Estrogen deficiency-associated bone loss in the maxilla: A methodology to quantify the changes in the maxillary intra-radicular alveolar bone in an ovariectomized rat osteoporosis model

The effects of estrogen deficiency on bone characteristics are site-dependent, with the most commonly studied sites being appendicular long bones (proximal femur and tibia) and axial bones (vertebra). The effect on the maxillary and mandibular bones is still inconsistent and requires further investigation. This study was designed to evaluate bone quality in the posterior maxilla of ovariectomized rats in order to validate this site as an appropriate model to study the effect of osteoporotic changes. Methods: Forty-eight 3-month-old female Sprague-Dawley rats were randomly divided into two groups: an ovariectomized group (OVX, n=24) and Sham-operated group (SHAM, n=24). Six rats were randomly sacrificed from both groups at time points 8, 12, 16 and 20 weeks. The samples from tibia and maxilla were collected for Micro CT and histological analysis. For the maxilla, the volume of interest (VOI) area focused on the furcation areas of the first and second molar. Trabecular bone volume fraction (BV/TV, %), trabecular thickness (Tb.Th.), trabecular number (Tb.N.), trabecular separation (Tb.Sp.), and connectivity density (Conn.Dens) were analysed after Micro CT scanning. Results: At 8 weeks the indices BV/TV, Tb.Sp, Tb.N and Conn.Dens showed significant differences (P<0.05) between the OVX and SHAM groups in the tibia. Compared with the tibia, the maxilla developed osteoporosis at a later stage, with significant changes in maxillary bone density only occurring after 12 weeks. Compared with the SHAM group, both the first and second molars of the OVX group showed significantly decreased BV/TV values from 12 weeks, and these changes were sustained through 16 and 20 weeks. For Tb.Sp, there were significant increases in bone values for the OVX group compared with the SHAM group at 12, 16 and 20 weeks. Histological changes were highly consistent with Micro CT results. Conclusion: This study established a method to quantify the changes of intra-radicular alveolar bone in the posterior maxilla in an accepted rat osteoporosis model. The degree of the osteoporotic changes to trabecular bone architecture is site-dependent and at least 3 months are required for the osteoporotic effects to be apparent in the posterior maxilla following rat OVX.

Using the Driver Behaviour Questionnaire to predict crashes and demerit point loss : does it get better with larger sample sizes?

The Driver Behaviour Questionnaire (DBQ) continues to be the most widely utilised self-report scale globally to assess crash risk and aberrant driving behaviours among motorists. However, the scale also attracts criticism regarding its perceived limited ability to accurately identify those most at risk of crash involvement. This study reports on the utilisation of the DBQ to examine the self-reported driving behaviours (and crash outcomes) of drivers in three separate Australian fleet samples (N = 443, N = 3414, & N = 4792), and whether combining the samples increases the tool’s predictive ability. Either on-line or paper versions of the questionnaire were completed by fleet employees in three organisations. Factor analytic techniques identified either three or four factor solutions (in each of the separate studies) and the combined sample produced expected factors of: (a) errors, (b) highway-code violations and (c) aggressive driving violations. Highway code violations (and mean scores) were comparable across the studies. However, across the three samples, multivariate analyses revealed that exposure to the road was the best predictor of crash involvement at work, rather than DBQ constructs. Furthermore, combining the scores to produce a sample of 8649 drivers did not improve the predictive ability of the tool for identifying crashes (e.g., 0.4% correctly identified) or for demerit point loss (0.3%). The paper outlines the major findings of this comparative sample study in regards to utilising self-report measurement tools to identify “at risk” drivers as well as the application of such data to future research endeavours.

Consumer misbehavior: a concurrent look at the impact that the size of the victim and size of the loss have on opinions regarding the acceptance or unacceptance of 12 questionable consumer actions

This study examines the role that the size of a victimised organisation and the size of the victim’s loss have on attitudes regarding the acceptance or unacceptance of 12 questionable consumer actions. A sample of 815 American adults rated each scenario on a scale anchored by very acceptable and very unacceptable. It was shown that the size of the victimised organisation tends to influence consumers’ opinions with more disdain directed towards consumers who take advantage of smaller businesses. Similarly, the respondents tended to be more critical of these actions when the loss incurred by the victimised organisation was large. A 2x2 matrix concurrently delineated the nature of the extent to which opinions regarding the 12 actions differed depending upon the mediating variable under scrutiny.

CORR Insights® : loss of cement-bone interlock in retrieved tibial components from total knee arthroplasties

Most surgeons cement the tibial component in total knee replacement surgery. Mid-term registry data from a number of countries, including those from the United Kingdom and Australia, support the excellent survivorship of cemented tibial components. In spite of this success, results can always be improved, and cementing technique can play a role. Cementing technique on the tibia is not standardized, and surgeons still differ about the best ways to deliver cement into the cancellous bone of the upper tibia. Questions remain regarding whether to use a gun or a syringe to inject the cement into the cancellous bone of the tibial plateau . The ideal cement penetration into the tibial plateau is debated, though most reports suggest that 4 mm to 10 mm is ideal. Thicker mantles are thought to be dangerous due to the risk of bone necrosis, but there is little in the literature to support this contention...

Improving treatment for obese women with early stage cancer of the uterus : rationale and design of the levonorgestrel intrauterine device ±Metformin ±weight loss in endometrial cancer (feMME) trial

Purpose Endometrial adenocarcinoma (EC) is the most common gynaecologic cancer. Up to 90% of EC patients are obese which poses a health threat to patients post-treatment. Standard treatment for EC includes hysterectomy, although this has significant side effects for obese women at high risk of surgical complications and for women of childbearing age. This trial investigates the effectiveness of non-surgical or conservative treatment options for obese women with early stage EC. The primary aim is to determine the efficacy of: levonorgestrel intrauterine device (LNG-IUD); with or without metformin (an antidiabetic drug); and with or without a weight loss intervention to achieve a pathological complete response (pCR) in EC at six months from study treatment initiation. The secondary aim is to enhance understanding of the molecular processes and to predict a treatment response by investigating EC biomarkers. Methods An open label, three-armed, randomised, phase-II, multi-centre trial of LNG-IUD ± metformin ± weight loss intervention. 165 participants from 28 centres are randomly assigned in a 3:3:5 ratio to the treatment arms. Clinical, quality of life and health behavioural data will be collected at baseline, six weeks, three and six months. EC biomarkers will be assessed at baseline, three and six months. Conclusions There is limited prospective evidence for conservative treatment for EC. Trial results could benefit patients and reduce health system costs through a reduction in hospitalisations and through lower incidence of adverse events currently observed with standard treatment.

In silico analyses reveal common cellular pathways affected by loss of heterozygosity (LOH) events in the lymphomagenesis of Non-Hodgkin’s lymphoma (NHL)

Background The analysis of cellular networks and pathways involved in oncogenesis has increased our knowledge about the pathogenic mechanisms that underlie tumour biology and has unmasked new molecular targets that may lead to the design of better anti-cancer therapies. Recently, using a high resolution loss of heterozygosity (LOH) analysis, we identified a number of potential tumour suppressor genes (TSGs) within common LOH regions across cases suffering from two of the most common forms of Non-Hodgkin’s lymphoma (NHL), Follicular Lymphoma (FL) and Diffuse Large B-cell Lymphoma (DLBCL). From these studies LOH of the protein tyrosine phosphatase receptor type J (PTPRJ) gene was identified as a common event in the lymphomagenesis of these B-cell lymphomas. The present study aimed to determine the cellular pathways affected by the inactivation of these TSGs including PTPRJ in FL and DLBCL tumourigenesis. Results Pathway analytical approaches identified that candidate TSGs located within common LOH regions participate within cellular pathways, which may play a crucial role in FL and DLBCL lymphomagenesis (i.e., metabolic pathways). These analyses also identified genes within the interactome of PTPRJ (i.e. PTPN11 and B2M) that when inactivated in NHL may play an important role in tumourigenesis. We also detected genes that are differentially expressed in cases with and without LOH of PTPRJ, such as NFATC3 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3). Moreover, upregulation of the VEGF, MAPK and ERBB signalling pathways was also observed in NHL cases with LOH of PTPRJ, indicating that LOH-driving events causing inactivation of PTPRJ, apart from possibly inducing a constitutive activation of these pathways by reduction or abrogation of its dephosphorylation activity, may also induce upregulation of these pathways when inactivated. This finding implicates these pathways in the lymphomagenesis and progression of FL and DLBCL. Conclusions The evidence obtained in this research supports findings suggesting that FL and DLBCL share common pathogenic mechanisms. Also, it indicates that PTPRJ can play a crucial role in the pathogenesis of these B-cell tumours and suggests that activation of PTPRJ might be an interesting novel chemotherapeutic target for the treatment of these B-cell tumours.

Bat colony size reduction coincides with clear-fell harvest operations and high rates of roost loss in plantation forest

Clear-fell harvest of forest concerns many wildlife biologists because of loss of vital resources such as roosts or nests, and effects on population viability. However, actual impact has not been quantified. Using New Zealand long-tailed bats (Chalinolobus tuberculatus) as a model species we investigated impacts of clear-fell logging on bats in plantation forest. C. tuberculatus roost within the oldest stands in plantation forest so it was likely roost availability would decrease as harvest operations occurred. We predicted that post-harvest: (1) roosting range sizes would be smaller, (2) fewer roosts would be used, and (3) colony size would be smaller. We captured and radiotracked C. tuberculatus to day-roosts in Kinleith Forest, an exotic plantation forest, over three southern hemisphere summers (Season 1 October 2006–March 2007; Season 2 November 2007–March 2008; and Season 3 November 2008–March 2009). Individual roosting ranges (100% MCPs) post harvest were smaller than those in areas that had not been harvested, and declined in area during the 3 years. Following harvest, bats used fewer roosts than those in areas that had not been harvested. Over 3 years 20.7% of known roosts were lost: 14.5% due to forestry operations and 6.2% due to natural tree fall. Median colony size was 4.0 bats (IQR = 2.0–8.0) and declined during the study, probably because of locally high levels of roost loss. Post harvest colonies were smaller than colonies in areas that had not been harvested. Together, these results suggest the impact of clear-fell harvest on long-tailed bat populations is negative.

An analysis of DNA methylation in human adipose tissue reveals differential modification of obesity genes before and after gastric bypass and weight loss

Background Environmental factors can influence obesity by epigenetic mechanisms. Adipose tissue plays a key role in obesity-related metabolic dysfunction, and gastric bypass provides a model to investigate obesity and weight loss in humans. Results Here, we investigate DNA methylation in adipose tissue from obese women before and after gastric bypass and significant weight loss. In total, 485,577 CpG sites were profiled in matched, before and after weight loss, subcutaneous and omental adipose tissue. A paired analysis revealed significant differential methylation in omental and subcutaneous adipose tissue. A greater proportion of CpGs are hypermethylated before weight loss and increased methylation is observed in the 3′ untranslated region and gene bodies relative to promoter regions. Differential methylation is found within genes associated with obesity, epigenetic regulation and development, such as CETP, FOXP2, HDAC4, DNMT3B, KCNQ1 and HOX clusters. We identify robust correlations between changes in methylation and clinical trait, including associations between fasting glucose and HDAC4, SLC37A3 and DENND1C in subcutaneous adipose. Genes investigated with differential promoter methylation all show significantly different levels of mRNA before and after gastric bypass. Conclusions This is the first study reporting global DNA methylation profiling of adipose tissue before and after gastric bypass and associated weight loss. It provides a strong basis for future work and offers additional evidence for the role of DNA methylation of adipose tissue in obesity.