Prostaglandin e2 receptors in abdominal aortic aneurysm and human aortic smooth muscle cells

AbstractBackgroundProstaglandin (PG) E2 (PGE2) appears to have a role in stimulating production of interleukin-6 (IL-6) and apoptosis of smooth muscle cells in diseased aortic tissue. These actions are mediated by cellular receptors for PGE2 EP receptors.ObjectiveThis study was undertaken to identify EP receptors associated with production of IL-6 by aortic explants.MethodsBiopsy specimens of abdominal aortic aneurysm were used for explant culture and preparation of messenger RNA. The presence of EP1, EP2, EP3, and EP4 receptors in tissue and cells was investigated with reverse-transcriptase polymerase chain reaction. IL-6 and cyclic adenosine monophosphate were measured with an enzyme-linked immunosorbent assay.ResultsPGE2 or 11-deoxy-PGE1 (EP 2/3/4 agonist) reversed partially the indomethacin suppression of IL-6 secretion from explant cultures, whereas butaprost (EP2 receptor agonist) and sulprostone (EP 1/3 receptor agonist) had no effect. Aortic biopsy specimens expressed EP2, EP3-III, and EP4 receptors. Aortic smooth muscle cells expressed EP2 receptor and four variants of EP3 receptor, ie, EP3-Ib, EP3-II, EP3-III, and EP3-IV, but PGE2 did not stimulate secretion of IL-6. In contrast, PGE2 or 11-deoxy-PGE1 stimulated secretion of IL-6 from aortic macrophages.ConclusionsIn aortic explants, PGE2 stimulates IL-6 secretion by activation of EP4 receptors, present in macrophages

Psychometric precision in phenotype definition is a useful step in molecular genetic investigation of psychiatric disorders

Affective disorders are highly heritable, but few genetic risk variants have been consistently replicated in molecular genetic association studies. The common method of defining psychiatric phenotypes in molecular genetic research is either a summation of symptom scores or binary threshold score representing the risk of diagnosis. Psychometric latent variable methods can improve the precision of psychiatric phenotypes, especially when the data structure is not straightforward. Using data from the British 1946 birth cohort, we compared summary scores with psychometric modeling based on the General Health Questionnaire (GHQ-28) scale for affective symptoms in an association analysis of 27 candidate genes (249 single-nucleotide polymorphisms (SNPs)). The psychometric method utilized a bi-factor model that partitioned the phenotype variances into five orthogonal latent variable factors, in accordance with the multidimensional data structure of the GHQ-28 involving somatic, social, anxiety and depression domains. Results showed that, compared with the summation approach, the affective symptoms defined by the bi-factor psychometric model had a higher number of associated SNPs of larger effect sizes. These results suggest that psychometrically defined mental health phenotypes can reflect the dimensions of complex phenotypes better than summation scores, and therefore offer a useful approach in genetic association investigations

Deroceras panormitanum and congeners from Malta and Sicily, with a redescription of the widespread pest slug as Deroceras invadens n. sp.

The name Deroceras panormitanum is generally applied to a terrestrial slug that has spread worldwide and can be a pest; earlier this tramp species had been called Deroceras caruanae. Neither name is appropriate. The taxonomic descriptions apply to a species from Sicily and Malta. This true D. panormitanum and the tramp species are distinct in morphology and mating behaviour. For instance, the penial caecum of D. panormitanum is more pointed, everting faster at copulation. The size of the penial lobe varies considerably in preserved specimens but is always prominent at copulation. D. panormitanum is distinct from the Maltese endemic Deroceras golcheri, but a phylogeny based on mtDNA COI sequences implies that they are more closely related than is the tramp species. D. golcheri has a still closer counterpart on Sicily, but we leave the taxonomy of this species X unresolved. In interspecific crosses, D. panormitanum may transfer sperm to the partner's sarcobelum whereas the partner fails to evert its penis (D. golcheri) or to transfer sperm (the tramp species). Names previously applied to the tramp species originally referred to D. panormitanum or are otherwise invalid, so it is here formally redescribed as D. invadens. Deroceras giustianum Wiktor, 1998 is synonymised with D. panormitanum

Flagging greens: hydrobiid snails as substrata for the development of green algal mats (Enteromorpha spp.) on tidal flats of North Atlantic coasts

During the past 3 decades, dense mats of green algae (especially Enteromorpha spp.) have been recorded regularly from tidal flats worldwide. The development of green algal mats on tidal flats may be initiated by overwintering and regrowth of adult plants or by the formation and release of small propagules, i.e. vegetative fragments, zoospores and zygotes. On soft sediments, macroinvertebrates may constitute prime substrata for germination of algal spores. Hydrobud (mud-) snails are widespread along North Atlantic soft sediment shores and were identified previously as important substrata for Enteromorpha spp. germlings in 1 of our study areas. To test the generality of this phenomenon, we investigated the presence of Enteromorpha spp. gerrnlings attached to hydrobud snails from November 1995 to December 1996 on 6 tidal flats of North Atlantic coasts (Tralebergslule, Sweden; Konigshafen Bay, Germany; Mondego Estuary, Portugal; Ria Formosa, Portugal; Cole Harbour, Nova Scotia, Canada; Lowes Cove, Maine, USA). With 1 exception, hydrobiid snails were present in all areas studied, and intensive growth of Enteromorpha spp. occurred during summer. Throughout winter 1995/96, hardly any Enteromorpha spp. gerrnlings were found on snail shells, but over the following months germlings developed on up to 60% of the hydrobiid snails present. In 2 areas (Konigshafen, Germany; Lowes Cove, USA), germhng abundance on hydrobuds began to rise before the peak of green algal mat development. In Tralebergskile, Sweden, high mat abundance occurred simultaneous to and after increased germling abundance on Hydrobia ulvae. Densities of snails were very low, however, and hydrobuds appeared to be unimportant as substratum. No clear temporal pattern between high germling abundance on snails followed by mat development was found in the other 3 study areas (Ria Formosa, Portugal; Mondego Estuary, Portugal; Cole Harbour, Canada). In Lowes Cove, USA, gerrnlings and juveniles of Enteromorpha spp. first grew at the site with high Hydrobia abundance and were subsequently drifted to another site where they developed into full mats. We conclude that initiation of green algal mats by germination on Hydrobia spp. may be a general phenomenon, but that other modes of development also occur frequently. Pelagic dnft of overwintering thalli to new sites, followed by prolific growth, might be of similar or greater importance

Quality-of-life assessment in dementia: the use of DEMQOL and DEMQOL-Proxy total scores

Purpose There is a need to determine whether health-related quality-of-life (HRQL) assessments in dementia capture what is important, to form a coherent basis for guiding research and clinical and policy decisions. This study investigated structural validity of HRQL assessments made using the DEMQOL system, with particular interest in studying domains that might be central to HRQL, and the external validity of these HRQL measurements. Methods HRQL of people with dementia was evaluated by 868 self-reports (DEMQOL) and 909 proxy reports (DEMQOL-Proxy) at a community memory service. Exploratory and confirmatory factor analyses (EFA and CFA) were conducted using bifactor models to investigate domains that might be central to general HRQL. Reliability of the general and specific factors measured by the bifactor models was examined using omega (?) and omega hierarchical (? h) coefficients. Multiple-indicators multiple-causes models were used to explore the external validity of these HRQL measurements in terms of their associations with other clinical assessments. Results Bifactor models showed adequate goodness of fit, supporting HRQL in dementia as a general construct that underlies a diverse range of health indicators. At the same time, additional factors were necessary to explain residual covariation of items within specific health domains identified from the literature. Based on these models, DEMQOL and DEMQOL-Proxy overall total scores showed excellent reliability (? h > 0.8). After accounting for common variance due to a general factor, subscale scores were less reliable (? h < 0.7) for informing on individual differences in specific HRQL domains. Depression was more strongly associated with general HRQL based on DEMQOL than on DEMQOL-Proxy (?0.55 vs ?0.22). Cognitive impairment had no reliable association with general HRQL based on DEMQOL or DEMQOL-Proxy. Conclusions The tenability of a bifactor model of HRQL in dementia suggests that it is possible to retain theoretical focus on the assessment of a general phenomenon, while exploring variation in specific HRQL domains for insights on what may lie at the ‘heart’ of HRQL for people with dementia. These data suggest that DEMQOL and DEMQOL-Proxy total scores are likely to be accurate measures of individual differences in HRQL, but that subscale scores should not be used. No specific domain was solely responsible for general HRQL at dementia diagnosis. Better HRQL was moderately associated with less depressive symptoms, but this was less apparent based on informant reports. HRQL was not associated with severity of cognitive impairment

Electronic Health Literacy Across the Lifespan: Measurement Invariance Study

Background: Electronic health (eHealth) information is ingrained in the healthcare experience to engage patients across the lifespan. Both eHealth accessibility and optimization are influenced by lifespan development, as older adults experience greater challenges accessing and using eHealth tools as compared to their younger counterparts. The eHealth Literacy Scale (eHEALS) is the most popular measure used to assess patient confidence locating, understanding, evaluating, and acting upon online health information. Currently, however, the factor structure of the eHEALS across discrete age groups is not well understood, which limits its usefulness as a measure of eHealth literacy across the lifespan. Objective: The purpose of this study was to examine the structure of eHEALS scores and the degree of measurement invariance among US adults representing the following generations: Millennials (18-35-year-olds), Generation X (36-51-year-olds), Baby Boomers (52-70-year-olds), and the Silent Generation (71-84-year-olds). Methods: Millennials (N=281, mean 26.64 years, SD 5.14), Generation X (N=164, mean 42.97 years, SD 5.01), and Baby Boomers/Silent Generation (N=384, mean 62.80 years, SD 6.66) members completed the eHEALS. The 3-factor (root mean square error of approximation, RMSEA=.06, comparative fit index, CFI=.99, Tucker-Lewis index, TLI=.98) and 4-factor (RMSEA=.06, CFI=.99, TLI=.98) models showed the best global fit, as compared to the 1- and 2-factor models. However, the 4-factor model did not have statistically significant factor loadings on the 4th factor, which led to the acceptance of the 3-factor eHEALS model. The 3-factor model included eHealth Information Awareness, Search, and Engagement. Pattern invariance for this 3-factor structure was supported with acceptable model fit (RMSEA=.07, Δχ2=P>.05, ΔCFI=0). Compared to Millennials and members of Generation X, those in the Baby Boomer and Silent Generations reported less confidence in their awareness of eHealth resources (P<.001), information seeking skills (P=.003), and ability to evaluate and act on health information found on the Internet (P<.001). Results: Young (18-48-year olds, N=411) and old (49-84-year olds, N=419) adults completed the survey. A 3-factor model had the best fit (RMSEA=.06, CFI=.99, TLI=.98), as compared to the 1-factor, 2-factor, and 4-factor models. These 3-factors included eHealth Information Awareness (2 items), Information Seeking (2 items), and Information and Evaluation (4 items). Pattern invariance was supported with the acceptable model fit (RMSEA=.06, Δχ2=P>.05, ΔCFI=0). Compared with younger adults, older adults had less confidence in eHealth resource awareness (P<.001), information seeking skills (P<.01), and ability to evaluate and act upon online health information (P<.001). Conclusions: The eHEALS can be used to assess, monitor uniquely, and evaluate Internet users’ awareness of eHealth resources, information seeking skills, and engagement abilities. Configural and pattern invariance was observed across all generation groups in the 3-factor eHEALS model. To meet gold the standards for factor interpretation (ie, 3 items or indicators per factor), future research is needed to create and assess additional eHEALS items. Future research is also necessary to identify and test items for a fourth factor, one that captures the social nature of eHealth

The 12-item World Health Organization Disability Assessment Schedule II (WHO-DAS II): a nonparametric item response analysis

<p>Abstract</p> <p>Background</p> <p>Previous studies have analyzed the psychometric properties of the World Health Organization Disability Assessment Schedule II (WHO-DAS II) using classical omnibus measures of scale quality. These analyses are sample dependent and do not model item responses as a function of the underlying trait level. The main objective of this study was to examine the effectiveness of the WHO-DAS II items and their options in discriminating between changes in the underlying disability level by means of item response analyses. We also explored differential item functioning (DIF) in men and women.</p> <p>Methods</p> <p>The participants were 3615 adult general practice patients from 17 regions of Spain, with a first diagnosed major depressive episode. The 12-item WHO-DAS II was administered by the general practitioners during the consultation. We used a non-parametric item response method (Kernel-Smoothing) implemented with the TestGraf software to examine the effectiveness of each item (item characteristic curves) and their options (option characteristic curves) in discriminating between changes in the underliying disability level. We examined composite DIF to know whether women had a higher probability than men of endorsing each item.</p> <p>Results</p> <p>Item response analyses indicated that the twelve items forming the WHO-DAS II perform very well. All items were determined to provide good discrimination across varying standardized levels of the trait. The items also had option characteristic curves that showed good discrimination, given that each increasing option became more likely than the previous as a function of increasing trait level. No gender-related DIF was found on any of the items.</p> <p>Conclusions</p> <p>All WHO-DAS II items were very good at assessing overall disability. Our results supported the appropriateness of the weights assigned to response option categories and showed an absence of gender differences in item functioning.</p