Multivariate analysis of FcR-mediated NK cell functions identifies unique clustering among humans and rhesus macaques.

Rhesus macaques (RMs) are a common pre-clinical model used to test HIV vaccine efficacy and passive immunization strategies. Yet, it remains unclear to what extent the Fc-Fc receptor (FcR) interactions impacting antiviral activities of antibodies in RMs recapitulate those in humans. Here, we evaluated the FcR-related functionality of natural killer cells (NKs) from peripheral blood of uninfected humans and RMs to identify intra- and inter-species variation. NKs were screened for FcγRIIIa (human) and FcγRIII (RM) genotypes (FcγRIII(a)), receptor signaling, and antibody-dependent cellular cytotoxicity (ADCC), the latter mediated by a cocktail of monoclonal IgG1 antibodies with human or RM Fc. FcγRIII(a) genetic polymorphisms alone did not explain differences in NK effector functionality in either species cohort. Using the same parameters, hierarchical clustering separated each species into two clusters. Importantly, in principal components analyses, ADCC magnitude, NK contribution to ADCC, FcγRIII(a) cell-surface expression, and frequency of phosphorylated CD3ζ NK cells all contributed similarly to the first principal component within each species, demonstrating the importance of measuring multiple facets of NK cell function. Although ADCC potency was similar between species, we detected significant differences in frequencies of NK cells and pCD3ζ+ cells, level of cell-surface FcγRIII(a) expression, and NK-mediated ADCC (P<0.001), indicating that a combination of Fc-FcR parameters contribute to overall inter-species functional differences. These data strongly support the importance of multi-parameter analyses of Fc-FcR NK-mediated functions when evaluating efficacy of passive and active immunizations in pre- and clinical trials and identifying correlates of protection. The results also suggest that pre-screening animals for multiple FcR-mediated NK function would ensure even distribution of animals among treatment groups in future preclinical trials.

Knowledge and intention to use long-acting reversible contraception among university students.

OBJECTIVE: To assess the relationship between knowledge of long-acting reversible contraception (LARC) and intention to use LARC among female students. PARTICIPANTS: Participants consisted of a convenience sample of 292 female undergraduate and graduate students at a large midwestern university. METHODS: We conducted a cross-sectional in-person survey and multivariate analysis of LARC knowledge and intention to use LARC. RESULTS: Total response rate was 84.9%. Among contraceptive users, 13.3% were using a LARC method. On average, respondents scored 4.8/10 (SD 2.5) on a 10-item LARC knowledge assessment. Higher levels of LARC knowledge were associated with the intent to use LARC in the future in our multivariate analysis (RR 1.7, 95% CI 1.14-2.54: p = .01). Common reasons for LARC hesitancy were a need for more information, safety concerns, and risk of undesirable side effects. CONCLUSIONS: Low LARC knowledge and students' self-identified need for further LARC information represent an opportunity for campus contraceptive interventions which empower students to make informed reproductive decisions.

Management of Severe Coarctation of the Aorta During Pregnancy.

An 18-year-old primigravida woman underwent emergent percutaneous balloon stent repair of a severe coarctation of the aorta, allowing her to undergo an uneventful remaining pregnancy and the delivery of a healthy baby. Her case also demonstrates the association between maternal coarctation and fetal Shone complex. (Level of Difficulty: Beginner.).