Our Baby, Whose Choice? Certainty, Ambivalence, and Belonging in Male Infant Circumcision.

Routine infant circumcision is one of the most common surgical procedures performed in the U.S. Despite its broad societal acceptance, the practice is not without controversy. The stories included in this symposium offer rich insight into the diverse set of attitudes, values, and beliefs related to the practice of circumcision. They additionally offer insight into the complex web of personal, interpersonal, and social dynamics that inform the circumcision choices parents make for their children, the reasons parents make them, and how others can influence decisional choices. More broadly, these narratives raise important ethical questions mirrored today in broader contemporary bioethical and public discourse on the scope and limits of parental authority to make decisions for their children, power dynamics in medical decision making, and the ethics of healthcare activism. In this commentary, I discuss three sets of themes related to the ethics of circumcision running through the symposium narratives, comment on the ethical tensions and questions which emerge from each set of themes, gently problematize some of the rhetoric surrounding the ethical permissibility of circumcision, and gesture towards the future of bioethical inquiry on circumcision discourse.

Gender by Dasein? A Heideggerian critique of Suzanne Kessler and the medical management of infants born with disorders of sexual development.

This article explores the relationship between gender, technology, language, and how infants and children born with disorders of sexual development are shaped into intelligible members of the community. The contemporary medical model maintains that children ought to be both socially and surgically assigned and reared as one particular gender. Gender scholar Suzanne Kessler rejects this position and argues for the acceptance of greater genital variability through the use of language. Using a Heideggerian lens, the main question I seek to answer in this article is: does Kessler's approach succeed in its aim to better treat individuals born with disorders of sexual development? I argue that Kessler is successful in offering practical solutions for persons with intersexed conditions to exist and flourish as intelligible members of the community, but that her project ultimately relies on power to "challenge forth" greater acceptance of genital variance. Building on the work of Kessler and Heidegger, I argue that a better approach to making intelligible the existence of an infant born with a disorder of sexual development is not to rely on the manipulation of language, but to instead reinvigorate a sense of the sacred in response to having an intersex condition.

Regulatory B cell-specific interleukin-10 is dispensable for atherosclerosis development in mice.

OBJECTIVE: To determine the role of regulatory B cell-derived interleukin (IL)-10 in atherosclerosis. APPROACH AND RESULTS: We created chimeric Ldlr(-/-) mice with a B cell-specific deficiency in IL-10, and confirmed that purified B cells stimulated with lipopolysaccharide failed to produce IL-10 compared with control Ldlr(-/-) chimeras. Mice lacking B-cell IL-10 demonstrated enhanced splenic B-cell numbers but no major differences in B-cell subsets, T cell or monocyte distribution, and unchanged body weights or serum cholesterol levels compared with control mice. After 8 weeks on high-fat diet, there were no differences in aortic root or aortic arch atherosclerosis. In addition to plaque size, plaque composition (macrophages, T cells, smooth muscle cells, and collagen) was similar between groups. CONCLUSIONS: In contrast to its prominent regulatory role in many immune-mediated diseases and its proposed modulatory role in atherosclerosis, B cell-derived IL-10 does not alter atherosclerosis in mice.

MHC Class II-restricted antigen presentation by plasmacytoid dendritic cells drives proatherogenic T cell immunity.

BACKGROUND: Plasmacytoid dendritic cells (pDCs) bridge innate and adaptive immune responses and are important regulators of immuno-inflammatory diseases. However, their role in atherosclerosis remains elusive. METHODS AND RESULTS: Here, we used genetic approaches to investigate the role of pDCs in atherosclerosis. Selective pDC deficiency in vivo was achieved using CD11c-Cre × Tcf4(-/flox) bone marrow transplanted into Ldlr(-/-) mice. Compared with control Ldlr(-/-) chimeric mice, CD11c-Cre × Tcf4(-/flox) mice had reduced atherosclerosis levels. To begin to understand the mechanisms by which pDCs regulate atherosclerosis, we studied chimeric Ldlr(-/-) mice with selective MHCII deficiency on pDCs. Significantly, these mice also developed reduced atherosclerosis compared with controls without reductions in pDC numbers or changes in conventional DCs. MHCII-deficient pDCs showed defective stimulation of apolipoprotein B100-specific CD4(+) T cells in response to native low-density lipoprotein, whereas production of interferon-α was not affected. Finally, the atheroprotective effect of selective MHCII deficiency in pDCs was associated with significant reductions of proatherogenic T cell-derived interferon-γ and lesional T cell infiltration, and was abrogated in CD4(+) T cell-depleted animals. CONCLUSIONS: This study supports a proatherogenic role for pDCs in murine atherosclerosis and identifies a critical role for MHCII-restricted antigen presentation by pDCs in driving proatherogenic T cell immunity.