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Thorburn A.N.,Hunter Medical Research Institute | Hansbro P.M.,Hunter Medical Research Institute
American Journal of Respiratory Cell and Molecular Biology | Year: 2010

Regulatory T cells (Tregs) play an essential role in maintaining the homeostatic balance of immune responses. Asthma is an inflammatory condition of the airways that is driven by dysregulated immune responses toward normally innocuous antigens. Individuals with asthma have fewer and less functional Tregs, which may lead to uncontrolled effector cell responses and promote proasthmatic responses of T helper type 2, T helper 17, natural killer T, antigen-presenting, and B cells. Tregs have the capacity to either directly or indirectly suppress these responses. Hence, the induced expansion of functional Tregs in predisposed or individuals with asthma is a potential approach for the prevention and treatment of asthma. Infection by a number of micro-organisms has been associated with reduced prevalence of asthma, and many infectious agents have been shown to induce Tregs and reduce allergic airways disease in mouse models. The translation of the regulatory and therapeutic properties of infectious agents for use in asthma requires the identification of key modulatory components and the development and trial of effective immunoregulatory therapies. Further translational and clinical research is required for the induction of Tregs to be harnessed as a therapeutic strategy for asthma.

The Hospital Anxiety and Depression Scale (HADS) is often used to screen for cancer caregivers' anxiety and depression, despite few studies examining the tool's psychometric performance within this population. The purpose of this article is to use Rasch analysis to assess the psychometric properties of the HADS in a sample of cancer caregivers. HADS was administered to 541 caregivers of a population-based sample of patients diagnosed with one of the eight most incident cancers in Australia. Rasch analysis was conducted using RUMM2020. More than two-thirds of caregivers were women and most participants were married (95.9%) and caring for their spouse/partner with cancer (89.8%). The HADS-Anxiety (HADS-A) subscale showed good fit to the model, with appropriate internal consistency after removal of item 11. There were no disordered thresholds and no differential item functioning (DIF) for sex or age. To achieve satisfactory model fit for the HADS-Depression (HADS-D) subscale item 8 was removed due to DIF for sex and item 14 was rescored to resolve disordered thresholds. Analyses supported the unidimensionality of the individual subscales; however, there was no support for the combination of subscales to form a HADS-Total. The results of Rasch analysis support the use of a modified version of the HADS-A and HADS-D among cancer caregivers. Further research is needed to confirm these findings and identify revised clinical cut-points. Findings reinforce the need for clinicians and researchers to formally test the psychometric properties of the instruments that they intend to use with different samples. Copyright © 2010 John Wiley & Sons, Ltd. Copyright © 2010 John Wiley & Sons, Ltd.

Aitken R.J.,Hunter Medical Research Institute
Reproduction | Year: 2014

There has never been a greater need for scientists trained in reproductive science. Most developed countries are witnessing unprecedented rates of recourse to assisted conception sitting cheek-by-jowl with high rates of induced abortion. This article addresses these two incongruous faces of reproductive healthcare. Every year at least 44 million abortions are performed worldwide, many under unsafe and insanitary conditions that carry a significant risk to the lives of women deprived of safe, effective methods for controlling their fertility. Although birth control is a complex issue involving myriad social and political factors, the technical vacuum in this area is significant. Through no fault of the family planning authorities, there have been no radically new methods of fertility control since the oral contraceptive pill was introduced in 1960 and even this contribution to planned parenthood has its roots in the biochemistry of the 1920s and 1930s. Moreover, the pharmaceutical industry has, by and large, turned its back on fundamental research activities in this area. At present, our major investment in reproductive healthcare involves treating ever-increasing numbers of couples with assisted reproductive technologies (ART). However, these treatments are often delivered without critically considering the underlying causes of this condition or seriously contemplating the long-term consequences of the current enthusiasm for such therapy. Significantly, the clinical factors underpinning the commitment of couples to ART include advanced maternal age and a variety of lifestyle factors, such as smoking and obesity, which are known to compromise the developmental potential of the oocyte and DNA integrity in spermatozoa. © 2014 Society for Reproduction and Fertility.

Keely S.,Hunter Medical Research Institute | Talley N.J.,Hunter Medical Research Institute | Hansbro P.M.,University of Newcastle
Mucosal Immunology | Year: 2012

Chronic obstructive pulmonary disease (COPD) and inflammatory bowel diseases (IBDs) are chronic inflammatory diseases of mucosal tissues that affect the respiratory and gastrointestinal tracts, respectively. They share many similarities in epidemiological and clinical characteristics, as well as in inflammatory pathologies. Importantly, both conditions are accompanied by systemic comorbidities that are largely overlooked in both basic and clinical research. Therefore, consideration of these complications may maximize the efficacy of prevention and treatment approaches. Here, we examine both the intestinal involvement in COPD and the pulmonary manifestations of IBD. We also review the evidence for inflammatory organ cross-talk that may drive these associations, and discuss the current frontiers of research into these issues.

Aitken R.J.,Hunter Medical Research Institute | Nixon B.,Hunter Medical Research Institute
Molecular Human Reproduction | Year: 2013

Capacitation is a remarkable process whereby spermatozoa prepare themselves for engagement with the oocyte. Although the existence of this process has been appreciated as a biological phenomenon for more than half a century, its molecular underpinnings still await clarification.We knowthat some of the major changes involve sterol oxidation and efflux from the plasma membrane, the anterior movement of lipid rafts, changes in the surface expression of a variety of proteins including hyaluronidase and receptors for the zona pellucida, an increase in intracellular cyclic adenosine monophosphate (cAMP), the induction of tyrosine phosphorylation and the expression of hyperactivated motility. These changes are dependent on the presence of bicarbonate, to facilitate cAMP generation, maintain an alkaline intracellular pH and support an optimal level of reactive oxygen species generation and are enhanced by the presence of albumin to provide antioxidant protection to the plasma membrane and promote cholesterol efflux. In vivo, the rate at which sperm cells capacitate is carefully controlled in order to ensure that the release of capacitated spermatozoa from a post-insemination reservoir in the isthmic region of the oviduct is synchronized with ovulation. The factors that control these critical events are now being resolved, aided by proteomic studies that are providing critical definitive information on the range of receptors that exist in the sperm plasma membrane and define the manner in which these exquisitely complex cells interact with their environment. Progress in this area has been enhanced by IVF technology pioneered by BobEdwards and will ultimately facilitate the design of safe, effective culture conditions for optimization of this revolutionary therapy. © The Author 2013.

Linden W.,University of British Columbia | Girgis A.,Hunter Medical Research Institute
Psycho-Oncology | Year: 2012

Objective: The effectiveness of psychological treatment for distress reduction in cancer patients has been frequently studied and reviewed in systematic reviews but reviewer conclusions vary considerably. Clear and consistent evidence is needed to assist clinicians and administrators with their decision-making. We hypothesized that uneven handling of confounding methodological features are at least partly the reason for disagreements and reviewed the literature in this light. Method: A systematic review of 14 published meta-analyses was conducted to determine whether due consideration of moderating variables in psycho-oncological treatments permits clearer recommendations. Quality of the reviews, treatment type, dosage, therapist qualities, outcomes at follow-up, and screening versus not screening for elevated distress were examined as moderator variables. Results: Treatment effects are consistently positive but also vary greatly in magnitude. There is lacking evidence for many important questions, in particular, differential treatment effects for different cancer types and stages. Regarding moderators of outcome, quality of review had no impact on results for depression but including lower quality reviews actually lead to underestimation of treatment effects for anxiety. The most potent negative moderator variable, however, is a floor effect that arises when patients are recruited for treatment studies without being selected for high levels of distress. Such indiscriminate recruitment is very frequent in psycho-oncology and leads to small reported treatment effects; when, however, patients are first screened for elevated distress, the ratio of observed treatment effects sizes is roughly three times greater. Conclusion: Sweeping judgments about the effectiveness of psycho-oncological treatments for distress reduction are somewhat misleading and counter-productive. Among moderator variables, floor effects are particularly pervasive and have a large suppressor effect on observed outcomes. Copyright © 2011 John Wiley & Sons, Ltd.

Murphy V.E.,Hunter Medical Research Institute | Schatz M.,Kaiser Permanente
European Respiratory Review | Year: 2014

Asthma commonly occurs in pregnant females, and recent data have outlined the risks of adverse perinatal outcomes among this population. There is an increased risk of low birth weight and small for gestational age, particularly among females with moderate-to-severe asthma and exacerbations during pregnancy. There is also an increased risk of preterm birth, especially with oral steroid use, a small but statistically significant increased risk of congenital malformations, particularly of cleft lip with or without cleft palate, and an increased risk of neonatal hospitalisation and death. Active management may reduce these risks, possibly through reductions in exacerbations. Additional reassuring data have been presented for asthma medication use, which support the benefits outweighing the risks of indicated asthma medication use in pregnancy. Viral infections are an important trigger of asthma exacerbations in pregnancy, and recent data provides possible immunological changes that may explain this. Poor medication adherence despite worsening asthma symptoms in pregnancy is a problem which continues to be demonstrated in the literature. Improving asthma control in pregnancy has the potential to improve not only the mother's health but also that of her child. © ERS 2014.

Bivard A.,Hunter Medical Research Institute
Journal of Cerebral Blood Flow and Metabolism | Year: 2014

The aim of acute stroke treatment is to reperfuse the penumbra. However, not all posttreatment reperfusion is associated with a good outcome. Recent arterial spin labeling (ASL) studies suggest that patients with hyperperfusion after treatment have a better clinical recovery. This study aimed to determine whether there was a distinctive magnetic resonance spectroscopy (MRS) metabolite profile in hyperperfused tissue after stroke reperfusion therapy. We studied 77 ischemic stroke patients 24 hours after treatment using MRS (single voxel spectroscopy, point resolved spectroscopy, echo time 30 ms), ASL, and diffusion-weighted imaging (DWI). Magnetic resonance spectroscopy voxels were placed in cortical tissue that was penumbral on baseline perfusion imaging but had reperfused at 24 hours (and did not progress to infarction). Additionally, 20 healthy age matched controls underwent MRS. In all, 24 patients had hyperperfusion; 36 had reperfused penumbra without hyperperfusion, and 17 were excluded due to no reperfusion. Hyperperfusion was significantly related to better 3-month clinical outcome compared with patients without hyperperfusion (P=0.007). Patients with hyperperfusion showed increased glutamate (P<0.001), increased N-Acetylaspartate (NAA) (P=0.038), and increased lactate (P<0.002) in reperfused tissue compared with contralateral tissue and healthy controls. Hyperperfused tissue has a characteristic metabolite signature, suggesting that it is more metabolically active and perhaps more capable of later neuroplasticity.Journal of Cerebral Blood Flow & Metabolism advance online publication, 1 October 2014; doi:10.1038/jcbfm.2014.166. © 2014 International Society for Cerebral Blood Flow & Metabolism, Inc.

Meeting the psychosocial needs of vulnerable groups such as cancer survivors remains an ongoing challenge. This is particularly so for those who have less access to the usual forms of medical specialist and in-person support networks. Internet-based approaches offer an opportunity to better meet patients' information and support needs by overcoming the barrier of geographic isolation. The aim of the study was to assess the reported level of access to the Internet, preferred sources of information, and preferred sources of support among survivors of hematologic cancers. A population-based, Australian state cancer registry invited eligible survivors to complete a survey about psychosocial needs, including items measuring Internet access and patterns of use. Of the 732 eligible survivors invited to participate, 268 (36.6%) completed and returned the pen-and-paper-based survey. The majority of participants (186/254, 73.2%) reported a high level of access to the Internet, with higher Internet access associated with a higher level of education, larger household, younger age, and being married or employed. A total of 62.2% (156/251) of survivors indicated they were likely to use the Internet for accessing information, with the percentage much lower (69/251, 28%) for accessing support via the Internet. Likelihood of using the Internet for support was associated with feeling anxious and being employed. While the Internet appears to offer promise in increasing equitable access to information and support for cancer survivors for both metropolitan and regional areas, it is viewed less favorably for support and by particular subgroups (eg, older people and those without a university degree) within the survivor population. Promoting greater understanding of this mode of support may be required to achieve its potential. Information and support options other than Web-based approaches may continue to be needed by vulnerable groups of cancer survivors.

Boyes A.W.,Hunter Medical Research Institute
Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2013

Few studies have examined psychological adjustment for cancer survivors in late treatment and early survivorship stages. Our study investigated the prevalence and short-term trajectories of anxiety, depression, and comorbid anxiety-depression among adult cancer survivors, and identified the individual, disease, health behavior, psychological, and social predictors of chronic and late psychological morbidity. A heterogeneous sample of adult cancer survivors was recruited from two state-based cancer registries. A total of 1,154 survivors completed self-report questionnaires at 6 (Time 1) and 12 months (Time 2) postdiagnosis. Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale with cases identified by a subscale cutoff score ≥ 8. Logistic regression analyses identified Time 1 characteristics associated with anxiety and/or depression at Time 2. The point prevalence of anxiety (Time 1, 22%; Time 2, 21%), depression (13% at both timepoints) and comorbid anxiety-depression (9% at both timepoints) was similar at 6 and 12 months postdiagnosis. The most prevalent Time 1 to Time 2 trajectory was noncase for anxiety (70%), depression (82%), and comorbid anxiety-depression (87%). While psychological morbidity at Time 1 was the strongest predictor of psychological morbidity at Time 2, being diagnosed with lung cancer and health risk behaviors (smoking, insufficient physical activity) were also strong predictors. Targeted psychological screening of vulnerable survivors and early intervention may prevent the onset and/or reduce the severity of psychological morbidity in early survivorship. Trials of risk reduction interventions targeting psychological functioning and health risk behaviors seem warranted.

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