Pathways In Children Research Articles

Children's Pathways into Commercial Sexual Exploitation in the United States: A Systematic Review.

This study examined current evidence on children's pathways into commercial sexual exploitation (CSE) in the United States to determine if characteristics, vulnerabilities, and social contexts were distinguishable by age, gender, race/ethnicity, and location. Using Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines, peer-reviewed studies and grey literature were included if they were focused on CSE pathways prior to age 18, available in English, U.S. based, and published in or after 2013. In total, 1,989 articles were screened and 306 were eligible for full-text review. In total, 22 studies were analyzed. Nine studies focused on cis girls or women. No studies exclusively focused on CSE among cis boys, gender diverse children, children identifying as LGBTQ+, or children initiated from infancy through preadolescence. Findings indicate that boys and girls at different life stages were initiated into CSE by five pathways, including: (a) family members and caregivers' paramours; (b) romantic partners; (c) peers, friends, and acquaintances; (d) strangers; and (e) circumstantial need. Girls and boys in infancy, toddlerhood, and preadolescence and across rural-urban classifications were exploited by family members, parent's romantic partners, and acquaintances known to their family. Adolescent girls, including those with intellectual disabilities, were trafficked by boyfriends, strangers, and out of circumstantial needs. This is the first review to provide a contemporary overview of dynamics that marked children's CSE pathways from infancy through adolescence. Findings revealed need for future research on CSE-impacted boys, gender diverse and LGBTQ+ children, and intellectually challenged children across early life stages and geographic areas.

The effects of family, culture and sex on linguistic development across 20 languages.

Languages vary in their complexity; caregivers vary in the way they structure their communicative interactions with children; and boys and girls can differ in their language skills. Using a multilevel modelling approach, we explored how these factors influence the path of language acquisition for young children growing up around the world (mean age 2-years 9-months; 56 girls). Across 43 different sites, we analysed 103 mother-child pairs who spoke 3,170,633 utterances, 16,209,659 morphemes, divided across 20 different languages: Afrikaans, Catalan, Cantonese, Danish, Dutch, English, Farsi, French, German, Hebrew, Icelandic, Irish, Italian, Japanese, Mandarin, Norwegian, Portuguese, Spanish, Swedish and Turkish. Using mean length of utterance (MLU) as a measure of language complexity and developmental skill, we found that variation in children's MLU was significantly explained by (a) between-language differences; namely the rate of child MLU growth was attuned to the complexity of their mother tongue, and (b) between-mother differences; namely mothers who used higher MLUs tended to have children with higher MLUs, regardless of which language they were learning and especially in the very young (<2.5 years-old). Controlling for family and language environment, we found no evidence of MLU sex differences in child speech nor in the speech addressed to boys and girls. By modelling language as a multilevel structure with cross-cultural variation, we were able to disentangle those factors that make children's pathway to language different and those that make it alike. RESEARCH HIGHLIGHTS: The speech of 103 mother-child pairs from 20 different languages showed large variation in the path of early language development. Language, family, but not the sex of the child, accounted for a significant proportion of individual differences in child speech, especially in the very young. The rate at which children learned language was attuned to the complexity of their mother tongue, with steeper trajectories for more complex language. Results demonstrate the relative influence of culture, family, and sex in shaping the path of language acquisition for different children.

Arteriolar Molecular Pathways in Children after Kidney Transplantation with Preceding Peritoneal Dialysis

Arteriolar Molecular Pathways in Children after Kidney Transplantation with Preceding Peritoneal Dialysis

Inulin Supplementation Altered Gut Microbiota and Microbial Functional Pathways in Children With Obesity: A Randomized, Double-Blinded Placebo-Controlled Study

Inulin Supplementation Altered Gut Microbiota and Microbial Functional Pathways in Children With Obesity: A Randomized, Double-Blinded Placebo-Controlled Study

Understanding the Endocrine and Molecular Signaling Cascade Regulation Pathways in Children with Hypospadias.

Hypospadias (HS) is a congenital defect that occurs due to defective androgenization. It is characterized by the aberrant location of the urinary meatus on the ventral aspect of the penis with various degrees of severity. The molecular mechanisms and genetic associations underlying the condition remain largely unknown. Existing literature revolves around surgical and medical management of the condition. Human chorionic gonadotropin pretreatment in HS is proposed to decrease the severity of the anomaly and improve the clinical outcome of surgery. The underlying mechanisms that drive these outcomes have not been explored. Few studies have explored the endocrine signaling and pathways which lead to the development of the condition. Hence, a prospective study was conducted to understand the same. Eighteen children with mid or proximal penile HS were included as cases, and nine children undergoing circumcision for phimosis (nonpathological) were included as controls. Serum samples from all these children and preputial skin samples taken during surgery were used in the analysis. The hormonal milieu was normal in all children in our cohort. A comparison of previously reported genes with our cohort sequencing revealed changes in several major pathways involved in cell proliferation and differentiation, cell signaling, angiogenesis, and immune response pathways. Compared with healthy controls, HS subjects had 152 differentially expressed genes. Of these, 93 genes were up-regulated, and 59 genes were found to be significantly down-regulated. The gene expression evaluation also showed changes in expression patterns in inflammatory genes and link RNAs, unlike previously reported genes.

The Relationship Between Tuber Load and White Matter Pathways in Children with Tuberous Sclerosis Complex: A Diffusion Tensor Imaging Study

The Relationship Between Tuber Load and White Matter Pathways in Children with Tuberous Sclerosis Complex: A Diffusion Tensor Imaging Study

Young people's pathways to a specialist suicide prevention service and the influence of caregiver prior suicidality and mental health treatment.

Timely help-seeking and pathways to care (PtC) have been linked to positive outcomes in suicidal adolescents. While the importance of formal contacts is recognized, caregivers also play a significant role in these pathways. Caregiver's familiarity with mental health issues may influence an adolescent's PtC. This study explores the relationship between a caregiver's prior suicidality and mental health treatment on their children's pathways to entering a specialist suicide prevention treatment program. Caregivers (n = 118, 35 males and 83 females) of young individuals (12-25 years) who were admitted into an outpatient suicide prevention service, completed a self-report questionnaire describing their child's onset of symptoms, help-seeking, PtC and the caregiver's prior suicidality and mental health treatment. Parents were the source most likely to recognize the onset of suicidality, with general practitioners and psychologists the most common first contacts. Significant delays were identified for onset duration averaging 48.0 weeks, and it was observed that shorter delays in treatment were related to fewer number of contacts. Caregiver prior suicidality was associated with longer delays in treatment but had no relationship with onset duration. Caregivers and professional contacts are vital agents in improving the PtC of suicidal adolescents. Results highlight the significant delays in treatment and the added complexity of a caregiver's prior experience of suicidality to these pathways. These complexities warrant further exploration to minimize obstacles that hinder help-seeking and lengthen PtC, as this may improve interventions and outcomes for suicidal adolescents and their caregivers.

Microstructural Changes in the Brainstem Auditory Pathway in Children With Hearing Loss.

To assess the utility of diffusion tensor imaging of the auditory pathway in children with sensorineural hearing loss (SNHL). Retrospective cohort study. A single academic tertiary children's hospital. Sixteen pediatric patients with bilateral SNHL of at least moderate severity in the poorer ear (eight male; mean age, 5.3 ± 4.9 yrs). Controls consisted of age- and sex-matched children with normal hearing who were imaged for nonotologic, non-neurologic medical concerns and found to have normal magnetic resonance imaging (MRI). Three Tesla MRI scanners were used for diffusion tensor imaging. Quantitative diffusion tensor metrics were extracted from the superior olivary nucleus (SON), inferior colliculus (IC), and ipsilateral fiber tracts between the SON and IC delineated by tractography. We identified differences in fractional anisotropy of the SON between the SNHL cohort and controls (0.377 ± 0.056 vs. 0.422 ± 0.052; p = 0.009), but not in the IC. There were no differences in the mean diffusivity (MD) values in the IC and SON. Among younger children (≤5 yrs), MD was decreased in the SNHL cohort compared with controls in the IC (0.918 ± 0.051 vs. 1.120 ± 0.142; p < 0.001). However, among older children (>5 yrs), there were no differences in MD (1.124 ± 0.198 vs. 0.997 ± 0.103; p = 0.119). There were no differences in MD or fractional anisotropy in the white matter fibers of the IC-SON tract. Our results suggest abnormal neural tracts along the central auditory pathway among children with SNHL. Longitudinal studies should assess the prognostic value of these MRI-based findings for assessing long-term outcomes and determining intervention efficacy.

The First “Hit” to the Endocannabinoid System? Associations Between Prenatal Cannabis Exposure and Frontolimbic White Matter Pathways in Children

BackgroundCannabis is the most used federally illicit substance among pregnant people in the United States. However, emerging preclinical data show that a significant portion of cannabis constituents, such as Δ9-tetrahydrocannabinol and its bioactive metabolites, readily cross the placenta and accumulate in the fetal brain, disrupting neurodevelopment. Recent research using the Adolescent Brain Cognitive Development (ABCD) Study cohort has linked prenatal cannabis exposure (PCE) to greater neurobehavioral problems and lower total gray and white matter volume in children. Here, we examined the impact of PCE on frontolimbic white matter pathways that are critical for cognitive- and emotion-related functioning, show a high density of cannabinoid receptors, and are susceptible to cannabis exposure during other periods of rapid neurodevelopment (e.g., adolescence). MethodsThis study included 11,530 children (mean ± SD age = 118.99 ± 7.49 months; 47% female) from the ABCD Study cohort. Linear mixed-effects models were used to examine the effects of caregiver-reported PCE on fractional anisotropy of 10 frontolimbic pathways (5 per hemisphere). ResultsPCE was associated with lower fractional anisotropy of the right (β = −0.005, p < .001) and left (β = −0.003, p = .007) fornix, and these results remained significant after adjusting for a variety of covariates, multiple comparisons, fractional anisotropy of all fibers, and using a quality-control cohort only. ConclusionsIn sum, we demonstrated small, yet reliable, effects of PCE on white matter integrity during childhood, particularly in the fornix, which plays a crucial role in emotion- and memory-related processes. Future studies are needed to understand the impacts of small changes in brain structure or function on neurodevelopment and risk of neurobehavioral problems.

Association of Myocardial Changes and Gene Expression of the NFATC1 and NFATC4-Calcineurin Signaling Pathway in Children with Bicuspid Aortic Valve.

The role of NFATC gene expression in bicuspid aortic valve (BAV) progression is not fully understood. The aim of this study is to determine the significance of NFATC1 and NFATC4 gene expression for myocardial changes in children with BAV. In 47 children with BAV, the standard Doppler echocardiographic characteristics were detected, and the expression of the NFATC1 and NFATC4 genes was studied. Posterior wall thickness in diastole (PWTd) and aortic valve peak pressure gradient (AoPPG) in BAV patients were significantly higher compared to healthy controls (PWTd median (min-max), 9 (7-10) mm vs. 7 (6-8) mm; and AoPPG median (min-max), 7.79 (2.98-15.09) mm Hg vs. 2.94 (2.42-3.72) mm Hg). The expression of the NFATC1 gene in BAV children was significantly higher compared to NFATC4 (NFATC1 median (min-max); 70.88 (8.79-106.51) e.u. vs. 7.72 (1.74-22.67) e.u., respectively p < 0.05). A significant correlation of NFATC1 expression with Ao found (R = +0.53, p < 0.05). In BAV patients with PWTd > 8 mm and Ao > 21 mm the NFATC1 expression was significantly higher compared to those with PWTd ≤ 8 mm and Ao ≤ 21 mm (NFATC1 median (min-max); 45.49 (5.01-101.52) e.u. vs. 15.53 (2.36-44.40) e.u., p < 0.05 and 81.11 (20.27-101.10) e.u. mm vs. 12.16 (2.40-45.49) e.u., p < 0.05, respectively). In children with BAV the high expression of the NFATC1 calcineurin signaling pathway gene is associated with elevated PWTd and Ao.

Impact of Childhood Trauma Exposure, Genetic Variation in Endocannabinoid Signaling, and Anxiety on Frontolimbic Pathways in Children.

Introduction: The endocannabinoid (eCB) system plays a key role in modulating brain development, including myelination processes. Recent studies link a common variant (C385A, rs324420) in the fatty acid amide hydrolase (FAAH) gene to higher circulating eCB levels, lower anxiety, and altered frontolimbic development. Frontolimbic pathways, which demonstrate a protracted maturational course across childhood and adolescence, are associated with anxiety, and are vulnerable to environmental stressors such as trauma exposure. Here, we examined the impact of trauma exposure, FAAH genotype, and anxiety on frontolimbic white matter microstructure in children. Materials and Methods: We leveraged baseline data from the Adolescent Brain Cognitive Development (ABCD) study (n=9969; mean±standard deviation age=9.92±0.62 years; 47.1% female). Saliva samples were used for genotyping, and caregivers reported on their child's anxiety symptoms and trauma exposure. Fractional anisotropy (FA), a nonspecific measure of white matter integrity, was estimated for frontolimbic tracts. Results: Thirty-six percent of youth experienced one or more potentially traumatic events according to DSM-5 Criterion A (64% controls), and 45% were FAAH A-allele carriers (55% noncarriers). Relative to controls, trauma-exposed youth demonstrated higher anxiety and higher FA of the left uncinate. The FAAH A-allele (vs. CC) was associated with lower FA in the left fornix and left parahippocampal cingulum, and there was an indirect effect of FAAH genotype on anxiety through FA of the left fornix. Moreover, genotype moderated the association between FA of the left cingulum and anxiety. Conclusions: Our findings demonstrate distinct effects of trauma exposure and the FAAH C385A variant on frontolimbic pathways and subsequent anxiety risk in preadolescent children. This line of work may provide important insights into neurodevelopmental mechanisms leading to anxiety risk, and potential targets for intervention.

Transseptal Approach Versus Transaortic Approach for Catheter Ablation of Left-Sided Accessory Pathways in Children.

BackgroundCatheter ablation is recommended to eradicate supraventricular tachycardia caused by left-sided accessory pathways (APs) in children. This study aims to compare the safety and efficacy of the transseptal approach (TS) and aortic approach (TA) for catheter ablation of left-sided APs in a pediatric cohort.MethodsPatients < 18 years of age with left-sided APs who had undergone ablation at Beijing Children’s Hospital between 13 January 2018 and 7 January 2020 were included and randomly categorized into either TS or TA group (follow-up for 22 months). In all, 60 patients in TS group and 41 patients in TA group were included in this study. Principal endpoints were success rate, recurrence rate, complications, procedure time, and radiation dose.ResultsFor TS group versus TA group, success rate was observed in 100 versus 97.56% (p = 0.402). The procedure time was 27.0 (32.0–23.0) versus 29.0 (38.0–24.5) min (p = 0.092). The rate of success or the procedure time was similar, but for the patients with Aps located in left posterior septum (LPS) or left posterior lateral (LPL), the TS group had a shorter procedure time compared with TA group (p < 0.01). The radiation dose was 28.0 (20.0–41.75) versus 0 mGy (p < 0.001). After successful ablation, no recurrence and complication were observed in either group.ConclusionBoth TS and TA for catheter ablation of left-sided Aps were shown to be safe and effective in children. Zero radiation and ease of mastery make TA the preferred choice. TS is recommended to be used by properly trained medical professionals, especially for patient with AP localized in the LPL or LPS. However, TS is a good alternative where patients have aortic lesions or when TA fails.

Altered Arginine/Nitric Oxide Pathway in Children Diagnosed Attention Deficit Hyperactivity Disorder, and the Effect of 10 Weeks Methylphenidate Treatment.

ObjectiveIn this study, we investigated the levels of arginine, nitric oxide (NO), asymmetric dimethylarginine (ADMA), and adrenomedullin that are presumed to play a role in attention deficit hyperactivity disorder (ADHD) etiology, and to compare the findings with healthy controls.MethodsThirty ADHD patients and thirty healthy control subjects aged 6−12 years were included in the study. Sociodemographic data form, Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version; Conners’ Parent/Teacher Rating Scale-Revised Long Form; Children’s Depression Inventory; and The State-Trait Anxiety Inventory for Children were applied to all cases. All participants included in the study were evaluated in terms of their serum arginine, NO, ADMA, and adrenomedullin levels. Subsequently, methylphenidate treatment was started in ADHD patients and blood parameters were tested again in the tenth week of treatment.ResultsAt the start of the study, arginine and ADMA levels were significantly higher and NO and adrenomedullin levels were significantly lower in the ADHD group compared to the control group. Post-treatment arginine and ADMA levels were found to be significantly lower than in the pre-treatment period. There were no significant differences in NO and adrenomedullin levels before and after treatment. There was no correlation between scale scores and blood parameters.ConclusionThese variations in the blood parameters of the ADHD group seem to be worth further investigation. Studies to be conducted with larger sample groups after longer-term treatment may provide new information about the alterations in neurobiological processes related to ADHD etiology and treatment.

Urban governance of liminal legality comparing the incorporation of migrant children in Tel-Aviv and Jerusalem

Increasing numbers of migrant children worldwide grow up with fragmentary and revocable legal statuses that perpetuate their liminal legality as socially present yet legally non-existent. Scholars of migration have mainly explored macro drivers and micro-level effects of liminal legality paying less attention to the role of urban governance and actors in shaping migrant children's pathways of incorporation amidst broader processes of local rescaling. Taking into consideration that neoliberal rescaling is anchored in the uneven institutional landscapes in which it unfolds, this comparative research shows how different trajectories of urban rescaling result in two modes of governance: centralized–segregated in Tel-Aviv, and particularistic–integrative in Jerusalem. Grounded on 101 in-depth interviews with local agents and surveys of municipal policies and NGO reports, we show that in cosmopolitan-oriented yet relatively less ethno-nationally heterogeneous Tel-Aviv, actors maneuver institutional ambivalence by emphasizing liberal status-blind principles in the provision of segregated services. Conversely, in ethno-religious oriented yet ethno-nationally heterogeneous Jerusalem, migrant children are incorporated in integrative frameworks that recognize their particularity. Drawing on an inter-city comparison, we argue that local actors both reflect and mobilize inherited institutional landscapes and legacies of sensemaking of “otherness” as they negotiate similar national restrictive migration policies. Integrating critical scholarship on urban rescaling, attentive to structures of social provision and policy paradigms, and local actors' sensemaking, we foreground the centrality of cities in forging liminal legality as a multidimensional space where policies, institutional contexts, and agency work together in emplacing migrant children, suspended between legal categories, as urban subjects.

Cellular, Antibody and Cytokine Pathways in Children with Acute SARS-CoV-2 Infection and MIS-C—Can We Match the Puzzle?

The newly identified strain of the Coronaviridae family called severe acute respiratory syndrome (SARS-CoV-2) recently became the most significant health threat for adults and children. Some main predictors of severe clinical course in patients with SARS-CoV-2 infection are age and concomitant health conditions. Therefore, the proper evaluation of SARS-CoV-2-specific immunity is urgently required to understand and predict the spectrum of possible clinical phenotypes and recommend vaccination options and regimens in children. Furthermore, it is critical to characterize the nature of SARS-CoV-2-specific immune responses in children following asymptomatic infection and COVID-19 and other related conditions such as multisystem inflammatory syndrome (MIS-C), para-infectious and late postinfectious consequences. Recent studies involving children revealed a variety of cytokines, T cells and antibody responses in the pathogenesis of the disease. Moreover, different clinical scenarios in children were observed-asymptomatic seroprevalence, acute SARS-CoV-2 infection, and rarely severe COVID-19 with typical cytokine storm, MIS-C, long COVID-19, etc. Therefore, to gain a better clinical view, adequate diagnostic criteria and treatment algorithms, it is essential to create a realistic picture of the immunological puzzle of SARS-CoV-2 infection in different age groups. Finally, it was demonstrated that children may exert a potent and prolonged adaptive anti-SARS-CoV-2 immune response, with significant cross-reactions against other human Corona Viruses, that might contribute to disease sparing effect in this age range. However, the immunopathology of the virus has to be elucidated first.

Downregulation of Three Immune-Specific Core Genes and the Regulatory Pathways in Children and Adult Friedreich's Ataxia: A Comprehensive Analysis Based on Microarray.

BackgroundFriedreich's ataxia (FRDA) is a familial hereditary disorder that lacks available therapy. Therefore, the identification of novel biomarkers and key mechanisms related to FRDA progression is urgently required.MethodsWe identified the up-regulated and down-regulated differentially expressed genes (DEGs) in children and adult FRDA from the GSE11204 dataset and intersected them to determine the co-expressed DEGs (co-DEGs). Enrichment analysis was conducted and a protein-protein interaction (PPI) network was constructed to identify key pathways and hub genes. The potential diagnostic biomarkers were validated using the GSE30933 dataset. Cytoscape was applied to construct interaction and competitive endogenous RNA (ceRNA) networks.ResultsGene Set Enrichment Analysis (GSEA) indicated that the genes in both the child and adult samples were primarily enriched in their immune-related functions. We identified 88 co-DEGs between child and adult FRDA samples. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome enrichment analysis suggested that these co-DEGs were primarily enriched in immune response, inflammatory reaction, and necroptosis. Immune infiltration analysis showed remarkable differences in the proportions of immune cell subtype between FRDA and healthy samples. In addition, ten core genes and one gene cluster module were screened out based on the PPI network. We verified eight immune-specific core genes using a validation dataset and found CD28, FAS, and ITIF5 have high diagnostic significance in FRDA. Finally, NEAT1-hsa-miR-24-3p-CD28 was identified as a key regulatory pathway of child and adult FRDA.ConclusionsDownregulation of three immune-specific hub genes, CD28, FAS, and IFIT5, may be associated with the progression of child and adult FRDA. Furthermore, NEAT1-hsa-miR-24-3p-CD28 may be the potential RNA regulatory pathway related to the pathogenesis of child and adult FRDA.

MRI Correlates of Ototoxicity in the Auditory Pathway in Children Treated for Medulloblastoma.

To assess diffusion and perfusion changes of the auditory pathway in pediatric medulloblastoma patients exposed to ototoxic therapies. Retrospective cohort study. A single academic tertiary children's hospital. Twenty pediatric medulloblastoma patients (13 men; mean age 12.0 ± 4.8 yr) treated with platinum-based chemotherapy with or without radiation and 18 age-and-sex matched controls were included. Ototoxicity scores were determined using Chang Ototoxicity Grading Scale. Three Tesla magnetic resonance was used for diffusion tensor and arterial spin labeling perfusion imaging. Quantitative diffusion tensor metrics were extracted from the Heschl's gyrus, auditory radiation, and inferior colliculus. Arterial spin labeling perfusion of the Heschl's gyrus was also examined. Nine patients had clinically significant hearing loss, or Chang grades more than or equal to 2a; 11 patients had mild/no hearing loss, or Chang grades less than 2a. The clinically significant hearing loss group showed reduced mean diffusivity in the Heschl's gyrus (p = 0.018) and auditory radiation (p = 0.037), and decreased perfusion in the Heschl's gyrus (p = 0.001). Mild/no hearing loss group showed reduced mean diffusivity (p = 0.036) in Heschl's gyrus only, with a decrease in perfusion (p = 0.008). There were no differences between groups in the inferior colliculus. There was no difference in fractional anisotropy between patients exposed to ototoxic therapies and controls. Patients exposed to ototoxic therapies demonstrated microstructural and physiological alteration of the auditory pathway. The present study shows proof-of-concept use of diffusion tensor imaging to gauge ototoxicity along the auditory pathway. Future larger cohort studies are needed to assess significance of changes in diffusion tensor imaging longitudinally, and the relationship between these changes and hearing loss severity and longitudinal changes of the developing auditory white matter.

Early Atherosclerotic Inflammatory Pathways in Children with Obstructive Sleep Apnea

To evaluate structural and functional carotid changes and inflammatory profiles in children with obstructive sleep apnea (OSA) and healthy controls. Patients with OSA and matched controls (ages 5-13years) were recruited. Proinflammatory cytokines and acute phase reactants were measured at 6:00 p.m. Common carotid artery measures were determined using ultrasound. Confirmatory factor analysis was used to determine subgroups of cytokines and their effects on carotid measures. Ninety-six patients participated (53 healthy controls, 43 patients with OSA). OSA was associated with increased proinflammatory cytokines (cluster of differentiation-40 ligand [CD40-L], interleukin [IL]-6, and IL-8) and high sensitivity C-reactive protein (P<.05 for all). One cytokine subgroup (IL-6 and IL-8) was negatively associated with markers of carotid function, indicating reduced arterial distensibility and increased stiffness (P<.05 for 3 ultrasound measures); and tumor necrosis factor-α had an opposing effect on carotid function compared with this cytokine subgroup (P<.05 for 2 ultrasound measures). Linear regression demonstrated significant associations between and tumor necrosis factor- α and 2 measures of carotid function (P<.05 for each). Children with OSA did not have functional or structural carotid changes compared with controls. OSA was not directly associated with structural and functional carotid changes but was associated with upregulation of key proinflammatory cytokines (sCD40-L, IL-6, and IL-8). Together, IL-6 and IL-8 were associated with changes in carotid function. Longitudinal studies are needed to demonstrate that the inflammatory milieu observed in our population is a precursor of atherosclerosis in children.

An Age-Specific Atlas for Delineation of White Matter Pathways in Children Aged 6-8 Years.

IntroductionDiffusion MRI allows non-invasive assessment of white matter connectivity in typical development and of changes due to brain injury or pathology. Probabilistic white matter atlases allow diffusion metrics to be measured in specific white matter pathways, and are a critical component in spatial normalisation for group analysis. However, given the known developmental changes in white matter it may be sub-optimal to use an adult template when assessing data acquired from children.MethodsBy averaging subject-specific fibre bundles from 28 children aged from 6 to 8 years, we created an age-specific probabilistic white matter atlas for 12 major white matter tracts. Using both the newly developed and Johns Hopkins adult atlases, we compared the atlas to subject-specific fibre bundles in two independent validation cohorts, assessing accuracy in terms of volumetric overlap and measured diffusion metrics.ResultsOur age-specific atlas gave better overall performance than the adult atlas, achieving higher volumetric overlap with subject-specific fibre tracking and higher correlation of FA measurements with those measured from subject-specific fibre bundles. Specifically, estimates of FA values for cortico-spinal tract, uncinate fasciculus, forceps minor, cingulate gyrus part of the cingulum and anterior thalamic radiation were all significantly more accurate when estimated with an age-specific atlas.DiscussionThe age-specific atlas allows delineation of white matter tracts in children aged 6-8 years, without the need for tractography, more accurately than when normalising to an adult atlas. To our knowledge, this is the first publicly available probabilistic atlas of white matter tracts for this age group.

Expression and Significance of Leucine-rich Repeat-containing G-protein Coupled Receptor 5/6 in Wnt Pathway in Children with Acute Lymphoblastic Leukemia

Objective To study the expression and significance of leucine-rich repeat-containing G-protein coupled receptor(LGR)5/6 in childhood acute lymphoblastic leukemia(ALL). Methods A total of 39 children who had ALL and achieved complete remission on day 33 after induction therapy were enrolled.The children before induction therapy were considered as the incipient group,and those who achieved complete remission on day 33 by induction therapy were considered as the remission group.According to the degree of risk,they were assigned into 3 groups:low-risk(n=16),intermediate-risk(n=9),and high-risk(n=14)groups.A total of 30 children with immune thrombocytopenia were taken as the control group.From each child in the incipient group,remission group,and control group,3 ml bone marrow sample was collected.Real-time fluorescent quantitative polymerase chain reaction was conducted to measure the mRNA expression of LGR5 and LGR6 in the blood cells of bone marrow.Western blot was employed to measure the protein expression of LGR5 and LGR6 in blood cells of bone marrow. Results Compared with the control(mRNA:1.541±0.409,protein:0.138±0.041)and remission(mRNA:1.418±0.324,protein:0.130±0.033)groups,the incipient group had significantly lower mRNA(0.850±0.279)and protein(0.083±0.027)expression of LGR5(PmRNA=0.000,Pprotein=0.000).Compared with the control(mRNA:0.928±0.373,protein:0.094±0.037)and remission(mRNA:0.886±0.390,protein:0.111±0.039)groups,the incipient group had significantly higher mRNA(2.444±1.160)and protein(0.298±0.088)expression of LGR6(PmRNA=0.000,Pprotein=0.000).In the incipient groups,low-risk children showed significantly higher mRNA(1.004±0.284)and protein(0.097±0.030)expression of LGR5 than the intermediate-risk children(mRNA:0.728±0.239,protein:0.071±0.022)and high-risk children(mRNA:0.752±0.222,protein:0.074±0.020)(PmRNA=0.012,Pprotein=0.016);low-risk children showed significantly lower mRNA(1.822±0.979)and protein(0.245±0.077)expression of LGR6 than the intermediate-risk children(mRNA:2.954±1.039,protein:0.338±0.081)and high-risk children(mRNA:2.827±1.165,protein:0.333±0.075)(PmRNA=0.016,Pprotein=0.004).In the remission groups,low-risk children showed significantly higher mRNA(1.597±0.329)and protein(0.150±0.035)expression of LGR5 than the intermediate-risk children(mRNA:1.277±0.288,protein:0.117±0.029)and high-risk children(mRNA:1.305±0.253,protein:0.116±0.023)(PmRNA=0.012,Pprotein=0.006);low-risk children showed significantly lower mRNA(0.662±0.334)and protein(0.089±0.034)expression of LGR6 than the intermediate-risk children(mRNA:1.066±0.273,protein:0.130±0.033)and high-risk children(mRNA:1.027±0.405,protein:0.126±0.038)(PmRNA=0.007,Pprotein=0.007). Conclusion The expression of LGR5 and LGR6 are closely related to the occurrence and risk of childhood ALL,but its mechanism needs further study.