This study shows that breastfeeding reduced the risk of sudden infant death syndrome by approximately 50% at all ages throughout infancy. We recommend including the advice to breastfeed through 6 months of age in sudden infant death syndrome risk-reduction messages.
As SGA-infants have an increased mortality rate and an increased risk for developing chronic lung disease, further studies should focus on prevention of intrauterine growth restriction and its complications.
Senescence or biological aging impacts a vast variety of molecular and cellular processes. To date, it is unknown whether CD4+ Th cells display an age-dependent bias for development into specific subpopulations. In this study, we show the appearance of a distinct CD4+ T cell subset expressing IL-4 at an early stage of development in infant adenoids and cord blood that is lost during aging. We identified by flow cytometric, fluorescent microscopic, immunoblot, and mass spectrometric analysis a population of CD4+ T cells that expressed an unglycosylated isoform of IL-4. This T cell subpopulation was found in neonatal but not in adult CD4+ T cells. Furthermore, we show that the mRNA of the Th2 master transcription factor GATA3 is preferentially expressed in neonatal CD4+ T cells. The Th2 phenotype of the IL-4+CD4+ T cells could be reinforced in the presence of TGF-β. Although the IL-4+CD4+ T cells most likely originate from CD31+CD4+ T recent thymic emigrants, CD31 was downregulated prior to secretion of IL-4. Notably, the secretion of IL-4 requires a so far unidentified trigger in neonatal T cells. This emphasizes that cytokine expression and secretion are differentially regulated processes. Our data support the hypothesis of an endogenously poised cytokine profile in neonates and suggest a link between cytokine production and the developmental stage of an organism. The determination of the IL-4 isoform–expressing cells in humans might allow the identification of Th2 precursor cells, which could provide novel intervention strategies directed against Th2-driven immunopathologies such as allergies.
The immunosuppressive strategies devised by neuroblastoma (NB), the most common solid extracranial childhood cancer, are poorly understood. Here, we identified an immunoevasive program triggered by NB through secretion of galectin-1 (Gal-1), a multifunctional glycan-binding protein. Human and mouse NB cells express and secrete Gal-1, which negatively regulates T cell and dendritic cell function. When injected subcutaneously in syngeneic A/J mice, knockdown transfectants expressing low amounts of Gal-1 (NXS2/L) showed reduction of primary tumor growth by 83-90% and prevented spontaneous liver metastases in contrast to NXS2 cell variants (NXS2/H, NXS2 wildtype) expressing high amounts of Gal-1. Splenocytes from mice receiving Gal-1 knockdown NXS2/L cells secreted higher amounts of IFN-c and displayed enhanced cytotoxic T-cell function compared to NXS2/H or NXS2 controls. Immunohistochemical analysis revealed a six-to tenfold increase in the frequency of CD4 1 and CD8 1 T cells infiltrating tumors from mice receiving knockdown transfectants. This effect was confirmed by in vitro migration assays. Finally, supernatants of NXS2/H or NXS2 cells suppressed dendritic cell (DC) maturation and induce T cell apoptosis, whereas these effects were only marginal on DCs and T cells exposed to supernatants from NXS2/L cells. These results demonstrate a novel immunoinhibitory role of the Gal-1-glycan axis in NB, highlighting an alternative target for novel immunotherapeutic modalities.Neuroblastoma (NB) is the most common extracranial solid malignancy in childhood. 1 This neuroendocrine tumor arising from neural crest cells is responsible for over 10-15% of pediatric cancer deaths. 1 The disease exhibits extreme heterogeneity, resulting in most recent stratification into very low, low, intermediate or high risk. 2 NB of lower risk groups occur during the first 18 months of life, and good outcomes are typical after surgery. 2 In contrast, high-risk NB, notably characterized by the amplification of NB-derived myelocytomatosis viral related oncogene (N-MYC), is resistant even to the most intensive treatment protocols available. 3,4 This suggests the need of more effective therapeutic strategies targeting nontraditional targets and lacking toxicity for treating high-risk aggressive NB.The introduction of monoclonal antibodies or chimeric T cells engineered to express chimeric antigen receptors targeting the GD2 antigen together with the implementation of dendritic cell (DC)-based vaccination have validated the critical function of the immune system in promoting NB regression. 5 Treatment with IL-2, GM-CSF, CD40 agonists or CTLA-4 blockade, in combination with other traditional approaches, has successfully improved immune effector functions in high-risk NB patient. 5,6 However, the success of these adjuvant immunotherapeutic approaches is hindered by a number of strategies used by tumors or tumor-associated stroma cells to elude immune recognition or thwart immune
Background: The incidence of sudden infant death syndrome (SIDS) has been falling in Germany over the last decade. However, little is known about the prevalence and the importance of well‐known risk factors in Germany since a local prevention campaign in 1992. Design: A 3‐y, population‐based, case‐control study was conducted in half of Germany, consisting of 333 cases. All sudden and unexpected deaths in infancy, if they fitted the inclusion criteria, were included in the study. Parental interview was carried out soon after the death, and three living control infants, matched for age, gender, region and sleep time, were recruited. Results: The prevalence of placing infants prone to sleep was only 4% in the control group, but this was associated with a markedly increased risk of SIDS (adjusted odds ration, aOR=6.08). Other modifiable risk factors for SIDS were: maternal smoking during pregnancy, breastfeeding for less than 2 wk (aOR=1.71) and co‐sleeping (aOR=2.71), while using a pacifier during the last sleep reduced the risk (aOR=0.39).
Conclusions: Previously recognized risk factors for SIDS also occur in Germany. Despite knowledge about the major modifiable risk factors for SIDS, these factors are still present in Germany. To reduce the incidence of SIDS in Germany, a continued effort is needed to inform all parents about preventable risk factors for SIDS.
The frequency of IVH could be reduced significantly, if extremely premature infants, the vast majority of patients suffering from IVH, did not have to be transferred postnatally to another hospital.
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