Engineering immunomodulatory nanoplatforms from commensal bacteria-derived polysaccharide A.

Capsular zwitterionic polysaccharides (CZPs), typically found on the surfaces of commensal gut bacteria, are important immunomodulatory molecules due to their ability to produce a T cell dependent immune response upon processing by antigen presenting cells (APCs). Their immunological activity makes them potentially useful for generating material constructs that are applicable for the treatment of diseases, or as vaccines. Herein, we explored synthetic strategies to generate immunologically active polymer-carbohydrate conjugates and nanomaterials of the CZP, Polysaccharide A (PSA) derived from Bacteroides fragilis. Initially, we addressed the purification of PSA, which is critical for the realization of materials applicable for biomedical purposes. Anion exchange high performance liquid chromatography in the presence of a surfactant (CHAPS) enabled the isolation of pure PSA. Through modification of purified PSA with azide groups, we demonstrated that polymers or antigens could be incorporated with PSA via click chemistry reactions to generate conjugates that can be fabricated into nanoparticles. By conjugation of PSA with a DBCO end functionalized polyphosphoester polymer with hydrophobic pendant terminal alkyne groups, an amphiphilic conjugate was obtained which formed nanoparticles of about 100 nm in aqueous solution. Moreover, terminal alkyne groups could be modified with charged thiol molecules (amine/carboxylate) via thiol-yne radical chemistry to generate conjugates, which could be incorporated into nanoparticles via electrostatic interactions building onto a charged nanoparticle template. The conjugates and nanoparticles exhibited immunological activity as assessed by the toll-like receptor 2 (TLR2) activation assay and positive cytokine production (IL-10) following their co-incubation with APCs and T cells. Summarily, this work plainly demonstrates chemical biology strategies for fabricating immunomodulatory nanomaterials from commensal microorganisms that can potentially be novel vaccines or immunotherapeutics.

Variation in specialty care hospitalization for children with chronic conditions in California.

OBJECTIVE: Despite the documented utility of regionalized systems of pediatric specialty care, little is known about the actual use of such systems in total populations of chronically ill children. The objective of this study was to evaluate variations and trends in regional patterns of specialty care hospitalization for children with chronic illness in California. METHODS: Using California's Office of Statewide Health Planning and Development unmasked discharge data set between 1999 and 2007, we performed a retrospective, total-population analysis of variations in specialty care hospitalization for children with chronic illness in California. The main outcome measure was the use of pediatric specialty care centers for hospitalization of children with a chronic condition in California. RESULTS: Analysis of 2 170 102 pediatric discharges revealed that 41% had a chronic condition, and 44% of these were discharged from specialty care centers. Specialty care hospitalization varied by county and type of condition. Multivariate analyses associated increased specialty care center use with public insurance and high pediatric specialty care bed supply. Decreased use of regionalized care was seen for adolescent patients, black, non-Hispanic children, and children who resided in zip codes of low income or were located farther from a regional center of care. CONCLUSIONS: Significant variation exists in specialty care hospitalization among chronically ill children in California. These findings suggest a need for greater scrutiny of clinical practices and child health policies that shape patterns of hospitalization of children with serious chronic disease.