Efficacy, safety and quality of life in a multi-center, randomized, placebo-controlled trial on low-dose peanut oral immunotherapy in peanut allergic children

Hydrocephalus is one of the most prevalent form of developmental central nervous system (CNS) malformations. Cerebrospinal fluid (CSF) flow depends on both heartbeat and body movement. Furthermore, it has been shown that CSF flow within and across brain ventricles depends on cilia motility of the ependymal cells lining the brain ventricles, which play a crucial role to maintain patency of the narrow sites of CSF passage during brain formation in mice. Using whole-exome and whole-genome sequencing, we identified an autosomal-dominant cause of a distinct motile ciliopathy related to defective ciliogenesis of the ependymal cilia in six individuals. Heterozygous de novo mutations in FOXJ1, which encodes a well-known member of the forkhead transcription factors important for ciliogenesis of motile cilia, cause a motile ciliopathy that is characterized by hydrocephalus internus, chronic destructive airway disease, and randomization of left/right body asymmetry. Mutant respiratory epithelial cells are unable to generate a fluid flow and exhibit a reduced number of cilia per cell, as documented by high-speed video microscopy (HVMA), transmission electron microscopy (TEM), and immunofluorescence analysis (IF). TEM and IF demonstrate mislocalized basal bodies. In line with this finding, the focal adhesion protein PTK2 displays aberrant localization in the cytoplasm of the mutant respiratory epithelial cells.

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A study was conducted with 20 barrows (average BW 25 kg) to determine the effect of various levels of neutral detergent fiber (NDF) in the diet on the apparent ileal nutrient digestibility and ileal diaminopimelic acid (DAPA) content, and consequently on the amount of ileal endogenous nitrogen. The pigs were fitted with a post-valvular T-cecal cannula. They were fed .8 kg/d of a corn starch-based semisynthetic diet formulated to contain equal amounts of protein and starch and 0, 60, 120, or 180 g of purified NDF/kg of diet, included at the expense of glucose. The purified NDF (pNDF) was isolated from wheat bran using an incubation procedure with pancreatin. Ileal digestibility of NDF was approximately 17% and was independent of the pNDF level in the diet. By increasing the amount of pNDF in the diets, apparent ileal digestibilities of dry matter (DM), nitrogen (N), neutral detergent insoluble N (NDF-N), and ash decreased linearly (P < .05). The DAPA content of the ileal digesta (g/d) was not affected by the percentage of pNDF in the diets. Calculation of the ileal bacterial N excretion indicated that more than 50% of the ileal N was of bacterial origin. With increased percentage of dietary pNDF, both endogenous and exogenous N in ileal chyme were linearly increased (P < .05). Thus, an increase in the dietary fiber content leads to a decreased apparent ileal protein digestibility due to increased ileal losses of both endogenous and exogenous protein.

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