (α-SMA), HBD-3, and the protein levels of phosphatidylinositol 3-kinase (PI3K) along with protein kinase B (AKT) were detected. Similarly, the N6-methyladenosine (m6A) content in the ASMCs and m6A levels of HBD-3 were also measured. Results indicated an upregulated HBD-3 in the asthmatic children. The ASMCs were found to be stimulated by PDGF-BB, in addition to the promotion of cell viability and migration. The INF-γ, IL-4, and α-SMA levels were reduced, while IL-10 was elevated in PDGF-BB-stimulated ASMCs. Silencing HBD-3 in PDGF-BB stimulated ASMCs was found to exert the opposite effect by inhibiting cell viability and migration, enhancing the levels of INF-γ, IL-4, and α-SMA, while the IL-10 levels were found to decline. PDGF-BB stimulation of ASMCs resulted in activation of the PI3K/AKT signaling pathway, which was blocked post HBD-3 silencing, while the role of si-hBD in PDGF-BB stimulated ASMCs was neutralized post-treatment with IGF-1. Finally, it was found that METTL3 overexpression prominently upregulated the m6A levels of HBD-3 and decreased the mRNA expression and stability of HBD-3 in the PDGF-BB-stimulated ASMCs. The study concluded that METTL3-mediated HBD-3 participates in the progression of asthma through the PI3K/AKT signaling pathway.