No abstract

We show that an inherent ability of two distinct cell types, keratinocytes and fibroblasts, can be relied upon to accurately reconstitute full-thickness human skin including the dermal-epidermal junction by a cell-sorting mechanism. A cell slurry containing both cell types added to silicone chambers implanted on the backs of severe combined immunodeficient mice sorts out to reconstitute a clearly defined dermis and stratified epidermis within 2 wk, forming a cell-sorted skin equivalent. Immunostaining of the cell-sorted skin equivalent with human cell markers showed patterns similar to those of normal full-thickness skin. We compared the cell-sorted skin equivalent model with a composite skin model also made on severe combined immunodeficient mice. The composite grafts were constructed from partially differentiated keratinocyte sheets placed on top of a dermal equivalent constructed of devitalized dermis. Electron microscopy revealed that both models formed ample numbers of normal appearing hemidesmosomes. The cell-sorted skin equivalent model, however, had greater numbers of keratin intermediate filaments within the basal keratinocytes that connected to hemidesmosomes, and on the dermal side both collagen filaments and anchoring fibril connections to the lamina densa were more numerous compared with the composite model. Our results may provide some insight into why, in clinical applications for treating burns and other wounds, composite grafts may exhibit surface instability and blistering for up to a year following grafting, and suggest the possible usefulness of the cell-sorted skin equivalent in future grafting applications.

Patients with delirium may fail to respond to standard therapies. Sixteen patients with management-refractory hyperactive delirium responded to adjunctive valproic acid, with complete resolution of hyperactive delirium in 13 cases. A rationale for using valproic acid in such circumstances is discussed.

Recent studies in higher plants or animals have shown that phospholipase D (PLD) signaling regulates many aspects of development, including organization of microtubules (MTs), actin and the endomembrane system. PLD hydrolyzes structural phospholipids to form the second messenger phosphatidic acid (PA). To begin to understand the signaling pathways and molecules that regulate cytoskeletal and endomembrane arrays during early development in the brown alga, Silvetia compressa, we altered PLD activity by applying butyl alcohols to zygotes. 1-Butanol activates PLD and is a preferred substrate, primarily forming phosphatidyl butanol (P-butanol), which is not a signaling molecule. Treatment with 1-butanol inhibited cell division and cytokinesis but not photopolarization or germination, suggesting an MT-based effect. Immunolabeling revealed that 1-butanol treatment rapidly disrupted MT arrays and caused zygotes to arrest in metaphase. MT arrays recovered rapidly following butanol washout, but subsequent development depended on the timing of the treatment regime. Additionally, treatment with 1-butanol early in development disrupted endomembrane organization, known to require functional MTs. Interestingly, treatment with higher concentrations of 2-butanol, which also activates PLD, mimicked the effects of 1-butanol. In contrast, the control t-butanol had no effect on MTs or development. These results indicate that S. compressa zygotes utilize PLD signaling to regulate MT arrays. In contrast, PLD signaling does not appear to regulate actin arrays or endomembrane trafficking directly. This is the first report describing the signaling pathways that regulate cytoskeletal organization in the stramenopile (heterokont) lineage.

Short Creek is a largely closed and isolated community on the border between Utah and Arizona, made up of the sister towns of Hildale, Utah, and Colorado City, Arizona. Beginning from childhood, the 6,000 or so members of the Fundamentalist Church of Jesus Christ of Latter-Day Saints (FLDS) are brought up in a lifestyle of plural marriage, meaning a marriage among one man and more than one woman, and are surrounded by their peers in "the covenant." A lifestyle of plural marriage is likely to affect the health of community members, but its effects have not been studied because of the community's isolation and distrust of outsiders. This paper addresses several questions that arise in contemplating the health of the Short Creek community: What are the health beliefs in this community, and what are their historical bases? Where do families seek medical care, and for what or at what threshold of illness or injury? What is the attitude of care providers serving this community, and how are the providers viewed by the community? More broadly, this paper examines the ways in which polygamy configures health. In order to meet this objective, this paper aims first to provide a brief account of this community's history and demographic profile, followed by a discussion of health care in this community and how it is affected by the practice of plural marriage, with the data comprised of qualitative interviews with health care providers to the community. The goals of this project are to gain a rich, historically nuanced understanding of the health of community members, and to identify directions for further academic and policy research. Our findings indicate that health in this community is shaped by limited resources, an attitude of health fatalism, and a profound insularity and corresponding isolation from the outside world.