A New Measure of Posterior Morphology in Sagittal Craniosynostosis: The Occipital Bullet Index.

INTRODUCTION: Sagittal craniosynostosis (SC) is associated with scaphocephaly, an elongated narrow head shape. Assessment of regional severity in the scaphocephalic head is limited by the use of serial computed tomographic (CT) imaging or complex computer programing. Three-dimensional measurements of cranial surface morphology provide a radiation-free alternative for assessing cranial shape. This study describes the creation of an occipital bulleting index (OBI), a novel tool using surface morphology to assess the regional severity in patients with SC. METHODS: Surface imaging from CT scans or 3D photographs of 360 individuals with SC and 221 normocephalic individuals were compared to identify differences in morphology. Cartesian grids were created on each individual's surface mesh using equidistant axial and sagittal planes. Area under the curve (AUC) analyses were performed to identify trends in regional morphology and create measures capturing population differences. RESULTS: The largest differences were located in the medial regions posteriorly. Using these population trends, a measure was created to maximize AUC. The OBI has an AUC of 0.72 with a sensitivity of 74% and a specificity of 61%. When the frontal bossing index is applied in tandem, the two have a sensitivity of 94.7% and a specificity of 93.1%. Correlation between the two scores in individuals with SC was found to be negligible with an intraclass correlation coefficient of 0.018. Severity was found to be independent of age under 24 months, sex, and imaging modality. CONCLUSIONS: This index creates a tool for differentiating control head shapes from those with SC and has the potential to allow for objective evaluation of the regional severity, outcomes of different surgical techniques, and tracking shape changes in individuals over time, without the need for radiation.

"Creation of the Scaphocephalic Index: Measurement of Global and Regional Severity in Scaphocephaly".

INTRODUCTION: The recently described frontal bossing index (FBI) and occipital bullet index (OBI) allow for quantification of scaphocephaly. A similar index examining biparietal narrowing has not been described. Addition of such an index measuring width would allow for direct evaluation of the primary growth restriction in sagittal craniosynostosis (SC) and the formation of an optimized global Width/Length measure. METHODS: CT scans and 3D photos were used to recreate scalp surface anatomy. Equidistant axial, sagittal, and coronal planes were overlaid creating a Cartesian grid. Points of intersection were analyzed for population trends in biparietal width. Using the most descriptive point coupled with the sellion's protrusion to control for head size, the vertex narrowing index (VNI) is formed. By combining this index with the FBI and OBI, the Scaphocephalic Index (SCI) is created as a tailored W/L measure. RESULTS: Using 221 control and 360 individuals with sagittal craniosynostosis, the greatest difference occurred superiorly and posteriorly at a point 70% of the head's height and 60% of the head's length. This point had an area under the curve (AUC) of 0.97 and sensitivity and specificity of 91.2% and 92.2% respectively. The SCI has an AUC of 0.9997, sensitivity and specificity >99%, and interrater reliability of 0.995. The correlation coefficients between the CT imaging and 3D photography was 0.96. CONCLUSION: The VNI, FBI, and OBI evaluate regional severity while the SCI is able to describe global morphology in patients with sagittal craniosynostosis. These allow for superior diagnosis, surgical planning, and outcome assessment, independent of radiation.

In-cell thermodynamics and a new role for protein surfaces.

There is abundant, physiologically relevant knowledge about protein cores; they are hydrophobic, exquisitely well packed, and nearly all hydrogen bonds are satisfied. An equivalent understanding of protein surfaces has remained elusive because proteins are almost exclusively studied in vitro in simple aqueous solutions. Here, we establish the essential physiological roles played by protein surfaces by measuring the equilibrium thermodynamics and kinetics of protein folding in the complex environment of living Escherichia coli cells, and under physiologically relevant in vitro conditions. Fluorine NMR data on the 7-kDa globular N-terminal SH3 domain of Drosophila signal transduction protein drk (SH3) show that charge-charge interactions are fundamental to protein stability and folding kinetics in cells. Our results contradict predictions from accepted theories of macromolecular crowding and show that cosolutes commonly used to mimic the cellular interior do not yield physiologically relevant information. As such, we provide the foundation for a complete picture of protein chemistry in cells.

Hydrogen exchange of disordered proteins in Escherichia coli.

A truly disordered protein lacks a stable fold and its backbone amide protons exchange with solvent at rates predicted from studies of unstructured peptides. We have measured the exchange rates of two model disordered proteins, FlgM and α-synuclein, in buffer and in Escherichia coli using the NMR experiment, SOLEXSY. The rates are similar in buffer and cells and are close to the rates predicted from data on small, unstructured peptides. This result indicates that true disorder can persist inside the crowded cellular interior and that weak interactions between proteins and macromolecules in cells do not necessarily affect intrinsic rates of exchange.