Ureaplasma species multiple banded antigen (MBA) variation is associated with the severity of chorioamnionitis in late preterm placentas

Background: Intra-amniotic infection accounts for 30% of all preterm births (PTB), with the human Ureaplasma species being the most frequently identified microorganism from the placentas of women who deliver preterm. The highest prevalence of PTB occurs late preterm (32-36 weeks) but no studies have investigated the role of infectious aetiologies associated with late preterm birth. Method: Placentas from women with late PTB were dissected aseptically and samples of chorioamnion tissue and membrane swabs were collected. These were tested for Ureaplasma spp. and aerobic/anaerobic bacteria by culture and real-time PCR. Western blot was used to assess MBA variation in ureaplasma clinical isolates. The presence of microorganisms was correlated with histological chorioamnionitis. Results: Ureaplasma spp. were isolated from 33/466 (7%) of placentas by culture or PCR. The presence of ureaplasmas, but not other microorganisms, was associated with histological chorioamnionitis (21/33 ureaplasma-positive vs. 8/42 other bacteria; p= 0.001). Ureaplasma clinical isolates demonstrating no MBA variation were associated with histological chorioamnionitis. By contrast, ureaplasmas displaying MBA variation were isolated from placentas with no significant histological chorioamnionitis (p= 0.001). Conclusion: Ureaplasma spp. within placentas delivered late preterm (7%) is associated with histological chorioamnionitis (p = 0.001). Decreased inflammation within chorioamnion was observed when the clinical ureaplasma isolates demonstrated variation of their surface-exposed lipoproteins (MBA). This variation may be a mechanism by which ureaplasmas modulate and evade the host immune response. So whilst ureaplasmas are present intra-amniotically they are not suspected because of the normal macroscopic appearance of the placentas and the amniotic fluid.

Stage-specific embryonic antigen-4 is not a marker for chondrogenic and osteogenic potential in cultured chondrocytes and mesenchymal progenitor cells

One important challenge for regenerative medicine is to produce a clinically relevant number of cells with consistent tissue-forming potential. Isolation and expansion of cells from skeletal tissues results in a heterogeneous population of cells with variable regenerative potential. A more consistent tissue formation could be achieved by identification and selection of potent progenitors based on cell surface molecules. In this study, we assessed the expression of stage-specific embryonic antigen-4 (SSEA-4), a classic marker of undifferentiated stem cells, and other surface markers in human articular chondrocytes (hACs), osteoblasts, and bone marrow-derived mesenchymal stromal cells (bmMSCs) and characterized their differentiation potential. Further, we sorted SSEA-4-expressing hACs and followed their potential to proliferate and to form cartilage in vitro. Cells isolated from cartilage and bone exhibited remarkably heterogeneous SSEA-4 expression profiles in expansion cultures. SSEA-4 expression levels increased up to approximately 5 population doublings, but decreased following further expansion and differentiation cultures; levels were not related to the proliferation state of the cells. Although SSEA-4-sorted chondrocytes showed a slightly better chondrogenic potential than their SSEA-4-negative counterparts, differences were insufficient to establish a link between SSEA-4 expression and chondrogenic potential. SSEA-4 levels in bmMSCs also did not correlate to the cells' chondrogenic and osteogenic potential in vitro. SSEA-4 is clearly expressed by subpopulations of proliferating somatic cells with a MSC-like phenotype. However, the predictive value of SSEA-4 as a specific marker of superior differentiation capacity in progenitor cell populations from adult human tissue and even its usefulness as a stem cell marker appears questionable.

Examining young recreational sportswomen's intentions to engage in sun-protective behavior : the role of group and image norms

Researchers examined the sun-protective intentions and behavior of young, Caucasian, Australian sportswomen aged between 17 and 35 years (N = 100). The study adopted a 2 x 2 experimental design, comparing group norms (supportive vs. non-supportive) and image norms (tanned vs. pale) related to sun protection and taking into account group identification with friends and peers in the sport. While no significant findings emerged involving image norms, regression analyses revealed a significant two-way interaction for group norm x identification on recreational sportswomen's intentions to engage in sun protection in the next fortnight. Participants identifying strongly with their group had stronger intentions to engage in sun protection when exposed to a norm reflecting fellow recreational sportswomen engaging in sun-protective actions in comparison to those exposed to a non-supportive group. In addition, while prior intentions to engage in sun protection were not significantly related to sun-protection behavior, post-manipulation intentions after exposure to the sun-protective information that was provided were significantly related to follow-up behavior. Overall, the findings supported the importance of group-based social influences, rather than tanned media images, on sun-protective decisions among young recreational sportswomen and provided a targeted source for intervention strategies encouraging sun safety among this at-risk group for repeated sun exposure.

Protective effects of sweroside on human MG-63 cells and rat osteoblasts

Herbal Fructus Corni is a folk medicine with a long history of safe use for treating osteoporosis in postmenopausal women or elderly men in Asia. Sweroside is a bioactive herbal ingredient isolated from Fructus Corni, which has been widely used for the treatment of osteoporosis in traditional Chinese medicine (TCM). Unfortunately, the working mechanisms of this compound are difficult to determine and thus remain unclear. The aim of the study was performed to determine the potential molecular mechanism of the anti-osteoporotic effect of sweroside on the human MG-63 cells and rat osteoblasts. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was used to observe the effect of sweroside on cell proliferation. The activity of alkaline phosphatase (ALP) and the amount of osteocalcin were also assayed the cell differentiation. Sweroside significantly increased the proliferation of human MG-63 cells and rat osteoblasts (P<0.01). It increased the activity of ALP, and osteocalcin was also elevated in response to sweroside (P<0.05). Of note, flowcytometer assay showed that sweroside can attenuate and inhibit apoptosis. Sweroside has a direct osteogenic effect on the proliferation and differentiation of cultured human MG-63 cells and rat osteoblasts in vitro. These data will help in understanding the molecular mechanisms of therapeutic efficacy of sweroside, and highlight insights into drug discovery. In the current study, sweroside has been suggested to be a promising osteoporosis therapeutic natural product.

The effects of risk factors and protective factors on influencing engagement in risky behaviours and injury experiences for high-risk adolescents

High-risk adolescents are most vulnerable to the negative outcomes of risk taking behaviour, such as injury. It has been theorised by Jessor (1987) that adolescent risk behaviours (e.g. violence, alcohol use) can be predicted by assessing the risk factors (e.g. peer models for violence) and protective factors (e.g. school connectedness) in a young person’s life. The aim of this research is to examine the influence of risk factors and protective factors on the proneness of high-risk adolescents to engage in risky behaviour. 2,521 Grade 9 students (13-14 years of age) from 35 schools in Queensland, Australia participated in this study. The findings examine the influence of risk factors and protective factors on self-reported risky behaviour and injury experiences for adolescents who have been categorized as high-risk. Thereby, providing insight that may be used to target preventive interventions aimed at high-risk adolescents.

The role of immunoglobulins and their transporters in urogenital Chlamydial infections

Chlamydia trachomatis infections of the male and female reproductive tracts are the world's leading sexually transmitted bacterial disease, and can lead to damaging pathology, scarring and infertility. The resolution of chlamydial infection requires the development of adaptive immune responses to infection, and includes cell-mediated and humoral immunity. Whilst cluster of differentiation (CD)4+ T cells are known to be essential in clearance of infection [1], they are also associated with immune cell infiltration, autoimmunity and infertility in the testes [2-3]. Conversely, antibodies are less associated with inflammation, are readily transported into the reproductive tracts, and can offer lumenal neutralization of chlamydiae prior to infection. Antibodies, or immunoglobulins (Ig), play a supportive role in the resolution of chlamydial infections, and this thesis sought to define the function of IgA and IgG, against a variety of chlamydial antigens expressed during the intracellular and extracellular stages of the chlamydial developmental cycle. Transport of IgA and IgG into the mucosal lumen is facilitated by receptor-mediated transcytosis yet the expression profile (under normal conditions and during urogenital chlamydial infection) of the polymeric immunoglobulin receptor (pIgR) and the neonatal Fc receptor (FcRn) remains unknown. The expression profile of pIgR and FcRn in the murine male reproductive tract was found to be polarized to the lower and upper reproductive tract tissues respectively. This demonstrates that the two receptors have a tissue tropism, which must be considered when targeting pathogens that colonize different sites. In contrast, the expression of pIgR and FcRn in the female mouse was found to be distributed in both the upper and lower reproductive tracts. When urogenitally infected with Chlamydia muridarum, both male and female reproductive tracts up-regulated expression of pIgR and down-regulated expression of FcRn. Unsurprisingly, the up-regulation of pIgR increased the concentration of IgA in the lumen. However, down-regulation of FcRn, prevented IgG uptake and led to an increase or pooling of IgG in lumenal secretions. As previous studies have identified the importance of pIgR-mediated delivery of IgA, as well as the potential of IgA to bind and neutralize intracellular pathogens, IgA against a variety of chlamydial antigens was investigated. The protection afforded by IgA against the extracellular antigen major outer membrane protein (MOMP), was found to be dependent on pIgR expression in vitro and in vivo. It was also found that in the absence of pIgR, no protection was afforded to mice previously immunized with MOMP. The protection afforded from polyclonal IgA against the intracellular chlamydial antigens; inclusion membrane protein A (IncA), inclusion membrane proteins (IncMem) and secreted chlamydial protease-like activity factor (CPAF) were produced and investigated in vitro. Antigen-specific intracellular IgA was found to bind to the respective antigen within the infected cell, but did not significantly reduce inclusion formation (p > 0.05). This suggests that whilst IgA specific for the selected antigens was transported by pIgR to the chlamydial inclusion, it was unable to prevent growth. Similarly, immunization of male mice with intracellular chlamydial antigens (IncA or IncMem), followed by depletion CD4+ T cells, and subsequent urogenital C. muridarum challenge, provided minimal pIgR-mediated protection. Wild type male mice immunized with IncA showed a 57 % reduction (p < 0.05), and mice deficient in pIgR showed a 35 % reduction (p < 0.05) in reproductive tract chlamydial burden compared to control antigen, and in the absence of CD4+ T cells. This suggests that pIgR and secretory IgA (SIgA) were playing a protective role (21 % pIgR-mediated) in unison with another antigen-specific immune mechanism (36 %). Interestingly, IgA generated during a primary respiratory C. muridarum infection did not provide a significant amount of protection to secondary urogenital C. muridarum challenge. Together, these data suggest that IgA specific for an extracellular antigen (MOMP) can play a strong protective role in chlamydial infections, and that IgA targeting intracellular antigens is also effective but dependent on pIgR expression in tissues. However, whilst not investigated here, IgA targeting and blocking other intracellular chlamydial antigens, that are more essential for replication or type III secretion, may be more efficacious in subunit vaccines. Recently, studies have demonstrated that IgG can neutralize influenza virus by trafficking IgG-bound virus to lysosomes [4]. We sought to determine if this process could also traffic chlamydial antigens for degradation by lysosomes, despite Chlamydia spp. actively inhibiting fusion with the host endocytic pathway. As observed in pIgR-mediated delivery of anti-IncA IgA, FcRn similarly transported IgG specific for IncA which bound the inclusion membrane. Interestingly, FcRn-mediated delivery of anti-IncA IgG significantly decreased inclusion formation by 36 % (p < 0.01), and induced aberrant inclusion morphology. This suggests that unlike IgA, IgG can facilitate additional host cellular responses which affect the intracellular niche of chlamydial growth. Fluorescence microscopy revealed that IgG also bound the inclusion, but unlike influenza studies, did not induce the recruitment of lysosomes. Notably, anti-IncA IgG recruited sequestosomes to the inclusion membrane, markers of the ubiquitin/proteasome pathway and major histocompatibility complex (MHC) class I loading. To determine if the protection against C. muridarum infection afforded by IncA IgG in vitro translated in vivo, wild type mice and mice deficient in functional FcRn and MHC-I, were immunized, depleted of CD4+, and urogenitally infected with C. muridarum. Unlike in pIgR-deficient mice, the protection afforded from IncA immunization was completely abrogated in mice lacking functional FcRn and MHC-I/CD8+. Thus, both anti-IncA IgA and IgG can bind the inclusion in a pIgR and FcRn-mediated manner, respectively. However, only IgG mediates a higher reduction in chlamydial infection in vitro and in vivo suggesting more than steric blocking of IncA had occurred. Unlike anti-MOMP IgA, which reduced chlamydial infection of epithelial cells and male mouse tissues, IgG was found to enhance infectivity in vitro, and in vivo. Opsonization of EBs with MOMP-IgG enhanced inclusion formation of epithelial cells in a MOMP-IgG dose-dependent and FcRn-dependent manner. When MOMP-IgG opsonized EBs were inoculated into the vagina of female mice, a small but non-significant (p > 0.05) enhancement of cervicovaginal C. muridarum shedding was observed three days post infection in mice with functional FcRn. Interestingly, infection with opsonized EBs reduced the intensity of the peak of infection (day six) but protracted the duration of infection by 60 % in wild type mice only. Infection with EBs opsonized in IgG also significantly increased (p < 0.05) hydrosalpinx formation in the oviducts and induced lymphocyte infiltration uterine horns. As MOMP is an immunodominant antigen, and is widely used in vaccines, the ability of IgG specific to extracellular chlamydial antigens to enhance infection and induce pathology needs to be considered. Together, these data suggest that immunoglobulins play a dichotomous role in chlamydial infections, and are dependent on antigen specificity, FcRn and pIgR expression. FcRn was found to be highly expressed in upper male reproductive tract, whilst pIgR was dominantly expressed in the lower reproductive tract. Conversely, female mice expressed FcRn and pIgR in both the lower and upper reproductive tracts. In response to a normal chlamydial infection, pIgR is up-regulated increasing secretory IgA release, but FcRn is down-regulated preventing IgG uptake. Similarly to other studies [5-6], we demonstrate that IgA and IgG generated during primary chlamydial infections plays a minor role in recall immunity, and that antigen-specific subunit vaccines can offer more protection. We also show that both IgA and IgG can be used to target intracellular chlamydial antigens, but that IgG is more effective. Finally, IgA against the extracellular antigen MOMP can afford protection, whist IgG plays a deleterious role by increasing infectivity and inducing damaging immunopathology. Further investigations with additional antigens or combination subunit vaccines will enhance our understanding the protection afforded by antibodies against intracellular and extracellular pathogenic antigens, and help improve the development of an efficacious chlamydial vaccine.

A qualitative exploration of young women's drinking experiences and associated protective behaviours

While initial research supports the effectiveness of protective strategies in mitigating young people’s alcohol-related harm, few studies have investigated these behaviours from a uniquely female perspective. Yet, young women consume alcohol within a social context that is distinctly different from that of young men and face risks that are specific to their gender. To explore a group of young Australian women’s experiences, perceptions of risks and use of protective strategies in relation to drinking in public places, we conducted either focus groups or one-on-one telephone interviews with a total of 40 women aged 18–24 years. While young women reported substantial risks associated with drinking, they also reported using a range of protective behaviours that moderated the adverse effects of alcohol, with most of these strategies being derived from the friendship group to which the women belonged. Our findings add to the limited body of knowledge on women’s insights into, and their use of protective strategies to minimise the negative consequences of alcohol.

A cross-discipline and collaborative approach to identifying the predictors of environmentally friendly and health protective behaviour

Background. As a society, our interaction with the environment is having a negative impact on human health. For example, an increase in car use for short trips, over walking or cycling, has contributed to an increase in obesity, diabetes and poor heart health and also contributes to pollution, which is associated with asthma and other respiratory diseases. In order to change the nature of that interaction, to be more positive and healthy, it is recommended that individuals adopt a range of environmentally friendly behaviours (such as walking for transport and reducing the use of plastics). Effective interventions aimed at increasing such behaviours will need to be evidence based and there is a need for the rapid communication of information from the point of research, into policy and practice. Further, a number of health disciplines, including psychology and public health, share a common mission to promote health and well-being. Therefore, the objective of this project is to take a cross-discipline and collaborative approach to reveal psychological mechanisms driving environmentally friendly behaviour. This objective is further divided into three broad aims, the first of which is to take a cross-discipline and collaborative approach to research. The second aim is to explore and identify the salient beliefs which most strongly predict environmentally friendly behaviour. The third aim is to build an augmented model to explain environmentally friendly behaviour. The thesis builds on the understanding that an interdisciplinary collaborative approach will facilitate the rapid transfer of knowledge to inform behaviour change interventions. Methods. The application of this approach involved two surveys which explored the psycho-social predictors of environmentally friendly behaviour. Following a qualitative pilot study, and in collaboration with an expert panel comprising academics, industry professionals and government representatives, a self-administered, Theory of Planned Behaviour (TPB) based, mail survey was distributed to a random sample of 3000 residents of Brisbane and Moreton Bay Region (Queensland, Australia). This survey explored specific beliefs including attitudes, norms, perceived control, intention and behaviour, as well as environmental altruism and green identity, in relation to walking for transport and switching off lights when not in use. Following analysis of the mail survey data and based on feedback from participants and key stakeholders, an internet survey was employed (N=451) to explore two additional behaviours, switching off appliances at the wall when not in use, and shopping with reusable bags. This work is presented as a series of interrelated publications which address each of the research aims. Presentation of Findings. Chapter five of this thesis consists of a published paper which addresses the first aim of the research and outlines the collaborative and multidisciplinary approach employed in the mail survey. The paper argued that forging alliances with those who are in a position to immediately utilise the findings of research has the potential to improve the quality and timely communication of research. Illustrating this timely communication, Chapter six comprises a report presented to Moreton Bay Regional Council (MBRC). This report addresses aim's one and two. The report contains a summary of participation in a range of environmentally friendly behaviours and identifies the beliefs which most strongly predicted walking for transport and switching off lights (from the mail survey). These salient beliefs were then recommended as targets for interventions and included: participants believing that they might save money; that their neighbours also switch off lights; that it would be inconvenient to walk for transport and that their closest friend also walks for transport. Chapter seven also addresses the second aim and presents a published conference paper in which the salient beliefs predicting the four specified behaviours (from both surveys) are identified and potential applications for intervention are discussed. Again, a range of TPB based beliefs, including descriptive normative beliefs, were predictive of environmentally friendly behaviour. This paper was also provided to MBRC, along with recommendations for applying the findings. For example, as descriptive normative beliefs were consistently correlated with environmentally friendly behaviour, local councils could engage in marketing and interventions (workshops, letter box drops, internet promotions) which encourage parents and friends to model, rather than simply encourage, environmentally friendly behaviour. The final two papers, presented in Chapters eight and nine, addresses the third aim of the project. These papers each present two behaviours together to inform a TPB based theoretical model with which to predict environmentally friendly behaviour. A generalised model is presented, which is found to predict the four specific behaviours under investigation. The role of demographics was explored across each of the behaviour specific models. It was found that some behaviour's differ by age, gender, income or education. In particular, adjusted models predicted more of the variance in walking for transport amongst younger participants and females. Adjusted models predicted more variance in switching off lights amongst those with a bachelor degree or higher and predicted more variance in switching off appliances amongst those on a higher income. Adjusted models predicted more variance in shopping with reusable bags for males, people 40 years or older, those on a higher income and those with a bachelor degree or higher. However, model structure and general predictability was relatively consistent overall. The models provide a general theoretical framework from which to better understand the motives and predictors of environmentally friendly behaviour. Conclusion. This research has provided an example of the benefits of a collaborative interdisciplinary approach. It has identified a number of salient beliefs which can be targeted for social marketing campaigns and educational initiatives; and these findings, along with recommendations, have been passed on to a local council to be used as part of their ongoing community engagement programs. Finally, the research has informed a practical model, as well as behaviour specific models, for predicting sustainable living behaviours. Such models can highlight important core constructs from which targeted interventions can be designed. Therefore, this research represents an important step in undertaking collaborative approaches to improving population health through human-environment interactions.

Comparative study on the protective effects of Yinchenhao Decoction against liver injury induced by alpha-naphthylisothiocyanate and carbon tetrachloride

OBJECTIVE: To optimize the animal model of liver injury that can properly represent the pathological characteristics of dampness-heat jaundice syndrome of traditional Chinese medicine. METHODS: The liver injury in the model rat was induced by alpha-naphthylisothiocyanate (ANIT) and carbon tetrachloride (CCl(4) ) respectively, and the effects of Yinchenhao Decoction (, YCHD), a proved effective Chinese medical formula for treating the dampness-heat jaundice syndrome in clinic, on the two liver injury models were evaluated by analyzing the serum level of alanine aminotransferase (ALT), asparate aminotransferase (AST), alkaline phosphatase (ALP), malondialchehyche (MDA), total bilirubin (T-BIL), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) as well as the ratio of liver weight to body weight. The experimental data were analyzed by principal component analytical method of pattern recognition. RESULTS: The ratio of liver weight to body weight was significantly elevated in the ANIT and CCl(4) groups when compared with that in the normal control (P<0.01). The contents of ALT and T-BIL were significantly higher in the ANIT group than in the normal control (P<0.05,P<0.01), and the levels of AST, ALT and ALP were significantly elevated in CCl(4) group relative to those in the normal control P<0.01). In the YCHD group, the increase in AST, ALT and ALP levels was significantly reduced (P<0.05, P<0.01), but with no significant increase in serum T-BIL. In the CCl(4) intoxicated group, the MDA content was significantly increased and SOD, GSH-PX activities decreased significantly compared with those in the normal control group, respectively (P<0.01). The increase in MDA induced by CCl(4) was significantly reduced by YCHD P<0.05). CONCLUSION: YCHD showed significant effects on preventing liver injury progression induced by CCl(4), and the closest or most suitable animal model for damp-heat jaundice syndrome may be the one induced by CCl(4).

Booster vaccination of toddlers with reduced antigen content diphtheria-tetanus-acellular pertussis vaccine

Immunogenicity and reactogenicity of DTPa and reduced antigen dTpa booster vaccines were compared to a hepatitis A control vaccine in DTPa-primed toddlers aged 18-20 months. Post-booster, all DTPa and dTpa recipients were seroprotected against diphtheria and tetanus, and >= 93.3% had a booster response to pertussis. There were similar reactogenicity rates in the DTPa and dTpa vaccine recipients. Few Grade 3 symptoms were reported. Just over one in four children in the control group had diphtheria antibody at or potentially below the correlate of protection benchmark (0.016 IU/ml). Larger studies should evaluate potential benefits of reduced antigen vaccines and seroprotection in children who do not receive a booster dose of DTPa at this age, including protection against diphtheria until subsequent booster doses are given. (C) 2009 Elsevier Ltd. All rights reserved.

Reshaping our protective systems : issues and options

Australia's systems for protecting children from child abuse and neglect are undergoing reform in light of the National Framework for Protecting Australia's Children and innumerable judicial and other inquiries into their operations and outcomes. This article examines the current context for child protection practice and critically examines the dominant policy and practice frameworks, highlighting issues confronting policy makers and practitioners. Within the current systematic reform agendas, it is posited, there are key priorities that must be attended to in order to bring about necessary change, workforce support and a renewed emphasis on quality professional practice and re-orientation of practice approaches. Also required is the embedding of ethics into a relationship-based practice framework, and revitalising localised community involvement in a protective web of care that provides practical, compassionate and accessible help to needy and vulnerable children and families.

The nature and correlates of young women's peer-directed protective behavioral strategies

Objective Recently, a number of studies have identified self-employed Protective Behavioral Strategies (PBS) as effective in decreasing the level of alcohol-related harm among young people. However, much of the published research has ignored important gender differences, such as women's increased tendency to rely on PBS that are social in nature. To further the understanding of women's PBS, the current study sought to investigate the nature and correlates of the strategies young women employ to keep their friends safe when drinking (i.e., peer-directed PBS). Method A scale measuring peer-directed PBS was developed and administered in conjunction with existing measures of alcohol consumption, personal PBS, and peer attachment. Participants consisted of 422 women aged 18–30 years, recruited among psychology students and the general public. Results Exploratory factor analysis revealed two clusters of peer-directed PBS; those that were aimed at reducing intoxication among one's friends and those that were designed to minimize alcohol-related harms. Further analysis found a positive relationship between women's tendency to implement personal and peer-directed PBS and that risky drinkers were less likely to engage in personal or peer-directed PBS (either type). Conclusion Findings indicate that personal and peer-directed PBS are related behaviors that are less frequently adopted by risky drinkers.

Physiological tolerance times while wearing explosive ordnance disposal protective clothing in simulated environmental extremes

Explosive ordnance disposal (EOD) technicians are required to wear protective clothing to protect themselves from the threat of overpressure, fragmentation, impact and heat. The engineering requirements to minimise these threats results in an extremely heavy and cumbersome clothing ensemble that increases the internal heat generation of the wearer, while the clothing’s thermal properties reduce heat dissipation. This study aimed to evaluate the heat strain encountered wearing EOD protective clothing in simulated environmental extremes across a range of differing work intensities. Eight healthy males [age 25±6 years (mean ± sd), height 180±7 cm, body mass 79±9 kg, V˙O2max 57±6 ml.kg−1.min−1] undertook nine trials while wearing an EOD9 suit (weighing 33.4 kg). The trials involved walking on a treadmill at 2.5, 4 and 5.5 km⋅h−1 at each of the following environmental conditions, 21, 30 and 37°C wet bulb globe temperature (WBGT) in a randomised controlled crossover design. The trials were ceased if the participants’ core temperature reached 39°C, if heart rate exceeded 90% of maximum, if walking time reached 60 minutes or due to fatigue/nausea. Tolerance times ranged from 10–60 minutes and were significantly reduced in the higher walking speeds and environmental conditions. In a total of 15 trials (21%) participants completed 60 minutes of walking; however, this was predominantly at the slower walking speeds in the 21°C WBGT environment. Of the remaining 57 trials, 50 were ceased, due to attainment of 90% maximal heart rate. These near maximal heart rates resulted in moderate-high levels of physiological strain in all trials, despite core temperature only reaching 39°C in one of the 72 trials.

Divergent outcomes following transcytosis of IgG targeting intracellular and extracellular chlamydial antigens

Antibodies can play a protective but non-essential role in natural chlamydial infections dependent on antigen specificity and antibody isotype. IgG is the dominant antibody in both male and female reproductive tract mucosal secretions, and is bi-directionally trafficked across epithelia by the neonatal Fc receptor (FcRn). Using physiologically relevant pH-polarized epididymal epithelia grown on Transwells®, IgG specifically targeting an extracellular chlamydial antigen; the Major Outer Membrane Protein (MOMP), enhanced uptake and translocation of infection at pH 6-6.5 but not at neutral pH. This was dependent on FcRn expression. Conversely, FcRn-mediated transport of IgG targeting the intracellular chlamydial inclusion membrane protein A (IncA), induced aberrant inclusion morphology, recruited autophagic proteins independent of lysosomes, and significantly reduced infection. Challenge of female mice with MOMP-specific IgG-opsonized C. muridarum delayed infection clearance but exacerbated oviduct occlusion. In male mice, MOMP-IgG elicited by immunization afforded no protection against testicular chlamydial infection, whereas; the transcytosis of IncA-IgG significantly reduced testicular chlamydial burden. Together these data show that the protective and pathological effects of IgG are dependent on FcRn-mediated transport as well as the specificity of IgG for intracellular or extracellular antigens.

Immunization with a MOMP-based vaccine protects mice against a Pulmonary Chlamydia challenge and identifies a disconnection between infection and pathology

Chlamydia pneumoniae is responsible for up to 20% of community acquired pneumonia and can exacerbate chronic inflammatory diseases. As the majority of infections are either mild or asymptomatic, a vaccine is recognized to have the greatest potential to reduce infection and disease prevalence. Using the C. muridarum mouse model of infection, we immunized animals via the intranasal (IN), sublingual (SL) or transcutaneous (TC) routes, with recombinant chlamydial major outer membrane protein (MOMP) combined with adjuvants CTA1-DD or a combination of cholera toxin/CpG-oligodeoxynucleotide (CT/CpG). Vaccinated animals were challenged IN with C. muridarum and protection against infection and pathology was assessed. SL and TC immunization with MOMP and CT/CpG was the most protective, significantly reducing chlamydial burden in the lungs and preventing weight loss, which was similar to the protection induced by a previous live infection. Unlike a previous infection however, these vaccinations also provided almost complete protection against fibrotic scarring in the lungs. Protection against infection was associated with antigen-specific production of IFNγ, TNFα and IL-17 by splenocytes, however, protection against both infection and pathology required the induction of a similar pro-inflammatory response in the respiratory tract draining lymph nodes. Interestingly, we also identified two contrasting vaccinations capable of preventing infection or pathology individually. Animals IN immunized with MOMP and either adjuvant were protected from infection, but not the pathology. Conversely, animals TC immunized with MOMP and CTA1-DD were protected from pathology, even though the chlamydial burden in this group was equivalent to the unimmunized controls. This suggests that the development of pathology following an IN infection of vaccinated animals was independent of bacterial load and may have been driven instead by the adaptive immune response generated following immunization. This identifies a disconnection between the control of infection and the development of pathology, which may influence the design of future vaccines.