These findings imply that treatment strategies for individuals at UHR for psychosis should be comprehensive, promoting resilience as well as targeting the reduction of positive and negative symptoms to foster social reintegration and recovery.

Aminoacyl-tRNA synthetases recognize cognate amino acids and tRNAs from their noncognate counterparts and catalyze the formation of aminoacyl-tRNAs. Halofuginone (HF), a coccidiostat used in veterinary medicine, exerts its effects by acting as a high-affinity inhibitor of the enzyme glutamyl-prolyl-tRNA synthetase (EPRS). In order to elucidate the precise molecular basis of this inhibition mechanism of human EPRS, the crystal structures of the prolyl-tRNA synthetase domain of human EPRS (hPRS) at 2.4 Å resolution (hPRS-apo), of hPRS complexed with ATP and the substrate proline at 2.3 Å resolution (hPRS-sub) and of hPRS complexed with HF at 2.62 Å resolution (hPRS-HF) are presented. These structures show plainly that motif 1 functions as a cap in hPRS, which is loosely opened in hPRS-apo, tightly closed in hPRS-sub and incorrectly closed in hPRS-HF. In addition, the structural analyses are consistent with more effective binding of hPRS to HF with ATP. Mutagenesis and biochemical analysis confirmed the key roles of two residues, Phe1097 and Arg1152, in the HF inhibition mechanism. These structures will lead to the development of more potent and selective hPRS inhibitors for promoting inflammatory resolution.

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ObjectiveThe aim of the study was to compare the accuracy of magnetic resonance imaging (MRI) and mammography for the detection and assessment of the size of ductal carcinoma in situ (DCIS).Materials and MethodsThe preoperative contrast-enhanced MRI and mammography were analyzed in respect of the detection and assessment of the size of DCIS in 72 patients (age range: 30-67 years, mean age: 47 years). The MRI and mammographic measurements were compared with the histopathologic size with using the Pearson's correlation coefficients and the Mann-Whitney u test. We evaluated whether the breast density, the tumor nuclear grade, the presence of comedo necrosis and microinvasion influenced the MRI and mammographic size estimates by using the chi-square test.ResultsOf the 72 DCIS lesions, 68 (94%) were detected by MRI and 62 (86%) were detected by mammography. Overall, the Pearson's correlation of the size between MRI and histopathology was 0.786 versus 0.633 between mammography and histopathology (p < 0.001). MRI underestimated the size by more than 1 cm (including false negative examination) in 12 patients (17%), was accurate in 52 patients (72%) and overestimated the size by more than 1 cm in eight patients (11%) whereas mammography underestimated the size in 25 patients (35%), was accurate in 31 patients (43%) and overestimated the size in 16 patients (22%). The MRI, but not the mammography, showed significant correlation for the assessment of the size of tumor in noncomedo DCIS (p < 0.001 vs p = 0.060). The assessment of tumor size by MRI was affected by the nuclear grade (p = 0.008) and the presence of comedo necrosis (p = 0.029), but not by the breast density (p = 0.747) or microinvasion (p = 0.093).ConclusionMRI was more accurate for the detection and assessment of the size of DCIS than mammography.