To test whether weaning to a bovine insulinfree cow's milk formula (CMF) reduces type 1 diabetes mellitus-associated autoantibodies in children at genetic risk.
Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0–14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.
An enhanced enrichment using the Portable Microbe Enrichment Unit (PMEU) with the microaerobic bubbling of broths was applied for the detection of thermotolerant Campylobacter species from water. This PMEU enrichment was compared with the conventional static enrichment of the international standard ISO 17995:2005. In addition, Campylobacter detection after enrichment using a real-time PCR detection was compared with colony counts. The tests with stressed Campylobacter jejuni cells in drinking water indicated that the PMEU enrichment yielded a significantly higher number of Campylobacter cells in the Bolton broth compared with the conventional static incubation. Application of the real-time PCR technique shortened the Campylobacter detection time. This combination of method modifications can be used for Campylobacter detection from water and adds methodological repertoire for the rapid survey and management of waterborne outbreaks.
Breastfeeding may increase the rate of mucosal maturation and IgA production. We sought to determine the effect of breastfeeding vs. formula-feeding on the maturation of oral mucosa by measuring the salivary total antibodies and cow's milk protein-specific IgA. Fifty-eight saliva samples were collected from 39 healthy, full term infants. At the age of 3 months (n = 25) eight infants received only breast milk and seventeen formula (cow's milk based n = 10, hydrolysed n = 7) and breast milk; and at the age of 6 months (n = 33) eleven received breast milk, seventeen formula and breast milk and five were not breastfed any more (cow's milk based n = 14, hydrolysed n = 8). Total IgA, IgG, IgM and protein, and beta-lactoglobulin specific IgA were measured from saliva with enzyme-linked immunoassay (ELISA). The antibody results were proportioned to total protein. No differences in antibody levels between the feeding groups were found at 3 months of age. At 6 months, total IgA, total IgM and beta-lactoglobulin-specific IgA were higher among the breastfed infants compared to those receiving formula as supplement to breast milk or not breastfed any more (breast milk vs. any formula p = 0.029, p = 0.015, p = 0.058; breast milk vs. cow's milk formula p = 0.025, p = 0.044, p = 0.038). To conclude, breastfeeding stimulated the mucosal immune system to produce IgA to saliva, which is a marker for immunological maturation and likely provides protection against environmental antigens.
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