Functional analysis of granulocyte and monocyte subpopulations in neonates
ConclusionsDifferentially regulated granulocyte and monocyte subpopulations indicate a unique state of neonatal immunity to fight infections and prevent dysregulation. Further studies are needed to investigate the role of reduced granulocytic ROS formation and reduced monocytic HLA-DR in active disease. (Source: Molecular and Cellular Pediatrics)
Source: Molecular and Cellular Pediatrics - November 28, 2019 Category: Cytology Source Type: research

Vegetarian diets in childhood and adolescence
AbstractIn Western countries, vegetarian diets are associated with lower intakes of energy, saturated fatty acids and animal protein and higher intakes of fibre and phytochemicals, compared to omnivorous diets. Whether the corresponding health benefits in vegetarians outweigh the risks of nutrient deficiencies has not been fully clarified. It should be noted that vegetarians often have a higher socioeconomic status, follow a more health-conscious lifestyle with higher physical activity, and refrain from smoking more often than non-vegetarians. The nutritional needs of growing children and adolescents can generally be met t...
Source: Molecular and Cellular Pediatrics - November 12, 2019 Category: Cytology Source Type: research

Vitamin D supplementation after the second year of life: joint position of the Committee on Nutrition, German Society for Pediatric and Adolescent Medicine (DGKJ e.V.), and the German Society for Pediatric Endocrinology and Diabetology (DGKED e.V.)
ConclusionBased on currently available studies, routine  vitamin D supplementation is not be recommended for children aged>  2 years, even when they have serum concentrations below reference values. Routine vitamin D supplementation is not recommended in children who do not have risk factors and chronic diseases which are associated with calcium or vitamin D resorption disorders. (Source: Molecular and Cellular Pediatrics)
Source: Molecular and Cellular Pediatrics - May 6, 2019 Category: Cytology Source Type: research

Complementary foods in baby food pouches: position statement from the Nutrition Commission of the German Society for Pediatrics and Adolescent Medicine (DGKJ, e.V.)
AbstractPureed complementary feeding products packed in squeezable plastic pouches, usually with a spout and a screw cap, have been increasingly marketed. The Committee on Nutrition recommends that infants and young children should not suck pureed or liquid complementary foods from baby food pouches. Complementary foods should be offered with a spoon or should be fed as finger foods. Infants and young children should be given the opportunity to get to know a variety of foods and food textures including pieces of foods, supported by responsive feeding between the child and their parents or caregivers. Complementary foods ma...
Source: Molecular and Cellular Pediatrics - March 6, 2019 Category: Cytology Source Type: research

KUNO-Kids birth cohort study: rationale, design, and cohort description
ConclusionsThe data and diverse biomaterial collected in the KUNO-Kids birth cohort study will provide extensive opportunities for investigating child health and its determinants in a holistic approach. The combination of a broad range of research questions in one study will allow for a cost-effective use of biomaterial and omics results and for a comprehensive analysis of biological and social determinants of health and disease. Aiming for low attrition and ensuring participants ’ long-term commitment will be crucial to fully exploit the potential of the study. (Source: Molecular and Cellular Pediatrics)
Source: Molecular and Cellular Pediatrics - January 9, 2019 Category: Cytology Source Type: research

Gene correction of HBB mutations in CD34 + hematopoietic stem cells using Cas9 mRNA and ssODN donors
AbstractBackgroundβ-Thalassemia is an inherited hematological disorder caused by mutations in the human hemoglobin beta (HBB) gene that reduce or abrogate β-globin expression. Although lentiviral-mediated expression of β-globin and autologous transplantation is a promising therapeutic approach, the risk of insertional mutagenesis or low transgene expression is apparent. However, targeted gene correction ofHBB mutations with programmable nucleases such as CRISPR/Cas9, TALENs, and ZFNs with non-viral repair templates ensures a higher safety profile and endogenous expression control.MethodsWe have compared thre...
Source: Molecular and Cellular Pediatrics - November 14, 2018 Category: Cytology Source Type: research

Chemotherapy and the pediatric brain
AbstractSurvival rates of children with cancer are steadily increasing. This urges our attention to neurocognitive and psychiatric outcomes, as these can markedly influence the quality of life of these children. Neurobehavioral morbidity in childhood cancer survivors affects diverse aspects of cognitive function, which can include attention, memory, processing speed, intellect, academic achievement, and emotional health. Reasons for neurobehavioral morbidity are multiple with one major contributor being chemotherapy-induced central nervous system (CNS) toxicity. Clinical studies investigating the effects of chemotherapy on...
Source: Molecular and Cellular Pediatrics - November 6, 2018 Category: Cytology Source Type: research

The role of S100 proteins in the pathogenesis and monitoring of autoinflammatory diseases
AbstractS100A8/A9 and S100A12 are released from activated monocytes and granulocytes and act as proinflammatory endogenous toll-like receptor (TLR)4-ligands. S100 serum concentrations correlate with disease activity, both during local and systemic inflammatory processes. In some autoinflammatory diseases such as familial Mediterranean fever (FMF) or systemic juvenile idiopathic arthritis (SJIA), dysregulation of S100 release may be involved in the pathogenesis. Moreover, S100 serum levels are a valuable supportive tool in the diagnosis of SJIA in fever of unknown origin. Furthermore, S100 levels can be used to monitor dise...
Source: Molecular and Cellular Pediatrics - September 25, 2018 Category: Cytology Source Type: research

Precision medicine in pediatric oncology
AbstractOutcome in treatment of childhood cancers has improved dramatically since the 1970s. This success was largely achieved by the implementation of cooperative clinical research trial groups that standardized and developed treatment of childhood cancer. Nevertheless, outcome in certain types of malignancies is still unfavorable. Intensification of conventional chemotherapy and radiotherapy improved outcome only marginally at the cost of acute and long-term side effects. Hence, it is necessary to develop targeted therapy strategies.Here, we review the developments and perspectives in precision medicine in pediatric onco...
Source: Molecular and Cellular Pediatrics - August 31, 2018 Category: Cytology Source Type: research

Anti-inflammatory monocytes —interplay of innate and adaptive immunity
AbstractMonocytes are central to our health as they contribute to both hemispheres of our immune system, the innate and the adaptive arm. Sensing signals from the outside world, monocytes govern the innate immunity by initiating inflammation, e.g., through production of IL-1 β. Uncontrolled and sustained inflammation, however, leads to auto-inflammatory syndromes and sometimes to autoimmune diseases. Monocytes can be a driving force for the establishment of such diseases when their ability to also contribute to the resolution of inflammation is impaired. It is therefor e of vast importance to gain knowledge about the ...
Source: Molecular and Cellular Pediatrics - April 3, 2018 Category: Cytology Source Type: research

Intrauterine growth restriction - impact on cardiovascular diseases later in life
AbstractIntrauterine growth restriction (IUGR) is a fetal pathology which leads to increased risk for certain neonatal complications. Furthermore, clinical and experimental studies revealed that IUGR is associated with a significantly higher incidence of metabolic, renal and cardiovascular diseases (CVD) later in life. One hypothesis for the higher risk of CVD after IUGR postulates that IUGR induces metabolic alterations that then lead to CVD.This minireview focuses on recent studies which demonstrate that IUGR is followed by early primary cardiovascular alterations which may directly progress to CVD later in life. (Source...
Source: Molecular and Cellular Pediatrics - March 20, 2018 Category: Cytology Source Type: research

The potential of antisense oligonucleotide therapies for inherited childhood lung diseases
AbstractAntisense oligonucleotides are an emerging therapeutic option to treat diseases with known genetic origin. In the age of personalised medicines, antisense oligonucleotides can sometimes be designed to target and bypass or overcome a patient ’s genetic mutation, in particular those lesions that compromise normal pre-mRNA processing. Antisense oligonucleotides can alter gene expression through a variety of mechanisms as determined by the chemistry and antisense oligomer design. Through targeting the pre-mRNA, antisense oligonucleotides can alter splicing and induce a specific spliceoform or disrupt the reading ...
Source: Molecular and Cellular Pediatrics - February 6, 2018 Category: Cytology Source Type: research

CISH promoter polymorphism effects on T cell cytokine receptor signaling and type 1 diabetes susceptibility
ConclusionsThis study provides no evidence for an association ofCISH promoter SNPs with susceptibility to T1D or severity of disease. In contrast to previous studies, no influence of different haplotypes on CIS mRNA expression or T cell-mediated functions was found. (Source: Molecular and Cellular Pediatrics)
Source: Molecular and Cellular Pediatrics - February 6, 2018 Category: Cytology Source Type: research

The potential of antisense oligonucleotide therapies for inherited childhood lung diseases
AbstractAntisense oligonucleotides are an emerging therapeutic option to treat diseases with known genetic origin. In the age of personalised medicines, antisense oligonucleotides can sometimes be designed to target and bypass or overcome a patient ’s genetic mutation, in particular those lesions that compromise normal pre-mRNA processing. Antisense oligonucleotides can alter gene expression through a variety of mechanisms as determined by the chemistry and antisense oligomer design. Through targeting the pre-mRNA, antisense oligonucleotides can alter splicing and induce a specific spliceoform or disrupt the reading ...
Source: Molecular and Cellular Pediatrics - February 6, 2018 Category: Cytology Source Type: research

CISH promoter polymorphism effects on T cell cytokine receptor signaling and type 1 diabetes susceptibility
ConclusionsThis study provides no evidence for an association ofCISH promoter SNPs with susceptibility to T1D or severity of disease. In contrast to previous studies, no influence of different haplotypes on CIS mRNA expression or T cell-mediated functions was found. (Source: Molecular and Cellular Pediatrics)
Source: Molecular and Cellular Pediatrics - February 6, 2018 Category: Cytology Source Type: research

Preserved in vitro immunoreactivity in children receiving long-term immunosuppressive therapy due to inflammatory bowel disease or autoimmune hepatitis
ConclusionsContrary to expectations of a strong influence of IS therapy on the immunoreactivity, this study showed only minor differences between the groups with high-level, low-level, and no IS. Particularly, the in vitro reactivity to adenovirus antigen was nearly the same in all three groups. We assume that —provided a normal distribution and count of lymphocyte subgroups—patients with moderate immunosuppression might be capable of raising an effective immune response to inactivated and live vaccines. (Source: Molecular and Cellular Pediatrics)
Source: Molecular and Cellular Pediatrics - January 19, 2018 Category: Cytology Source Type: research

Concepts for a therapeutic prolongation of nephrogenesis in preterm and low-birth-weight babies must correspond to structural-functional properties in the nephrogenic zone
AbstractNumerous investigations are dealing with anlage of the mammalian kidney and primary development of nephrons. However, only few information is available about the last steps in kidney development leading at birth to a downregulation of morphogen activity in the nephrogenic zone and to a loss of stem cell niches aligned beyond the organ capsule. Surprisingly, these natural changes in the developmental program display similarities to processes occurring in the kidneys of preterm and low-birth-weight babies. Although those babies are born at a time with a principally intact nephrogenic zone and active niches, a high pr...
Source: Molecular and Cellular Pediatrics - December 7, 2017 Category: Cytology Source Type: research

The BPD trio? Interaction of dysregulated PDGF, VEGF, and TGF signaling in neonatal chronic lung disease
AbstractThe development of neonatal chronic lung disease (nCLD), i.e., bronchopulmonary dysplasia (BPD) in preterm infants, significantly determines long-term outcome in this patient population. Risk factors include mechanical ventilation and oxygen toxicity impacting on the immature lung resulting in impaired alveolarization and vascularization. Disease development is characterized by inflammation, extracellular matrix remodeling, and apoptosis, closely intertwined with the dysregulation of growth factor signaling. This review focuses on the causes and consequences of altered signaling in central pathways like transformin...
Source: Molecular and Cellular Pediatrics - November 7, 2017 Category: Cytology Source Type: research

Estimated prevalence of potentially damaging variants in the leptin gene
ConclusionUsing exome sequencing data from ExAC, in silico prediction tools and by applying a knowledge-driven approach, we identified 27 probably damaging variants in the leptin gene of 58 heterozygous subjects. With this information, we estimate the prevalence for heterozygosity at 1:1050 corresponding to an prevalence of homozygosity of 1:4,400,000 in this large pluriethnic cohort. (Source: Molecular and Cellular Pediatrics)
Source: Molecular and Cellular Pediatrics - November 3, 2017 Category: Cytology Source Type: research

Transcatheter atrial septal defect closure in an infant (body weight 6.4  kg) using the GORE CARDIOFORM septal occluder (GCSO)
We report on a 10-month-old infant, body weight of 6.4  kg, with a large ASD who was referred for failure to thrive and dyspnea on exertion. Echocardiography showed two neighboring ASDs centrally located within an atrial septum with a length of 27 mm resulting in significant left-to-right shunting. During cardiac catheterization, hemodynamic significa nce of the defect as well as normal pulmonary vascular resistance was demonstrated. Balloon sizing of the central ASD showed a stretched defect diameter of 12 × 11 mm. A 20-mm GORE CARDIOFORM septal occluder (GCSO; Goremedical, W. L. Gore& A...
Source: Molecular and Cellular Pediatrics - November 3, 2017 Category: Cytology Source Type: research

Estimated prevalence of potentially damaging variants in the leptin gene
ConclusionUsing exome sequencing data from ExAC, in silico prediction tools and by applying a knowledge-driven approach, we identified 27 probably damaging variants in the leptin gene of 58 heterozygous subjects. With this information, we estimate the prevalence for heterozygosity at 1:1050 corresponding to an incidence of homozygosity of 1:4,400,000 in this large pluriethnic cohort. (Source: Molecular and Cellular Pediatrics)
Source: Molecular and Cellular Pediatrics - November 3, 2017 Category: Cytology Source Type: research

Transcatheter atrial septal defect closure in an infant (body weight 6.4  kg) using the GORE CARDIOFORM septal occluder (GCSO)
We report on a 10-month-old infant, body weight of 6.4  kg, with a large ASD who was referred for failure to thrive and dyspnea on exertion. Echocardiography showed two neighboring ASDs centrally located within an atrial septum with a length of 27 mm resulting in significant left-to-right shunting. During cardiac catheterization, hemodynamic significa nce of the defect as well as normal pulmonary vascular resistance was demonstrated. Balloon sizing of the central ASD showed a stretched defect diameter of 12 × 11 mm. A 20-mm GORE CARDIOFORM septal occluder (GCSO; Goremedical, W. L. Gore& A...
Source: Molecular and Cellular Pediatrics - November 3, 2017 Category: Cytology Source Type: research

Autism spectrum disorder and Li-Fraumeni syndrome: purely coincidental or mechanistically associated?
ConclusionsSome of the oncogenes and tumor suppressor genes causing cancer susceptibility syndromes overlap with those involved in autism. This functional overlap between autism and cancer is novel and particularly compelling. The surprising coincidence of LFS and ASD in our patient raises the question whether this is purely coincidental or mechanistically associated. (Source: Molecular and Cellular Pediatrics)
Source: Molecular and Cellular Pediatrics - October 5, 2017 Category: Cytology Source Type: research

The molecular pathophysiology of chronic non-bacterial osteomyelitis (CNO) —a systematic review
AbstractChronic non-bacterial osteomyelitis (CNO) belongs to the growing spectrum of autoinflammatory diseases and primarily affects the skeletal system. Peak onset ranges between 7 and 12  years of age. The clinical spectrum of CNO covers sometimes asymptomatic inflammation of single bones at the one end and chronically active or recurrent multifocal osteitis at the other.Despite the intense scientific efforts, the exact molecular mechanisms of CNO remain unknown. Recent data suggest CNO as a genetically complex disorder with dysregulated TLR4/MAPK/inflammasome signaling cascades resulting in an imbalance between pro...
Source: Molecular and Cellular Pediatrics - July 6, 2017 Category: Cytology Source Type: research

Pediatric precursor B acute lymphoblastic leukemia: are T helper cells the missing link in the infectious etiology theory?
AbstractPrecursor B acute lymphoblastic leukemia (BCP-ALL), the most common childhood malignancy, arises from an expansion of malignant B cell precursors in the bone marrow. Epidemiological studies suggest that infections or immune responses to infections may promote such an expansion and thus BCP-ALL development. Nevertheless, a specific pathogen responsible for this process has not been identified. BCP-ALL cells critically depend on interactions with the bone marrow microenvironment. The bone marrow is also home to memory T helper (Th) cells that have previously expanded during an immune response in the periphery. In sec...
Source: Molecular and Cellular Pediatrics - May 16, 2017 Category: Cytology Source Type: research

Abstracts of the 52nd Workshop for Pediatric Research
(Source: Molecular and Cellular Pediatrics)
Source: Molecular and Cellular Pediatrics - May 10, 2017 Category: Cytology Source Type: research

Human perinatal immunity in physiological conditions and during infection
AbstractThe intrauterine environment was long considered sterile. However, several infectious threats are already present during fetal life. This review focuses on the postnatal immunological consequences of prenatal exposure to microorganisms and related inflammatory stimuli. Both the innate and adaptive immune systems of the fetus and neonate are immature, which makes them highly susceptible to infections. There is good evidence that prenatal infections are a primary cause of preterm births. Additionally, the association between antenatal inflammation and adverse neonatal outcomes has been well established. The lung, gas...
Source: Molecular and Cellular Pediatrics - April 21, 2017 Category: Cytology Source Type: research

Role of second-hand smoke (SHS)-induced proteostasis/autophagy impairment in pediatric lung diseases
ConclusionsSHS-exposure induced proteostasis/autophagy impairment can mediate the initiation of chronic lung disease in pediatric subjects. Hence, our data warrants the evaluation of proteostasis/autophagy-inducing drugs, such as cysteamine, as a potential therapeutic intervention strategy for SHS-induced pediatric lung diseases. (Source: Molecular and Cellular Pediatrics)
Source: Molecular and Cellular Pediatrics - February 2, 2017 Category: Cytology Source Type: research

Renal consequences of preterm birth
ConclusionAwareness of renal implications of therapeutic interventions and renal conservation efforts may lead to a variety of short and long-term benefits. Adequate monitoring and supplementation of microelement losses, gathering improved data on renal handling, and exploration of new avenues such as reliable markers of injury and new therapeutic strategies in contemporary populations, as well as long-term follow-up of renal function, is warranted. (Source: Molecular and Cellular Pediatrics)
Source: Molecular and Cellular Pediatrics - January 18, 2017 Category: Cytology Source Type: research

Acquisition and adaptation of the airway microbiota in the early life of cystic fibrosis patients
The objective of this mini-review is to give an update on the current knowledge about the development of the microbiota in the early life of CF patients. Microbial acquisition in the human airways can be described by the island model: Microbes found in the lower airways of CF patients represent “islands” that are at first populated from the upper airways reflecting the “mainland.” Colonization can be modeled following the neutral theory in which the most abundant bacteria in the mainland are also frequently found in the lower airways initially. At later times, however, the colonization process of th...
Source: Molecular and Cellular Pediatrics - January 17, 2017 Category: Cytology Source Type: research

Neutrophil plasticity enables the development of pathological microenvironments: implications for cystic fibrosis airway disease
ConclusionsThe elucidation of molecular mechanisms driving neutrophil plasticity in vivo will open new treatment opportunities designed to modulate, rather than block, the crucial adaptive functions fulfilled by neutrophils. This review aims to outline emerging mechanisms of neutrophil plasticity and their participation in the building of pathological microenvironments in the context of cystic fibrosis and other diseases with similar features. (Source: Molecular and Cellular Pediatrics)
Source: Molecular and Cellular Pediatrics - December 5, 2016 Category: Cytology Source Type: research

Severe changes in colon epithelium in the Mecp2 -null mouse model of Rett syndrome
ConclusionsIn summary, we showed that the colon is severely affected by Mecp2 silencing in mice. Changes in colon length and epithelial histology are similar to those observed in colitis. Changes in the localization of proteins that participate in fluid absorption can explain watery stools, but the exclusive deletion of Mecp2 from the intestine did not reproduce colon changes observed in theMecp2-null mice, indicating the participation of other cells in this phenotype and the complex interaction between different cell types in this disease. (Source: Molecular and Cellular Pediatrics)
Source: Molecular and Cellular Pediatrics - November 21, 2016 Category: Cytology Source Type: research

Wilms ’ tumor susceptibility: possible involvement of FOXP3 and CXCL12 genes
AbstractBackgroundWilms ’ tumor is an embryonal neoplasm of the kidney that accounts for approximately 6 % of all childhood tumors. The chemokine CXCL12 (C-X-C chemokine ligand 12) and its ligand CXCR4 (C-X-C chemokine receptor type 4) are involved in the development of several organs, including the kidney, and are also associated with tumor growth and metastasis. FOXP3 (forkhead transcription factor 3) was initially described as a marker for regulatory T cells; however, its expression in several types of tumor cells has already been described and may have prognostic significance. The aim of the present study wa...
Source: Molecular and Cellular Pediatrics - November 10, 2016 Category: Cytology Source Type: research

Leukocyte recruitment in preterm and term infants
AbstractImpaired cellular innate immune defense accounts for susceptibility to sepsis and its high morbidity and mortality in preterm infants. Leukocyte recruitment is an integral part of the cellular immune response and follows a well-defined cascade of events from rolling of leukocytes along the endothelium to firm adhesion and finally transmigration which is concerted by a variety of adhesion molecules. Recent analytical advances such as fetal intravital microscopy have granted new insights into ontogenetic regulation and maturation of fetal immune cell recruitment. Understanding the fetal innate immune system is essent...
Source: Molecular and Cellular Pediatrics - October 24, 2016 Category: Cytology Source Type: research