Peripheral Proinsulin Expression Controls Low-Avidity Proinsulin-Reactive CD8 T Cells in Type 1 Diabetes.

Low-avidity autoreactive CD8 T cells (CTLs) escape from thymic negative selection, and peripheral tolerance mechanisms are essential for their regulation. We report the role of proinsulin (PI) expression on the development and activation of insulin-specific CTLs in the NOD mouse model of type 1 diabetes. We studied insulin B-chain-specific CTL from different T-cell receptor transgenic mice (G9Cα-/-) expressing normal PI1 and PI2 or altered PI expression levels. In the absence of PI2 (Ins2-/-), CTL in pancreatic lymph nodes (PLNs) were more activated, and male G9Cα-/- mice developed T1D. Furthermore, when the insulin-specific CTLs developed in transgenic mice lacking their specific PI epitope, the CTLs demonstrated increased cytotoxicity and proliferation in vitro and in vivo in the PLNs after adoptive transfer into NOD recipients. Dendritic cell-stimulated proliferation of insulin-specific T cells was reduced in the presence of lymph node stromal cells (LNSCs) from NOD mice but not from mice lacking the PI epitope. Our study shows that LNSCs regulate CTL activation and suggests that exposure to PI in the periphery is very important in maintenance of tolerance of autoreactive T cells. This is relevant for human type 1 diabetes and has implications for the use of antigen-specific therapy in tolerance induction.

Peer-assisted teaching of basic surgical skills.

BACKGROUND: Basic surgical skills training is rarely emphasised in undergraduate medical curricula. However, the provision of skills tutorials requires significant commitment from time-constrained surgical faculty. PURPOSE: We aimed to determine how a peer-assisted suturing workshop could enhance surgical skills competency among medical students and enthuse them towards a career in surgery. METHODS: Senior student tutors delivered two suturing workshops to second- and third- year medical students. Suturing performance was assessed before and after teaching in a 10-min suturing exercise (variables measured included number of sutures completed, suture tension, and inter-suture distance). Following the workshop, students completed a questionnaire assessing the effect of the workshop on their suturing technique and their intention to pursue a surgical career. RESULTS: Thirty-five students attended. Eighty-one percent believed their medical school course provided insufficient basic surgical skills training. The mean number of sutures completed post-teaching increased significantly (p < 0.001), and the standard deviation of mean inter-suture distance halved from ± 4.7 mm pre-teaching, to ± 2.6 mm post-teaching. All students found the teaching environment to be relaxed, and all felt the workshop helped to improve their suturing technique and confidence; 87% found the peer-taught workshop had increased their desire to undertake a career in surgery. DISCUSSION: Peer-assisted learning suturing workshops can enhance medical students' competence with surgical skills and inspire them towards a career in surgery. With very little staff faculty contribution, it is a cheap and sustainable way to ensure ongoing undergraduate surgical skills exposure.

Soccer shin guard reactions: allergic and irritant reactions.

In spite of the worldwide popularity of soccer among youth and the common requirement of the use of protective shin guards, reports of allergy to shin guards is sparse. This is surprising in light of the fact that this equipment is often made of materials that are reported to cause allergies, and that friction and moisture from the use of these shin guards during the sport would seem to predispose soccer players to the development of an allergic response. We present eight patients that presented for evaluation of dermatitis under their shin guards--some of which had allergy to their shin guards and some of which were diagnosed as having an irritant reaction.

Adenoma of anogenital mammary-like glands.

Adenomas in the anogenital region are uncommon. There has been debate about the origin, including ectopic breast tissue, cutaneous apocrine gland, and most recently anogenital mammary-like gland. An anogenital mass in a 36-year-old woman was excised, and histopathologic examination and immunostaining were performed. Microscopic tissue sections showed a morphologic pattern similar to that of a mammary fibroadenoma, and immunostaining demonstrated the presence of estrogen receptors and progesterone receptors. The possibility of adenomas of anogenital mammary-like glands should be considered when evaluating patients with a mass in this area with confirmation by tissue biopsy or aspiration cytology.