Intramacrophage survival of uropathogenic Escherichia coli : differences between diverse clinical isolates and between mouse and human macrophages

Uropathogenic E. coli (UPEC) are the primary cause of urinary tract infections. Recent studies have demonstrated that UPEC can invade and replicate within epithelial cells, suggesting that this bacterial pathogen may occupy an intracellular niche within the host. Given that many intracellular pathogens target macrophages, we assessed the interactions between UPEC and macrophages. Colonization of the mouse bladder by UPEC strain CFT073 resulted in increased expression of myeloid-restricted genes, consistent with the recruitment of inflammatory macrophages to the site of infection. In in vitro assays, CFT073 was able to survive within primary mouse bone marrow-derived macrophages (BMM) up to 24 h post-infection. Three additional well-characterized clinical UPEC isolates associated with distinct UTI symptomatologies displayed variable long-term survival within BMM. UPEC strains UTI89 and VR50, originally isolated from patients with cystitis and asymptomatic bacteriuria respectively, showed elevated bacterial loads in BMM at 24 h post-infection as compared to CFT073 and the asymptomatic bacteriuria strain 83972. These differences did not correlate with differential effects on macrophage survival or initial uptake of bacteria. E. coli UTI89 localized to a Lamp1+ vesicular compartment within BMM. In contrast to survival within mouse BMM, intracellular bacterial loads of VR50 were low in both human monocyte-derived macrophages (HMDM) and in human T24 bladder epithelial cells. Collectively, these data suggest that some UPEC isolates may subvert macrophage anti-microbial pathways, and that host species differences may impact on intracellular UPEC survival.

Species differences in acrylonitrile metabolism and toxicity between experimental animals and humans based on observations in human accidental poisonings

The high acute toxicity of acrylonitrile may be a result of its intrinsic biological reactivity or of its metabolite cyanide. Intravenous N-acetylcysteine has been recommended for treatment of accidental intoxications in acrylonitrile workers, but such recommendations vary internationally. Acrylonitrile is metabolized in humans and experimental animals via two competing pathways; the glutathione-dependent pathway is considered to represent an avenue of detoxication whilst the oxidative pathway leads to a genotoxic epoxide, cyanoethylene oxide, and to elimination of cyanide. Cases of acute acrylonitrile overexposure or intoxication have occurred within persons having industrial contact with acrylonitrile; the route of exposure was by inhalation and/or by skin contact. The combined observations lead to the conclusion of a much higher impact of the oxidative metabolism of acrylonitrile in humans than in rodents. This is confirmed by differences in the clinical picture of acute life-threatening intoxications in both species, as well as by differential efficacies of antidotes. A combination of N-acetylcysteine with sodium thiosulfate seems an appropriate measure for antidote therapy of acute acrylonitrile intoxications. Clinical observations also highlight the practical importance of human individual susceptibility differences. Furthermore, differential adduct monitoring, assessing protein adducts with different rates of decay, enables the development of more elaborated biological monitoring strategies for the surveillance of workers with potential acrylonitrile contact.

Species differences in the glutathione transferase GSTT1-1 activity towards the model substrates methyl chloride and dichloromethane in liver and kidney

Glutathione transferase (GST) GSTT1-1 is involved in the biotransformation of several chemicals widely used in industry, such as butadiene and dichloro methane DCM. The polymorphic hGSTT1-1 may well play a role in the development of kidney tumours after high and long-term occupational exposure against trichloroethylene. Although several studies have investigated the association of this polymorphism with malignant diseases little is known about its enzyme activity in potential extrahepatic target tissues. The known theta-specific substrates methyl chloride (MC) dichloromethane and 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) were used to assay GSTT1-1 activity in liver and kidney of rats, mice, hamsters and humans differentiating the three phenotypes (non-conjugators, low conjugators, high conjugators) seen in humans. In addition GSTT1-1 activity towards MC and DCM was determined in human erythrocytes. No GSTT1-1 activity was found in any tissue of non-conjugators (NC). In all organs high conjugators (HC) showed twofold higher activity towards MC and DCM than low conjugators (LC). The activity in human samples towards EPNP was too close to the detection limit to differentiate between the three conjugator phenotypes. GSTT1-1 activity towards MC was two to seven-times higher in liver cytosol than in kidney cytosol. The relation for MC between species was identical in both organs: mouse > HC > rat > LC > hamster > NC. In rats, mice and hamsters GSTT1-1 activity in liver cytosol towards DCM was also two to seven-times higher than in the kidney cytosol. In humans this activity was twice as high in kidney cytosol than in liver cytosol. The relation between species was mouse > rat > HC > LC > hamster > NC for liver, but mouse > HC > LC/rat > hamster/NC for kidney cytosol. The importance to heed the specific environment at potential target sites in risk assessment is emphasized by these results.

Morphometric modelling of ageing in the human pubic symphysis : sexual dimorphism in an Australian population

Despite the prominent use of the pubic symphysis for age estimation in forensic anthropology, little has been documented regarding the quantitative morphological and micro-architectural changes of this surface. Specifically, utilising post-mortem computed tomography data from a large, contemporary Australian adult population, this study aimed to evaluate sexual dimorphism in the morphology and bone composition of the symphyseal surface; and temporal characterisation of the pubic symphysis in individuals of advancing age. The sample consisted of multi-slice computed tomography (MSCT) scans of the pubic symphysis(slice thickness: 0.5 mm, overlap: 0.1 mm) of 200 individuals of Caucasian ancestry aged 15–70 years, obtained in 2011. Surface rendering reconstruction of the symphyseal surface was conducted in OsiriX1 (v.4.1) and quantitative analyses in Rapidform XOSTM and OsteomeasureTM. Morphometric variables including inter-pubic distance, surface area, circumference, maximum height and width of the symphyseal surface and micro-architectural assessment of cortical and trabecular bone compositions were quantified using novel automated engineering software capabilities. The major results of this study are correlated with the macroscopic ossification and degeneration pattern of the symphyseal surface, demonstrating significant age-related changes in the morphometric and bone tissue variables between 15 and 70 years. Regardless of sex, the overall dimensions of the symphyseal surface increased with age, coupled with a decrease in bone mass in the trabecular and cortical bone compartments. Significant differences between the ventral, dorsal and medial cortical surfaces were observed, which may be correlated to bone formation activity dependent on muscle activity and ligamentous attachments. Our study demonstrates significant sexual dimorphism at this site, with males exhibiting greater surface dimensions than females. These baseline results provide a detailed insight into the changes in the structure of the pubic symphysis with ageing and sexually dimorphic features associated with the cortical and trabecular bone profiles.

Weight-related differences in glucose metabolism and free fatty acid production in two South African population groups

OBJECTIVE The effects of free fatty acids (FFA), leptin, tumour necrosis factor (TNF) alpha and body fat distribution on in vivo oxidation of a glucose load were studied in two South African ethnic groups. DESIGN AND MEASUREMENTS Anthropometric and various metabolic indices were measured at fasting and during a 7h oral glucose tolerance test (OGTT). Body composition was measured using bioelectrical impedance analysis and subcutaneous and visceral fat mass was assessed using a five- and two-level CT-scan respectively. Glucose oxidation was evaluated by measuring the ratio of (13)CO(2) to (12)CO(2) in breath following ingestion of 1-(13)C-labelled glucose. SUBJECTS Ten lean black women (LBW), ten obese black women (OBW), nine lean white women (LWW) and nine obese white women (OWW) were investigated after an overnight fast. RESULTS Visceral fat levels were significantly higher (P < 0.01) in obese white than black women, despite similar body mass indexes (BMIs). There were no ethnic differences in glucose oxidation however; in the lean subjects of both ethnic groups the area under the curve (AUC) was higher than in obese subjects (P < 0.05 for both) and was found to correlate negatively with weight (r = -0.69, P < 0.01) after correcting for age. Basal TNF alpha concentrations were similar in all groups. Percentage suppression of FFAs at 30 min of the OCTT was 24 +/- 12% in OWW and - 38 +/- 23% (P < 0.05) in OBW, ie the 30 min FFA level was higher than the fasting level in the latter group. AUC for FFAs during the late postprandial period (120 - 420 min) was significantly higher in OWW than OBW (P < 0.01) and LWW (P < 0.01) and correlated positively with visceral fat mass independent of age (r = 0.78, P < 0.05) in the OWW only. Leptin levels were higher (P < 0.01) both at fasting and during the course of the OCTT in obese women from both ethnic groups compared to the lean women. CONCLUSIONS Glucose oxidation is reduced in obese subjects of both ethnic groups; inter- and intra-ethnic differences were observed in visceral fat mass and FFA production and it is possible that such differences may play a role in the differing prevalences of obesity-related disorders that have been reported in these two populations.

Ethnic differences in lipid metabolism in two groups of obese South African women

There is a higher prevalence of ischemic heart disease (IHD) in South African white than black women. The objective of this study was to determine biochemical explanations for this prevalence. The study group contained 15 obese black women (OBW) and 14 obese white women (OWW), ah premenopausal, who were examined after an overnight fast. Anthropometric measurements and blood concentrations of glucose, non-esterified fatty acids (NEFAs), catecholamines, plasminogen activator inhibitor-1, C-peptide, proinsulin, lipograms, cortisol, growth hormone, and post-heparin Lipoprotein Lipase activity were measured during an oral glucose tolerance test (OGTT), Body composition was measured using bioelectrical impedance analysis, and subcutaneous and visceral fat mass were assessed with CT-scans. Visceral fat area was higher in OWW (139.7 +/- 10.7 cm(2)) than in OBW (72.3 +/- 3.9 cm(2)) (P < 0.01), as were fasting and 3 h triglyceride concentrations (P < 0.05 for all). OWW also had higher NEFA levels than OBW at 3 and 4 h compared, with OBW (P < 0.05 for both). Fasting cortisol (266 +/- 24 vs. 197 +/- 19 nmol/l; P < 0.05) was higher in OWW than in OBW. These data demonstrate that OWW have higher visceral fat mass than OBW, which may lead to a more atherogenic fasting and postprandial Lipid profile. The higher cortisol levels of the OWW may promote visceral fat deposition. - Punyadeera, C., M-T. van der Merwe, N.J. Crowther, M. Toman, C. P. Schlaphoff, and I. P. Gray. Ethnic differences in lipid metabolism in two groups of obese South African women.

Serosorting may increase the risk of HIV acquisition among men who have sex with men

Background: Serosorting, the practice of seeking to engage in unprotected anal intercourse with partners of the same HIV status as oneself, has been increasing among men who have sex with men. However, the effectiveness of serosorting as a strategy to reduce HIV risk is unclear, especially since it depends on the frequency of HIV testing. Methods: We estimated the relative risk of HIV acquisition associated with serosorting compared with not serosorting by using a mathematical model, informed by detailed behavioral data from a highly studied cohort of gay men. Results: We demonstrate that serosorting is unlikely to be highly beneficial in many populations of men who have sex with men, especially where the prevalence of undiagnosed HIV infections is relatively high. We find that serosorting is only beneficial in reducing the relative risk of HIV transmission if the prevalence of undiagnosed HIV infections is less than ∼20% and ∼40%, in populations of high (70%) and low (20%) treatment rates, respectively, even though treatment reduces the absolute risk of HIV transmission. Serosorting can be expected to lead to increased risk of HIV acquisition in many settings. In settings with low HIV testing rates serosorting can more than double the risk of HIV acquisition. Conclusions: Therefore caution should be taken before endorsing the practice of serosorting. It is very important to continue promotion of frequent HIV testing and condom use, particularly among people at high risk.

Sex workers can be screened too often : a cost-effectiveness analysis in Victoria, Australia

Objectives Commercial sex is licensed in Victoria, Australia such that sex workers are required to have regular tests for sexually transmitted infections (STIs). However, the incidence and prevalence of STIs in sex workers are very low, especially since there is almost universal condom use at work. We aimed to conduct a cost-effectiveness analysis of the financial cost of the testing policy versus the health benefits of averting the transmission of HIV, syphilis, chlamydia and gonorrhoea to clients. Methods We developed a simple mathematical transmission model, informed by conservative parameter estimates from all available data, linked to a cost-effectiveness analysis. Results We estimated that under current testing rates, it costs over $A90 000 in screening costs for every chlamydia infection averted (and $A600 000 in screening costs for each quality-adjusted life year (QALY) saved) and over $A4 000 000 for every HIV infection averted ($A10 000 000 in screening costs for each QALY saved). At an assumed willingness to pay of $A50 000 per QALY gained, HIV testing should not be conducted less than approximately every 40 weeks and chlamydia testing approximately once per year; in comparison, current requirements are testing every 12 weeks for HIV and every 4 weeks for chlamydia. Conclusions Mandatory screening of female sex workers at current testing frequencies is not cost-effective for the prevention of disease in their male clients. The current testing rate required of sex workers in Victoria is excessive. Screening intervals for sex workers should be based on local STI epidemiology and not locked by legislation.

Implications of differences in technical efficiency of fishing boats for capacity measurement and reduction

Capacity measurement and reduction is a major international issue to emerge in the new millennium. However, there has been limited assessment of the success of capacity reduction schemes (CRS). In this paper, the success of a CRS is assessed for a European fishery characterised by differences in efficiency levels of individual boats. In such a fishery, given it is assumed that the least efficient producers are the first to exit through a CRS, the reduction in harvesting capacity is less than the nominal reduction in physical fleet capacity. Further, there is potential for harvesting capacity to increase if remaining vessels improve their efficiency.

Troubling silences and taboo texts : constructing safer and more positive school climates for same-sex attracted high school students in Australia

This chapter offers three insights into the relationship between curriculum decision making, positive school climate, and academic achievement for same-sex attracted (SSA) students, highlighting the need for students to be offered more than heteronormative narratives and silence on issues of sexuality in the official school curriculum. The authors firstly provide a review of research and report on findings of a doctoral study (Mikulsky, 2007) explaining the impact of SSA students’ perceptions of school climate on their motivation and academic self-concept. Situating the work in the context of the Australian Curriculum for English and associated classroom texts, the dominant discourse of ‘straight, white female’ heroines as exemplified in the globally popular young adult novel The hunger games and other texts popular with Australian students are critiqued, with an argument made for expanding notions of what it means to ‘attend to’ gender and sexuality through textual choice and critical pedagogy. The authors show how texts that feature LGBTQ characters and storylines continue to be marginalized and constructed as taboo and demonstrate how curricular choices can and do impact academic outcomes for marginalized students. Issues of gender and sexuality are framed as a cross-curriculum imperative, with recommendations made for the explicit inclusion of materials exploring gender and sexuality in the official curriculum of all key learning areas.

Suicide and religion : new evidence on the differences between Protestantism and Catholicism

Suicide has remained a persistent social phenomenon and now accounts for more deaths than motor vehicle accidents. There has been much debate, however, over which religious constructs might best explain the variation in suicide rates. Our empirical analysis reveals that even though theological and social differences between Catholicism and Protestantism have decreased, Catholics are still less likely than Protestants to commit or accept suicide. This difference holds even after we control for such confounding factors as social and religious networks. In addition, although religious networks do mitigate suicides among Protestants, the influence of church attendance is more dominant among Catholics. Our analysis also indicates that alternative concepts such as religious commitment and religiosity strongly reduce suicide acceptance.

Age related differences in the validity of the OMNI perceived exertion scale during lifestyle activities

PURPOSE The OMNI Perceived Exertion Scale was developed for children to report perceived effort while performing physical activity; however no studies have formally examined age-related differences in validity. This study evaluated the validity of the OMNI-RPE in four age groups performing a range of lifestyle activities. METHODS 206 participants were stratified into four age groups: 6-8 years (n = 42), 9-10 years (n = 46), 11-12 years (n = 47), and 13-15 years (n = 71). Heart rate and VO2 were measured during 11 activity trials ranging in intensity from sedentary to vigorous. After each trial, participants reported effort from the OMNI walk/run scale. Concurrent validity was assessed by calculating within-subject correlations between OMNI ratings and the two physiological indices. RESULTS The average correlation between OMNI ratings and VO2 was 0.67, 0.77, 0.85 and 0.87 for the 6-8, 9-10, 11-12 and 13-15 y age groups, respectively. CONCLUSION The OMNI RPE scale demonstrated fair to good evidence of validity across a range of lifestyle activities among 6-15 year old children. The validity of the scale appears to be developmentally related with RPE reports closely reflecting physiological responses among children older than 8 years.

Seed germination may explain differences in invasiveness and prevalence : a case study using cat's claw creeper (Dolichandra unguis-cati)

High germination rates and rapid germination behavior in response to different environmental cues are traits that may be associated with invasiveness. Cat’s claw creeper (Dolichandra unguis-cati (L.) Lohmann (syn. Macfadyena unguis-cati (L.) Gentry), a Weed of National Significance has two forms, a long-pod (LP) form and a short-pod (SP) from. The LP form occurs in only a few localities in southeast Queensland while the SP form is widely distributed in Queensland and New South Wales. The aims of this investigation were: to evaluate whether there are significant differences in germination traits between the two forms of cat’s claw creeper; and if there are any significant differences, to find out whether the differences in germination can be related to prevalence and invasiveness levels for the two forms. Long pod and short pod seeds collected in 2009, 2010, 2011, 2012 and 2013 from various localities in Qld were germinated in growth chambers in early 2013. The growth chambers were set to 10/20 ºC, 15/25 ºC and 20/30 ºC temperature cycles. Seeds from 2009-2012 of either form did not germinate, while for the fresh seeds (2013), SP exhibited significantly higher total germination percentage and rates than LP. Assuming that the two forms were introduced in Australia at around the same period, these results could explain why SP is widely distributed (and therefore more invasive) in Qld and NSW while LP is only confined to a few localities in southeast Qld.

Bang and bust: almost everything you wanted to know about sex and the mining boom (but were afraid to ask)

Recent growth and expansion of the fly-in/fly-out (FIFO) model of mining in remote rural Australia has led to concerns about the health and well-being of those employed by the mines and those in the small rural communities where they are based. A particular concern has been the potential disruption to sexual norms in mining towns and increases in sexually transmitted infections (STIs) and HIV.

Understanding the new context of the male sex work industry

The article reviews past and recent research on male sex work to offer a context to understand violence in the industry. It provides a critical review of research to show, first, the assumptions made about male sex workers and violence and, second, how such discourses have shaped thinking on the topic. The article presents a case study and original findings from two studies conducted by the authors in Australia and Argentina on violence in the male sex industry. Finally, the article reviews examples of legislative reforms to show how the sex industry is being regulated.