Publications

Long-lasting Ab responses rely on the germinal center (GC), where B cells bearing high-affinity Ag receptors are selected from a randomly mutated pool to populate the memory and plasma cell compartments. Signaling downstream of the BCR is dampened in GC B cells, raising the possibility that Ag presentation and competition for T cell help, rather than Ag-dependent signaling per se, drive these critical selection events. In this study we use an in vivo reporter of BCR signaling, Nur77-eGFP, to demonstrate that although BCR signaling is reduced among GC B cells, a small population of cells exhibiting GC light zone phenotype (site of Ag and follicular helper T cell encounter) express much higher levels of GFP. We show that these cells exhibit somatic hypermutation, gene expression characteristic of signaling and selection, and undergo BCR signaling in vivo.

OBJECTIVE

This study estimates how making oral contraceptive pills (OCPs) available without a prescription may affect contraceptive use, unintended pregnancies and associated contraceptive and pregnancy costs among low-income women.

STUDY DESIGN

Based on published figures, we estimate two scenarios [low over-the-counter (OTC) use and high OTC use] of the proportion of low-income women likely to switch to an OTC pill and predict adoption of OCPs according to the out-of-pocket costs per pill pack. We then estimate cost-savings of each scenario by comparing the total public sector cost of providing OCPs OTC and medical care for unintended pregnancy.

RESULTS

Twenty-one percent of low-income women at risk for unintended pregnancy are very likely to use OCPs if they were available without a prescription. Women's use of OTC OCPs varies widely by the out-of-pocket pill pack cost. In a scenario assuming no out-of-pocket costs for the over-the counter pill, an additional 11-21% of low-income women will use the pill, resulting in a 20-36% decrease in the number of women using no method or a method less effective than the pill, and a 7-25% decrease in the number of unintended pregnancies, depending on the level of use and any effect on contraceptive failure rates.

CONCLUSIONS

If out-of-pocket costs for such pills are low, OTC access could have a significant effect on use of effective contraceptives and unintended pregnancy. Public health plans may reduce expenditures on pregnancy and contraceptive healthcare services by covering oral contraceptives as an OTC product.

IMPLICATIONS

Interest in OTC access to oral contraceptives is high. Removing the prescription barrier, particularly if pill packs are available at low or zero out-of-pocket cost, could increase the use of effective methods of contraception and reduce unintended pregnancy and healthcare costs for contraceptive and pregnancy care.

While modernization has dramatically increased lifespan, it has also witnessed the increasing prevalence of diseases such as obesity, hypertension, and type 2 diabetes. Such chronic, acquired diseases result when normal physiologic control goes awry and may thus be viewed as failures of homeostasis. However, while nearly every process in human physiology relies on homeostatic mechanisms for stability, only some have demonstrated vulnerability to dysregulation. Additionally, chronic inflammation is a common accomplice of the diseases of homeostasis, yet the basis for this connection is not fully understood. Here we review the design of homeostatic systems and discuss universal features of control circuits that operate at the cellular, tissue, and organismal levels. We suggest a framework for classification of homeostatic signals that is based on different classes of homeostatic variables they report on. Finally, we discuss how adaptability of homeostatic systems with adjustable set points creates vulnerability to dysregulation and disease. This framework highlights the fundamental parallels between homeostatic and inflammatory control mechanisms and provides a new perspective on the physiological origin of inflammation.