The structural characteristics of a mucin glycopeptide motif derived from the N-terminal fragment STTAV of the cell surface glycoprotein CD43 have been investigated by NMR. In this study, a series of molecules prepared by total synthesis were examined, consisting of the peptide itself, three glycopeptides having clustered sites of alpha-O-glycosylation on the serine and threonine side chains with the Tn, TF, and STF carbohydrate antigens, respectively, and one with the beta-O-linked TF antigen. Additionally, a glycopeptide having the sequence SSSAVAV, triglycosylated with the Le(y) epitope, was investigated. NMR data for the tri-STF-STTAV glycopeptide were used to solve the structure of this construct through restrained molecular dynamics calculations. The calculations revealed a defined conformation for the glycopeptide core rooted in the interaction of the peptide and the first N-acetylgalactosamine residue. The similarity of the NMR data for each of the alpha-O-linked glycopeptides demonstrates that this structure persists for each construct and that the mode of attachment of the first sugar and the peptide is paramount in establishing the organization of the core. The core provides a common framework on which a variety of glycans may be displayed. Remarkably, while there is a profound organizational effect on the peptide backbone with the alpha-linked glycans, attachment via a beta-linkage has little apparent consequence.

This study provides preliminary tests of two hypotheses: (1) Anxiety-disordered children show an attentional bias toward emotionally threatening stimuli, and (2) normal controls show an attentional bias away from emotionally threatening stimuli. Twelve children, 9 to 14 years of age, with primary diagnoses of anxiety disorder were compared with 12 normal controls matched for age, gender, vocabulary level, and reading ability. Subjects completed a reaction time task that measured visual attention toward threatening versus neutral words. The anxious group showed the predicted attentional bias toward threat words. However, controls did not show the predicted bias away from threat words. These results are the first showing that biased attentional processing occurs among clinically anxious children. The potential role of such an attentional bias in childhood anxiety disorders and future direction for research are discussed.

A new amide synthesis strategy based on a fundamental mechanistic revision of the reaction of thio acids and organic azides is presented. The data demonstrate that amines are not formed as intermediates in this reaction. Alternative mechanisms proceeding through a thiatriazoline intermediate are suggested. The reaction has been applied to the preparation of simple and architecturally complex amides that are difficult to access using conventional methods. The reaction is chemoselective, effective for unprotected substrates, and compatible with aprotic and protic solvents, including water.

The relationship among after-school time, parental monitoring, and problem behavior was examined in a sample of 1,170 early adolescents. Those spending unsupervised time with peers reported higher levels of aggression, delinquency, substance use, and susceptibility to peer pressure, and lower levels of parental monitoring, than did adolescents at home with parents. Adolescents home alone after school were similar to those who spent time with adults or in school activities.

The carbohydrate antigen globo H commonly found on breast cancer cells is a potential target for vaccine therapy. The objectives of this trial were to determine the toxicity and immunogenicity of three synthetic globo H-keyhole limpet hemocyanin conjugates plus the immunologic adjuvant QS-21. Twenty-seven metastatic breast cancer patients received five vaccinations each. The vaccine was well tolerated, and no definite differences were observed among the three formulations. Serologic analyses demonstrated the generation of IgM antibody titers in most patients, with minimal IgG antibody stimulation. There was significant binding of IgM antibodies to MCF-7 tumor cells in 16 patients, whereas IgG antibody reactivity was observed in a few patients. There was evidence of complement-dependent cytotoxicity in several patients. Affinity column purification supported the specificity of IgM antibodies for globo H. On the basis of these data, globo H will constitute one component of a polyvalent vaccine for evaluation in high-risk breast cancer patients.

BACKGROUND: Enhanced Recovery After Surgery Society publishes guidelines on perioperative care, but these guidelines should be validated prospectively. OBJECTIVE: To evaluate the association between compliance with Enhanced Recovery After Surgery Gynecologic/Oncology guideline elements and postoperative outcomes in an international cohort. STUDY DESIGN: The study comprised 2101 patients undergoing elective gynecologic/oncology surgery between January 2011 and November 2017 in 10 hospitals across Canada, the United States, and Europe. Patient demographics, surgical/anesthesia details, and Enhanced Recovery After Surgery protocol compliance elements (pre-, intra-, and postoperative phases) were entered into the Enhanced Recovery After Surgery Interactive Audit System. Surgical complexity was stratified according to the Aletti scoring system (low vs medium/high). The following covariates were accounted for in the analysis: age, body mass index, smoking status, presence of diabetes, American Society of Anesthesiologists class, International Federation of Gynecology and Obstetrics stage, preoperative chemotherapy, radiotherapy, operating time, surgical approach (open vs minimally invasive), intraoperative blood loss, hospital, and Enhanced Recovery After Surgery implementation status. The primary end points were primary hospital length of stay and complications. Negative binomial regression was used to model length of stay, and logistic regression to model complications, as a function of compliance score and covariates. RESULTS: Patient demographics included a median age 56 years, 35.5% obese, 15% smokers, and 26.7% American Society of Anesthesiologists Class III-IV. Final diagnosis was malignant in 49% of patients. Laparotomy was used in 75.9% of cases, and the remainder minimally invasive surgery. The majority of cases (86%) were of low complexity (Aletti score 3). In patients with ovarian cancer, 69.5% had a medium/high complexity surgery (Aletti score 4e11). Median length of stay was 2 days in the low-and 5 days in the medium/high-complexity group. Every unit increase in Enhanced Recovery After Surgery guideline score was associated with 8% (IRR, 0.92; 95% confidence interval, 0.90e0.95; P<.001) decrease in days in hospital among lowcomplexity, and 12% (IRR, 0.88; 95% confidence interval, 0.82e0.93; P<.001) decrease among patients with medium/highcomplexity scores. For every unit increase in Enhanced Recovery After Surgery guideline score, the odds of total complications were estimated to be 12% lower (P<.05) among low-complexity patients. CONCLUSION: Audit of surgical practices demonstrates that improved compliance with Enhanced Recovery After Surgery Gynecologic/Oncology guidelines is associated with an improvement in clinical outcomes, including length of stay, highlighting the importance of Enhanced Recovery After Surgery implementation.

A combined experimental and computational mechanistic study of amide formation from thio acids and azides is described. The data support two distinct mechanistic pathways dependent on the electronic character of the azide component. Relatively electron-rich azides undergo bimolecular coupling with thiocarboxylates via an anion-accelerated [3+2] cycloaddition to give a thiatriazoline. Highly electron-poor azides couple via bimolecular union of the terminal nitrogen of the azide with sulfur of the thiocarboxylate to give a linear adduct. Cyclization of this intermediate gives a thiatriazoline. Decomposition to amide is found to proceed via retro-[3+2] cycloaddition of the neutral thiatriazoline intermediates. Computational analysis (DFT, 6-31+G(d)) identified pathways by which both classes of azide undergo [3+2] cycloaddition with thio acid to give thiatriazoline intermediates, although these paths are higher in energy than the thiocarboxylate amidations. These studies also establish that the reaction profile of electron-poor azides is attributable to a prior capture mechanism followed by intramolecular acylation.

This report describes the results of transvaginal color Doppler sonography (TV-CDS) of 43 surgically proved ovarian masses. Waveform analyses of the signals arising from specific vessels (i.e., peripheral, central, septal) adjacent to and within these masses were correlated to those seen on macroscopic pathologic evaluation. The mean and standard deviation of the pulsatility indices (PI) of 32 benign lesions (1.8 +/- 0.8) were higher than 11 malignant ones (0.8 +/- 0.6) (P = 0.03). However, the range of benign (4.0 to 0.7) and malignant (1.5 to 0.4) lesions did overlap. Low PIs (less than 1.0) were found in five relatively benign lesions (one case each of dermoid cyst, cystadenoma containing a dermoid cyst, endometrioma, benign sclerosing stromal tumor, and thecoma), but also in all 11 malignant or borderline malignant lesions (nine cystadenocarcinomas, two germ cell tumors), causing an overlap between the PIs of some benign and malignant masses. With a 100% negative predictive value, our preliminary data suggest that TV-CDS can effectively exclude malignancy. However, with a positive predictive value of 73%, one in four malignant lesions diagnosed by TV-CDS will be benign.