Experimental Gonococcal Infection in Male Volunteers: Cumulative Experience with Neisseria gonorrhoeae Strains FA1090 and MS11mkC

Experimental infection of male volunteers with Neisseria gonorrhoeae is safe and reproduces the clinical features of naturally acquired gonococcal urethritis. Human inoculation studies have helped define the natural history of experimental infection with two well-characterized strains of N. gonorrhoeae, FA1090 and MS11mkC. The human model has proved useful for testing the importance of putative gonococcal virulence factors for urethral infection in men. Studies with isogenic mutants have improved our understanding of the requirements for gonococcal LOS structures, pili, opacity proteins, IgA1 protease, and the ability of infecting organisms to obtain iron from human transferrin and lactoferrin during uncomplicated urethritis. The model also presents opportunities to examine innate host immune responses that may be exploited or improved in development and testing of gonococcal vaccines. Here we review results to date with human experimental gonorrhea

Correlative analyses of RET and RAS mutations in a phase 3 trial of cabozantinib in patients with progressive, metastatic medullary thyroid cancer

BACKGROUND: Cabozantinib significantly prolonged progression-free survival (PFS) versus a placebo in patients with progressive, metastatic medullary thyroid cancer (MTC; P <.001). An exploratory analysis of phase 3 trial data evaluated the influence of rearranged during transfection (RET) and RAS (HRAS, KRAS, and NRAS) mutations on cabozantinib clinical activity. METHODS: Patients (n = 330) were randomized to cabozantinib (140 mg/day) or a placebo. The primary endpoint was PFS. Additional outcome measures included PFS, objective response rates (ORRs), and adverse events in RET and RAS mutation subgroups. RESULTS: Among all study patients, 51.2% were RET mutation–positive (38.2% with RET M918T), 34.8% were RET mutation–unknown, and 13.9% were RET mutation–negative. Sixteen patients were RAS mutation–positive. Cabozantinib appeared to prolong PFS versus the placebo in the RET mutation–positive subgroup (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.14-0.38; P <.0001), the RET mutation–unknown subgroup (HR, 0.30; 95% CI, 0.16-0.57; P =.0001), and the RAS mutation–positive subgroup (HR, 0.15; 95% CI, 0.02-1.10; P =.0317). The RET M918T subgroup achieved the greatest observed PFS benefit from cabozantinib versus the placebo (HR, 0.15; 95% CI, 0.08-0.28; P <.0001). The ORRs for RET mutation–positive, RET mutation–negative, and RAS mutation–positive patients were 32%, 22%, and 31%, respectively. No PFS benefit was observed in patients lacking both RET and RAS mutations, although the ORR was 21%. The safety profile for all subgroups was similar to that for the overall cabozantinib arm. CONCLUSIONS: These data suggest that cabozantinib provides the greatest clinical benefit to patients with MTC who have RET M918T or RAS mutations. However, a prospective trial is needed to confirm the relation between genetic variation and the response to cabozantinib. Cancer 2016;122:3856–3864. © 2016 American Cancer Society

Parental bonding and identity style as correlates of self-esteem among adult adoptees and nonadoptees

Adult adoptees (n equals 100) and non-adoptees (n equals 100) were compared with regard to selfesteem, identity processing style, and parental bonding. While some differences were found with regard to self-esteem, maternal care, and maternal overprotection, these differences were qualified by reunion status such that only reunited adoptees differed significantly from nonadoptees. Moreover, hierarchical regression analyses indicated that parental bonding and identity processing style were more important than adoptive status per se in predicting self esteem. Implications for practitioners who work with adoptees are discussed

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

Gender and sexual orientation differences in cognition across adulthood : age is kinder to women than to men regardless of sexual orientation

Despite some evidence of greater age-related deterioration of the brain in males than in females, gender differences in rates of cognitive aging have proved inconsistent. The present study employed web-based methodology to collect data from people aged 20-65 years (109,612 men; 88,509 women). As expected, men outperformed women on tests of mental rotation and line angle judgment, whereas women outperformed men on tests of category fluency and object location memory. Performance on all tests declined with age but significantly more so for men than for women. Heterosexuals of each gender generally outperformed bisexuals and homosexuals on tests where that gender was superior; however, there were no clear interactions between age and sexual orientation for either gender. At least for these particular tests from young adulthood to retirement, age is kinder to women than to men, but treats heterosexuals, bisexuals, and homosexuals just the same

Identity Formation in Adolescence: Change or Stability?

The aim of this five-wave longitudinal study of 923 early to middle adolescents (50.7% boys; 49.3% girls) and 390 middle to late adolescents (43.3% boys and 56.7% girls) is to provide a comprehensive view on change and stability in identity formation from ages 12 to 20. Several types of change and stability (i.e., mean-level change, rank-order stability, and profile similarity) were assessed for three dimensions of identity formation (i.e., commitment, in-depth exploration, and reconsideration), using adolescent self-report questionnaires. Results revealed changes in identity dimensions towards maturity, indicated by a decreasing tendency for reconsideration, increasingly more in-depth exploration, and increasingly more stable identity dimension profiles. Mean levels of commitment remained stable, and rank-order stability of commitment, in-depth exploration, and reconsideration did not change with age. Overall, girls were more mature with regard to identity formation in early adolescence, but boys had caught up with them by late adolescence. Taken together, our findings indicate that adolescent identity formation is guided by progressive changes in the way adolescents deal with commitments, rather than by changes in the commitments themselves

Multigroup Ethnic Identity Measure (MEIM) Expansion: Measuring Racial, Religious, and National Aspects of Sense of Ethnic Identity Within the United Kingdom

These studies examined the degree to which racial, religious, and national aspects of individuals' sense of ethnic identity stand as interrelated, yet distinct, constructs. Results of exploratory factor analyses in Study 1 (n = 272) revealed that a three-factor model specifying racial, religious, and national identities yielded optimal fit to correlational data from an expanded, 36-item version of the Multigroup Ethnic Identity Measure (MEIM; Roberts et al., 1999), although results left room for improvement in model fit. Subsequently, results of confirmatory factor analyses in Study 2 (n = 291) revealed that, after taking covariance among the items into account, a six-factor model specifying exploration and commitment dimensions within each of the racial, religious, and national identity constructs provided optimal fit. Implications for the utility of Goffman's (1963b) interactionist role theory and Erikson's (1968) ego psychology for understanding the full complexity of felt ethnic identity are discussed

Beverage specific alcohol intake in a population-based study: Evidence for a positive association between pulmonary function and wine intake

BACKGROUND: Lung function is a strong predictor of cardiovascular and all-cause mortality. Previous studies suggest that alcohol exposure may be linked to impaired pulmonary function through oxidant-antioxidant mechanisms. Alcohol may be an important source of oxidants; however, wine contains several antioxidants. In this study we analyzed the relation of beverage specific alcohol intake with forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC) in a random sample of 1555 residents of Western New York, USA. METHODS: We expressed pulmonary function as percent of predicted normal FEV(1) (FEV(1)%) and FVC (FVC%) after adjustment for height, age, gender and race. To obtain information on alcohol intake we used a questionnaire that reliably queries total alcohol and beverage specific recent (past 30 days) and lifetime alcohol consumption. Results: Using multiple linear regression analysis after adjustment for covariates (pack-years of smoking, weight, smoking status, education, nutritional factors and for FEV(1)%, in addition, eosinophil count), we observed no significant correlation between total alcohol intake and lung function. However, we found positive associations of recent and lifetime wine intake with FEV(1)% and FVC%. When we analyzed white and red wine intake separately, the association of lung function with red wine was weaker than for white wine. CONCLUSION: While total alcohol intake was not related to lung function, wine intake showed a positive association with lung function. Although we cannot exclude residual confounding by healthier lifestyle in wine drinkers, differential effects of alcoholic beverages on lung health may exist