Aims/hypothesis Leptin has profound glucose-lowering effects in rodent models of type 1 diabetes, and is currently being tested clinically to treat this disease. In addition to reversing hyperglycaemia, leptin therapy corrects multiple lipid, energy and neuroendocrine imbalances in rodent models of type 1 diabetes, yet the precise mechanism has not been fully defined. Thus, we performed metabolic analyses to delineate the downstream metabolic pathway mediating leptin-induced glucose lowering in diabetic mice. Methods Mice were injected with streptozotocin (STZ) to induce insulin-deficient diabetes, and were subsequently treated with 20 μg/day recombinant murine leptin or vehicle for 5 to 14 days. Energy-yielding substrates were measured in the liver and plasma, and endogenous glucose production was assessed by tolerance to extended fasting. Results STZ-leptin-treated mice developed severe hypoketotic hypoglycaemia during prolonged fasting, indicative of suppressed endogenous ketone and glucose production. STZ-leptin mice displayed normal gluconeogenic and glycogenolytic capacity, but had depleted circulating glycerol and NEFA. The depletion of glycerol and NEFA correlated tightly with the kinetics of glucose lowering in response to chronic leptin administration, and was not mimicked by single leptin injection. Administration of glycerol acutely reversed fasting-induced hypoglycaemia in leptin-treated mice. Conclusions/interpretation The findings of this study suggest that the diminution of circulating glycerol reduces endogenous glucose production, contributing to severe fastinginduced hypoglycaemia in leptin-treated rodent models of type 1 diabetes, and support that depletion of glycerol contributes to the glucose-lowering action of leptin.

The low-density lipoprotein receptor (Ldlr) is a key molecule involved with lipid clearance. The Ldlr Ϫ/Ϫ mouse has been used extensively as a model for studying atherosclerosis.

In comparison to published reference values, the TBI in young, healthy individuals is significantly higher. Whereas no gender difference existed, greater variability of the TBI was observed in women. Further studies are recommended to determine if the threshold for diagnosis of peripheral arterial disease based on TBI should be raised.

Islet transplantation is an effective method to obtain long-term glycemic control for patients with type 1 diabetes, yet its widespread use is limited by an inadequate supply of donor islets. The hormone leptin has profound glucose-lowering and insulin-sensitizing action in type 1 diabetic rodent models. We hypothesized that leptin administration could reduce the dose of transplanted islets required to achieve metabolic control in a mouse model of type 1 diabetes. We first performed a leptin dose-response study in C57Bl/6 mice with streptozotocin (STZ)-induced diabetes to determine a leptin dose insufficient to reverse hyperglycemia. Subsequently, we compared the ability of suboptimal islet transplants of 50 or 125 syngeneic islets to achieve glycemic control in STZ-induced diabetic C57Bl/6 mice treated with or without this dose of leptin. The dose-response study revealed that leptin reverses STZ-induced diabetes in a dose-dependent manner. Supraphysiological leptin levels were necessary to restore euglycemia but simultaneously increased risk of hypoglycemia, and also lost efficacy after 12 days of administration. In contrast, 1 µg/day leptin only modestly reduced blood glucose but maintained efficacy throughout the study duration. We then administered 1 µg/day leptin to diabetic mice that underwent transplantation of 50 or 125 islets. Although these islet doses were insufficient to ameliorate hyperglycemia alone, coadministration of leptin with islet transplantation robustly improved control of glucose and lipid metabolism, without increasing circulating insulin levels. This study reveals that low-dose leptin administration can reduce the number of transplanted islets required to achieve metabolic control in STZ-induced diabetic mice.

Summary:Keloids are a manifestation of a fibroproliferative scarring disorder of the skin and develop in response to dermal injury in patients with a susceptible background. Local, systemic, and genetic factors contribute to keloid susceptibility. These factors include tension on the edges of the wound, hormonal influences, and ethnicity, respectively. Castleman’s disease is a rare lymphoproliferative disorder that is characterized by the unregulated overproduction of interleukin-6, which leads to systemic lymphadenopathy and constitutional inflammatory symptoms. This case report shows that the bilateral auricular keloids of an adult woman were greatly exacerbated by the onset of Castleman’s disease. We present our multimodal management algorithm for auricular keloids, which involves core excision and radiation therapy and achieves excellent aesthetic outcomes. The current treatment pathway for auricular keloids and the possible relationship between interleukin-6 and keloid progression will be discussed.

Background Whether to undergo postmastectomy breast reconstruction (PMBR) is a challenging, preference-sensitive decision. It is therefore paramount to optimize decision quality through ensuring patients' knowledge and aligning treatments with their personal preferences. This study assessed the effects of a preconsultation educational group intervention (PEGI) on patient knowledge, state-trait anxiety, and decisional conflict (patient uncertainty in decision making) during the decision-making process. Methods This phase 3 randomized controlled trial assessed effects of a PEGI in women without active breast cancer undergoing delayed PMBR, or prophylactic mastectomy with immediate PMBR. Both groups underwent routine education before consultation. In addition, the intervention group underwent a PEGI composed of presentations from a plastic surgeon and nurse, a value clarification exercise, and shared experiences from PMBR patients before the consultation with the plastic surgeon. Before and 1-week after consultation, outcome measures were assessed using the Decisional Conflict Scale, State-Trait Anxiety Inventory, and the BREAST-Q. Results Of the 219 women deemed eligible, a total of 156 women were recruited and randomized. Treatment fidelity was 96% and retention was 88%. At baseline, there were no significant differences in terms of demographic or clinical status, knowledge, state-trait anxiety, and decisional conflict. Patient knowledge about PMBR improved in both groups; however, the degree of knowledge attainment was significantly greater in the PEGI group (24.5% improvement in the intervention group compared with 13.5% in the routine education group, P < 0.001). The reduction in decisional conflict from baseline to follow-up was greater in the intervention group compared with the routine education; however, the difference only approached significance ( P = 0.09). Conclusions The provision of a preconsultation educational group intervention has been shown to significantly close the knowledge gap on PMBR in patients seeking delayed breast reconstruction or prophylactic mastectomy with immediate breast reconstruction compared with routine education alone.

ObjectiveLeptin reverses hyperglycemia in rodent models of type 1 diabetes (T1D). Direct application of leptin to the brain can lower blood glucose in diabetic rodents, and can activate autonomic efferents and non-shivering thermogenesis in brown adipose tissue (BAT). We investigated whether leptin reverses hyperglycemia through a mechanism that requires autonomic innervation, or uncoupling protein 1 (UCP1)-mediated thermogenesis.MethodsTo examine the role of parasympathetic and sympathetic efferents in the glucose-lowering action of leptin, mice with a subdiaphragmatic vagotomy or 6-hydroxydopamine induced chemical sympathectomy were injected with streptozotocin (STZ) to induce hyperglycemia, and subsequently leptin treated. To test whether the glucose-lowering action of leptin requires activation of UCP1-mediated thermogenesis in BAT, we administered leptin in STZ-diabetic Ucp1 knockout (Ucp1−/−) mice and wildtype controls.ResultsLeptin ameliorated STZ-induced hyperglycemia in both intact and vagotomised mice. Similarly, mice with a partial chemical sympathectomy did not have an attenuated response to leptin-mediated glucose lowering relative to sham controls, and showed intact leptin-induced Ucp1 expression in BAT. Although leptin activated BAT thermogenesis in STZ-diabetic mice, the anti-diabetic effect of leptin was not blunted in Ucp1−/− mice.ConclusionsThese results suggest that leptin lowers blood glucose in insulin-deficient diabetes through a manner that does not require parasympathetic or sympathetic innervation, and thus imply that leptin lowers blood glucose through an alternative CNS-mediated mechanism or redundant target tissues. Furthermore, we conclude that the glucose lowering action of leptin is independent of UCP1-dependent thermogenesis.

With consideration of these requirements, we describe our surgical technique in terminal myelocystocele repair, which combines a novel surgical incision and for the first time in a neurosurgical setting, the use of a de-epithelialized skin flap to augment the closure. We report successful operative outcomes in three infant patients with terminal myelocystocele.