ABSTRACT
Betaglycan (BG) is a transmembrane co-receptor of the transforming growth factor-ß (TGF-ß) family of signaling ligands. It is essential for embryonic development and tissue homeostasis and fertility in adults. It functions by enabling binding of the three TGF-ß isoforms to their signaling receptors and is additionally required for inhibin A (InhA) activity. Despite its requirement for the functions of TGF-ßs and InhA in vivo, structural information explaining BG ligand selectivity and its mechanism of action is lacking. Here, we determine the structure of TGF-ß bound both to BG and the signaling receptors, TGFBR1 and TGFBR2. We identify key regions responsible for ligand engagement, which has revealed novel binding interfaces that differ from those described for the closely related co-receptor of the TGF-ß family, endoglin, thus demonstrating remarkable evolutionary adaptation to enable ligand selectivity. Finally, we provide a structural explanation for the hand-off mechanism underlying TGF-ß signal potentiation.
ABSTRACT
We compared the distribution of organisms in the nasopharynx and the middle ear fluid in 164 episodes of acute otitis media in children 6-35 months of age. In contrast to Streptococcus pneumoniae and Haemophilus influenzae , Moraxella catarrhalis is isolated from the middle ear in only 11% of episodes with nasopharyngeal colonization with this organism.
ABSTRACT
Background: The current reference standard for pediatric urinary tract infection (UTI) screening, the leukocyte esterase (LE) dipstick test, has suboptimal accuracy. The objective of this study was to compare the accuracy of novel urinary biomarkers to that of the LE test. Methods: We prospectively enrolled febrile children who were evaluated for UTI based on their presenting symptoms. We compared the accuracy of urinary biomarkers to that of the test. Results: We included 374 children (50 with UTI, 324 without UTI, ages 1-35 months) and examined 35 urinary biomarkers. The urinary biomarkers that best discriminated between febrile children with and without UTI were urinary neutrophil gelatinase-associated lipocalin (NGAL), IL-1ß, CXCL1, and IL-8. Of all examined urinary biomarkers, the urinary NGAL had the highest accuracy with a sensitivity of 90% (CI: 82-98) and a specificity of 96% (CI: 93-98). Conclusion: Because the sensitivity of the urinary NGAL test is slightly higher than that of the LE test, it can potentially reduce missed UTI cases. Limitations of using urinary NGAL over LE include increased cost and complexity. Further investigation is warranted to determine the cost-effectiveness of urinary NGAL as a screening test for UTI.
ABSTRACT
Importance: A previously reported prediction model included a child's race to estimate risk of urinary tract infection (UTI), but race-conscious medicine encourages investigating how race is likely to be a proxy for other factors that should instead be used for risk prediction. Objectives: To systematically review the available literature to evaluate the robustness of the association between race and UTI and to assess whether other variables could replace race as a variable in a previously developed prediction tool without adversely affecting its accuracy. Data Source: MEDLINE was searched through May 28, 2021. Study Selection: English-language studies that reported data on the prevalence of UTI according to race for children younger than 18 years were included. Data Extraction and Synthesis: Two independent reviewers assessed studies for risk of bias and abstracted data. Random-effects models were used to pool odds ratios, and meta-regression was used to explore heterogeneity. Main Outcomes and Measures: Odds of UTI among non-Black children vs Black children. Results: Sixteen studies (17â¯845 children) were included. In the primary analysis, which included 11 studies, the pooled odds ratio of UTI among non-Black children was 2.44-fold higher (95% CI, 1.87-3.20) than among Black children. The corresponding odds ratio in studies with low or very low risk of bias was 4.84-fold higher (95% CI, 3.16-7.41; I2 = 0%) among non-Black children than among Black children. Replacing race with history of UTI and duration of fever resulted in a model with similar accuracy (training cohort: overall sensitivity, 96% [95% CI, 94%-98%]; overall specificity, 35% [95%, 32%-38%]; overall area under the receiver operating characteristic curve, 0.80 [95% CI, 0.77-0.82]; validation cohort: overall sensitivity, 97% [95% CI, 90%-100%]; overall specificity, 32% [95% CI, 26%-37%]; overall area under the receiver operating characteristic curve, 0.84 [95% CI, 0.77-0.92]). Conclusions and Relevance: Although previous studies suggested that an association between race and UTI exists, because of the issues associated with the inclusion of race in decision models, we replaced the variable of race with history of UTI and duration of fever in a previously developed risk prediction model and found similar accuracy.