Development and Evaluation of Modified Criteria for Infant and Toddler Anaphylaxis.

BACKGROUND: Current clinical criteria for identifying anaphylaxis do not account for unique aspects of infant anaphylaxis presentation and have not been validated in patients younger than 2 years of age. This may contribute to under recognition and is thus an unmet need. OBJECTIVE: To demonstrate age-specific signs and symptoms that more accurately identify anaphylaxis in young children and to develop and compare modified criteria for "likely anaphylaxis" against the widely used 2006 National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria. METHODS: Retrospective chart review of 337 clinical encounters presenting with suspected allergic or anaphylactic reactions to a pediatric emergency department. Modified criteria for likely anaphylaxis were developed and evaluated against the NIAID/FAAN criteria. RESULTS: The study population included 33% infants (age < 12 mo), 39% toddlers (age 12 mo to < 36 mo), and 29% children (age ≥ 36 mo). The NIAID/FAAN criteria captured 85% of all patient encounters in the study and the modified criteria captured 98% (P < .001). Compared with NIAID/FAAN criteria, modified criteria had 22.8% improved performance among infants (p < .001) and 10.3% improved performance among toddlers (P = .04). CONCLUSIONS: We developed modified anaphylaxis clinical criteria that incorporated symptoms specific to infants and young children. The modified criteria increased identification of anaphylaxis in infants and potentially toddlers. Future research is needed to validate our findings on a larger cohort.

Needs assessment for an infant and toddler food allergy curriculum for pediatric residents.

Background: The prevalence of pediatric food allergies is increasing. Although pediatric residents are frontline providers for children with food allergies, little is known about pediatric residents' educational experiences and comfort with infant and toddler food allergy. Methods: An anonymous online needs assessment survey was created and distributed to 64 residents in one residency program. The survey explored residents' knowledge sources, experience, and comfort in diagnosing, treating, and counseling patients with regard to food allergy and anaphylaxis. Results: Fifty-one pediatric residents (79.7%) completed the survey. Pediatric residents who had formal engagement with allergy-trained clinicians had 8.27 times the odds (odds ratio 8.27 [95% confidence interval, 1.16-59.01]; p = 0.035) of feeling comfortable in treating infant and toddler anaphylaxis compared with those who did not feel comfortable. Conclusion: These findings suggest that a standardized pediatric residency curriculum, in partnership with pediatric allergists, may present enhanced educational opportunities for pediatric residents.

Solution structure and assembly of ß-amylase 2 from Arabidopsis thaliana.

Starch is a key energy-storage molecule in plants that requires controlled synthesis and breakdown for effective plant growth. ß-Amylases (BAMs) hydrolyze starch into maltose to help to meet the metabolic needs of the plant. In the model plant Arabidopsis thaliana there are nine BAMs, which have apparently distinct functional and domain structures, although the functions of only a few of the BAMs are known and there are no 3D structures of BAMs from this organism. Recently, AtBAM2 was proposed to form a tetramer based on chromatography and activity assays of mutants; however, there was no direct observation of this tetramer. Here, small-angle X-ray scattering data were collected from AtBAM2 and its N-terminal truncations to describe the structure and assembly of the tetramer. Comparison of the scattering of the AtBAM2 tetramer with data collected from sweet potato (Ipomoea batatas) BAM5, which is also reported to form a tetramer, showed there were differences in the overall assembly. Analysis of the N-terminal truncations of AtBAM2 identified a loop sequence found only in BAM2 orthologs that appears to be critical for AtBAM2 tetramer assembly as well as for activity.

Resilience of BST-2/Tetherin structure to single amino acid substitutions.

Human tetherin, also known as BST-2 or CD317, is a dimeric, extracellular membrane-bound protein that consists of N and C terminal membrane anchors connected by an extracellular domain. BST-2 is involved in binding enveloped viruses, such as HIV, and inhibiting viral release in addition to a role in NF-kB signaling. Viral tethering by tetherin can be disrupted by the interaction with Vpu in HIV-1 in addition to other viral proteins. The structural mechanism of tetherin function is not clear and the effects of human tetherin mutations identified by sequencing consortiums are not known. To address this gap in the knowledge, we used data from the Ensembl database to construct and model known human missense mutations within the ectodomain to investigate how the structure of the ectodomain influences function. From the data, we identified an island of sequence stability within the ectodomain, which corresponds to a functionally and structurally important region identified in previous biochemical and biophysical studies. Most of the modeled mutations had little effect on the structure of the dimer and the coiled-coil, suggesting that the coiled-coil compensates for changes in primary structure. Thus, many of the functional defects observed in previous studies may not be due to changes in tetherin structure, but rather, due to in changes in protein-protein interactions or in aspects of tetherin not currently understood. The lack of structural effects by mutations known to decrease function further illustrates the need for more study of the structure-function connection for this system. Finally, apparent flexibility in tetherin sequence may allow for greater anti-viral activities with a larger number of viruses by reducing specific interactions with anti-tetherin proteins, while maintaining virus restriction.