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This study’s goal was to better understand risk tolerance associated with wearing flip-flops. A review of existing biomechanical data revealed substantial differences in gait kinematics and kinetics and an increased risk of falling when wearing flip-flops. However, users’ awareness of this increased risk and its potential influence on footwear decisions have not been studied. Nearly 800 participants were surveyed to evaluate usage behaviors of flip-flop wearers. Most participants found flip-flops comfortable and easy to wear, recognized the increased likelihood of a slip, trip, or misstep when wearing flip-flops, and reported experiencing such an event, mostly without injury. Older adults were less likely to have these attitudes and experiences regarding flip-flops. Despite the collective practical knowledge of an increased risk of a slip, trip, or misstep, most participants accepted the risk and chose to wear flip-flops, i.e., footwear choice was infrequently affected by awareness of the increased risk.

Healing of the burn injury site is a critical component of the patient's successful recovery from this form of trauma. Previous studies from our laboratory have demonstrated that T-cells via the production of growth factors are important in burn wound healing. Nonetheless, the role of these cells in burn wound inflammation remains unknown. To study this, wild-type (WT) and T-cell receptor-deficient ( TCR−/−) C57BL/6 male mice were subjected to burn injury or sham procedure. Wound cells were collected by implantation of polyvinyl alcohol sponges beneath the burn site in injured mice or beneath uninjured skin in sham mice. At 3 days after injury, infiltrating cells, wound fluid, and skin were collected for analysis. Burn injury markedly increased skin tumor necrosis factor- (TNF-) and monocyte chemoattractant protein 1 levels. In WT mice, the numbers of infiltrating cells were similar between nonburn wounds and burn wounds. In contrast, TCR−/−mice displayed a 6-fold reduction in the cellular infiltrate. Burn injury in WT mice caused a marked increase in burn wound TNF-, monocyte chemoattractant protein 1, and interleukin 6 content as compared with nonburn wounds, whereas in TCR−/−mice, the burn-induced increase of TNF- and interleukin 6 was not observed. The wound cell infiltrate at 3 days postinjury was devoid of T-cells in WT mice. It was predominately of myeloid origin expressing high levels of CD11b and F4/80. In conclusion, these findings suggest that resident T-cells are important in the recruitment of inflammatory cells and regulation of the inflammatory response at the wound site after thermal injury.

We hypothesized that administration of androgen receptors antagonist flutamide following trauma‐hemorrhage (T‐H) in metestrus females will maintain immune function and reduce remote organ damage under those conditions. Female B57BL/J6 mice (metestrus state, 8–12 weeks old) underwent laparotomy and hemorrhagic shock (35.0±5.0 mmHg for 90 min) and then received 17β‐estradiol (E2; 50 μg/25 g), flutamide (625 μg/25 g), or E2 + flutamide. Four hours after resuscitation, plasma cytokine and chemokine (TNF‐α, IL‐6, IL‐10, IFN‐γ, and MCP‐1) concentrations and their release in vitro by hepatic and pulmonary tissue macrophages (MΦ) were determined by flow cytometry. Organ damage was assessed by edema formation (wet‐to‐dry weight ratio) and neutrophil infiltration [myeloperoxidase (MPO) activity]. Administration of E2, flutamide, or E2 + flutamide following T‐H resulted in a significant decrease in systemic TNF‐α, IL‐6, and MCP‐1 concentrations under those conditions. This was accompanied by significantly decreased in vitro TNF‐α release by Kupffer cells after administration of E2, flutamide, or E2 + flutamide. The in vitro release of proinflammatory cytokines by alveolar MΦ, however, was reduced significantly only by the addition of E2 or E2 + flutamide but not by the addition of flutamide. A significant decrease in pulmonary and hepatic edema formation as well as neutrophil infiltration in the lung was observed after E2, flutamide and E2 + flutamide administration. In contrast, hepatic neutrophil infiltration was only significantly reduced following E2 and E2 + flutamide administration. Thus, although flutamide does not produce synergistic, salutary effects with E2, its administration in females following T‐H also produces salutary effects on the immune and organ function, similar to E2 administration under those conditions.

The depression in cell‐mediated immune function following trauma‐hemorrhage is shown to be restored by 17β‐estradiol (E2) administration. However, it remains unknown which of the two estrogen‐receptors, (ER)‐α or ER‐β, plays the predominant role in mediating the beneficial effects of E2. Female B57BL/J6 ER‐β−/−transgenic mice [knockout (KO)] and corresponding ovariectomized wild‐type (WT) mice were subjected to laparotomy and hemorrhagic shock (35.0±5.0 mmHg for 90 min) and treated with E2 (50 μg/25 g) or ER‐α agonist propyl pyrazole triol (PPT; 50 μg/25 g) following trauma‐hemorrhage. Four hours after resuscitation, systemic cytokine concentrations and cytokine release by splenocytes and splenic macrophages were determined by cytometric bead array. Trauma‐hemorrhage resulted in a significant increase in plasma tumor necrosis factor α (TNF‐α), interleukin (IL)‐6, and IL‐10. In contrast, the release of these cytokines by splenic macrophages was decreased significantly in WT and KO animals. Administration of E2 or PPT following trauma‐hemorrhage produced a significant reduction in systemic TNF‐α and IL‐6 concentrations in WT and KO mice. Although the suppression in the productive capacity of these cytokines following trauma‐hemorrhage by macrophages and splenocyte was also prevented in E2‐ and PPT‐treated WT mice, the release of cytokines by macrophages and splenocytes in E2‐ and PPT‐treated KO mice was not restored to the levels observed in sham animals. These findings collectively suggest that both receptors appear to play a significant role in mediating the immunoprotective effects of E2 in different tissue compartments following trauma‐hemorrhage.

A methodology was developed for the direct substitution of allylic alcohols and acetates by alcohol nucleophiles in order to synthesize allylic ethers. The reaction was mediated by highly concentrated ethereal solutions of lithium perchlorate and proceeded with high regiospecificity. Additionally, the methodology was extended to enable allyl ether exchanges to occur.

Abstract: Glial cell line-derived neurotrophic factor (GDNF) mediates signaling across the cell membrane by interaction with the RET-GDNFRα receptor complex. We identified a family in which one member had medullary thyroid carcinoma (MTC) and four members had vesicoureteral reflux (VUR). Knowledge that mutations in the RET proto-oncogene cause MTC and studies documenting genitourinary abnormalities in RET or GDNF knockout mice led us to examine the GDNF/RET-GDNFRα signaling complex in this family. RET and GDNF were excluded as the causative VUR gene by haplotype and sequence analysis. The GDNFRα gene was mapped to chromosome 10q25-26 by radiation hybrid techniques and was eliminated as the causative gene by haplotype analysis and sequencing of cDNA from an obligate carrier. Sequencing identified a 15-nucleotide deletion in GDNFRα mRNA, which was found to code for a single exon; analysis of several cell types revealed an identical mRNA form, indicating that this variant is a product of alternative RNA processing. We conclude that GDNFRα maps to 10q25-26 and that its RNA transcript is alternatively processed. Mutation abnormalities in the GDNF/RET-GDNFRα signaling system do not cause VUR in this family.

A separation chamber for continuous electrophoresis in a free flowing buffer curtain is described. The feature of our construction is the non-planar separation chamber and the assemblage of the electrodes within a constructive unit, the electrode block. This effects a handy and mechanically stable device. Furthermore, it enables the set-up of separation chambers of different size and shape, simply by the exchange of the chamber units.

A 74 year old woman with hepatitis C of long duration was admitted to hospital in hyperammonaemic coma. Despite aggressive treatment of hepatic encephalopathy, there was no clinical improvement. As part of her evaluation for other causes of altered mental status, she was found to be profoundly hypothyroid. Treatment with thyroid replacement hormone was accompanied by prompt normalisation of her mental status and hyperammonaemia. Hypothyroidism may exacerbate hyperammonaemia and portosystemic encephalopathy in patients with otherwise well compensated liver disease. Hyopthyroidism should be considered in the differential diagnosis of encephalopathy in patients with liver disease.