Dental general anaesthetic receipt among Australians aged 15+ years, 1998–1999 to 2004–2005

Background Adults receive dental general anaesthetic (DGA) care when standard dental treatment is not possible. Receipt of DGA care is resource-intensive and not without risk. This study explores DGA receipt among 15+-year-old Australians by a range of risk indicators. Methods DGA data were obtained from Australia's Hospital Morbidity Database from 1998–1999 to 2004–2005. Poisson regression modeling was used to examine DGA rates in relation to age, sex, Indigenous status, location and procedure. Results The overall DGA rate was 472.79 per 100,000 (95% CI 471.50–474.09). Treatment of impacted teeth (63.7%) was the most common reason for DGA receipt, followed by dental caries treatment (12.4%), although marked variations were seen by age-group. After adjusting for other covariates, DGA rates among 15–19-year-olds were 13.20 (95% CI 12.65–13.78) times higher than their 85+-year-old counterparts. Females had 1.46 (95% CI 1.45–1.47) times the rate of their male counterparts, while those living in rural/remote areas had 2.70 (95% CI 2.68–2.72) times the rate of metropolitan-dwellers. DGA rates for non-Indigenous persons were 4.88 (95% CI 4.73–5.03) times those of Indigenous persons. The DGA rate for 1+ extractions was 461.9 per 100,000 (95% CI 460.6–463.2), compared with a rate of 23.6 per 100,000 (95% CI 23.3–23.9) for 1+ restorations. Conclusion Nearly two-thirds of DGAs were for treatment of impacted teeth. Persons aged 15–19 years were disproportionately represented among those receiving DGA care, along with females, rural/remote-dwellers and those identifying as non-Indigenous. More research is required to better understand the public health implications of DGA care among 15+-year-olds, and how the demand for receipt of such care might be reduced.Lisa M Jamieson and Kaye F Roberts-Thomso

Pharmacological targeting of apelin impairs glioblastoma growth

Glioblastoma are highly aggressive brain tumours that are associated with an extremely poor prognosis. Within these tumours, a subpopulation of highly plastic self-renewing cancer cells exist that retain the ability to expand ex vivo as tumourspheres, induce tumour growth in mice, and have been implicated in radio- and chemo-resistance. Although their identity and fate are regulated by external cues emanating from endothelial cells, the nature of such angiocrine signals remains unknown. Here, we deployed a mass spectrometry proteomic approach to characterise the factors released by brain endothelial cells. We report the identification of the vasoactive peptide apelin as a central regulator for endothelial-mediated maintenance of glioblastoma patient-derived cells with stem-like properties (GSCs). Genetic and pharmacological targeting of apelin cognate receptor APLNR abrogates apelin- and endothelial-mediated expansion of GSCs and suppresses tumour initiation and growth. Functionally, selective competitive antagonists of APLNR were shown to be safe and effective in lengthening the survival of intracranially xenografted mice. Therefore, the APLN/APLNR signalling nexus may operate as a paracrine signal that sustains tumour cell expansion and progression, suggesting that apelin is a druggable factor in glioblastoma.WT107715/Z/15/

Differential expression of Lp-PLA2 in obesity and type 2 diabetes and the influence of lipids

Aims/hypothesis Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a circulatory macrophage-derived factor that increases with obesity and leads to a higher risk of cardiovascular disease (CVD). Despite this, its role in adipose tissue and the adipocyte is unknown. Therefore, the aims of this study were to clarify the expression of Lp-PLA2 in relation to different adipose tissue depots and type 2 diabetes, and ascertain whether markers of obesity and type 2 diabetes correlate with circulating Lp-PLA2. A final aim was to evaluate the effect of cholesterol on cellular Lp-PLA2 in an in vitro adipocyte model. Methods Analysis of anthropometric and biochemical variables from a cohort of lean (age 44.4 ± 6.2 years; BMI 22.15 ± 1.8 kg/m2, n = 23), overweight (age 45.4 ± 12.3 years; BMI 26.99 ± 1.5 kg/m2, n = 24), obese (age 49.0 ± 9.1 years; BMI 33.74 ± 3.3 kg/m2, n = 32) and type 2 diabetic women (age 53.0 ± 6.13 years; BMI 35.08 ± 8.6 kg/m2, n = 35), as part of an ethically approved study. Gene and protein expression of PLA2 and its isoforms were assessed in adipose tissue samples, with serum analysis undertaken to assess circulating Lp-PLA2 and its association with cardiometabolic risk markers. A human adipocyte cell model, Chub-S7, was used to address the intracellular change in Lp-PLA2 in adipocytes. Results Lp-PLA2 and calcium-independent PLA2 (iPLA2) isoforms were altered by adiposity, as shown by microarray analysis (p < 0.05). Type 2 diabetes status was also observed to significantly alter gene and protein levels of Lp-PLA2 in abdominal subcutaneous (AbdSc) (p < 0.01), but not omental, adipose tissue. Furthermore, multivariate stepwise regression analysis of circulating Lp-PLA2 and metabolic markers revealed that the greatest predictor of Lp-PLA2 in non-diabetic individuals was LDL-cholesterol (p = 0.004). Additionally, in people with type 2 diabetes, oxidised LDL (oxLDL), triacylglycerols and HDL-cholesterol appeared important predictors, accounting for 59.7% of the variance (p < 0.001). Subsequent in vitro studies determined human adipocytes to be a source of Lp-PLA2, as confirmed by mRNA expression, protein levels and immunochemistry. Further in vitro experiments revealed that treatment with LDL-cholesterol or oxLDL resulted in significant upregulation of Lp-PLA2, while inhibition of Lp-PLA2 reduced oxLDL production by 19.8% (p < 0.05). Conclusions/interpretation Our study suggests adipose tissue and adipocytes are active sources of Lp-PLA2, with differential regulation by fat depot and metabolic state. Moreover, levels of circulating Lp-PLA2 appear to be influenced by unfavourable lipid profiles in type 2 diabetes, which may occur in part through regulation of LDL-cholesterol and oxLDL metabolism in adipocytes

Assessing the adequacy of self-reported alcohol abuse measurement across time and ethnicity: cross-cultural equivalence across Hispanics and Caucasians in 1992, non-equivalence in 2001–2002

<p>Abstract</p> <p>Background</p> <p>Do estimates of alcohol abuse reflect true levels across United States Hispanics and non-Hispanic Caucasians, or does culturally-based, systematic measurement error (i.e., measurement bias) affect estimates? Likewise, given that recent estimates suggest alcohol abuse has increased among US Hispanics, the field should also ask, "Does cross-ethnic change in alcohol abuse across time reflect true change or does measurement bias influence change estimates?"</p> <p>Methods</p> <p>To address these questions, I used confirmatory factor analyses for ordered-categorical measures to probe for measurement bias on two large, standardized, nationally representative, US surveys of alcohol abuse conducted in 1992 and 2001–2002. In 2001–2002, analyses investigated whether 10 items operationalizing DSM-IV alcohol abuse provided equivalent measurement across Hispanic (<it>n </it>= 4,893) and non-Hispanic Caucasians (<it>n </it>= 16,480). In 1992, analyses examined whether a reduced 6 item item-set provided equivalent measurement among 834 Hispanic and 14,8335 non-Hispanic Caucasians.</p> <p>Results</p> <p>In 1992, findings demonstrated statistically significant measurement bias for two items. However, sensitivity analyses showed that item-level bias did not appreciably bias item-set based alcohol abuse estimates among this cohort. For 2001–2002, results demonstrated statistically significant bias for seven items, suggesting caution regarding the cross-ethnic equivalence of alcohol abuse estimates among the current US Hispanic population. Sensitivity analyses indicated that item-level differences <it>did </it>erroneously impact alcohol abuse rates in 2001–2002, underestimating rates among Hispanics relative to Caucasians.</p> <p>Conclusion</p> <p>1992's item-level findings suggest that estimates of drinking related social or legal problems may underestimate these specific problems among Hispanics. However, impact analyses indicated no appreciable effect on alcohol abuse estimates resulting from the item-set. Efforts to monitor change in alcohol abuse diagnoses among the Hispanic community can use 1992 estimates as a valid baseline. In 2001–2002, item-level measurement bias on seven items did affect item-set based estimates. Bias underestimated Hispanics' self-reported alcohol abuse levels relative to non-Hispanic Caucasians. Given the cross-ethnic equivalence of 1992 estimates, bias in 2001–2002 speciously minimizes current increases in drinking behavior evidenced among Hispanics. Findings call for increased public health efforts among the Hispanic community and underscore the necessity for cultural sensitivity when generalizing measures developed in the majority to minorities.</p