Disease In Infants Research Articles

Oral prevention starts with the mother.

ECC is considered as one of the most prevalent diseases in childhood globally. When compared with other infancy diseases, it is fivefold more common than asthma and sevenfold more common than hay fever. Sugar has a pivotal role in caries development, mostly during the first years of life (Paglia et al., 2019). This, together with poor oral hygiene, increases the chance of caries onset tremendously. Thus, it is clear that preventive measures are focused on oral health-related behaviours and dietary habits. Based on these premises, paediatric dentists should focus on the mother's education in order to avoid the development of caries. The paediatric dentist has the duty to be the mothers' dentist, before of the child's. Mothers should be educated on their diet and oral hygiene and on the correct nutrition of the child, starting from the first month of age, limiting the child's intake of sugars and avoiding free sugars up to 2 years of age; dentists should inform the parents on when they have to start cleaning teeth and when fluoride is needed. Caries preventive measures should be established as early as possible. For a pediatric dentist, the only real success is not treating ECC with the latest technology, but visiting ECC-free children.

Moyamoya Disease in Infancy: Application of a Novel Indirect Revascularization Technique for Bihemispheric Cortical Synangiosis

Abstract INTRODUCTION Moyamoya disease (MMD) is a rare progressive cerebral arteriopathy characterized by nonatherosclerotic steno-occlusive lesions of the Circle of Willis. Presentation in infancy is rare and usually presents with ischemic stroke. We present a 7-mo old female with bilateral MMD who presented for indirect revascularization after 2 successive strokes in multiple vascular territories. METHODS We demonstrate a novel indirect revascularization technique in infant MMD whereby the patient's multifocal ischemic burden and STA caliber precluded arterial and myosynangiosis. We instead utilized bihemispheric pericranium for revascularization of bilateral oligemic cerebrum. Through a bicoronal scalp incision and inverted T-shaped pericranial incision, large anteriorly-based pericranial flaps were applied to the exposed pial surface using bilateral hemicraniotomies. Synangiosis extended from the frontal pole into parieto-occipital territories. We additionally performed a literature search on bypass approaches used for infant MMD. RESULTS A total of 10 infant MMD cases have been reported in the literature. Our case represents the only use of a pericranial graft in an infant without a combined approach. Pial synangiosis, EDAS, and conservative management represent techniques described in this population. Two case series utilized pericranial flaps with EDAS, however, no infants were included nor did revascularization extend beyond traditional margins. Our patient remains stroke and seizure-free for at least 16-months. She is ambulating independently and meeting her pediatric milestones. CONCLUSION Indirect revascularization is favored in pediatric MMD with approaches primarily utilizing native vessel donor grafts. Bilateral revascularization is performed in a delayed, sequential fashion if indicated. Further, collateralization is limited by the anatomical graft parameters, making hemispheric pathology difficult to comprehensively treat with these approaches. Our case demonstrates the safety and efficacy of utilizing a large bihemispheric pericranial flap on its native pedicle with bilateral hemicraniotomies for revascularization of multiple cerebrovascular territories in severe infant MMD. Our technique also allows for preservation of critical native vessels should the need for reoperation arise.

Liver Organoids Generated from Mice with Necrotizing Enterocolitis Have Reduced Regenerative Capacity.

Necrotizing enterocolitis (NEC) is one of the most severe gastrointestinal diseases in infancy. NEC can cause metabolic derangements, multi-organ injury including severe liver damage. The mechanism leading to hepatic damage in NEC remains unclear. The aim of this study is to establish and characterize liver organoids from NEC mice. Following ethical approval (#44032), we induced experimental NEC from postnatal day 5 (P5) to P9 using C57BL/6 mice pups. NEC was induced by gavage formula feeding, gavage lipopolysaccharide (LPS) administration, and hypoxia. Breastfed pups were used as control. On P9, NEC and control pups were sacrificed and liver tissue was harvested and organoids were generated. Organoid size was recorded daily (day 2-4) by measuring their surface area and organoid growth was calculated. RNA was extracted on day 4 after liver organoid generation. Organoid growth rate was significantly lower in NEC liver organoids compared to control liver organoids. mRNA expression of liver progenitor cells markers of LGR5 and SOX9 was lower in NEC liver organoids compared to control liver organoids. Similarly, expression of proliferation markers of Ki67 and PCNA was lower in NEC liver organoids. We report a novel technique to generate liver organoids during NEC. These organoids are characterized by reduced progenitor cells, reduced proliferation, and overall impaired regenerative capacity. Liver progenitor cells are important targets to prevent liver damage in NEC and promote recovery.

A Randomized, Double-Blind, Placebo-Controlled Trial Assessing the Oral Administration of a Heat-Treated Lactobacillus paracasei Supplement in Infants with Atopic Dermatitis Receiving Topical Corticosteroid Therapy

Background/Aims: Atopic dermatitis (AD) is a common disease in infancy, for which topical steroids are the first-line therapy but have side effects. Innovative approaches are needed to reduce the burden of AD and corticosteroid usage in infants. Methods: The once-daily consumption of heat-treated probiotic Lactobacillus paracasei GM-080 or placebo for 16 weeks as supplementary approach to topical treatment with fluticasone propionate cream was compared in AD infants aged 4–30 months. Outcomes were SCORAD and its subscores, TEWL, Infants’ Dermatitis Quality of Life Index (IDQOL), corticoid “sparing effect,” CCL17/TARC, and IgE status. Results: SCORAD, objective SCORAD, itching, and IDQOL decreased significantly (p < 0.001) over the treatment period in both treatment groups. Slight decreases (ns) were noted in TEWL in lesional and unaffected skin and CCL17 levels. There were no differences between the treatment groups. Total IgE increased over the treatment period in both groups, with significantly higher increase in the heat-treated probiotic group (p = 0.038). There was no evidence of a corticoid “sparing effect” by the probiotic. Conclusions: In this design, the probiotic L. paracasei was not beneficial as a complementary approach to topical corticosteroids in infants with AD. However, slight beneficial effects may have been masked by the moderate potency corticoid.

EPO enhances the protective effects of MSCs in experimental hyperoxia-induced neonatal mice by promoting angiogenesis.

Bronchopulmonary dysplasia (BPD) is the most common type of chronic lung disease in infancy; however, there is no effective treatment for it. In the present study, a neonatal mouse BPD model was established by continuous exposure to high oxygen (HO) levels. Mice were divided randomly into 5 groups: control, BPD, EPO, MSCs, and MSCs+EPO. At 2 weeks post-treatment, vessel density and the expression levels of endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1), and its receptor C-X-C chemokine receptor type 4 (CXCR4) were significantly increased in the MSC+EPO group compared with the EPO or MSCs group alone; moreover, EPO significantly enhanced MSCs proliferation, migration, and anti-apoptosis ability in vitro. Furthermore, the MSCs could differentiate into cells that were positive for the type II alveolar epithelial cell (AECII)-specific marker surfactant protein-C, but not positive for the AECI-specific marker aquaporin 5. Our present results suggested that MSCs in combination with EPO could significantly attenuate lung injury in a neonatal mouse model of BPD. The mechanism may be by the indirect promotion of angiogenesis, which may involve the SDF-1/CXCR4 axis.

Neurodevelopmental and health-related quality-of-life outcomes in adolescence after surgery for congenital heart disease in infancy.

To assess outcomes in adolescence after surgery for congenital heart disease (CHD) in infancy. Domains analysed included cognition and executive function, social and emotional well-being, adaptive behaviour, academic achievement, and health-related quality of life (HRQoL). Twenty-one participants (10 males, 11 females) ranged in age from 14 to 17years (mean 15y 4.8mo, SD 8.4mo). Twenty had biventricular repairs. All were classified as New York Heart Association class I. Measures included: Wechsler Intelligence and Achievement scales; Wide Range Assessment of Memory and Learning, Second Edition; California Verbal Learning Test - Children's Version; Behaviour Rating Inventory of Executive Function; Conners, Third Edition; Adaptive Behavior Assessment System, Second Edition; Behavior Assessment System for Children, Second Edition; Rey-Osterrieth Complex Figure; and Pediatric Quality of Life Inventory. Outcomes were significantly lower (p≤0.01) than population norms for processing speed, mathematical achievement, attention, and visual-spatial ability. Participants reported more frequent learning problems but more positive family relations. HRQoL was significantly lower across most domains by self- and parent-proxy report. Individuals with CHD may experience difficulties across a range of domains. These findings emphasize the importance of comprehensive screening, early intervention, and long-term follow-up, as deficits may extend into young adulthood. Identified cognitive, learning, and attentional impairments in adolescents after congenital heart disease surgery in infancy. Combined self-report, caregiver report, and laboratory tasks in a comprehensive neurodevelopmental assessment protocol. Health-related quality of life was lower across most domains.

The risk of atopic dermatitis in post-term gestational age at Sanglah Hospital Denpasar: A preliminary study

Backgrounds: Several studies reported that Atopic Dermatitis (AD) increases with gestational age. Prolong dominancy of Th2 activity during gestation might contribute to the risk of atopic disease in infancy or beyond the period. This study aimed to evaluate the risk AD in post-term gestational age.Methods: A prospective observational study was conducted among 73 living births at Sanglah Hospital Denpasar from December 2015 to January 2016 period. Infants were classified into 2 such as exposed (post-term) and non exposed (term and preterm) group. Parents-follow up by phone was carried out in 1 until 2 months interval. The study was finished once AD diagnosed, subject died or lost to follow up. Statistical analysis was carried out using SPSS ver. 20 software whereas P-value &gt; 0.05 was considered significant.Results: About 20 (233%) infants were preterm, 36 (49.3%) a term, and 17 (23,3%) post-term. The median value of follow up duration was 28 (14-35) days. Based on AD, there were total 24 cases which divided into 15(62.5%), 8(33.3%) and 1(4.17%) cases of AD in post-term, aterm, and preterm respectively. The incidence rate of AD in post-term was 88.2% while in non-post-term the incidence rate was 16.1%. The relative risk (RR) of AD in post-term was 5.47 (95% CI 2.94-10.23; P = 0.001)Conclusion: Post-term is 5.47 times more likely to develop AD compared with aterm and preterm infant. In addition, the incidence rate of AD in post-term infant was 88.2% at Sanglah Hospital Denpasar

An improved and easy protocol for primary epithelial cell culture from atretic tissue in biliary atresia.

Biliary atresia (BA) is a lethal disease of infancy with obscure etiology. Insight into the pathogenesis of this disorder is limited by lack of availability of adequate epithelial tissue. Primary culture of human biliary epithelium may help to provide material for diagnostic and research purposes. However, culture of these cells from atretic tissue is a challenging task. We aimed to develop a reliable and easier protocol for culture of human biliary epithelial cells from excised atretic extrahepatic bile duct. An explant culture was performed using tissue obtained from 30 children with diseases of biliary tract. The culture showed florid cell growth in less than 3 weeks. Epithelial nature and biliary origin of cultured cells was confirmed using pancytokeratin and cytokeratin -7 antibodies. The protocol showed 100% success rate as cells could be cultured in all 30 patients. Moreover, the cells remained viable for a duration of over 3 months in most of the cases. This easier culture technique is likely to have an impact on the study of biliary cell pathophysiology, particularly in BA.

The Effects of Rufinamide on &amp;lt;i&amp;gt;in Vitro&amp;lt;/i&amp;gt; Spinal Muscular Atrophy Model

Spinal muscular atrophy (SMA) is devastating genetic disease characterized by progressive loss of motor neuron and skeletal muscle weakness. SMA is the most common lethal genetic disease in infancy. SMA is caused by deletion or mutation of SMN1 gene and subsequent lack of SMN protein. Our purpose in this study was to evaluate the therapeutic potential of rufinamide, an antiepileptic drug. In this study, SMA patient-derived fibroblasts and differentiated spinal motor neurons (MNs) using SMA patient-derived iPSCs were used as in vitro SMA model. SMN mRNA was significantly increased by addition of rufinamide in type III SMA patient-derived fibroblasts. Furthermore, rufinamide stimulated neurite elongation in type III SMA patient derived-iPSCs-MNs. In contrast of the result using type III SMA patient-derived fibroblasts, the expression level of SMN mRNA was not changed after rufinamide treatment in type I SMA patient-derived fibroblasts, and rufinamide did not affect neurite outgrowth in type I SMA patients derived-iPSCs-MNs. These findings indicate that rufinamide may be one of the potential candidate drugs for mild type of SMA.

Uncertainties in Screening and Prevention of Group B Streptococcus Disease.

In autumn 2016, the UK Department of Health (now Department of Health and Social Care) convened 2 meetings to discuss how to address research evidence gaps in order to minimize the impact of infant group B streptococcus (GBS) disease in the United Kingdom. At that meeting, a number of research priorities were highlighted, including improving the screening for GBS colonization in pregnant women, offering intrapartum antibiotic prophylaxis and point-of-care testing, and understanding the effect of widespread intrapartum antibiotic use on long-term infant health. Further discussions involved investigating the feasibility of a large prospective study of pregnant women and their infants in order to understand the role of antibodies in the protection against GBS disease in infancy following maternal exposure to GBS colonization. Here, we summarize the research uncertainties identified at that meeting.

738. Role of Respiratory Syncytial Virus and Mycoplasma pneumoniae in Pediatric Community-Acquired Lower Respiratory Tract Infections

BackgroundRespiratory syncytial virus (RSV) infection is a major cause of serious lower respiratory disease in infancy and early childhood and Mycoplasma pneumoniae (M. pneumoniae) is a common cause of respiratory tract infections in all age groups. This study was conducted to determine the role of RSV and M. pneumoniae and in pediatric lower respiratory tract infections employing serological tests, polymerase chain reaction (PCR) and reverse transcriptase PCR analysis.MethodsIn this prospective study, 75 children aged 1 month to 5 years with acute lower respiratory tract infections (LRTIs) were investigated. Paired serum samples were obtained on admission and after 4–6 weeks to assay for M. pneumonia antibodies. Nasopharyngeal aspirates were obtained for the detection of RSV antigen by using the immunochromatographic test, reverse transcriptase-polymerase chain reaction (RT-PCR) for RSV and M. pneumoniae by PCR.ResultsRSV infection was positive in 20(60.60%) children aged <1 year and 13 (39.40%) aged 2–5 years, the difference being statistically insignificant (P = 0.360). M. pneumoniae infection was documented in a 15(57.6%) children aged <1 year age and 11(42.4%) in age 2–5 years which was statistically significant(P = 0.026). Clinical and radiological features among RSV and M. pnemoniae positive and negative cases were comparable. Thirty (40%) children were positive for RSV antigen and by RT-PCR and 3(12%) only by RT-PCR. Serological evidence of M pneumoniae infection was documented in 24(32%) children. M. pnemoniae PCR was positive in 8 (10.66%) patients. Together, serology and PCR detected M. pneumoniae in 26(34.66%) children. Considering RT-PCR as a diagnostic standard, the sensitivity of RSV antigen by immunochromatography was 90.90%, specificity 100%, positive predictive value 100% and a negative predictive value of 93.3%.The sensitivity of M. pneumoniae serology was 75%, specificity 73.3%, positive predictive value 25% and a negative predictive value of 96% considering PCR as a diagnostic standard,.ConclusionOur data underline the role of RSV and M. pneumoniae as the major cause of community-acquired lower respiratory tract infections in children aged <5 years.Disclosures All authors: No reported disclosures.

End-stage kidney disease in infancy: an educational review.

An increasing number of infants with end-stage kidney disease (ESKD) are surviving and receiving renal replacement therapy (RRT). Unique clinical issues specific to this age group of patients influence their short- and long-term outcomes. This review summarizes current epidemiology, clinical characteristics, ethical dilemmas, management concerns, and outcomes of infants requiring chronic dialysis therapy. Optimal care during infancy requires a multidisciplinary team working closely with the patient's family. Nutritional management, infection prevention, and attention to cardiovascular status are important treatment targets. Although mortality rates remain higher among infants on dialysis compared to older pediatric dialysis patients, outcomes have improved over time. Most importantly, infants who subsequently receive a kidney transplant are now experiencing graft survival rates that are comparable to older pediatric patients.

Leigh Syndrome: Report of a Rare Case with Late Onset Presentation

Leigh's syndrome, or sub acute necrotizing encephalomyelopathy, is a rare inherited neurometabolic disease of infancy and early childhood with variable course and prognosis. Rarely, it occurs in juveniles and adults. The diagnosis is difficult and still remains to challenge the clinicians on the basis of history; hence the role of imaging is very essential. It is the neuroimaging, chiefly the Magnetic Resonance Imaging showing characteristic symmetrical necrotic lesions in the basal ganglia and/or brain stem that leads to the diagnosis. Late-onset varieties are rare and only few cases were reported all over the world. Here, I report a case of late onset (juvenile) Leigh syndrome presenting with an acute polyneuropathy. Neuroimaging confirmed it to be a case of Leigh syndrome.

Progress of the effect of maternal diet avoidance on infant eczema

Eczema is the most common and earliest allergic disease in infancy, which seriously affects the quality of life of infants.In recent years, the incidence of infant eczema has been on the rise and there is no radical cure .This article reviews the etiology of eczema, the concept and the mechanism of food intolerance associated with food-specific IgG, and the relationship between infant eczema and maternal food-specific IgG detection, and discusses the literatures about avoiding eczema and improving the mechanism of eczema in lactating mothers, aiming at helping to solve the problem of eczema partially from the source, reducing the pain of recurrent eczema in infant, and avoiding or reducing the adverse reactions to the babies. Key words: Infant eczema; Food intolerance; Food-specific IgG detection; Maternal diet

Bronchial hyper-responsiveness in preterm-born subjects: A systematic review and meta-analysis.

Preterm-born survivors have increased respiratory symptoms and decreased lung function, but the nature of bronchial hyper-responsiveness (BHR) is unclear. We conducted a systematic review and meta-analysis for BHR in preterm-born survivors including those with and without chronic lung disease in infancy (CLD) comparing results to term-born subjects. We searched eight databases up to December 2016. Included articles compared BHR in preterm-born and term-born subjects. Studies reporting BHR as decreases in forced expiratory volume in 1second (FEV1 ) after provocation stimuli were included. The analysis used Review Manager V5.3. From 10638 titles, 265 full articles were screened, and 28 included in a descriptive analysis. Eighteen articles were included in a meta-analysis as they reported the proportion of subjects who had BHR. Pooled odds ratio (OR) estimates (95% confidence interval) for BHR comparing the preterm and term-born groups was 1.88 (1.32, 2.66). The majority of the studies reported BHR after a methacholine challenge or an exercise test. Odds ratio was 1.89 (1.12, 3.19) after methacholine challenge and 2.59 (1.50, 4.50) after an exercise test. Nine of fifteen articles reporting BHR in CLD subjects were included in a meta-analysis. Differences for BHR including for methacholine (OR 4.35; 2.36, 8.03) and exercise (OR 5.13; 1.82, 14.47) were greater in the CLD group compared to the term group. Preterm-born subjects especially those who had CLD had increased rates of BHR to direct (methacholine) and indirect (exercise) stimuli compared to term-born subjects suggesting subgroups might benefit from anti-inflammatory or bronchodilator therapies.

Differences of Medical Care for Acute Severe Viral Bronchiolitis in Two Urban Areas in Europe.

Acute viral bronchiolitis is a frequent disease in infancy. There is little knowledge on medical care of severely affected infants in different European countries. Infants (n=146) with bronchiolitis requiring respiratory support in winter season 2015/2016 treated in either one of two regions in Central Europe: South of greater Paris region in France (group 1) and Ruhr area in Germany (group 2). Retrospective chart review. Primary outcome parameter was duration of respiratory support. Infants in group 1 (n=96) were younger, suffered less frequently from neurologic disorders and had lower respiratory rates than in group 2 (n=50). CO2 levels and dyspnea score were similar. Ninety percent of infants in group 1 were treated by nasal Continuous Airway Pressure CPAP, while 80% of infants in group 2 were treated by High Flow Nasal Cannula HFNC. Duration of respiratory support was significantly shorter in group 1. Infants in group 2 received more frequently infusion therapy, more antibiotics and more inhalation therapy. Our results show better outcome for infants with viral bronchiolitis treated in France. Striking differences were the practice of respiratory support (nasal CPAP vs. HFNC) and the prescription of supportive treatments. Treatment approaches in severe acute viral bronchiolitis differ widely between a French and a German urban region.

The outcomes of Perthes\u2019 disease of the hip: a study protocol for the development of a core outcome set

BackgroundPerthes’ disease is an idiopathic osteonecrosis of a developmental hip that is most frequent in Northern Europe. Currently, the absence of a common set of standardised outcomes makes comparisons between studies of different interventions challenging. This study aims to summarise the outcomes used in clinical research of interventions for Perthes’ disease and define a set of core outcomes (COS) to ensure that the variables of primary importance are measured and reported in future research studies investigating Perthes’ disease.MethodsA systematic review of the current literature will be used to identify a list of outcomes reported in previous studies. Additional important outcomes will be sought by interviewing a group of children with Perthes’ disease, adults who were treated with the disease in infancy and parents of children with the disease. This list will then be evaluated by experts in Perthes’ disease using a Delphi survey divided into two rounds to ascertain the importance of each outcome. The final outcomes list obtained from the Delphi survey will be then discussed during a consensus meeting of representative key stakeholders in order to define the COS to be reported in future clinical trials related to Perthes’ disease.DiscussionThe absence of high-quality research and clear guidelines concerning the management of Perthes’ disease is, at least in part, due to the difficulties in the comparing the results from previous studies. The development of a COS seeks to standardise outcomes collected in future research studies to enable comparisons between studies to be made and to facilitate meta-analyses of results.Trial registrationCore Outcome Measures in Effectiveness Trials Initiative (COMET), 1003. Registered on 20 July 2017. Prospero International Prospective Register of Systematic Reviews, CRD 42017069742. Registered on 10 July 2017.

The Role of Liver Biopsy in Investigation of Cholestatic Liver Disease in Infancy.

ObjectivesThe objective of this study was to assess the diagnostic yield and impact on management of liver biopsy in infants with cholestatic jaundice.MethodsA retrospective cohort study of infants with cholestasis who underwent liver biopsy before one year of age between December 2002 and December 2013 at the Montreal Children’s Hospital was conducted. Biopsies were reviewed by a single pathologist. The diagnostic yield of the biopsy was assessed in terms of its role in establishing a diagnosis, excluding an important diagnosis or changing management.ResultsSeventy-nine biopsies were performed within the time frame outlined, with 58 fulfilling inclusion criteria. Liver biopsies were found to add novel information in 21 cases (36.2%). The diagnostic yield of the biopsy was unrelated to the severity of direct hyperbilirubinemia, age at biopsy, age at admission, co-morbidities, stool color at presentation and TPN exposure. Among infants under 90 days of age, 21 also underwent cholangiography, the results of which were consistent with biopsy findings. There were four (6.9%) documented complications from biopsies, including bleeding and accumulation of free fluid in the peri-hepatic area.ConclusionsLiver biopsy is an invasive test used with other clinical modalities to determine the etiology of neonatal cholestasis. These results suggest that biopsy added novel information to the diagnostic workup in 36.2% of cases with a complication rate of 6.9%. Consequently, the role and timing of liver biopsy need to be reassessed to determine which patients would most benefit from this procedure.

MicroRNA-29b/142-5p contribute to the pathogenesis of biliary atresia by regulating the IFN-\u03b3 gene

Biliary atresia is one of the most common liver disease in infancy. The cause and pathogenesis remain largely unknown. This study aimed to investigate the potential regulatory effect of miR-29b/142-5p on IFN-γ gene methylation. miRNAs microarray was performed on four pairs of liver and blood specimens from biliary atresia and choledochal cysts. We found the overexpression of miR-142-5p and mRNA level of DNA methyltransferase (DNMT) 1, and miR-29b and DNMT3a/DNMT3b were significantly negatively correlated in biliary atresia livers. Meanwhile, the methylation of the LINE-1, ALU and SAT2 repetitive sequences and the IFN-γ promoter was lower, but the expression of IFN-γ was upregulated. After transfected with DNMTs siRNAs, downregulation of DNMTs exerted a significant hypomethylating effect on the repetitive sequences, which led to upregulation of IFN-γ in Jurkat cells. The direct interactions between miR-29b and DNMT3a/3b, and miR-142-5p and DNMT1 were identified using luciferase reporter assays. By transfecting mimics of miR-29b/142-5p into Jurkat cells, we found overexpression of miR-29b/142-5p markedly suppressed expression of DNMTs. Furthermore, the methylation of repetitive sequences and the IFN-γ promoter region were remarkably downregulated, and with elevated IFN-γ expression. After transfecting the miRNA inhibitors, the levels of DNMTs and the methylation of the IFN-γ gene promoter region was upregulated, while levels of IFN-γ were markedly suppressed. Our study suggested that miRNA-29b/142-5p overexpression and targeted inhibition of DNMTs expression resulted in decreased overall gene methylation and overexpression of the methylation-sensitive IFN-γ gene.

Exploring Immune Development in Infants With Moderate to Severe Atopic Dermatitis.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in infancy with a complex pathology. In adults, the clinical severity of AD has been associated with increases in T helper cell type (Th) 2, Th22, and Th17 serum markers, including high levels of CC chemokine ligand (CCL) 17 and CCL22 chemokines. To explore the possible association between serum chemokine levels and AD severity in infants with moderate-to-severe AD and elevated immunoglobulin E (IgE). Serum samples (n = 41) obtained from a randomized, double-blind, and clinical dietary intervention study were used to study biomarkers in infants with AD. Baseline- and post-intervention samples (4 months) were used, six chemokines and nine ratios thereof were analyzed using Luminex and correlated to AD severity. In the initial study, the infants were randomized to receive extensively hydrolyzed whey-based formula without (control) or with short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides (9:1) and Bifidobacterium breve M-16V (active). 31 Infants up to 11 months of age, with an objective-SCORAD score (oSCORAD) ≥ 20 and elevated total-IgE and/or specific-IgE levels were included. In time, the median oSCORAD decreased in both groups by -8 (control, p < 0.05; active, p < 0.01). Irrespective of dietary intervention, several changes in Th2 chemokines (CCL17 and CCL22), inflammatory chemokine (CCL20), and the Th1 chemokine, CXC chemokine ligand (CXCL) 9, were detected over time. Overall CCL17 correlated to oSCORAD (r = 0.446, p < 0.01). After 4 months of dietary intervention, CXCL9 was higher (p < 0.01) in the active group compared with control [active, 2.33 (1.99-2.89); controls, 1.95 (1.77-2.43) log 10 median (range)]. In addition, a reduction in Th2/Th1 chemokine ratios for CCL17/CXCL9, CCL22/CXCL9, CCL20/CXCL10, and CCL20/CXCL11 was detected associated with the active intervention. While this study is small and exploratory in nature, these data contribute to immune biomarker profiling and understanding of AD in infants.