In this review we discuss the effects of microbial exposure on the B cell repertoire. Neonatal exposure to conserved bacterial carbohydrates and phospholipids permanently reprograms the natural antibody repertoire directed toward these antigens by clonal expansion, alterations in clonal dominance, and increased serum antibody levels. These epitopes are present not only in bacterial cell walls, but also in common environmental allergens. Neonatal immunization with bacterial polysaccharide vaccines results in attenuated allergic airway responses to fungi-, house dust mite-, and cockroach-associated allergens in mouse models. The similarities between mouse and human natural antibody repertoires suggest that reduced microbial exposure in children may have the opposite effect, providing a potential mechanistic explanation for the hygiene hypothesis. We propose that understanding the effects of childhood infections on the natural antibody repertoire and the mechanisms of antibody-mediated immunoregulation observed in allergy models will lead to the development of prevention/interventional strategies for treatment of allergic asthma.
A transitory, interleukin-25 (IL-25)–responsive, group 2 innate lymphoid cell (ILC2) subset induced during type 2 inflammation was recently identified as iILC2s. This study focuses on understanding the significance of this population in relation to tissue-resident nILC2s in the lung and intestine. RNA-sequencing and pathway analysis revealed the AP-1 superfamily transcription factor BATF (basic leucine zipper transcription factor, activating transcription factor–like) as a potential modulator of ILC2 cell fate. Infection of BATF-deficient mice with Nippostrongylus brasiliensis showed a selective defect in IL-25–mediated helminth clearance and a corresponding loss of iILC2s in the lung characterized as IL-17RBhigh, KLRG1high, BATFhigh, and Arg1low. BATF deficiency selectively impaired iILC2s because it had no impact on tissue-resident nILC2 frequency or function. Pulmonary-associated iILC2s migrated to the lung after infection, where they represented an early source of IL-4 and IL-13. Although the composition of ILC2s in the small intestine was distinct from those in the lung, their frequency and IL-13 expression remained dependent on BATF, which was also required for optimal goblet and tuft cell hyperplasia. Findings support IL-25–responsive ILC2s as early sentinels of mucosal barrier integrity.
The present study aims to determine the risk of early secondary nasal revisions in patients with complete unilateral and bilateral cleft lip and palate (U/BCLP) treated with and without nasoalveolar molding (NAM) and examine the associated costs of care. A retrospective cohort study from 1990 to 1999 was performed comparing the risk of early secondary nasal revision surgery in patients with a CLP treated with NAM and surgery (cleft lip repair and primary surgical nasal reconstruction) versus surgery alone in a private practice and tertiary level clinic. The NAM treatment group consisted of 172 patients with UCLP and 71 patients with BCLP, whereas the non-NAM-prepared group consisted of 28 patients with UCLP and 5 with BCLP. The risk of secondary nasal revision for patients with UCLP was 3% in the NAM group and 21% in the non-NAM group. The risk of secondary nasal revision for patients with BCLP was 7% in the NAM group compared with 40% in the non-NAM group. Using multicenter averages, the non-NAM revision rates were calculated at 37.8% and 48.5% for U/BCLP, respectively. Applying these risks of revision, NAM treatment led to an estimated savings of between $491 and $4893 depending on the type of cleft. In conclusion, NAM can reduce the number of early secondary nasal revision surgeries and, therefore, reduce the overall cost of care.
Currently, approximately 20% of the global population suffers from an allergic
disorder. Allergies and asthma occur at higher rates in developed and industrialized
countries. It is clear that many human atopic diseases are initiated neonatally, and
herald more severe IgE-mediated disorders, including allergic asthma, which is driven by
the priming of TH2 effector T cells. The “hygiene hypothesis” attempts to
link the increased excessively sanitary conditions early in life, to a default TH2
response and increasing allergic phenomena. Despite the substantial involvement of IgE
antibodies in such conditions, little attention has been paid to the effects of early
microbial exposure on the B cell repertoire prior to the initiation of these diseases.
Here, we use antibody-binding assays to demonstrate that Streptococcus
pneumoniae and house dust mite (HDM) bear similar phosphorylcholine (PC)
epitopes. Neonatal C57BL/6 mice immunized with a PC-bearing pneumococcal vaccine expressed
increased frequencies of PC-specific B cells in the lungs following sensitizing exposure
to HDM as adults. Anti-PC IgM antibodies in the lung decreased the interaction of HDM with
pulmonary APCs and were affiliated with lowered allergy-associated cell infiltration into
the lung, IgE production, development of airway hyperresponsiveness, and TH2 T cell
priming. Thus, exposure of neonatal mice to PC-bearing pneumococci significantly reduced
the development of HDM-induced allergic disease during adult life. Our findings
demonstrate that B cells generated against conserved epitopes expressed by bacteria,
encountered early in life, are also protective against the development of allergic disease
during adult life.
Virtual surgical planning using "in office" 3D printing is feasible and allows for a more cost-effective and less time consuming method for creating surgical models and guides. By bringing 3D printing to the office setting, we hope to improve intraoperative efficiency, surgical precision, and overall cost for various types of craniofacial and reconstructive surgery.
Craniosynostosis repair is safe; however, the risk of complications increases with age at intervention. Presence of a syndromic congenital deformity at any age carries the greatest increased risk of perioperative complications. This suggests that optimal timing of intervention is within the first year of life, especially in those cases with additional factors increasing perioperative risk. These data support the importance of counseling patients of the increased risk associated with delaying craniosynostosis repair.
After changing our tissue expander protocol, the complication rates at our institution have remained stable during the 10-year follow-up period. Tissue expansion in the pediatric burn population continues to be a safe and effective reconstructive option with acceptable complication rates.
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