Comparative phytochemical investigation of Salvia miltiorrhiza and Salvia triloba

From the aerial parts of Chinese Salvia miltiorrhiza Bunge a novel sesquiterpene (1), which possesses a rare substitution pattern, together with seven known abietane type diterpenes has been isolated. Structure 1 was elucidated on the basis of spectral analysis, including 2D-NMR spectroscopy, especially long range 1H-13C correlation (COLOC). At the same time royleanone, 7alpha-acetoxyroyleanone, and sugiol were identified for the first time from the roots of Salvia triloba L. f.     

Diffusion parameter mapping with the combined intravoxel incoherent motion and kurtosis model using artificial neural networks at 3 T

Artificial neural networks (ANNs) were used for voxel‐wise parameter estimation with the combined intravoxel incoherent motion (IVIM) and kurtosis model facilitating robust diffusion parameter mapping in the human brain. The proposed ANN approach was compared with conventional least‐squares regression (LSR) and state‐of‐the‐art multi‐step fitting (LSR‐MS) in Monte‐Carlo simulations and in vivo in terms of estimation accuracy and precision, number of outliers and sensitivity in the distinction between grey (GM) and white (WM) matter. Both the proposed ANN approach and LSR‐MS yielded visually increased parameter map quality. Estimations of all parameters (perfusion fraction f, diffusion coefficient D, pseudo‐diffusion coefficient D*, kurtosis K) were in good agreement with the literature using ANN, whereas LSR‐MS resulted in D* overestimation and LSR yielded increased values for f and D*, as well as decreased values for K. Using ANN, outliers were reduced for the parameters f (ANN, 1%; LSR‐MS, 19%; LSR, 8%), D* (ANN, 21%; LSR‐MS, 25%; LSR, 23%) and K (ANN, 0%; LSR‐MS, 0%; LSR, 15%). Moreover, ANN enabled significant distinction between GM and WM based on all parameters, whereas LSR facilitated this distinction only based on D and LSR‐MS on f, D and K. Overall, the proposed ANN approach was found to be superior to conventional LSR, posing a powerful alternative to the state‐of‐the‐art method LSR‐MS with several advantages in the estimation of IVIM–kurtosis parameters, which might facilitate increased applicability of enhanced diffusion models at clinical scan times.     

A role for dynamin in triggering ethanol tolerance

Background: A prevailing hypothesis is that the set of genes that underlie the endophenotypes of alcoholism overlap with those responsible for the addicted state. Functional ethanol tolerance, an endophenotype of alcoholism, is defined as a reduced response to ethanol caused by prior ethanol exposure. The neuronal origins of functional rapid tolerance are thought to be a homeostatic response of the nervous system that counters the effects of the drug. Synaptic proteins that regulate neuronal activity are an important evolutionarily conserved target of ethanol. Methods: We used mutant analysis in Drosophila to identify synaptic proteins that are important for the acquisition of rapid tolerance to sedation with ethanol. Tolerance was assayed by sedating flies with ethanol vapor and comparing the recovery time of flies after their first sedation and their second sedation. Temperature‐sensitive paralytic mutants that alter key facets of synaptic neurotransmission, such as the propagation of action potentials, synaptic vesicle fusion, exocytosis, and endocytosis, were tested for the ability to acquire functional tolerance at both the permissive and restrictive temperatures. Results: The shibire gene encodes Drosophila Dynamin. We tested 2 temperature‐sensitive alleles of the gene. The shi^ts1 allele blocked tolerance at both the permissive and restrictive temperatures, while shi^ts2 blocked only at the restrictive temperature. Using the temperature‐sensitive property of shi^ts2, we showed that Dynamin function is required concomitant with exposure to ethanol. A temperature‐sensitive allele of the Syntaxin 1A gene, Syx1A^3–69, also blocked the acquisition of ethanol tolerance. Conclusions: We have shown that shibire and Syntaxin 1A are required for the acquisition of rapid functional tolerance to ethanol. Furthermore, the shibire gene product, Dynamin, appears to be required for an immediate early response to ethanol that triggers a cellular response leading to rapid functional tolerance.     

Combined activation and deactivation of visual cortex during tactile sensory processing

The involvement of occipital cortex in sensory processing is not restricted solely to the visual modality. Tactile processing has been shown to modulate higher-order visual and multisensory integration areas in sighted as well as visually deprived subjects; however, the extent of involvement of early visual cortical areas remains unclear. To investigate this issue, we employed functional magnetic resonance imaging in normally sighted, briefly blindfolded subjects with well-defined visuotopic borders as they tactually explored and rated raised-dot patterns. Tactile task performance resulted in significant activation in primary visual cortex (V1) and deactivation of extrastriate cortical regions V2, V3, V3A, and hV4 with greater deactivation in dorsal subregions and higher visual areas. These results suggest that tactile processing affects occipital cortex via two distinct pathways: a suppressive top-down pathway descending through the visual cortical hierarchy and an excitatory pathway arising from outside the visual cortical hierarchy that drives area V1 directly.     

The cellular HIV-1 Rev cofactor hRIP is required for viral replication

An important goal of contemporary HIV type 1 (HIV-1) research is to identify cellular cofactors required for viral replication. The HIV-1 Rev protein facilitates the cytoplasmic accumulation of the intron-containing viral gag-pol and env mRNAs and is required for viral replication. We have previously shown that a cellular protein, human Rev-interacting protein (hRIP), is an essential Rev cofactor that promotes the release of incompletely spliced HIV-1 RNAs from the perinuclear region. Here, we use complementary genetic approaches to ablate hRIP activity and analyze HIV-1 replication and viral RNA localization. We find that ablation of hRIP activity by a dominant-negative mutant or RNA interference inhibits virus production by mislocalizing Rev-directed RNAs to the nuclear periphery. We further show that depletion of endogenous hRIP by RNA interference results in the loss of viral replication in human cell lines and primary macrophages; virus production was restored to wild-type levels after reintroduction of hRIP protein. Taken together, our results indicate that hRIP is an essential cellular cofactor for Rev function and HIV-1 replication. Because hRIP is not required for cell viability, it may be an attractive target for the development of new antiviral strategies.     

Tailored versus general information on early detection of cancer: a comparison of the reactions of Dutch adults and the impact on attitudes and behaviors

This article describes the process evaluation of two interventions (tailored or general information) to encourage people to behave in a manner conducive to the early detection of cancer. A total of 1040 Dutch adults participated in the study. Tailored information is adapted to the characteristics, needs and interests of the individual, and hence has more personal relevance and contains less redundant information. It was therefore hypothesized that tailored information would be evaluated better than general information, does not increase worries, influences attitude and behavior change, and that no differences in subgroups would be found in the reactions to the tailored information. The results showed that both kinds of information were read by a large majority of the participants. Recipients of the tailored information saved and discussed the information with others more often, and they were more appreciative of its format and content. Tailored information resulted significantly more often in changes in attitudes and behavior after the intervention. It is concluded that information adapted to individuals' characteristics is an accepted method of health education in early detection of cancer.     

13C-labelling of xanthohumol in hop cones (Humulus lupulus)

Biolabelling conditions in hop cones of xanthohumol (Xn) were studied by feeding [U-13C]glucose, [1-13C]glucose, [ring-13C6]phenylalanine, [2-13C]sodium acetate or [2-13C]malonic acid as biosynthetic precursors to hop sprouts. Quantitative 13C-NMR spectroscopic analysis of the resulting labelled Xn showed different labelling patterns and ratios depending on precursor and feeding concentrations. The highest incorporation rate was achieved with [U-13C]glucose (9.41 +/- 1.22 %). With [ring-13C6]phenylalanine only ring B was labelled (3.51 +/- 0.08 % enrichment). [2-13C]sodium acetate and [2-13C]malonic acid allowed labelling of the A-ring (1.82 +/- 0.02 % and 1.74 +/- 0.03 % enrichment). The specific labelling pattern of the prenyl side chain with [1-13C]glucose (2.36 +/- 0.27 % enrichment) confirmed the biosynthetic origin to be MEP pathway-derived. On the basis of these results radiolabelling of Xn will be performed for in vivo bioavailability studies.     

Determinants of forward stage transition from precontemplation and contemplation for fruit consumption

PURPOSE: To examine associations between decisional balance, self-efficacy, fruit intake, and stage of change transition from precontemplation and contemplation with cross-sectional and longitudinal methods. DESIGN: A longitudinal cohort study with the use of electronic questionnaires was conducted. Three measurements were analyzed cross-sectionally, and the two intervals between the measurements were analyzed longitudinally. SETTING: A random sample of 1500 individuals from an existing Dutch Internet panel resulted in a cohort of 735 individuals. Of the cohort, 648 (response rate 88%), 592 (response rate 81%), and 570 (response rate 78%) respondents completed questionnaires at the start of the present study (T1), 53 days after T1 (T2), and 106 days after T1 (T3), respectively. SUBJECTS: Mean age was 37.5 years, 51% were women, and 57% ate less than the recommended intake of 250 g of fruit per day. MEASURES: Questionnaires included items measuring stage of change, factors favoring (pros) or working against (cons) behavior change, and self-efficacy. A food frequency questionnaire was used to assess fruit intake. RESULTS: Logistic regression analyses showed that pros, fruit intake, and self-efficacy predicted forward stage transition from precontemplation. Self-efficacy predicted forward stage transition from contemplation. Cons did not predict stage transitions. Results from longitudinal analyses were similar to cross-sectional results, except for self-efficacy: no differences between early stages in self-efficacy were found, whereas self-efficacy predicted these early stage transitions. CONCLUSIONS: Within the limitations posed by the sampling frame, results provided support for the Transtheoretical Model, although determinants might not always be stage specific.     

SARS: a quality management test of our public health safety net

Emergence of severe acute respiratory syndrome in March 2003 tested all aspects of BC Centre for Disease Control (BCCDC) operations. In addition to its public health responsibilities, BCCDC was pivotal in the science defining SARS. These events occurred under international scientific and media scrutiny over a 4-month period and were seen as an opportunity to learn about how the Centre performed under extreme pressure as a QM-based (quality-management-based) organization. A retrospective review of the QM practices over the previous 6-months was initiated on June 30, 2003. Key management documentation during the study period was reviewed. Structured interviews were conducted with front line personnel. Customized instrumentation was developed to correlate management decisions with recognized QM criteria: anticipatory management; keeping programs on track; ongoing adjustment, improvement, and revision; identifying and improving sources of error, waste, and redundancy; feedback from key stakeholders; and data-driven decision-making methods. The team structure between laboratory science and epidemiology was critical. This was attributed to the culture of scientific discovery of the organization. All knowledge gained was shared with other organizations around the world. The consensus is that British Columbia was very lucky this time around. This review is part of BCCDC's commitment to fighting emerging infectious diseases.     

Social psychological correlates of paying attention to cancer symptoms and seeking medical help

Social psychological correlates of two main aspects of the process of cancer detection, viz. passive detection (i.e., paying attention to cancer symptoms) and help-seeking intention, were studied among a-symptomatic Dutch adults. Two written questionnaires, with a six-week interval, identified correlates of both variables, using a determinant model based on the theory of planned behavior. Knowledge, advantages, self-efficacy, being female and being more highly educated were associated with passive detection. Knowledge, advantages, moral obligation, anticipated regret, social norm, and self-efficacy were correlated with the intention to seek help. We suggest that educational programs need to address the two variables separately and also need to tailor their content to the various social psychological correlates of these two aspects.