Follicular helper T cells are required for systemic autoimmunity

Production of high-affinity pathogenic autoantibodies appears to be central to the pathogenesis of lupus. Because normal high-affinity antibodies arise from germinal centers (GCs), aberrant selection of GC B cells, caused by either failure of negative selection or enhanced positive selection by follicular helper T (TFH) cells, is a plausible explanation for these autoantibodies. Mice homozygous for the san allele of Roquin, which encodes a RING-type ubiquitin ligase, develop GCs in the absence of foreign antigen, excessive TFH cell numbers, and features of lupus. We postulated a positive selection defect in GCs to account for autoantibodies. We first demonstrate that autoimmunity in Roquinsan/san (sanroque) mice is GC dependent: deletion of one allele of Bcl6 specifically reduces the number of GC cells, ameliorating pathology. We show that Roquinsan acts autonomously to cause accumulation of TFH cells. Introduction of a null allele of the signaling lymphocyte activation molecule family adaptor Sap into the sanroque background resulted in a substantial and selective reduction in sanroque TFH cells, and abrogated formation of GCs, autoantibody formation, and renal pathology. In contrast, adoptive transfer of sanroque TFH cells led to spontaneous GC formation. These findings identify TFH dysfunction within GCs and aberrant positive selection as a pathway to systemic autoimmunity

Uterine Artery Embolization and Its Effect on Fertility

A systematic review of literature analyzing fertility following uterine artery embolization (UAE) is presented. Twenty-one studies describing pregnancy and complications of pregnancy following UAE were included. Low-level evidence from these studies suggests that pregnancy rates following UAE are comparable to the age-adjusted rates in the general population. Although pregnancy complication rates were similar to those in patients with untreated fibroid tumors, a few studies have reported higher miscarriage rates following UAE. Further randomized controlled trials comparing UAE versus other fertility-preserving treatments are necessary to confirm these findings

Fostering better policy adoption and inter-disciplinary communication in healthcare: A qualitative analysis of practicing physicians' common interests.

PURPOSE:In response to limited physician adoption of various healthcare initiatives, we sought to propose and assess a novel approach to policy development where one first characterizes diverse physician groups' common interests, using a medical student and constructivist grounded theory. METHODS:In 6 months, a medical student completed 36 semi-structured interviews with interventional radiologists, gynecologists, and vascular surgeons that were systematically analyzed according to constructivist grounded theory to identifying common themes. Common drivers of clinical decision making and professional values across 3 distinct specialty groups were derived from physicians' descriptions of their clinical decision making, stories, and concerns. RESULTS:Common drivers of clinical decision making included patient preference/benefit, experience, reimbursement, busyness/volume, and referral networks. Common values included honesty, trustworthiness, loyalty, humble service, compassion and perseverance, and practical wisdom. Although personal gains were perceived as important interests, such values were easily sacrificed for the good of patients or other non-financial interests. This balance was largely dependent on the incentives and security provided by physicians' environments. CONCLUSIONS:Using a medical student interviewer and constructivist grounded theory is a feasible means of collecting rich qualitative data to guide policy development. Healthcare administrators and medical educators should consider incorporating this methodology early in policy development to anticipate how value differences between physician groups will influence their acceptance of policies and other broad healthcare initiatives

Physician interview demographics.

<p>Physician interview demographics.</p