HtrA, RseP, and Tsp do not elicit a pathology related serum IgG response during sexually transmitted infection with Chlamydia trachomatis

Chlamydia trachomatis sexually transmitted infection can cause serious reproductive morbidities. This study determined the prevalence of serum IgG response to C. trachomatis putative stress response proteins in females to test for an association with genital tract pathology. There was no significant association of serum IgG to HtrA, Tsp, or RseP with infection or pathology. cHSP60 serum IgG prevalence was significantly associated with infection compared to negative (infertile) controls (p = 0.002), but not with upper genital tract pathology. Serum IgG1-4 antibody subclasses reactive with the antigens was not significantly different between cohorts, although different responses to each antigen were detected.

Palliative care curriculum for speech–language pathology students

This paper reports on the experience of undergraduate speech–language pathology students at one university chosen for the implementation stage of the Palliative Care Curriculum for Undergraduates (PCC4U) Project. Funded by a government department for health and ageing through a national palliative care programme, the project was managed by a team of researchers from the discipline of nursing. The PCC4U project championed the inclusion of palliative care education as an integral part of medical, nursing, and allied healthcare undergraduate training. Of the pilot sites chosen for the PCC4U project, only one site, reported here, included both speech–language pathology and social work disciplines, providing an important opportunity for interdisciplinary collaboration on novel curriculum development in an area of mutual interest. This synergy served as an excellent foundation for ongoing opportunities for interdisciplinary teaching and learning in the university. Speech–language pathology students reported that the project was an invaluable addition to their education and preparation for clinical practice.

Identification of novel markers for uncomplicated lower genital tract infections and upper genital tract pathology due to Chlamydia trachomatis.

Background: Untreated Chlamydia trachomatis infections in women can result in disease sequelae such as salpingitis and pelvic inflammatory disease (PID), ultimately culminating in tubal occlusion and infertility. Whilst nucleic acid amplification tests can effectively diagnose uncomplicated lower genital tract (LGT) infections, they are not suitable for diagnosing upper genital tract (UGT) pathological sequelae. As a consequence, this study aimed to identify serological markers that can, with a high degree of sensitivity and specificity, discriminate between LGT infections and UGT pathology. Methods: Plasma was collected from 73 women with a history of LGT infection, UGT pathology due to C. trachomatis or no serological evidence of C. trachomatis infection. Western blotting was used to analyse antibody reactivity against extracted chlamydial proteins. Sensitivity and specificity of differential markers were also calculated. Results: Four antigens (CT157, CT423, CT727 and CT396) were identified and found to be capable of discriminating between the infection and disease sequelae state. Sensitivity and specificity calculations showed that our assay for diagnosing LGT infection had a sensitivity and specificity of 75% and 76% respectively, whilst the assay for identifying UGT pathology demonstrated 80% sensitivity and 86% specificity. Conclusions: The use of these assays could potentially facilitate earlier diagnoses in women suffering UGT pathology due to C. trachomatis.

Chlamydia muridarum major outer membrane protein-specific antibodies inhibit in vitro infection but enhance pathology in vivo

PROBLEM Chlamydia trachomatis is a significant worldwide health problem, and the often-asymptomatic disease can result in infertility. To develop a successful vaccine, a complete understanding of the immune response to chlamydial infection and development of genital tract pathology is required. METHOD OF STUDY We utilized the murine genital model of chlamydial infection. Mice were immunized with chlamydial major outer membrane protein, and vaginal lavage was assessed for the presence of neutralizing antibodies. These samples were then pre-incubated with Chlamydia muridarum and administered to the vaginal vaults of immune-competent female BALB/c mice to determine the effect on infection. RESULTS The administration of C. muridarum in conjunction with neutralizing antibodies reduced the numbers of mice infected, but a surprising finding was that this accelerated the development of severe oviduct pathology. CONCLUSION Antibodies play an under-recognized role in chlamydial infection and pathology development, which possibly involves interaction with Th1 immunity.

Questioning a "Compulsory Ontology of Pathology" regarding suicide and the suicidal

Review of Suicide : Foucault, History and Truth, by Ian Marsh

Integration of medical images to the teaching of systematic pathology : an evaluation of relevance

A sound knowledge of pathological disease processes is required for professional practice within health professions. The project described in this paper reviewed the resources currently available for the delivery of systematic pathology tutorials. Additional complementary resources were developed and the inclusion of these additional learning resources in practical tutorial sessions was evaluated for their impact on student learning. Student evaluation of the learning resources was undertaken across one semester with two different cohorts of health profession students using questionnaires and focus group discussion. Both cohorts reported an enhancement to their understanding of pathological disease processes through the use of the additional resources. Results indicate student perception of the value of the resources correlates with staff perception and is independent of prior experiences.

Vaccination of healthy and diseased koalas (Phascolarctos cinereus) with a Chlamydia pecorum multi-subunit vaccine : evaluation of immunity and pathology

Chlamydial infections represent a major threat to the long-term survival of the koala and a successful vaccine would provide a valuable management tool. Vaccination however has the potential to enhance inflammatory disease in animals exposed to a natural infection prior to vaccination, a finding in early human and primate trials of whole cell vaccines to prevent trachoma. In the present study, we vaccinated both healthy koalas as well as clinically diseased koalas with a multi-subunit vaccine consisting of Chlamydia pecorum MOMP and NrdB mixed with immune stimulating complex as adjuvant. Following vaccination, there was no increase in inflammatory pathological changes in animals previously infected with Chlamydia. Strong antibody (including neutralizing antibodies) and lymphocyte proliferation responses were recorded in all vaccinated koalas, both healthy and clinically diseased. Vaccine induced antibodies specific for both vaccine antigens were observed not only in plasma but also in ocular secretions. Our data shows that an experimental chlamydial vaccine is safe to use in previously infected koalas, in that it does not worsen infection-associated lesions. Furthermore, the prototype vaccine is effective, as demonstrated by strong levels of neutralizing antibody and lymphocyte proliferation responses in both healthy and clinically diseased koalas. Collectively, this work illustrates the feasibility of developing a safe and effective Chlamydia vaccine as a tool for management of disease in wild koalas.

Chromatin modifications involved in the DNA damage response to double strand breaks

In eukaryotes, genomic DNA is tightly compacted into a protein-DNA complex known as chromatin. This dense structure presents a barrier to DNA-dependent processes including transcription, replication and DNA repair. The repressive structure of chromatin is overcome by ATP-dependent chromatin remodelling complexes and chromatin-modifying enzymes. There is now ample evidence that DNA double-strand breaks (DSBs) elicit various histone modifications (such as acetylation, deacetylation, and phosphorylation) that function combinatorially to control the dynamic structure of the chromatin microenvironment. The role of these mechanisms during transcription and replication has been well studied, while the research into their impact on regulation of DNA damage response is rapidly gaining momentum. How chromatin structure is remodeled in response to DNA damage and how such alterations influence DSB repair are currently significant questions. This review will summarise the major chromatin modifications and chromatin remodelling complexes implicated in the DNA damage response to DSBs.

The confidence of speech-language pathology students regarding communicating with people with aphasia

Background Aphasia is an acquired language disorder that can present a significant barrier to patient involvement in healthcare decisions. Speech-language pathologists (SLPs) are viewed as experts in the field of communication. However, many SLP students do not receive practical training in techniques to communicate with people with aphasia (PWA) until they encounter PWA during clinical education placements. Methods This study investigated the confidence and knowledge of SLP students in communicating with PWA prior to clinical placements using a customised questionnaire. Confidence in communicating with people with aphasia was assessed using a 100-point visual analogue scale. Linear, and logistic, regressions were used to examine the association between confidence and age, as well as confidence and course type (graduate-entry masters or undergraduate), respectively. Knowledge of strategies to assist communication with PWA was examined by asking respondents to list specific strategies that could assist communication with PWA. Results SLP students were not confident with the prospect of communicating with PWA; reporting a median 29-points (inter-quartile range 17–47) on the visual analogue confidence scale. Only, four (8.2%) of respondents rated their confidence greater than 55 (out of 100). Regression analyses indicated no relationship existed between confidence and students‘ age (p = 0.31, r-squared = 0.02), or confidence and course type (p = 0.22, pseudo r-squared = 0.03). Students displayed limited knowledge about communication strategies. Thematic analysis of strategies revealed four overarching themes; Physical, Verbal Communication, Visual Information and Environmental Changes. While most students identified potential use of resources (such as images and written information), fewer students identified strategies to alter their verbal communication (such as reduced speech rate). Conclusions SLP students who had received aphasia related theoretical coursework, but not commenced clinical placements with PWA, were not confident in their ability to communicate with PWA. Students may benefit from an educational intervention or curriculum modification to incorporate practical training in effective strategies to communicate with PWA, before they encounter PWA in clinical settings. Ensuring students have confidence and knowledge of potential communication strategies to assist communication with PWA may allow them to focus their learning experiences in more specific clinical domains, such as clinical reasoning, rather than building foundation interpersonal communication skills.

Factors influencing research engagement : research interest, confidence and experience in an Australian speech-language pathology workforce

Background Recent initiatives within an Australia public healthcare service have seen a focus on increasing the research capacity of their workforce. One of the key initiatives involves encouraging clinicians to be research generators rather than solely research consumers. As a result, baseline data of current research capacity are essential to determine whether initiatives encouraging clinicians to undertake research have been effective. Speech pathologists have previously been shown to be interested in conducting research within their clinical role; therefore they are well positioned to benefit from such initiatives. The present study examined the current research interest, confidence and experience of speech language pathologists (SLPs) in a public healthcare workforce, as well as factors that predicted clinician research engagement. Methods Data were collected via an online survey emailed to an estimated 330 SLPs working within Queensland, Australia. The survey consisted of 30 questions relating to current levels of interest, confidence and experience performing specific research tasks, as well as how frequently SLPs had performed these tasks in the last 5 years. Results Although 158 SLPs responded to the survey, complete data were available for only 137. Respondents were more confident and experienced with basic research tasks (e.g., finding literature) and less confident and experienced with complex research tasks (e.g., analysing and interpreting results, publishing results). For most tasks, SLPs displayed higher levels of interest in the task than confidence and experience. Research engagement was predicted by highest qualification obtained, current job classification level and overall interest in research. Conclusions Respondents generally reported levels of interest in research higher than their confidence and experience, with many respondents reporting limited experience in most research tasks. Therefore SLPs have potential to benefit from research capacity building activities to increase their research skills in order to meet organisational research engagement objectives. However, these findings must be interpreted with the caveats that a relatively low response rate occurred and participants were recruited from a single state-wide health service, and therefore may not be representative of the wider SLP workforce.

Epigenetics underpinning the regulation of the CXC (ELR+) chemokines in non-small cell lung cancer

Background: Angiogenesis may play a role in the pathogenesis of Non-Small Cell Lung cancer (NSCLC). The CXC (ELR+) chemokine family are powerful promoters of the angiogenic response. Methods: The expression of the CXC (ELR+) family members (CXCL1-3/GROα-γ, CXCL8/IL-8, CXCR1/2) was examined in a series of resected fresh frozen NSCLC tumours. Additionally, the expression and epigenetic regulation of these chemokines was examined in normal bronchial epithelial and NSCLC cell lines. Results: Overall, expression of the chemokine ligands (CXCL1, 2, 8) and their receptors (CXCR1/2) were down regulated in tumour samples compared with normal, with the exception of CXCL3. CXCL8 and CXCR1/2 were found to be epigenetically regulated by histone post-translational modifications. Recombinant CXCL8 did not stimulate cell growth in either a normal bronchial epithelial or a squamous carcinoma cell line (SKMES-1). However, an increase was observed at 72 hours post treatment in an adenocarcinoma cell line. Conclusions: CXC (ELR+) chemokines are dysregulated in NSCLC. The balance of these chemokines may be critical in the tumour microenvironment and requires further elucidation. It remains to be seen if epigenetic targeting of these pathways is a viable therapeutic option in lung cancer treatment. © 2011 Baird et al.

Histone deacetylase inhibitors target diabetes via chromatin remodeling or as chemical chaperones?

Globally, obesity and diabetes (particularly type 2 diabetes) represents a major challenge to world health. Despite decades of intense research efforts, the genetic basis involved in diabetes pathogenesis & conditions associated with obesity are still poorly understood. Recent advances have led to exciting new developments implicating epigenetics as an important mechanism underpinning diabetes and obesity related disease. One epigenetic mechanism known as the "histone code" describes the idea that specific patterns of post-translational modifications to histones act like a molecular "code" recognised and used by non-histone proteins to regulate specific chromatin functions. One modification which has received significant attention is that of histone acetylation. The enzymes which regulate this modification are described as lysine acetyltransferases or KATs and histone deacetylases or HDACs. Due to their conserved catalytic domain HDACs have been actively targeted as a therapeutic target. Some of the known inhibitors of HDACs (HDACi) have also been shown to act as "chemical chaperones" to alleviate diabetic symptoms. In this review, we discuss the available evidence concerning the roles of HDACs in regulating chaperone function and how this may have implications in the management of diabetes. © 2009 Bentham Science Publishers Ltd.

Oxidative stress induced lung cancer and COPD : opportunities for epigenetic therapy

Reactive oxygen species (ROS) form as a natural by-product of the normal metabolism of oxygen and play important roles within the cell. Under normal circumstances the cell is able to maintain an adequate homeostasis between the formation of ROS and its removal through particular enzymatic pathways or via antioxidants. If however, this balance is disturbed a situation called oxidative stress occurs. Critically, oxidative stress plays important roles in the pathogenesis of many diseases, including cancer. Epigenetics is a process where gene expression is regulated by heritable mechanisms that do not cause any direct changes to the DNA sequence itself, and disruption of epigenetic mechanisms has important implications in disease. Evidence is emerging that histone deacetylases (HDACs) play decisive roles in regulating important cellular oxidative stress pathways including those involved with sensing oxidative stress and those involved with regulating the cellular response to oxidative stress. In particular aberrant regulation of these pathways by HDACs may play critical roles in cancer progression. In this review we discuss the current evidence linking epigenetics and oxidative stress and cancer, using chronic obstructive pulmonary disease and non-small cell lung cancer to illustrate the importance of epigenetics on these pathways within these disease settings. © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.