Efficacy of Intra-arterial Norcantharidin in Suppressing Tumour 14C-labelled Glucose Oxidative Metabolism in rat Morris Hepatoma

Norcantharidin is the demethylated form of Cantharidin, which is the active ingredient of the blister beetle, Mylabris, a long used Chinese traditional medicine. Though not well publicised outside China, Norcantharidin is known to possess significant anti-hepatoma activity, and is relatively free from side effects. In the present study, glucose oxidation in tumour and liver tissue slices harvested from hepatomabearing animals was quantified by measuring the radioactivity of 14C-labelled CO released from 14C-glucose in oxygen-enriched incubation medium. Results were expressed asa tumour/liver ratio. For comparison, treatments with Norcantharidin, Adriamycin and with hepatic artery ligation were studied. The mean tumour/liver ratio was 4.2+2.2 in untreated controls, but dropped significantly to 2.3+0.5 (p<0.05) with intra-arterial Norcantharidin (0.5 mg/kg) and to 2.3+0.7 (p<0.05) with intra-arterial Adriamycin (2.4 mg/kg), and to 2.2+0.7 (p<0.05) with hepatic artery ligation. However, with intravenous Adriamycin at 2.4 mg/kg, the mean tumour/liver ratio was reduced to only 3.5+2.0 and was not significantly different from untreated controls. It is concluded that intra-arterial Norcantharidin is as effective as intraarterial Adriamycin and hepatic artery ligation in suppressing tumour glucose oxidative metabolism. These results imply that Norcantharidin may have a role to play in the chemotherapy ofprimary livercancer

The HIV Genomic Incidence Assay Meets False Recency Rate and Mean Duration of Recency Infection Performance Standards.

HIV incidence is a primary metric for epidemic surveillance and prevention efficacy assessment. HIV incidence assay performance is evaluated via false recency rate (FRR) and mean duration of recent infection (MDRI). We conducted a meta-analysis of 438 incident and 305 chronic specimens' HIV envelope genes from a diverse global cohort. The genome similarity index (GSI) accurately characterized infection stage across diverse host and viral factors. All except one chronic specimen had GSIs below 0.67, yielding a FRR of 0.33 [0-0.98] %. We modeled the incidence assay biomarker dynamics with a logistic link function assuming individual variabilities in a Beta distribution. The GSI probability density function peaked close to 1 in early infection and 0 around two years post infection, yielding MDRI of 420 [361, 467] days. We tested the assay by newly sequencing 744 envelope genes from 59 specimens of 21 subjects who followed from HIV negative status. Both standardized residuals and Anderson-Darling tests showed that the test dataset was statistically consistent with the model biomarker dynamics. This is the first reported incidence assay meeting the optimal FRR and MDRI performance standards. Signatures of HIV gene diversification can allow precise cross-sectional surveillance with a desirable temporal range of incidence detection

The Dawn of Open Access to Phylogenetic Data

The scientific enterprise depends critically on the preservation of and open access to published data. This basic tenet applies acutely to phylogenies (estimates of evolutionary relationships among species). Increasingly, phylogenies are estimated from increasingly large, genome-scale datasets using increasingly complex statistical methods that require increasing levels of expertise and computational investment. Moreover, the resulting phylogenetic data provide an explicit historical perspective that critically informs research in a vast and growing number of scientific disciplines. One such use is the study of changes in rates of lineage diversification (speciation - extinction) through time. As part of a meta-analysis in this area, we sought to collect phylogenetic data (comprising nucleotide sequence alignment and tree files) from 217 studies published in 46 journals over a 13-year period. We document our attempts to procure those data (from online archives and by direct request to corresponding authors), and report results of analyses (using Bayesian logistic regression) to assess the impact of various factors on the success of our efforts. Overall, complete phylogenetic data for ~60% of these studies are effectively lost to science. Our study indicates that phylogenetic data are more likely to be deposited in online archives and/or shared upon request when: (1) the publishing journal has a strong data-sharing policy; (2) the publishing journal has a higher impact factor, and; (3) the data are requested from faculty rather than students. Although the situation appears dire, our analyses suggest that it is far from hopeless: recent initiatives by the scientific community -- including policy changes by journals and funding agencies -- are improving the state of affairs

Older Aboriginal Australians' Health Concerns and Preferences for Healthy Ageing Programs.

While there is strong evidence of the need for healthy ageing programs for older Aboriginal Australians, few are available. It is important to understand older Aboriginal Australians' perspectives on healthy ageing in order to co-design culturally-appropriate programs, including views on technology use in this context. Semi-structured interviews were conducted with 34 Aboriginal Australians aged 50 years and older from regional and urban communities to explore participants' health concerns, preferences for healthy ageing programs, and receptiveness to technology. Qualitative data were analyzed using a grounded theory approach. This study found that older Aboriginal Australians are concerned about chronic health conditions, social and emotional well-being, and difficulties accessing health services. A range of barriers and enablers to participation in current health programs were identified. From the perspective of older Aboriginal people, a successful healthy ageing program model includes physical and cognitive activities, social interaction, and health education. The program model also provides culturally safe care and transport for access as well as family, community, cultural identity, and empowerment regarding ageing well as central tenets. Technology could also be a viable approach for program delivery. These findings can be applied in the implementation and evaluation of culturally-appropriate, healthy ageing programs with older Aboriginal people

CT-guided intratumoural administration of cisplatin/epinephrine gel for treatment of malignant liver tumours

To analyze prospectively the interventional and clinical aspects of computed tomography-guided direct intratumoural injection of a novel chemotherapeutic administration and the parenchymal changes of tumour and necrosis in malignant liver tumours. Eight patients with 17 colorectal liver metastases were treated with a mean of 5.1 injections and nine patients with 13 hepatocellular carcinoma nodules with a mean of 3.1 treatments with computed tomography guided local applications of a novel cisplatin/epinephrine gel. This application provides a higher local and lower systemic drug concentration. Volumes of tumour and necrosis prior and after treatment were measured by computer generated volumetric analysis. Contrast enhanced studies verified pretherapeutic viable tumour volumes with a value of 77.4 ml in the metastases and 29.2 ml in the hepatocellular carcinoma nodules. Intratumoural drug application resulted in a significant increase of necrosis and a decrease in viable tumour volume to be 68.3 ml in metastases and 14.5 ml in hepatocellular carcinoma. Local therapy control rate for the follow up to 6 months was 38 and 71% for the group of metastases and hepatocellular carcinoma, respectively. Direct intratumoural injection of cisplatin/epinepthrine injectable gel is a feasible and good tolerated method and results in the development of a statistically significant increase in necrosis in malignant liver tumours. For hepatocellular carcinoma a higher local therapy control rate compared to colorectal metastases can be reported

Oral health service utilization by elderly beneficiaries of the Mexican Institute of Social Security in México city

<p>Abstract</p> <p>Background</p> <p>The aging population poses a challenge to Mexican health services. The aim of this study is to describe recent oral health services utilization and its association with socio-demographic characteristics and co-morbidity in Mexican Social Security beneficiaries 60 years and older.</p> <p>Methods</p> <p>A sample of 700 individuals aged 60+ years was randomly chosen from the databases of the Mexican Institute of Social Security (IMSS). These participants resided in the southwest of Mexico City and made up the final sample of a cohort study for identifying risk factors for root caries in elderly patients. Sociodemographic variables, presence of cognitive decline, depression, morbidity, medication consumption, and utilization of as well as reasons for seeking oral health services within the past 12 months were collected through a questionnaire. Clinical oral assessments were carried out to determine coronal and root caries experience.</p> <p>Results</p> <p>The sample consisted of 698 individuals aged 71.6 years on average, of whom 68.3% were women. 374 participants (53.6%) had made use of oral health services within the past 12 months. 81% of those who used oral health services sought private medical care, 12.8% sought social security services, and 6.2% public health services. 99.7% had experienced coronal caries and 44.0% root caries. Female sex (OR = 2.0), 6 years' schooling or less (OR = 1.4), and caries experience in more than 22 teeth (OR = 0.6) are factors associated with the utilization of these services.</p> <p>Conclusion</p> <p>About half the elderly beneficiaries of social security have made use of oral health services within the past 12 months, and many of them have to use private services. Being a woman, having little schooling, and low caries experience are factors associated with the use of these services.</p

Of Asian Forests and European Fields: Eastern U.S. Plant Invasions in a Global Floristic Context

Background: Biogeographic patterns of species invasions hold important clues to solving the recalcitrant ‘who’, ‘where’, and ‘why ’ questions of invasion biology, but the few existing studies make no attempt to distinguish alien floras (all non-native occurrences) from invasive floras (rapidly spreading species of significant management concern), nor have invasion biologists asked whether particular habitats are consistently invaded by species from particular regions. Methodology/Principal Findings: Here I describe the native floristic provenances of the 2629 alien plant taxa of the Eastern Deciduous Forest of the Eastern U.S. (EUS), and contrast these to the subset of 449 taxa that EUS management agencies have labeled ‘invasive’. Although EUS alien plants come from all global floristic regions, nearly half (45%) have native ranges that include central and northern Europe or the Mediterranean (39%). In contrast, EUS invasive species are most likely to come from East Asia (29%), a pattern that is magnified when the invasive pool is restricted to species that are native to a single floristic region (25 % from East Asia, compared to only 11 % from northern/central Europe and 2 % from the Mediterranean). Moreover, East Asian invaders are mostly woody (56%, compared to just 23 % of the total alien flora) and are significantly more likely to invade intact forests and riparian areas than European species, which dominate managed or disturbed ecosystems. Conclusions/Significance: These patterns suggest that the often-invoked ‘imperialist dogma ’ view of global invasion

PIAS1 regulates CP2c localization and active promoter complex formation in erythroid cell-specific α-globin expression

Data presented here extends our previous observations on α-globin transcriptional regulation by the CP2 and PIAS1 proteins. Using RNAi knockdown, we have now shown that CP2b, CP2c and PIAS1 are each necessary for synergistic activation of endogenous α-globin gene expression in differentiating MEL cells. In this system, truncated PIAS1 mutants lacking the ring finger domain recruited CP2c to the nucleus, as did wild-type PIAS1, demonstrating that this is a sumoylation-independent process. In vitro, recombinant CP2c, CP2b and PIAS1 bound DNA as a stable CBP (CP2c/CP2b/PIAS1) complex. Following PIAS1 knockdown in MEL cells, however, the association of endogenous CP2c and CP2b with the α-globin promoter simultaneously decreased. By mapping the CP2b- and CP2c-binding domains on PIAS1, and the PIAS1-binding domains on CP2b and CP2c, we found that two regions of PIAS1 that interact with CP2c/CP2b are required for its co-activator function. We propose that CP2c, CP2b, and PIAS1 form a hexametric complex with two units each of CP2c, CP2b, and PIAS1, in which PIAS1 serves as a clamp between two CP2 proteins, while CP2c binds directly to the target DNA and CP2b mediates strong transactivation

Using Mitochondrial and Nuclear Sequence Data for Disentangling Population Structure in Complex Pest Species: A Case Study with Dermanyssus gallinae

Among global changes induced by human activities, association of breakdown of geographical barriers and impoverishered biodiversity of agroecosystems may have a strong evolutionary impact on pest species. As a consequence of trade networks' expansion, secondary contacts between incipient species, if hybrid incompatibility is not yet reached, may result in hybrid swarms, even more when empty niches are available as usual in crop fields and farms. By providing important sources of genetic novelty for organisms to adapt in changing environments, hybridization may be strongly involved in the emergence of invasive populations