Naive Children Research Articles

Evolution of sleep disordered breathing in infants with achondroplasia.

Children with achondroplasia (ACH) are at risk for sudden death in infancy due to sleep disordered breathing (SDB) and foramen magnum stenosis (FMS). Sleep studies and neuroimaging are performed in infants with ACH, but interpretation of infant studies is challenging. We sought to describe baseline data on polysomnography (PSG) indices in infants with achondroplasia as well as effects of age and surgery on these parameters. Retrospective data were abstracted from the multisite CLARITY ACH database from years 2008-2017. Both obstructive apnea hypopnea index (OAHI) and central apnea index (CAI) were extracted, and effects of age and surgical intervention (adenoidectomy [AD] or cervicomedullary decompression [CMD]) were analyzed. 172 PSGs from 86 infants were analyzed. In surgically naive children, OAHI decreased over the first year but then increased in the second year, while CAI was mostly stagnant over the first two years. There were no significant differences between age at first PSG or PSG indices for surgically naive infants versus those who underwent AD or CMD. OAHI decreased after AD and CAI decreased after CMD. Similar to average stature infants, our results demonstrate the need to interpret sleep study findings of children with ACH in the context of age, particularly for obstructive indices. Neither OAHI nor CAI differentiated those infants who subsequently underwent surgery, suggesting that there were other important clinical factors in the surgical decision-making process. Independent of age, AD resulted in improvement in OSA and CMD with improvement in central sleep apnea.

Sleep, cognitive functions, behavioral, and emotional disturbance in self-limited focal childhood epilepsies

BackgroundSelf-limited focal epilepsies of childhood, including self-limited epilepsy with centrotemporal spikes (SeLECTS), idiopathic childhood occipital epilepsy of Gastaut (ICOE-G), and self-limited epilepsy with autonomic seizures (SeLEAS), were considered benign conditions. However, recent research assumed potential adverse impacts on sleep, cognition, behavior, and emotional well-being. Our aim was to investigate the effects of self-limited focal epilepsies on sleep architecture, cognitive functions, behavior, and emotional disturbances in drug naive children. A cross-sectional study was conducted on 46 newly diagnosed children (ages 6–12) with SeLECTS (n = 22), ICOE-G (n = 12), SeLEAS (n = 12), and 20 healthy controls. Overnight polysomnography was performed. Cognitive assessments included intelligence scales, executive function tests, verbal fluency, visuospatial abilities, and memory. Behavioral and emotional problems were evaluated using standardized questionnaires and psychiatric interviews.ResultsChildren with epilepsy exhibited significant disturbances in sleep architecture, impairments in cognitive domains (executive functions, verbal fluency, visuospatial skills, and memory), and higher rates of internalizing/externalizing problems, social issues, attention deficit hyperactive disorder, depression, and anxiety compared to controls. No significant differences were found among the three epilepsy subtypes.ConclusionSelf-limited focal epilepsies in childhood are associated with sleep disruption, cognitive deficits, behavioral issues, and psychiatric comorbidities, challenging their traditional "benign" perception. Comprehensive management approaches addressing these multidimensional impacts are warranted.

Impact of Pre-Existing Immunity and Age on Antibody Responses to Live Attenuated Influenza Vaccine.

Live attenuated influenza vaccines (LAIV) typically induce a poor hemagglutination inhibition (HI) response, which is the standard correlate of protection for inactivated influenza vaccines. The significance of the HI response is complicated because the LAIV vaccine primarily induces the local mucosal immune system, while the HI assay measures the circulating serum antibody response. However, age and pre-existing immunity have been identified as important factors affecting LAIV immunogenicity. This study aimed to extend our understanding of LAIV-induced immunity, particularly, the impact age and pre-existing immunity have on eliciting functional and neutralising antibody responses in paediatric and adult populations vaccinated with LAIV. Thirty-one children and 26 adults were immunized with the trivalent LAIV during the 2013-2014 influenza season in Norway. Children under 9 years received a second dose of LAIV 28 days after the first dose. Blood samples were collected pre- and post-vaccination. HI, microneutralization (MN) and enzyme-linked lectin assay for neuraminidase (NA) antibodies were measured against the vaccine strains. IgG antibody avidity against hemagglutinin (HA) and NA proteins from the vaccine strains was also assessed. Significant correlations were observed between HI and MN responses to A/California/7/2009 (A/H1N1)pdm09-like strain and B/Massachusetts/2/2012-like strain, suggesting that MN is a potential immunological correlate for LAIV. However, the relationship between recipient age (or priming status) and serological response varied between vaccine strains. There was a notable increase in HI and MN responses in all cohorts except naive children against the H1N1 strain, where most recipients had responses below the protective antibody threshold. NAI responses were generally weak in naive children against all vaccine strains compared with adults or antigen-primed children. Post-vaccination antibody avidity increased only in primed children below nine years of age against the A/H1N1 strain. Overall, our findings indicate that LAIV elicits functional and neutralizing antibody responses in both naive and antigen experienced cohorts, however, the magnitude and kinetics of the response varies between vaccine strains.

Characterization of bacterial and viral pathogens in the respiratory tract of children with HIV-associated chronic lung disease: a case–control study

IntroductionChronic lung disease is a major cause of morbidity in African children with HIV infection; however, the microbial determinants of HIV-associated chronic lung disease (HCLD) remain poorly understood. We conducted a case–control study to investigate the prevalence and densities of respiratory microbes among pneumococcal conjugate vaccine (PCV)-naive children with (HCLD +) and without HCLD (HCLD-) established on antiretroviral treatment (ART).MethodsNasopharyngeal swabs collected from HCLD + (defined as forced-expiratory-volume/second < -1.0 without reversibility postbronchodilation) and age-, site-, and duration-of-ART-matched HCLD- participants aged between 6–19 years enrolled in Zimbabwe and Malawi (BREATHE trial-NCT02426112) were tested for 94 pneumococcal serotypes together with twelve bacteria, including Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), Moraxella catarrhalis (MC), and eight viruses, including human rhinovirus (HRV), respiratory syncytial virus A or B, and human metapneumovirus, using nanofluidic qPCR (Standard BioTools formerly known as Fluidigm). Fisher's exact test and logistic regression analysis were used for between-group comparisons and risk factors associated with common respiratory microbes, respectively.ResultsA total of 345 participants (287 HCLD + , 58 HCLD-; median age, 15.5 years [IQR = 12.8–18], females, 52%) were included in the final analysis. The prevalence of SP (40%[116/287] vs. 21%[12/58], p = 0.005) and HRV (7%[21/287] vs. 0%[0/58], p = 0.032) were higher in HCLD + participants compared to HCLD- participants. Of the participants positive for SP (116 HCLD + & 12 HCLD-), 66% [85/128] had non-PCV-13 serotypes detected. Overall, PCV-13 serotypes (4, 19A, 19F: 16% [7/43] each) and NVT 13 and 21 (9% [8/85] each) predominated. The densities of HI (2 × 104 genomic equivalents [GE/ml] vs. 3 × 102 GE/ml, p = 0.006) and MC (1 × 104 GE/ml vs. 1 × 103 GE/ml, p = 0.031) were higher in HCLD + compared to HCLD-. Bacterial codetection (≥ any 2 bacteria) was higher in the HCLD + group (36% [114/287] vs. (19% [11/58]), (p = 0.014), with SP and HI codetection (HCLD + : 30% [86/287] vs. HCLD-: 12% [7/58], p = 0.005) predominating. Viruses (predominantly HRV) were detected only in HCLD + participants. Lastly, participants with a history of previous tuberculosis treatment were more likely to carry SP (adjusted odds ratio (aOR): 1.9 [1.1 -3.2], p = 0.021) or HI (aOR: 2.0 [1.2 – 3.3], p = 0.011), while those who used ART for ≥ 2 years were less likely to carry HI (aOR: 0.3 [0.1 – 0.8], p = 0.005) and MC (aOR: 0.4 [0.1 – 0.9], p = 0.039).ConclusionChildren with HCLD + were more likely to be colonized by SP and HRV and had higher HI and MC bacterial loads in their nasopharynx. The role of SP, HI, and HRV in the pathogenesis of CLD, including how they influence the risk of acute exacerbations, should be studied further.Trial registrationThe BREATHE trial (ClinicalTrials.gov Identifier: NCT02426112, registered date: 24 April 2015).

Contribution of SARS-CoV-2 infection preceding COVID-19 mRNA vaccination to generation of cellular and humoral immune responses in children.

Primary COVID-19 vaccination for children, 5-17 years of age, was offered in the Netherlands at a time when a substantial part of this population had already experienced a SARS-CoV-2 infection. While vaccination has been shown effective, underlying immune responses have not been extensively studied. We studied immune responsiveness to one and/or two doses of primary BNT162b2 mRNA vaccination and compared the humoral and cellular immune response in children with and without a preceding infection. Antibodies targeting the original SARS-CoV-2 Spike or Omicron Spike were measured by multiplex immunoassay. B-cell and T-cell responses were investigated using enzyme-linked immunosorbent spot (ELISpot) assays. The activation of CD4+ and CD8+ T cells was studied by flowcytometry. Primary vaccination induced both a humoral and cellular adaptive response in naive children. These responses were stronger in those with a history of infection prior to vaccination. A second vaccine dose did not further boost antibody levels in those who previously experienced an infection. Infection-induced responsiveness prior to vaccination was mainly detected in CD8+ T cells, while vaccine-induced T-cell responses were mostly by CD4+ T cells. Thus, SARS-CoV-2 infection prior to vaccination enhances adaptive cellular and humoral immune responses to primary COVID-19 vaccination in children. As most children are now expected to contract infection before the age of five, the impact of infection-induced immunity in children is of high relevance. Therefore, considering natural infection as a priming immunogen that enhances subsequent vaccine-responsiveness may help decision-making on the number and timing of vaccine doses.

Identification of Attention-Deficit-Hyperactivity Disorder Subtypes Based on Structural MRI Grey Matter Volume and Phenotypic Information.

One of the neurodevelopmental disorders widely affecting school-aged children in recent years is attention deficit hyperactivity disorder (ADHD). In many neurodevelopmental disorders, grey matter may be used as a clinical indicator by looking at MRIs. The study aimed to segment grey matter from brain MRI using a proposed fuzzy c-means clustering-based technique for the detection of ADHD and its subtypes (ADHD-Inattentive, ADHDHyperactive, and ADHD-Combined). The grey matter volume, age, gender, and medication status of the subjects were investigated to identify ADHD subtypes. A modified fuzzy c-means with an elbow approach has been proposed to overcome the drawbacks of previous fuzzy c-means methods and improve segmentation performance. The volume of segmented grey matter was included with the phenotypic information of the ADHD-200 dataset for data analysis of typically developing (TD) and ADHD subtypes. The proposed segmentation exhibited a dice similarity index of 95%. ADHD-Inattentive exhibited a loss of grey matter in the prefrontal cortex, while ADHD-hyperactive exhibited a loss of grey matter in the cerebellum when compared to TD. The analysis of ADHD subtypes based on age and gender showed that children transitioning to adolescence are mostly affected by ADHD-inattentive and female kids are less prone to ADHD-hyperactive. The whole grey matter volume of ADHD-inattentive children, on average, was found to be approximately 4% less than ADHD-combined. Furthermore, the whole grey matter volume was less in non-medication naive children. This study may support healthcare providers in giving appropriate occupational therapy based on the identification of different ADHD subtypes.

Respiratory syncytial virus in children: epidemiology and clinical impact post-COVID-19.

Respiratory syncytial virus (RSV) remains a leading cause of mortality and morbidity worldwide. RSV seasonality was disrupted by COVID-19-associated nonpharmaceutical interventions (NPIs). We review RSV seasonality, molecular epidemiology, clinical manifestations, and community awareness to inform future prevention strategies. An initial reduction of RSV disease observed with NPIs, and subsequent global resurgence was associated with a collapse in genetic diversity. A lack of immunity is suggested to have contributed to the resurgence of RSV cases experienced post COVID-19. The median age of children admitted with RSV increased during the resurgence, likely secondary to the expanded cohort of RSV-immune naive children. The pandemic also played a role in increased community awareness, which can be utilized as part of a coordinated public health effort to introduce prevention strategies. Further education on signs and symptoms of RSV is still required. mAbs and maternal vaccines targeting RSV have the potential to reduce paediatric morbidity, however this new era of RSV prevention will require ongoing research to facilitate community awareness and engagement, and better respiratory surveillance. Tackling the global burden of RSV will require a coordinated effort and measures to ensure access and affordability of new prevention strategies.

William Wordsworth’ün The Prelude’unda Eko-felsefi ve Fenomenolojik Bir Yolculuk

The present paper analyses William Wordsworth’s The Prelude form an eco-philosophical perspective, which suggests a harmonical existence of human and nonhuman worlds. The main argument is based on Arne Næss’ “ecosophy” following his deep ecological thoughts and David Bohm’s “undivided wholeness” supporting the intimate interconnectedness of human and Nature. Following this eco-philosophical vision, Wordsworth believes that Nature has an essential place in children’s learning. He even suggests stopping formal education of children and meditating them through the subjective experiences in Nature. This study investigates how Wordsworth reflects a child’s journey of gaining poetic consciousness through his interaction with Nature in his The Prelude. Nature is personified as a mother, a friend and a teacher helping his maturity. As a child and the speaker of his poem, Wordsworth feels freedom and joy while acquiring a great deal of knowledge at every step through different experiences. From this perspective, this study bases its arguments on Edmund Husserl and Martin Heidegger’s phenomenological insights to comprehend the essence of our “Being” through subjective experiences collected in our “life world”. Wordsworth emphasizes the growing maturity of the child in Nature by conceiving his existence in this perfect universe. The power of intuition and imagination, which preserves Nature in our minds, is also accentuated as the main factor educating and maturing us in time by shaping our ideas and feelings. In parallel with the eco-philosophical and phenomenological thoughts, Wordsworth stresses the truth, pureness, peace, and pleasure accompanied by the solitude in Nature. This paper observes the transformation of a naive child into a wise poet through the eco-philosophical and phenomenological journey in Nature through the power of intuition and imagination in Wordsworth’s The Prelude.

Referrals for Recurrent Acute Otitis Media With and Without Spontaneous Tympanic Membrane Perforation Through COVID-19: A Cross-Sectional Comparative Study.

To the Editors: Most children experience at least one episode of acute otitis media (AOM) and approximately one-third of them suffer from recurrent episodes (rAOM) with or without spontaneous tympanic membrane perforation (STMP).1 Data on the epidemiology of rAOM and STMP during the COVID-19 pandemic are scarce. The aim of this report is to evaluate the number and characteristics of children presenting with rAOM with and without STMP before and during the pandemic. This study was conducted at the otitis media pediatric outpatient clinic of the Ospedale Maggiore Policlinico, Milan (Italy), from 2019 to 2022. All consecutive children referring to the outpatient clinic for a first-time visit for rAOM2 were eligible and the following information was extracted: sex, age (≤2 and >2 years), date of first visit and history of STMP. Data were obtained from patient’s online medical records. Four periods were considered for the analysis: the year preceding the pandemic (2019), the 2 years with the strictest measures to limit the spread of COVID-19 (2020 and 2021) and the year in which these measures were progressively relaxed (2022). The Fisher exact test or the χ2 test were used for the analysis, as appropriate. A P value <0.05 was assumed as significant. The study was approved by the Ethical Committee of the Ca’ Granda Ospedale Maggiore, Milan (Comitato Etico Area2). A total of 786 children (53% >2 years of age and 45% females) were included (Table 1). A decreasing trend in the number of children with rAOM was observed in the first 3 years of the study. Furthermore, the percentage of children <2 years of age increased in 2021 and 2022. Similar data were observed for children with rAOM without STMP. No age difference (P = 0.319) was found for children with rAOM and STMP. TABLE 1. - Total Number of Patients and Number of First-Time Visits for rAOM With and Without STMP All 2019 2020 2021 2022 P Value rAOM N 786 300 141 108 237 Male 437 165 71 54 147 0.072 Age ≤2 yr 367 (47%) 120 (40%) 61 (43%) 59 (55%) 127 (53%) 0.004 >2 yr 419 (53%) 180 (60%) 80 (57%) 49 (45%) 110 (47%) rAOM without STMP N 441 143 59 72 167 Male 248 79 30 36 103 0.273 Age ≤2 yr 190 (43%) 44 (31%) 21 (36%) 41 (57%) 84 (50%) 0.0002 >2 yr 251 (57%) 99 (69%) 38 (64%) 31 (43%) 83 (50%) rAOM with STMP N 344 157 81 36 70 Male 189 87 41 18 43 0.544 Age ≤2 yr 177 (51%) 77 (40%) 39 (48%) 18 (51%) 43 (62%) 0.319 >2 yr 167 (49%) 80 (60%) 42 (52%) 18 (49%) 27 (38%) rAOM indicates recurrent acute otitis media; STMP, spontaneous tympanic membrane perforation P values <0.05 are in bold. The changes in rAOM frequency during the study period is consistent with prior research indicating a reduction in AOM cases.3,4 However, the main finding of this investigation pertains to a notable shift in the age distribution of children affected by rAOM. This age bracket presumably comprises children born during the peak of the stringent control measures. As such, the infection control protocols might have limited their exposure to pathogens, creating a cohort of immunologically naive children more susceptible to rAOM once the restrictions were lifted. Contrary to initial expectations, a significant rise in rAOM with STMP cases in 2022 and the decrease in the age of affected children were not observed. Recent data point out a change in antibiotic prescription in children after 2020.5 The early and widespread use of broad-spectrum antibiotics for respiratory infections and AOM may have decreased the incidence of common complications such as STMP. The main limitation of this study relies on its retrospective, monocentric design. In conclusion, this investigation reveals a rise in rAOM cases in 2022 with a noticeable increase in the younger age groups. These data underscore the possible medium to long-term repercussions of infection control measures.

Luiza and her Naive Children: Judicial Duel and Crony Relationships in Feira de Santana, Bahia, 1871-1888

RESUMO Neste trabalho, reconstituo a experiência da libertanda Luiza enquanto lutava pela liberdade legal para si mesma e, sobretudo, para suas filhas e seus filhos, nas últimas décadas da escravidão no Brasil. Para tanto, segui, especialmente, sua trajetória e a de suas seis crianças ingênuas − Ritta, Felippa, Jeronyma, Pedro, Francelina e Aurelio −, cruzando uma ação de liberdade, bem como inventários, leis emancipacionistas e milhares de assentos de batismos de Feira de Santana, Bahia, entre 1871 e 1888. A partir de uma abordagem qualitativa e quantitativa das fontes foi possível situar suas escolhas dentro do universo mais amplo das escolhas de outras mulheres negras de seu tempo, e constatar que, a despeito de enfrentarem a opressão interseccional de gênero, raça e classe, as mulheres negras protagonizavam na linha de frente da luta por liberdade.

Ustekinumab for steroid-refractory pancolitis in a biologically naive child: A case report and literature review.

Ustekinumab is not recommended for the treatment of children with inflammatory bowel disease, but its off-label use is increasing despite a lack of pediatric pharmacokinetic data. The purpose of this review is to evaluate the therapeutic effects of Ustekinumab on children with inflammatory bowel disease and to recommend the best treatment regimen. Ustekinumab was the first biological treatment for a 10-year-old Syrian boy with steroid-refractory pancolitis who weighed 34 kg. A 260 mg/kg (~6 mg/kg) intravenous dose was followed by 90 mg of subcutaneous Ustekinumab at week 8 (induction). The patient was supposed to receive the first maintenance dose after twelve weeks, but after ten weeks, he developed acute severe ulcerative colitis which was managed according to treatment guidelines, except receiving 90 mg of subcutaneous Ustekinumab when he was discharged. The maintenance dose of 90 mg subcutaneous Ustekinumab was intensified to every 8 weeks. Throughout the treatment period, he achieved and maintained clinical remission. In pediatric inflammatory bowel disease, a dose of intravenous ~6 mg/kg of Ustekinumab is a common induction regimen, while children weighing < 40 kg may require a dose of 9 mg/kg. For maintenance, children may require 90 mg of subcutaneous Ustekinumab every 8 weeks. The outcome of this case report is interesting with improved clinical remission and highlighting the expansion of clinical trials on Ustekinumab for children.

Drug-Induced Sleep Endoscopy Differences by Age in Surgically Naive Children With Sleep-Disordered Breathing

Drug-induced sleep endoscopy (DISE) is increasingly used to guide treatment decisions in children with sleep-disordered breathing (SDB). Previous reports of DISE findings in children have typically included a broad age range, but it is unclear how these patterns of obstruction vary with age. To compare patterns of airway obstruction observed during DISE in 3 age groups of surgically naive children with SDB. This cross-sectional analysis of a prospective cohort of surgically naive nonsyndromic children with SDB or obstructive sleep apnea [OSA] at risk for residual disease after adenotonsillectomy (defined as having at least 1 of these criteria: severe OSA, older than 7 years, obesity, or Black race) who were recruited between May 1, 2015, and February 28, 2020, was conducted at a tertiary children's hospital. Data analysis was conducted from September 2021 to February 2022. DISE. DISE findings were rated at 6 anatomic sites using the Sleep Endoscopy Rating Scale (SERS). The association between age and severity of obstruction at each anatomic site and overall were compared using correlation (Kendall τ) and ordinal logistic regression analysis. Data from 288 children (144 girls [50%]; 20 American Indian/Alaska Native [7%], 4 Asian [1%], 19 Black [7%], 93 Hispanic [33%], 2 Middle Eastern [1%], 6 Native Hawaiian/Pacific Islander [2%], and 203 White [70%] individuals; median [IQR] age, 9.2 [7.0-11.7] years) were stratified by participant age into preschool (age 2-5 years; 27 [9%]), younger school-aged (age 5-10 years; 146 [51%]), and older school-aged (age 10-18 years; 115 [40%]). Among these subgroups, the prevalence of multilevel obstruction was 59%, 51%, and 30%, respectively. Increasing age was inversely correlated with obstruction of the nasal airway (τb, -0.19; 95% CI, -0.29 to -0.09), nasopharynx (τb, -0.20; 95% CI, -0.31 to -0.10), velopharynx (τb, -0.16; 95% CI, -0.26 to -0.06), and overall obstruction (SERS total score: τb, -0.24; 95% CI, -0.33 to -0.14). An adjusted analysis demonstrated an inverse association between age and nasopharyngeal obstruction (odds ratio [OR], 0.84; 95% CI, 0.76 to 0.92), SERS total score (OR, 0.83; 95% CI, 0.76 to 0.90), and the number of sites of complete obstruction (OR, 0.87; 95% CI, 0.87 to 0.95). This cross-sectional analysis of data from a prospective cohort study of surgically naive children with SDB found that preschool-aged children had more frequent multilevel obstruction, more severe overall obstruction, and nasopharyngeal obstruction compared with older children. Understanding the most common sites of obstruction and expected changes with age could inform personalized treatment for children with SDB.

Precision medicine for developmental and epileptic encephalopathies in Africa—strategies for a resource-limited setting

PurposeSub-Saharan Africa bears the highest burden of epilepsy worldwide. A presumed proportion is genetic, but this etiology is buried under the burden of infections and perinatal insults in a setting of limited awareness and few options for testing. Children with developmental and epileptic encephalopathies (DEEs) are most severely affected by this diagnostic gap in Africa, because the rate of actionable findings is highest in DEE-associated genes. MethodsWe tested 234 genetically naive South African children diagnosed with/possible DEE using gene panels, exome sequencing, and chromosomal microarray. Statistical comparison of electroclinical features in children with and children without candidate variants was performed to identify characteristics most likely predictive of a positive genetic finding. ResultsOf the 41 (of 234) children with likely/pathogenic variants, 26 had variants supporting precision therapy. Multivariate regression modeling highlighted neonatal or infantile-onset seizures and movement abnormalities as predictive of a positive genetic finding. We used this, coupled with an emphasis on precision medicine outcomes, to propose the pragmatic “Think-Genetics” strategy for early recognition of a possible genetic etiology. ConclusionOur findings emphasize the importance of an early genetic diagnosis in DEE. We designed the Think-Genetics strategy for early recognition, appropriate interim management, and genetic testing for DEE in resource-constrained settings.

Hypoxia induces transgenerational epigenetic inheritance of small RNAs

Animals sense and adapt to decreased oxygen availability, but whether and how hypoxia exposure in ancestors can elicit phenotypic consequences in normoxia-reared descendants are unclear. We show that hypoxia educes an intergenerational reduction in lipids and a transgenerational reduction in fertility in the nematode Caenorhabditis elegans. The transmission of these epigenetic phenotypes is dependent on repressive histone-modifying enzymes and the argonaute HRDE-1. Feeding naive C.elegans small RNAs extracted from hypoxia-treated worms is sufficient to induce a fertility defect. Furthermore, the endogenous small interfering RNA F44E5.4/5 is upregulated intergenerationally in response to hypoxia, and soaking naive normoxia-reared C.elegans with F44E5.4/5 double-stranded RNA (dsRNA) is sufficient to induce an intergenerational fertility defect. Finally, we demonstrate that labeled F44E5.4/5 dsRNA is itself transmitted from parents to children. Our results suggest that small RNAs respond to the environment and are sufficient to transmit non-genetic information from parents to their naive children.

The association between autistic traits and serum testosterone, oxytocin, and androstenedione levels in prepubertal male drug naive children with attention-deficit/hyperactivity disorder.

Children with attention-deficit/hyperactivity disorder (ADHD) might have similar problems as in autism spectrum disorder (ASD) and show impairment in social behaviour. Also, there is a relationship between social relationship skills and ToM (theory of mind) skills of children with ADHD. Besides, ASD is associated with prenatal exposure to high levels of androgens, and oxytocin plays a role in the modulation of emotions, coping with stress, and social behaviour like ASD. In this study, the relationship between autistic traits and serum oxytocin, testosterone, and androstenedione levels in prepubertal male drug naive children with ADHD has been investigated. Eighty-three prepubertal children, who were diagnosed with ADHD between the ages of 6-10years old, are included in the study. For the study, intelligence levels were evaluated by using WISC-4, and autistic traits were measured by using both social responsiveness scale and theory of mind tests. In addition, serum oxytocin, testosterone, and androstenedione levels were measured by using ELISA. It has been found that serum testosterone levels of patients with lower autistic traits are significantly lower than those with moderate and severe autistic traits, while the serum oxytocin levels are significantly higher. Also, patients with severe autistic traits have had significantly higher serum androstenedione levels than those with lower and moderate autistic traits. This study suggests that patients who have higher autistic traits have elevated testosterone and androstenedione levels and lower serum oxytocin levels. Further studies are needed to clarify this relationship.

Effects of a single-dose methylphenidate challenge on resting-state functional connectivity in stimulant-treatment naive children and adults with ADHD.

Prior studies suggest that methylphenidate, the primary pharmacological treatment for attention‐deficit/hyperactivity disorder (ADHD), alters functional brain connectivity. As the neurotransmitter systems targeted by methylphenidate undergo significant alterations throughout development, the effects of methylphenidate on functional connectivity may also be modulated by age. Therefore, we assessed the effects of a single methylphenidate challenge on brain network connectivity in stimulant‐treatment naïve children and adults with ADHD. We obtained resting‐state functional MRI from 50 boys (10–12 years of age) and 49 men (23–40 years of age) with ADHD (DSM IV, all subtypes), before and after an oral challenge with 0.5 mg/kg methylphenidate; and from 11 boys and 12 men as typically developing controls. Connectivity strength (CS), eigenvector centrality (EC), and betweenness centrality (BC) were calculated for the striatum, thalamus, dorsal anterior cingulate cortex (dACC), and prefrontal cortex (PFC). In line with our hypotheses, we found that methylphenidate decreased measures of connectivity and centrality in the striatum and thalamus in children with ADHD, but increased the same metrics in adults with ADHD. Surprisingly, we found no major effects of methylphenidate in the dACC and PFC in either children or adults. Interestingly, pre‐methylphenidate, participants with ADHD showed aberrant connectivity and centrality compared to controls predominantly in frontal regions. Our findings demonstrate that methylphenidate's effects on connectivity of subcortical regions are age‐dependent in stimulant‐treatment naïve participants with ADHD, likely due to ongoing maturation of dopamine and noradrenaline systems. These findings highlight the importance for future studies to take a developmental perspective when studying the effects of methylphenidate treatment.

Increased Serum Level of CCL5 in Children with Attention‑Deficit/Hyperactivity Disorder: First Results about Serum Chemokines.

ObjectiveAttention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder and its aetiology is not fully understood. This study aimed to determine whether the CCL5 and CCL11 influence the ADHD aetiology by comparing serum CCL5 and CCL11 levels of children with ADHD and typical development.MethodsThis study included 45 (27 males, mean age = 8.9 ± 1.7 years) treatment-naive patients diagnosed with ADHD and 35 (20 males, mean age = 8.8 ± 1.6 years) healthy controls. Participants ranged in age between 6−12 years and completed the Conners Teacher Rating Scale that assesses ADHD presentation and severity. CCL5 and CCL11 serum levels were also measured using enzyme-linked immunosorbent assay kits.ResultsSignificantly higher serum CCL5 levels were found in children with ADHD compared to healthy controls (p < 0.001). No significant difference was found between the mean serum CC11 level of the patients and controls (p = 0.93). In addition, there was no significant correlation between the serum CCL5 and CCL11 levels and predominant presentations of ADHD and disease severity.ConclusionThis study suggests that there are higher levels of serum CCL5 in drug naive children with ADHD, this findings suggest that CCL5 might play a role in the pathophysiology of ADHD. Moreover, these changes in peripheral blood may have therapeutic value. In addition, these results help to understand the role of chemokines in elucidating the etiopathogenesis of ADHD. Our results can be considered as the first step in investigating the role of CCL5 in ADHD, and further research is needed to support these initial findings.

Reduced Cross-Sectional Muscle Growth Six Months after Botulinum Toxin Type-A Injection in Children with Spastic Cerebral Palsy.

Botulinum Neurotoxin type-A (BoNT-A) injections are widely used as first-line spasticity treatment in spastic cerebral palsy (SCP). Despite improved clinical outcomes, concerns regarding harmful effects on muscle morphology have been raised. Yet, the risk of initiating BoNT-A to reduce muscle growth remains unclear. This study investigated medial gastrocnemius (MG) morphological muscle growth in children with SCP (n = 26, median age of 5.2 years (3.5)), assessed by 3D-freehand ultrasound prior to and six months post-BoNT-A injections. Post-BoNT-A MG muscle growth of BoNT-A naive children (n = 11) was compared to (a) muscle growth of children who remained BoNT-A naive after six months (n = 11) and (b) post-BoNT-A follow-up data of children with a history of BoNT-A treatment (n = 15). Six months after initiating BoNT-A injection, 17% decrease in mid-belly cross-sectional area normalized to skeletal growth and 5% increase in echo-intensity were illustrated. These muscle outcomes were only significantly altered when compared with children who remained BoNT-A naive (+4% and −3%, respectively, p < 0.01). Muscle length growth persevered over time. This study showed reduced cross-sectional growth post-BoNT-A treatment suggesting that re-injections should be postponed at least beyond six months. Future research should extend follow-up periods investigating muscle recovery in the long-term and should include microscopic analysis.

Inactivated and live-attenuated seasonal influenza vaccines boost broadly neutralizing antibodies in children

SummaryThe induction of broadly neutralizing antibodies (bNAbs) that target the hemagglutinin stalk domain is a promising strategy for the development of “universal” influenza virus vaccines. bNAbs can be boosted in adults by sequential exposure to heterosubtypic viruses through natural infection or vaccination. However, little is known about if or how bNAbs are induced by vaccination in more immunologically naive children. Here, we describe the impact of repeated seasonal influenza vaccination and vaccine type on induction of bNAbs against group 1 influenza viruses in a pediatric cohort enrolled in randomized controlled trials of seasonal influenza vaccination. Repeated seasonal vaccination results in significant boosting of a durable bNAb response. Boosting of serological bNAb titers is comparable within inactivated and live attenuated (LAIV) vaccinees and declines with age. These data provide insights into vaccine-elicited bNAb induction in children, which have important implications for the design of universal influenza vaccine modalities in this critical population.

Outcomes of Ileoanal Pouch Anastomosis in Pediatric Ulcerative Colitis Are Worse in the Modern Era: A Time Trend Analysis Outcomes Following Ileal Pouch-Anal Anastomosis in Pediatric Ulcerative Colitis.

Despite significant differences in surgical outcomes between pediatric and adult patients with ulcerative colitis (UC) undergoing colectomy, counseling on pediatric outcomes has largely been guided by data from adults. We compared differences in pouch survival between pediatric and adult patients who underwent total proctocolectomy with ileal pouch-anal anastomosis (IPAA). This was a retrospective single-center study of patients with UC treated with IPAA who subsequently underwent pouchoscopy between 1980 and 2019. Data were collected via electronic medical records. We stratified the study population based on age at IPAA. Differences between groups were assessed using t tests and chi-square tests. Kaplan-Meier curves were used to compare survival probabilities. Differences between groups were assessed using a log-rank test. We identified 53 patients with UC who underwent IPAA before 19 years of age and 329 patients with UC who underwent IPAA at or after 19 years of age. Subjects who underwent IPAA as children were more likely to require anti-tumor nerosis factor (TNF) postcolectomy compared with adults (41.5% vs 25.8%; P < .05). Kaplan-Meier estimates revealed that pediatric patients who underwent IPAA in the last 10 years had a 5-year pouch survival probability that was 28% lower than that of those who underwent surgery in the 1990s or 2000s (72% vs 100%; P < .001). Further, children who underwent IPAA and received anti-TNF therapies precolectomy had the most rapid progression to pouch failure when compared with anti-TNF-naive children and with adults who were either exposed or naive precolectomy (P < .05). There are lower rates of pouch survival for children with UC who underwent IPAA following the uptake of anti-TNF therapy compared with both historical pediatric control subjects and contemporary adults.