Self-reported use of natural health products:A cross-sectional telephone survey in older Ontarians

Background: The self-reported use of natural health products (NHPs) (herbal products and vitamin and mineral supplements) has increased over the past decade in Canada. Because the elderly population might have comorbidities and concurrently administered medications, there is a need to explore the perceptions and behaviors associated with NHPs in this age group. Objective: The goal of this study was to assess the use of NHPs in a cohort of older Canadian residents and the characteristics, perceptions, and behaviors associated with NHP use. Methods: Survey participants aged =60 years were randomly selected from telephone listings in the area of greater Hamilton, Ontario, Canada. Data were collected using a standardized computer-assisted telephone interview system. Self-reported data covering 7 domains were collected: (1) demographics; (2) self-reported 12-month NHP use; (3) reasons for NHP use; (4) self-reported 12-month prescription medication use; (5) expenditures on NHPs; (6) patient-reported adverse events and drug-NHP interactions; and (7) perceptions of physicians' attitudes regarding NHPs. Descriptive statistics were used to compare the characteristics of NHP users with those of nonusers and to assess the characteristics of NHP users across these 7 domains. Multivariate regression analysis was conducted to determine the demographic variables that might be associated with NHP user status. Results: Of 2528 persons identified as age =60 years, 1206 (48%) completed the telephone interview. Six hundred sixteen of these respondents (51%) reported the use of =1 NHP during the previous 12 months. On the initial univariate analysis, younger age and higher income were significantly associated with reporting NHP use (mean age, users vs nonusers, 71.1 vs 72.7 years, respectively; 95% CI, 1.02-1.06; P <0.001; income more than Can $26,000 was 28% and 22% in users and nonusers, respectively; P = 0.028). One hundred seventy of 616 users (28%) used an NHP to treat the same condition for which they were concurrently receiving a prescription medication, and 43 (25%) had not informed their physicians about their NHP use. Patients' characteristics such as sex, education, smoking status, and self-reported health status did not differ significantly between users and nonusers. In individuals who regularly spent money to purchase NHPs (n = 394), the mean cost was $20.38/mo. NHP expenditure was not significantly associated with age, sex, or income. Conclusion: Based on these findings, a substantial proportion of those Ontarians aged =60 years reported NHP use, and there is a need for greater communication with physicians to avoid potential drug-NHP interactions. © 2009 Excerpta Medica Inc. All rights reserved.

Resolution theory, and static and frequency-dependent cross-talk in piezoresponse force microscopy

Probing the functionality of materials locally by means of scanning probe microscopy (SPM) requires a reliable framework for identifying the target signal and separating it from the effects of surface morphology and instrument non-idealities, e.g. instrumental and topographical cross-talk. Here we develop a linear resolution theory framework in order to describe the cross-talk effects, and apply it for elucidation of frequency-dependent cross-talk mechanisms in piezoresponse force microscopy. The use of a band excitation method allows electromechanical/electrical and mechanical/topographic signals to be unambiguously separated. The applicability of a functional fit approach and multivariate statistical analysis methods for identification of data in band excitation SPM is explored.

A potential vulnerability locus for schizophrenia on chromosome 6p24-22:evidence for genetic heterogeneity

In 265 Irish pedigrees, with linkage analysis we find evidence for a vulnerability locus for schizophrenia in region 6p24-22. The greatest lod score, assuming locus heterogeneity, is 3.51 (P = 0.0002) with D6S296. Another test, the C test, also supported linkage, the strongest results being obtained with D6S296 (P = 0.00001), D6S274 (P = 0.004) and D6S285 (P = 0.006). Non-parametric analysis yielded suggestive, but substantially weaker, findings. This locus appears to influence the vulnerability to schizophrenia in roughly 15 to 30% of our pedigrees. Evidence for linkage was maximal using an intermediate phenotypic definition and declined when this definition was narrowed or was broadened to include other psychiatric disorders.

Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia

Prior evidence has supported the existence of multiple susceptibility genes for schizophrenia. Multipoint linkage analysis of the 270 Irish high-density pedigrees that we have studied, as well as results from several other samples, suggest that at least one such gene is located in region 6p24-21. In the present study, family-based association analysis of 36 simple sequence-length-polymorphism markers and of 17 SNP markers implicated two regions, separated by approximately 7 Mb. The first region, and the focus of this report, is 6p22.3. In this region, single-nucleotide polymorphisms within the 140-kb gene DTNBP1 (dystrobrevin-binding protein 1, or dysbindin) are strongly associated with schizophrenia. Uncorrected, empirical P values produced by the program TRANSMIT were significant (P

Support for a possible schizophrenia vulnerability locus in region 5q22-31 in Irish families

In our genome scan for schizophrenia genes in 265 Irish pedigrees, marker D5S818 in 5q22 produced the second best result of the first 223 markers tested (P = 0.002). We then tested an additional 13 markers and the evidence suggests the presence of a vulnerability locus for schizophrenia in region 5q22-31. This region appears to be distinct from those chromosome 5 regions studied in two prior reports, but the same as that producing positive results in the report by Wildenauer and colleagues found elsewhere in this issue. The largest pairwise heterogeneity LOD (H-LOD) score was found with marker D5S393 (max 3.04, P = 0.0005), assuming a narrow phenotypic category, and a genetic model with intermediate heterozygotic liability. In marked contrast to the H-LOD scores from our sample with markers from the regions of interest on chromosomes 6p and 8p, expanding the disease definition to include schizophrenia spectrum or nonspectrum disorders produced substantially smaller scores, with a number of markers failing to yield positive values at any recombination fraction. Using multipoint H-LODS, the strongest evidence for linkage occurs under the narrow phenotypic definition and recessive genetic model, with a peak at marker D5S804 (max 3.35, P = 0.0002). Multipoint nonparametric linkage analysis produced a peak in the same location (max z = 2.84, P = 0.002) with the narrow phenotypic definition. This putative vulnerability locus appears to be segregating in 10-25% of the families studied, but this estimate is tentative. Comparison of individual family multipoint H-LOD scores at the regions of interest on chromosomes 6p, 8p and 5q showed that only a minority of families yield high lod scores in two or three regions.

A schizophrenia locus may be located in region 10p15-p11

In our genomic scan of 265 Irish families with schizophrenia, we have thus far generated modest evidence for the presence of vulnerability genes in three chromosomal regions, i.e., 5q21-q31, 6p24-p22, and 8p22-p21. Outside of those regions, of all markers tested to date, D10S674 produced one of the highest pairwise heterogeneity lod (H-LOD) scores, 3.2 (P = 0.0004), when initially tested on a subset of 88 families. We then tested a total of 12 markers across a region of 32 centimorgans in region 10p15-p11 of all 265 families. The strongest evidence for linkage occurred assuming an intermediate phenotypic definition, and a recessive genetic model. The largest pairwise H-LOD score was found with marker D10S2443 (maximum 1.95, P = 0.005). Using multipoint H-LODs, we found a broad peak (maximum 1.91, P = 0.006) extending over the 11 centimorgans from marker D10S674 to marker D10S1426. Multipoint nonparametric linkage analysis produced a much broader peak, but with the maximum in the same location near D10S2443 (maximum z = 1.88, P = 0.03). Based on estimates from the multipoint analysis, this putative vulnerability locus appears to be segregating in 5-15% of the families studied, but this estimate should be viewed with caution. When evaluated in the context of our genome scan results, the evidence suggests the possibility of a fourth vulnerability locus for schizophrenia in these Irish families, in region 10p15-p11.

Discriminating Taxonomic Categories and Domains in Mental Simulations of Concepts of Varying Concreteness

Most studies of conceptual knowledge in the brain focus on a narrow range of concrete conceptual categories, rely on the researchers' intuitions about which object belongs to these categories, and assume a broadly taxonomic organization of knowledge. In this fMRI study, we focus on concepts with a variety of concreteness levels; we use a state of the art lexical resource (WordNet 3.1) as the source for a relatively large number of category distinctions and compare a taxonomic style of organization with a domain-based model (associating concepts with scenarios). Participants mentally simulated situations associated with concepts when cued by text stimuli. Using multivariate pattern analysis, we find evidence that all Taxonomic categories and Domains can be distinguished from fMRI data and also observe a clear concreteness effect: Tools and Locations can be reliably predicted for unseen participants, but less concrete categories (e.g., Attributes, Communications, Events, Social Roles) can only be reliably discriminated within participants. A second concreteness effect relates to the interaction of Domain and Taxonomic category membership: Domain (e.g., relation to Law vs. Music) can be better predicted for less concrete categories. We repeated the analysis within anatomical regions, observing discrimination between all/most categories in the left middle occipital and temporal gyri, and more specialized discrimination for concrete categories Tool and Location in the left precentral and fusiform gyri, respectively. Highly concrete/abstract Taxonomic categories and Domain were segregated in frontal regions. We conclude that both Taxonomic and Domain class distinctions are relevant for interpreting neural structuring of concrete and abstract concepts.

Evaluating the use of testate amoebae for palaeohydrological reconstruction in permafrost peatlands

The melting of high-latitude permafrost peatlands is a major concern due to a potential positive feedback on global climate change. We examine the ecology of testate amoebae in permafrost peatlands, based on sites in Sweden (~ 200 km north of the Arctic Circle). Multivariate statistical analysis confirms that water-table depth and moisture content are the dominant controls on the distribution of testate amoebae, corroborating the results from studies in mid-latitude peatlands. We present a new testate amoeba-based water table transfer function and thoroughly test it for the effects of spatial autocorrelation, clustered sampling design and uneven sampling gradients. We find that the transfer function has good predictive power; the best-performing model is based on tolerance-downweighted weighted averaging with inverse deshrinking (performance statistics with leave-one-out cross validation: R2 = 0.87, RMSEP = 5.25 cm). The new transfer function was applied to a short core from Stordalen mire, and reveals a major shift in peatland ecohydrology coincident with the onset of the Little Ice Age (c. AD 1400). We also applied the model to an independent contemporary dataset from Stordalen and find that it outperforms predictions based on other published transfer functions. The new transfer function will enable palaeohydrological reconstruction from permafrost peatlands in Northern Europe, thereby permitting greatly improved understanding of the long-term ecohydrological dynamics of these important carbon stores as well as their responses to recent climate change.

Inactivating mutations in an SH2 domain-encoding gene in X-linked lymphoproliferative syndrome

X-linked lymphoproliferative syndrome (XLP) is an inherited immunodeficiency characterized by increased susceptibility to Epstein-Barr virus (EBV). In affected males, primary EBV infection leads to the uncontrolled proliferation of virus-containing B cells and reactive cytotoxic T cells, often culminating in the development of high-grade lymphoma. The XLP gene has been mapped to chromosome band Xq25 through linkage analysis and the discovery of patients harboring large constitutional genomic deletions. We describe here the presence of small deletions and intragenic mutations that specifically disrupt a gene named DSHP in 6 of 10 unrelated patients with XLP. This gene encodes a predicted protein of 128 amino acids composing a single SH2 domain with extensive homology to the SH2 domain of SHIP, an inositol polyphosphate 5-phosphatase that functions as a negative regulator of lymphocyte activation. DSHP is expressed in transformed T cell lines and is induced following in vitro activation of peripheral blood T lymphocytes. Expression of DSHP is restricted in vivo to lymphoid tissues, and RNA in situ hybridization demonstrates DSHP expression in activated T and B cell regions of reactive lymph nodes and in both T and B cell neoplasms. These observations confirm the identity of DSHP as the gene responsible for XLP, and suggest a role in the regulation of lymphocyte activation and proliferation. Induction of DSHP may sustain the immune response by interfering with SHIP-mediated inhibition of lymphocyte activation, while its inactivation in XLP patients results in a selective immunodeficiency to EBV.

Autosomal dominant retinitis pigmentosa:a new multi-allelic marker (D3S621) genetically linked to the disease locus (RP4)

We report the characterization of a new eight-allele microsatellite (D3S621) isolated from a human chromosome 3 library. Two-point and multi-locus genetic linkage analysis have shown D3S621 to co-segregate with the previously mapped RP4 (theta m = 0.12, Zm = 4.34) and with other genetic markers on the long arm of the chromosome, including D3S14 (R208) (theta m = 0.00, Zm = 15.10), D3S47 (C17) (theta m = 0.11, Zm = 4.95), Rho (theta m = 0.07, Zm = 1.37), D3S21 (L182) (theta m = 0.07, Zm = 2.40) and D3S19 (U1) (theta m = 0.13, Zm = 2.78). This highly informative marker, with a polymorphic information content of 0.78, should be of considerable value in the extension of linkage data for autosomal dominant retinitis pigmentosa with respect to locii on the long arm of chromosome 3.

Serum- and HDL3-serum amyloid A and HDL3-LCAT activity are influenced by increased CVD-burden

BACKGROUND: High density lipoproteins (HDL) protect against cardiovascular disease (CVD). However, increased serum amyloid-A (SAA) related inflammation may negate this property. This study investigated if SAA was related to CVD-burden.

METHODS: Subjects referred to the rapid chest pain clinic (n = 240) had atherosclerotic burden assessed by cardiac computerised tomography angiography. Subjects were classified as: no-CVD (n = 106), non-obstructive-CVD, stenosis<50% (n = 58) or moderate/significant-CVD, stenosis ≥50% (n = 76). HDL was subfractionated into HDL2 and HDL3 by rapid-ultracentrifugation. SAA-concentration was measured by ELISA and lecithin cholesterol acyltransferase (LCAT) activity measured by a fluorimetric assay.

RESULTS: We illustrated that serum-SAA and HDL3-SAA-concentration were higher and HDL3-LCAT-activity lower in the moderate/significant-CVD-group, compared to the no-CVD and non-obstructive-CVD-groups (percent differences: serum-SAA, +33% & +30%: HDL3-SAA, +65% and +39%: HDL3-LCAT, -6% & -3%; p < 0.05 for all comparisons). We also identified a positive correlation between serum-SAA and HDL3-SAA (r = 0.698; p < 0.001) and a negative correlation between HDL3-SAA and HDL3-LCAT-activity (r = -0.295; p = 0.003), while CVD-burden positively correlated with serum-SAA (r = 0.150; p < 0.05) and HDL3-SAA (r = 0.252; p < 0.001) and negatively correlated with HDL3-LCAT-activity (r = -0.182; p = 0.006). Additionally, multivariate regression analysis adjusted for age, gender, CRP and serum-SAA illustrated that HDL3-SAA was significantly associated with modifying CVD-risk of moderate/significant CVD-risk (p < 0.05).

CONCLUSION: This study has demonstrated increased SAA-related inflammation in subjects with moderate/significant CVD-burden, which appeared to impact on the antiatherogenic potential of HDL. We suggest that SAA may be a useful biomarker to illustrate increased CVD-burden, although this requires further investigation.

Do women who intermittently attend breast screening differ from those women who attend every invitation and those who never attend?

OBJECTIVES:

Analysis of screening uptake usually dichotomizes women into attenders and non-attenders, though many women respond positively to some but not all invitations. This paper studies these intermittent attenders.

METHODS:

A cohort of 8,571 women invited for consecutive breast screens in the Northern Ireland Breast Screening Programme were followed in a study linking screening and census records. Multivariate logistic analysis was used to analyze the characteristics of those who attended both times (consistent), once (intermittent or 'one-time only'), or not at all (non-attenders).

RESULTS:

Overall, 15.5% of women attended once and 13.4% were non-attenders. Non-attenders were characteristically disadvantaged (as measured by social renting, car access, and employment status), less likely to be married, and more likely to be healthy. One-time attenders were younger, and suffering poor health, though there was no association with either social renting or employment status. Privately rented accommodation and city living was associated with both one-time attendance and non-attendance.

CONCLUSIONS:

One-time attenders are an important and distinct subgroup of screening invitees in this analysis. Their distinct characteristics suggest that transitory factors, such as change in marital status, ill-health, or addressing difficulties through change of residence are important. These distinct characteristics suggest the need for different approaches to increase attendance, among both intermittent attenders and those not attending at all.

Alzheimer's disease-like pathology has transient effects on the brain and blood metabolome

The pathogenesis of Alzheimer's disease (AD) is complex involving multiple contributing factors. The extent to which AD pathology impacts upon the metabolome is still not understood, nor is it known how disturbances change as the disease progresses. For the first time we have profiled longitudinally (6, 8, 10, 12 and 18 months) both the brain and plasma metabolome of APP/PS1 double transgenic and wild type (WT) mice. A total of 187 metabolites were quantified using a targeted metabolomics methodology. Multivariate statistical analysis produced models that distinguished APP/PS1 from WT mice at 8, 10 and 12 months.Metabolic pathway analysis found perturbed polyamine metabolism in both brain and blood plasma. There were other disturbances in essential amino acids,branched chain amino acids and also in the neurotransmitter serotonin.Pronounced imbalances in phospholipid and acylcarnitine homeostasis was evident in two age groups. AD-like pathology therefore impacts greatly on both the brain and blood metabolomes, although there appears to be a clear temporal sequence whereby changes to brain metabolites precede those in blood.

Outcomes of surgical bleb revision for complications of trabeculectomy.

OBJECTIVE: To describe the results of revision surgery for complications of trabeculectomy in a case series from an academic glaucoma service. DESIGN: Retrospective case series. PARTICIPANTS: A total of 177 eyes of 167 adult patients who underwent revision of trabeculectomy at the Wilmer Eye Institute between 1994 and 2007. METHODS: Three indications for surgery were identified: hypotony without leak, bleb leak, and bleb dysesthesia. Revision was deemed successful when all of the following were true: the primary indication was eliminated, further intraocular pressure (IOP)-lowering surgery was not required, no major complication occurred, and a new bleb-related problem did not develop. Patients with less than 3 months of follow-up were excluded unless failure occurred earlier. Surgical procedures included variations on excision of thin or leaking conjunctiva with advancement. MAIN OUTCOME MEASURES: Change in IOP, change in visual acuity, need for further IOP-lowering surgery, and complications after bleb revision. RESULTS: Subjects' mean age was 67+/-14 years, 54% were female, and mean follow-up was 2.8+/-2.7 years, with a mean interval from trabeculectomy to revision of 3.5+/-3.7 years. Overall success rate was 63% (112/177), which was slightly higher for leak repair (65%; 64/98) and hypotony (63%; 32/51) than for dysesthesia (57%; 16/28) indications. By Kaplan-Meier analysis, overall cumulative success rates at 1, 2, 5, and 10 years after bleb revision were 80%, 75%, 50%, and 41%, respectively. IOP and visual acuity improved significantly in both hypotony and leak groups (P values ranging from 0.004 to <0.0001). Additional IOP-lowering surgery was required in 9%. In multivariate regression analysis adjusting for age, gender, and number of prior surgeries, patients with glaucoma other than primary open-angle glaucoma were twice as likely to have failed bleb revision. CONCLUSIONS: Surgical bleb revision often provides successful resolution of bleb-related complications. Most patients maintain IOP control without need for further IOP-lowering surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Risk indicators associated with root decay in independently living older adults

Objective: To determine the risk indicators associated with root caries experience in a cohort of independently living older adults in Ireland.
Methods: The data reported in the present study were obtained from a prospective longitudinal study conducted on the risk factors associated with root caries incidence in a cohort of independently living older adults (n=334). Each subject underwent an oral examination, performed by a single calibrated examiner, to determine the root caries index and other clinical variables. Questionnaires were used to collect data on oral hygiene habits, diet, smoking and alcohol habits and education level. A regression analysis with the outcome variable of root caries experience (no/yes) was conducted.
Results: A total of 334 older adults with a mean age of 69.1 years were examined. 53.3% had at least one filled or decayed root surface. The median root caries index was 3.13 (IQR 0.00, 13.92). The results from the multivariate regression analysis indicated that individuals with poor plaque control (OR 9.59, 95%CI 3.84-24.00), xerostomia (OR 18.49, 95%CI 2.00-172.80), two or more teeth with coronal decay (OR 4.50, 95% CI 2.02-10.02) and 37 or more exposed root surfaces (OR 5.48, 95% CI 2.49-12.01) were more likely to have been affected by root caries.
Conclusions: The prevalence of root caries was high in this cohort. This study suggests a correlation between root caries and the variables poor plaque control, xerostomia, coronal decay (≥2 teeth affected) and exposed root surfaces (≥37). The significance of these risk indicators and the resulting prediction model should be further evaluated in a prospective study of root caries incidence.
Clinical Significance: Identification of risk indicators for root caries in independently living older adults would facilitate dental practitioners to identify those who would benefit most from interventions aimed at prevention.