Implementation of a health surveillance clinic for children with Down syndrome.

The implementation of the multidisciplinary Down Syndrome Health Surveillance clinic at Children's Health Ireland at Tallaght, Dublin has shown significant improvements in the adherence to guidelines as well as providing health promotion strategies such as information on immunisations. Our project provides a framework which would be potentially emulated and used in other medical conditions. The reduction in clinic attendances and co-ordination of same-day appointments has improved parental satisfaction as well as the quality of care.

Development of Spiroligomer-Peptoid Hybrids.

Creating functional macromolecules that possess the diversity and functionality of proteins poses an enormous challenge, as this requires large, preorganized macromolecules to facilitate interactions. Peptoids have been shown to interact with proteins, and combinatorial libraries of peptoids have been useful in discovering new ligands for protein binding. We have created spiroligomer-peptoid hybrids that have a spirocyclic core that preorganizes functional groups in three-dimensional space. By utilizing spiroligomers, we can reduce the number of rotatable bonds between functional groups while increasing the stereochemical diversity of the molecules. We have synthesized 15 new spiroligomer monomer amines that contain two stereocenters and three functional groups (67-84% yields from a common hydantoin starting material) as well as a spiroligomer trimer 25 with six stereocenters and five functional groups. These 16 amines were used to synthesize five first-generation spiroligomer-peptoids hybrids.

One-Pot Synthesis of Chiral, Spirocyclic 4-Hydantoin-Proline Derivatives for Incorporation into Spiroligomer-Based Macromolecules.

Derivatives of 4-hydantoin-proline have been synthesized via a direct two-step alkylation method. This method is valuable in the development of applications of N,N'-disubstituted hydantoin bearing α-amino acids by improving yields, reducing the time and number of steps required to synthesize these substituted molecules, and enabling late stage functionalization of spiroligomer termini. Over 20 unique electrophiles have been tested, highlighting the inherent versatility of this chemistry.

GlnH, a Novel Antigen That Offers Partial Protection against Verocytotoxigenic Escherichia coli Infection.

Verotoxin-producing Escherichia coli (VTEC) causes zoonotic infections, with potentially devastating complications, and children under 5 years old are particularly susceptible. Antibiotic treatment is contraindicated, and due to the high proportion of infected children that suffer from severe and life-changing complications, there is an unmet need for a vaccine to prevent VTEC infections. Bacterial adhesins represent promising candidates for the successful development of a vaccine against VTEC. Using a proteomic approach to identify bacterial proteins interacting with human gastrointestinal epithelial Caco-2 and HT-29 cells, we identified eleven proteins by mass spectrometry. These included a glutamine-binding periplasmic protein, GlnH, a member of the ABC transporter family. The glnH gene was identified in 13 of the 15 bovine and all 5 human patient samples tested, suggesting that it is prevalent. We confirmed that GlnH is involved in the host cell attachment of an O157:H7 prototype E. coli strain to gastrointestinal cells in vitro. Recombinant GlnH was expressed and purified prior to the immunisation of mice. When alum was used as an adjuvant, GlnH was highly immunogenic, stimulating strong serological responses in immunised mice, and it resulted in a modest reduction in faecal shedding but did not reduce colonisation. GlnH immunisation with a T-cell-inducing adjuvant (SAS) also showed comparable antibody responses and an IgG1/IgG2a ratio suggestive of a mixed Th1/Th2 response but was partially protective, with a 1.5-log reduction in colonisation of the colon and caecum at 7 days relative to the adjuvant only (p = 0.0280). It is clear that future VTEC vaccine developments should consider the contribution of adjuvants in addition to antigens. Moreover, it is likely that a combined cellular and humoral response may prove more beneficial in providing protective interventions against VTEC.

Correction: Quinn et al. GlnH, a Novel Antigen That Offers Partial Protection against Verocytotoxigenic Escherichia coli Infection. Vaccines 2023, 11, 175.

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