The association between hysterectomy and ovarian cancer risk: A population-based record-linkage study

Background: Recent studies have called into question the long-held belief that hysterectomy without oophorectomy protects against ovarian cancer. This population-based longitudinal record-linkage study aimed to explore this relationship, overall and by age at hysterectomy, time period, surgery type, and indication for hysterectomy. Methods: We followed the female adult Western Australian population (837 942 women) across a 27-year period using linked electoral, hospital, births, deaths, and cancer records. Surgery dates were determined from hospital records, and ovarian cancer diagnoses (n¼1640) were ascertained from cancer registry records.We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between hysterectomy and ovarian cancer incidence. Results: Hysterectomy without oophorectomy (n¼78 594) was not associated with risk of invasive ovarian cancer overall (HR ¼ 0.98, 95% CI ¼ 0.85 to 1.11) or with the most common serous subtype (HR ¼ 1.05, 95% CI ¼ 0.89 to 1.23). Estimates did not vary statistically significantly by age at procedure, time period, or surgical approach. However, among women with endometriosis (5.8%) or with fibroids (5.7%), hysterectomy was associated with substantially decreased ovarian cancer risk overall (HR ¼ 0.17, 95% CI ¼ 0.12 to 0.24, and HR ¼ 0.27, 95% CI ¼ 0.20 to 0.36, respectively) and across all subtypes. Conclusions: Our results suggest that for most women, having a hysterectomy with ovarian conservation is not likely to substantially alter their risk of developing ovarian cancer. However, our results, if confirmed, suggest that ovarian cancer risk reduction could be considered as a possible benefit of hysterectomy when making decisions about surgical management of endometriosis or fibroids

Research-led education: challenges and experiences

The role of a university education in science is changing. In the new knowledge economy, the factcentred, narrowly-focussed education often acquired in a traditional science degree is no longer valued for its own sake, partly because such knowledge, and associated technical skills, can rapidly become outdated, but also because people entering the workforce can expect to have to change jobs and duties several times during their lifetimes. Instead, the skills that are most valued in the science graduate are the logical approach, the inquisitiveness and the adaptability that characterise a lifelong learner. This change is reflected in the new emphasis on training students in ‘research skills’ evident in the changing nature of science degrees in many Australian universities, since the skills of the lifelong learner are similar to those of the effective researcher

Altering DNA Base Excision Repair: Use of Nuclear and Mitochondrial-Targeted N-Methylpurine DNA Glycosylase to Sensitize Astroglia to Chemotherapeutic Agents

Primary astrocyte cultures were used to investigate the modulation of DNA repair as a tool for sensitizing astrocytes to genotoxic agents. Base excision repair (BER) is the principal mechanism by which mammalian cells repair alkylation damage to DNA and involves the processing of relatively nontoxic DNA adducts through a series of cytotoxic intermediates during the course of restoring normal DNA integrity. An adenoviral expression system was employed to target high levels of the BER pathway initiator, N-methylpurine glycosylase (MPG), to either the mitochondria or nucleus of primary astrocytes to test the hypothesis that an alteration in BER results in increased alkylation sensitivity. Increasing MPG activity significantly increased BER kinetics in both the mitochondria and nuclei. Although modulating MPG activity in mitochondria appeared to have little effect on alkylation sensitivity, increased nuclear MPG activity resulted in cell death in astrocyte cultures treated with methylnitrosourea (MNU). Caspase-3 cleavage was not detected, thus indicating that these alkylation sensitive astrocytes do not undergo a typical programmed cell death in response to MNU. Astrocytes were found to express relatively high levels of antiapoptotic Bcl-2 and Bcl-XL and very low levels of proapoptotic Bad and Bid suggesting that the mitochondrial pathway of apoptosis may be blocked making astrocytes less vulnerable to proapoptotic stimuli compared with other cell types. Consequently, this unique characteristic of astrocytes may be responsible, in part, for resistance of astrocytomas to chemotherapeutic agents

Incidental Findings on Brain MRI in People with HIV Infection

BACKGROUND: Incidental findings are a well-known complication of imaging studies done for both diagnostic and research purposes. Little is known about the rates and types of incidental findings found on brain MRI in patients with HIV infection, who may be at risk for HIV-Associated Neurocognitive Disorders (HAND). METHODS: The parent study included 108 adults with HIV infection and 125 demographically-matched uninfected controls who completed MRI and neuropsychological testing. Incidental findings were classified by the study team as vascular, neoplastic, congenital, other neurologic, or non-neurologic. Categorical measures were compared using Pearson chi-square tests; continuous measures were compared using t-tests. RESULTS: Among participants with HIV infection, 36/108 (33%) had incidental findings compared to 33/125 (26%) controls (p = 0.248). Rates of incidental findings were significantly correlated with increasing age in both participants with HIV infection (p = 0.013) and controls (p = 0.022). We found no correlation between presence of incidental findings and sex or race/ethnicity among either cohort, and no correlation with CD4 count or HAND status for the HIV-infected cohort. CONCLUSIONS: Incidental findings were common in both participants with HIV infection and controls, at higher rates than previously reported in healthy populations. There was no significant difference in prevalence between the groups

Oxidative stress-induced apoptosis in neurons correlates with mitochondrial DNA base excision repair pathway imbalance

Neurodegeneration can occur as a result of endogenous oxidative stress. Primary cerebellar granule cells were used in this study to determine if mitochondrial DNA (mtDNA) repair deficiencies correlate with oxidative stress-induced apoptosis in neuronal cells. Granule cells exhibited a significantly higher intracellular oxidative state compared with primary astrocytes as well as increases in reductants, such as glutathione, and redox sensitive signaling molecules, such as AP endonuclease/redox effector factor-1. Cerebellar granule cultures also exhibited an increased susceptibility to exogenous oxidative stress. Menadione (50 μM) produced twice as many lesions in granule cell mtDNA compared with astrocytes, and granule cell mtDNA repair was significantly less efficient. A decreased capacity to repair oxidative mtDNA damage correlates strongly with mitochondrial initiated apoptosis in these neuronal cultures. Interestingly, the mitochondrial activities of initiators for base excision repair (BER), the bifunctional glycosylase/AP lyases as well as AP endonuclease, were significantly higher in cerebellar granule cells compared with astrocytes. The increased mitochondrial AP endonuclease activity in combination with decreased polymerase γ activity may cause an imbalance in oxidative BER leading to an increased production and persistence of mtDNA damage in neurons when treated with menadione. This study provides evidence linking neuronal mtDNA repair capacity with oxidative stress-related neurodegeneration

BCG and adverse events in the context of leprosy

Background: Notwithstanding its beneficial immunoprophylactic outcomes regarding leprosy and childhood TB, BCG vaccination may cause adverse events, particularly of the skin. However, this local hyper-immune reactivity cannot be predicted before vaccination, nor is its association with protection against leprosy known. In this study we investigated the occurrence of adverse events after BCG (re)vaccination in contacts of leprosy patients and analyzed whether the concomitant systemic anti-mycobacterial immunity was associated with these skin manifestations. Methods: Within a randomized controlled BCG vaccination trial in Bangladesh, 14,828 contacts of newly diagnosed leprosy patients received BCG vaccination between 2012 and 2017 and were examined for adverse events 8 to 12 weeks post-vaccination. From a selection of vaccinated contacts, venous blood was obtained at follow-up examination and stimulated with Mycobacterium leprae (M. leprae) antigens in overnight whole-blood assays (WBA). M. leprae phenolic glycolipid-I-specific antibodies and 32 cytokines were determined in WBAs of 13 individuals with and 13 individuals without adverse events after vaccination. Results: Out of the 14,828 contacts who received BCG vaccination, 50 (0.34%) presented with adverse events, mainly (80%) consisting of skin ulcers. Based on the presence of BCG scars, 30 of these contacts (60%) had received BCG in this study as a booster vaccination. Similar to the pathological T-cell immunity observed for tuberculoid leprosy patients, contacts with adverse events at the site of BCG vaccination showed elevated IFN-γ levels in response to M. leprae-specific proteins in WBA. However, decreased levels of sCD40L in serum and GRO (CXCL1) in response to M. leprae simultaneously indicated less T-cell regulation in these individuals, potentially causing uncontrolled T-cell immunity damaging the skin. Conclusion: Skin complications after BCG vaccination present surrogate markers for protective immunity against leprosy, but also indicate a higher risk of developing tuberculoid leprosy

Responses to the Assurance Game in Monkeys, Apes, and Humans Using Equivalent Procedures

There is great interest in the evolution of economic behavior. In typical studies, species are asked to play one of a series of economic games, derived from game theory, and their responses are compared. The advantage of this approach is the relative level of consistency and control that emerges from the games themselves; however, in the typical experiment, procedures and conditions differ widely, particularly between humans and other species. Thus, in the current study, we investigated how three primate species, capuchin monkeys, chimpanzees, and humans, played the Assurance (or Stag Hunt) game using procedures that were, to the best of our ability, the same across species, particularly with respect to training and pretesting. Our goal was to determine what, if any, differences existed in the ways in which these species made decisions in this game. We hypothesized differences along phylogenetic lines, which we found. However, the species were more similar than might be expected. In particular, humans who played using “nonhuman primate-friendly” rules did not behave as is typical. Thus, we find evidence for similarity in decision-making processes across the order Primates. These results indicate that such comparative studies are possible and, moreover, that in any comparison rating species’ relative abilities, extreme care must be taken in ensuring that one species does not have an advantage over the others due to methodological procedures

Comparative Economics: Responses to the Assurance Game in Monkeys, Apes, and Humans Using Equivalent Procedures

There is great interest in the evolution of economic behavior. In typical studies, species are asked to play one of a series of economic games, derived from game theory, and their responses are compared. The advantage of this approach is the relative level of consistency and control that emerges from the games themselves; however in the typical experiment, procedures and conditions differ widely, particularly between humans and other species. Thus, in the current study we investigated how three primate species, capuchin monkeys, chimpanzees, and humans, played the Assurance (or Stag Hunt) Game using procedures which were, to the best of our ability, the same across species, particularly with respect to training and pre-testing. Our goal was to determine what, if any, differences existed in the ways in which these species made decisions in this game. We hypothesized differences along phylogenetic lines, which we found. However, the species were more similar than might be expected. In particular, humans who played using ‘non-human primate-friendly’ rules did not behave as is typical. Thus, we find evidence for similarity in decision-making processes across the Order Primates. These results indicate that such comparative studies are possible and moreover that in any comparison rating species’ relative abilities, extreme care must be taken in ensuring that one species does not have an advantage over the others due to methodological procedures

Gridmapping the northern plains of Mars: Geomorphological, Radar and Water-Equivalent Hydrogen results from Arcadia Plantia

A project of mapping ice-related landforms was undertaken to understand the role of sub-surface ice in the northern plains. This work is the first continuous regional mapping from CTX (“ConTeXt Camera”, 6 m/pixel; Malin et al., 2007) imagery in Arcadia Planitia along a strip 300 km across stretching from 30°N to 80°N centred on the 170° West line of longitude. The distribution and morphotypes of these landforms were used to understand the permafrost cryolithology. The mantled and textured signatures occur almost ubiquitously between 35° N and 78° N and have a positive spatial correlation with inferred ice stability based on thermal modelling, neutron spectroscopy and radar data. The degradational features into the LDM (Latitude Dependent Mantle) include pits, scallops and 100 m polygons and provide supporting evidence for sub-surface ice and volatile loss between 35-70° N in Arcadia with the mantle between 70-78° N appearing much more intact. Pitted terrain appears to be much more pervasive in Arcadia than in Acidalia and Utopia suggesting that the Arcadia study area had more wide-spread near-surface sub-surface ice, and thus was more susceptible to pitting, or that the ice was less well-buried by sediments. Correlations with ice stability models suggest that lack of pits north of 65-70° N could indicate a relatively young age (~1Ma), however this could also be explained through regional variations in degradation rates. The deposition of the LDM is consistent with an airfall hypothesis however there appears to be substantial evidence for fluvial processes in southern Arcadia with older, underlying processes being equally dominant with the LDM and degradation thereof in shaping the landscape