Childhood cognitive ability accounts for associations between cognitive ability and brain cortical thickness in old age.

Associations between brain cortical tissue volume and cognitive function in old age are frequently interpreted as suggesting that preservation of cortical tissue is the foundation of successful cognitive aging. However, this association could also, in part, reflect a lifelong association between cognitive ability and cortical tissue. We analyzed data on 588 subjects from the Lothian Birth Cohort 1936 who had intelligence quotient (IQ) scores from the same cognitive test available at both 11 and 70 years of age as well as high-resolution brain magnetic resonance imaging data obtained at approximately 73 years of age. Cortical thickness was estimated at 81 924 sampling points across the cortex for each subject using an automated pipeline. Multiple regression was used to assess associations between cortical thickness and the IQ measures at 11 and 70 years. Childhood IQ accounted for more than two-third of the association between IQ at 70 years and cortical thickness measured at age 73 years. This warns against ascribing a causal interpretation to the association between cognitive ability and cortical tissue in old age based on assumptions about, and exclusive reference to, the aging process and any associated disease. Without early-life measures of cognitive ability, it would have been tempting to conclude that preservation of cortical thickness in old age is a foundation for successful cognitive aging when, instead, it is a lifelong association. This being said, results should not be construed as meaning that all studies on aging require direct measures of childhood IQ, but as suggesting that proxy measures of prior cognitive function can be useful to take into consideration.

In situ azimuthal rotation device for linear dichroism measurements in scanning transmission x-ray microscopy.

A novel miniature rotation device used in conjunction with a scanning transmission x-ray microscope is described. It provides convenient in situ sample rotation to enable measurements of linear dichroism at high spatial resolution. The design, fabrication, and mechanical characterization are presented. This device has been used to generate quantitative maps of the spatial distribution of the orientation of proteins in several different spider and silkworm silks. Specifically, quantitative maps of the dichroic signal at the C 1s-->pi* (amide) transition in longitudinal sections of the silk fibers give information about the spatial orientation, degree of alignment, and spatial distribution of protein peptide bonds. A new approach for analyzing the dichroic signal to extract orientation distributions, in addition to magnitudes of aligned components, is presented and illustrated with results from Nephila clavipes dragline spider silk measured using the in situ rotation device.

Serial analysis of gene expression in the southern cattle tick following acaricide treatment of larvae from organophosphate resistant and susceptible strains.

Organophosphate resistant and susceptible tick larvae from laboratory strains of the southern cattle tick, Rhipicephalus (Boophilus) microplus were exposed to low doses of the organophosphate (OP) acaricide, coumaphos. Serial analysis of gene expression (SAGE) was used to analyse differential gene expression in response to OP treatment and to compare the responses of OP-treated and -untreated resistant and susceptible tick larvae. An R. microplus Gene Index was used as an EST database to identify genes which corresponded to SAGE tags whose abundance changed in response to acaricide exposure. Relative quantitative RT-PCR was used to confirm the differential expression results from the SAGE experiments. Of particular interest is a SAGE tag which corresponds to a cytochrome P450-like EST in the Gene Index which was more abundant in untreated OP resistant larvae compared to untreated OP susceptible larvae. This SAGE tag was also more abundant in OP resistant larvae treated with OP compared to OP susceptible larvae treated with OP.

BmiGI: a database of cDNAs expressed in Boophilus microplus, the tropical/southern cattle tick.

We used an expressed sequence tag approach to initiate a study of the genome of the southern cattle tick, Boophilus microplus. A normalized cDNA library was synthesized from pooled RNA purified from tick larvae which had been subjected to different treatments, including acaricide exposure, heat shock, cold shock, host odor, and infection with Babesia bovis. For the acaricide exposure experiments, we used several strains of ticks, which varied in their levels of susceptibility to pyrethroid, organophosphate and amitraz. We also included RNA purified from samples of eggs, nymphs and adult ticks and dissected tick organs. Plasmid DNA was prepared from 11,520 cDNA clones and both 5' and 3' sequencing performed on each clone. The sequence data was used to search public protein databases and a B. microplus gene index was constructed, consisting of 8270 unique sequences whose associated putative functional assignments, when available, can be viewed at the TIGR website (http://www.tigr.org/tdb/tgi). A number of novel sequences were identified which possessed significant sequence similarity to genes, which might be involved in resistance to acaricides.

Evidence-based practice in women's health: hormone therapy for women at menopause.

Women's health providers, especially midwives, must take into account the known benefits and risks, as well as the "unknown," when recommending the use of hormone therapy for menopausal women, especially as it relates to heart disease, breast cancer, impaired cognition, and osteoporosis. The most recent evidence available from various studies about the benefits and risks of estrogen and hormone therapy at menopause suggests that, although hormone therapy may be protective in some women against heart disease and osteoporosis, evidence is less certain about the benefits of hormone protection against impaired cognition and the risks of breast cancer with use. The clinical approach used by midwives in which individualizing care based on each woman's health status history as well as preferences is highly appropriate for women in the perimenopausal and menopausal period.

Cysteines 431 and 1074 are responsible for inhibitory disulfide cross-linking between the two nucleotide-binding sites in human P-glycoprotein.

Human wild-type and Cys-less P-glycoproteins were expressed in Pichia pastoris and purified in high yield in detergent-soluble form. Both ran on SDS gels as a single 140-kDa band in the presence of reducing agent and showed strong verapamil-stimulated ATPase activity in the presence of added lipid. The wild type showed spontaneous formation of higher molecular mass species in the absence of reducing agent, and its ATPase was activated by dithiothreitol. Oxidation with Cu(2+) generated the same higher molecular mass species, primarily at 200 and approximately 300 kDa, in high yield. Cross-linking was reversed by dithiothreitol and prevented by pretreatment with N-ethylmaleimide. Using proteins containing different combinations of naturally occurring Cys residues, it was demonstrated that an inhibitory intramolecular disulfide bond forms between Cys-431 and Cys-1074 (located in the Walker A sequences of nucleotide-binding sites 1 and 2, respectively), giving rise to the 200-kDa species. In addition, dimeric P-glycoprotein species ( approximately 300 kDa) form by intermolecular disulfide bonding between Cys-431 and Cys-1074. The ready formation of the intramolecular disulfide between Cys-431 and Cys-1074 establishes that the two nucleotide-binding sites of P-glycoprotein are structurally very close and capable of intimate functional interaction, consistent with available information on the catalytic mechanism. Formation of such a disulfide in vivo could, in principle, underlie a regulatory mechanism and might provide a means of intervention to inhibit P-glycoprotein.

Mutational analysis of conserved carboxylate residues in the nucleotide binding sites of P-glycoprotein.

Mutagenesis was used to investigate the functional role of six pairs of aspartate and glutamate residues (D450/D1093, E482/E1125, E552/E1197, D558/D1203, D592/D1237, and E604/E1249) that are highly conserved in the nucleotide binding sites of P-glycoprotein (Mdr3) and of other ABC transporters. Removal of the charge in E552Q/E1197Q and D558N/D1203N produced proteins with severely impaired biological activity when the proteins were analyzed in yeast cells for cellular resistance to FK506 and restoration of mating in a ste6Delta mutant. Mutations at other acidic residues had no apparent effect in the same assays. These four mutants were expressed in Pichia pastoris, purified to homogeneity, and biochemically characterized with respect to ATPase activity. Studies with purified proteins showed that mutants D558N and D1203N retained 14 and 30% of the drug-stimulated ATPase activity of wild-type (WT) Mdr3, respectively, and vanadate trapping of 8-azido[alpha-(32)P]nucleotide confirmed slower basal and drug-stimulated 8-azido-ATP hydrolysis compared to that for WT Mdr3. The E552Q and E1197Q mutants showed no drug-stimulated ATPase activity. Surprisingly, drugs did stimulate vanadate trapping of 8-azido[alpha-(32)P]nucleotide in E552Q and E1197Q at a level similar to that of WT Mdr3. This suggests that formation of the catalytic transition state can occur in these mutants, and that the bond between the beta- and gamma-phosphates is hydrolyzed. In addition, photolabeling by 8-azido[alpha-(32)P]nucleotide in the presence or absence of drug was also detected in the absence of vanadate in these mutants. These results suggest that steps after the transition state, possibly involved in release of MgADP, are severely impaired in these mutant enzymes.

Therapeutic use of selected herbs.

An increasing number of people in the United States are using herbs for health promotion and specific symptom management. Herbs are used to initiate healing through synergistic responses unlike the specific properties of pharmaceuticals. Anecdotal data comprise much of the popular information available about herbs. Scientific studies of the efficacy and safety of herbs, although on the rise, are less available than other drug trials. Clinicians need an appropriate knowledge base for dealing with patients who take herbal preparations as well as the ability to confidently include herbal preparations in their formulary. In this article, five common herbs are reviewed. The effects, clinical studies, side effects, and dosing regimens for aloe vera, arnica, black cohosh, evening primrose oil, and saw palmetto are described.

Selected hormonal agents in gynecology.

Hormonal agents are used to treat many conditions, including endometriosis, amenorrhea, fibroids, and dysfunctional uterine bleeding. Because women visit their care provider for various gynecologic problems more than any other reason, application of therapeutic uses in this rapidly expanding field is essential for nurses working in endocrine gynecology. Strategies for hormone use are discussed in light of the goals of patient education and treatment in the areas of pain relief, fertility, and cycle regulation.

Hormone replacement therapy.

For the large number of women who become menopausal each year, the decision of whether to use hormone replacement therapy is central. The author outlines treatment options, risks, and benefits of hormone therapy and examines likelihoods of outcomes. Based on the latest research, types of hormones available, prescription regimens, side effects, and alternatives to hormone therapy are discussed.

Women's midlife health. Reframing menopause.

In primary care and gynecologic settings, midwives will manage the care of women during the perimenopause transition as well as throughout the postmenopausal period. As such, they will need to understand the issues that are at the heart of the debate regarding menopause and aging. This article reviews the endocrinology of menopause, the history of menopause treatment in this century, and the various physical, psychological, and role changes that accompany the developmental processes of menopause. Bleeding pattern changes, hot flashes, sleep disturbances, and genital, skin, and weight changes are discussed. Sexuality, breast, cardiovascular, skeletal, as well as hormone therapy issues are examined. The basics of the midlife health office visit are included.

Dietary prevention of osteoporosis.

Osteoporosis is a major health problem facing women and men, and the number of people affected is likely to increase substantially as the population ages. The gold standard for treatment has always been prevention. This article reviews therapeutic options, with an emphasis on nutrition; outlines current recommendations for calcium and vitamin D throughout the life span; and discusses food and supplemental sources of calcium. Guidelines are given for identifying high- and low-risk patients, and appropriate interventions are highlighted.

The menopausal experience of African American women: overview and suggestions for research.

Menopause and its effects on women's health status and needs have only recently received the increased attention of scholars and clinicians that many feel is long overdue. However, one major area of neglect that continues today regards the climacteric in minority populations within the United States, including the largest minority group, African Americans. This review summarizes issues that have potentially limited the amount of information available regarding menopause in African Americans. These issues include differing perspectives on the climacteric within research and clinical arenas, the difficulty of studying race as a variable in scholarly investigations, and methodological factors that have led to underrepresentation of minorities in studies of menopause. General considerations, as well as specific suggestions, for research questions when investigating the climacteric experiences of African American women are offered.

Skin changes in menopause.

Skin signs and symptoms were examined in 46 menopausal women prior to estrogen replacement therapy. Several symptoms such as pruritus, bruising, dryness and thinning were seen more frequently in sun-exposed skin emphasizing the contribution of photoaging. At the end of a 6-mth treatment period, no significant difference was observed in the prevalence or severity of the cutaneous signs and symptoms when patients receiving transdermal 17 beta-estradiol (Estraderm) were compared with controls (the only exception was cutaneous flushing). Elastic fibers from sun-protected (buttock) skin of menopausal women were studied by light and electron microscopy. In 3 women (ages 30-37) with a history of premature menopause, the elastic fibers had several degenerative changes including coalescence of cystic spaces into lacunae, peripheral fragmentation, granular degeneration and splitting of the fibers into strands. Similar age-related ultrastructural changes are normally found in individuals that are at least 20 yrs older than these patients. These findings are suggestive of a relationship between premature aging of the dermal elastic fibers and estrogen deprivation.