Grass pollen allergens globally: The contribution of subtropical grasses to burden of allergic respiratory diseases

Grass pollens of the temperate (Pooideae) subfamily and subtropical subfamilies of grasses are major aeroallergen sources worldwide. The subtropical Chloridoideae (e.g. Cynodon dactylon; Bermuda grass) and Panicoideae (e.g. Paspalum notatum; Bahia grass) species are abundant in parts of Africa, India, Asia, Australia and the Americas, where a large and increasing proportion of the world's population abide. These grasses are phylogenetically and ecologically distinct from temperate grasses. With the advent of global warming, it is conceivable that the geographic distribution of subtropical grasses and the contribution of their pollen to the burden of allergic rhinitis and asthma will increase. This review aims to provide a comprehensive synthesis of the current global knowledge of (i) regional variation in allergic sensitivity to subtropical grass pollens, (ii) molecular allergenic components of subtropical grass pollens and (iii) allergic responses to subtropical grass pollen allergens in relevant populations. Patients from subtropical regions of the world show higher allergic sensitivity to grass pollens of Chloridoideae and Panicoideae grasses, than to temperate grass pollens. The group 1 allergens are amongst the allergen components of subtropical grass pollens, but the group 5 allergens, by which temperate grass pollen extracts are standardized for allergen content, appear to be absent from both subfamilies of subtropical grasses. Whilst there are shared allergenic components and antigenic determinants, there are additional clinically relevant subfamily-specific differences, at T- and B-cell levels, between pollen allergens of subtropical and temperate grasses. Differential immune recognition of subtropical grass pollens is likely to impact upon the efficacy of allergen immunotherapy of patients who are primarily sensitized to subtropical grass pollens. The literature reviewed herein highlights the clinical need to standardize allergen preparations for both types of subtropical grass pollens to achieve optimal diagnosis and treatment of patients with allergic respiratory disease in subtropical regions of the world. © 2014 John Wiley & Sons Ltd.

A comparative study of antibody expressions in primary biliary cirrhosis and autoimmune cholangitis using phage display

Primary biliary cirrhosis (PBC) and autoimmune cholangitis (AIC) are serologic expressions of an autoimmune liver disease affecting biliary ductular cells. Previously we screened a phage-displayed random peptide library with polyclonal IgG from 2 Australian patients with PBC and derived peptides that identified a single conformational (discontinuous) epitope in the inner lipoyl domain of the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the characteristic autoantigen in PBC. Here we have used phage display to investigate the reactivity of PBC sera from 2 ethnically and geographically distinct populations, Japanese and Australian, and the 2 serologic expressions, PBC and AIC. Random 7-mer and 12-mer peptide libraries were biopanned with IgG from 3 Japanese patients with PBC and 3 with AIC who did not have anti-PDC-E2. The phage clones (phagotopes) obtained were tested by capture enzyme-linked immunosorbent assay (ELISA) for reactivity with affinity-purified anti-PDC-E2, and compared with those obtained from Australian patients with PBC. Peptide sequences of the derived phagotopes and sequences derived by biopanning with irrelevant antisera were aligned to develop a guide tree based on physicochemical similarity. Both Australian and Japanese PBC-derived phagotopes were distributed in branches of the guide tree that contained the peptide sequences MH and FV previously identified as part of an immunodominant conformational epitope of PDC-E2, indicating that epitope selection was not influenced by the racial origin of the PBC sera. Biopanning with either PBC or AIC-derived IgG yielded phagotopes that reacted with anti-PDC-E2 by capture ELISA, further establishing that there is a similar autoimmune targeting in PBC and AIC.

Multiple primary cancers associated with Merkel cell carcinoma in Queensland, Australia, 1982-2011

The relatively high incidence of Merkel cell carcinoma (MCC) in Queensland provides a valuable opportunity to examine links with other cancers. A retrospective cohort study was performed using data from the Queensland Cancer Registry. Standardized incidence ratios (SIRs) were used to approximate the relative risk of being diagnosed with another primary cancer either following or prior to MCC. Patients with an eligible first primary MCC (n=787) had more than double the expected number of subsequent primary cancers (SIR=2.19, 95% confidence interval (CI)=1.84–2.60; P<0.001). Conversely, people who were initially diagnosed with cancers other than MCC were about two and a half times more likely to have a subsequent primary MCC (n=244) compared with the general population (SIR=2.69, 95% CI=2.36–3.05; P<0.001). Significantly increased bi-directional relative risks were found for melanoma, lip cancer, head and neck cancer, lung cancer, myelodysplastic diseases, and cancer with unknown primary site. In addition, risks were elevated for female breast cancer and kidney cancer following a first primary MCC, and for subsequent MCCs following first primary colorectal cancer, prostate cancer, non-Hodgkin lymphoma, or lymphoid leukemia. These results suggest that several shared pathways are likely for MCC and other cancers, including immunosuppression, UV radiation, and genetics.

Comparing multilevel and Bayesian spatial random effects survival models to assess geographical inequalities in colorectal cancer survival: a case study

Background Multilevel and spatial models are being increasingly used to obtain substantive information on area-level inequalities in cancer survival. Multilevel models assume independent geographical areas, whereas spatial models explicitly incorporate geographical correlation, often via a conditional autoregressive prior. However the relative merits of these methods for large population-based studies have not been explored. Using a case-study approach, we report on the implications of using multilevel and spatial survival models to study geographical inequalities in all-cause survival. Methods Multilevel discrete-time and Bayesian spatial survival models were used to study geographical inequalities in all-cause survival for a population-based colorectal cancer cohort of 22,727 cases aged 20–84 years diagnosed during 1997–2007 from Queensland, Australia. Results Both approaches were viable on this large dataset, and produced similar estimates of the fixed effects. After adding area-level covariates, the between-area variability in survival using multilevel discrete-time models was no longer significant. Spatial inequalities in survival were also markedly reduced after adjusting for aggregated area-level covariates. Only the multilevel approach however, provided an estimation of the contribution of geographical variation to the total variation in survival between individual patients. Conclusions With little difference observed between the two approaches in the estimation of fixed effects, multilevel models should be favored if there is a clear hierarchical data structure and measuring the independent impact of individual- and area-level effects on survival differences is of primary interest. Bayesian spatial analyses may be preferred if spatial correlation between areas is important and if the priority is to assess small-area variations in survival and map spatial patterns. Both approaches can be readily fitted to geographically enabled survival data from international settings

Contribution of psychosocial factors to the association between socioeconomic position and takeaway food consumption

Objective To examine whether psychosocial factors mediate (explain) the association between socioeconomic position and takeaway food consumption. Design A cross-sectional postal survey conducted in 2009. Setting Participants reported their usual consumption of 22 takeaway food items, and these were grouped into a “healthy” and “less healthy” index based on each items' nutritional properties. Principal Components Analysis was used to derive three psychosocial scales that measured beliefs about the relationship between diet and health (α = 0.73), and perceptions about the value (α = 0.79) and pleasure (α = 0.61) of takeaway food. A nutrition knowledge index was also used. Socioeconomic position was measured by highest attained education level. Subjects Randomly selected adults (n = 1,500) aged between 25–64 years in Brisbane, Australia (response rate  =  63.7%, N = 903). Results Compared with those with a bachelor degree or higher, participants with a diploma level of education were more likely to consume “healthy” takeaway food (p = 0.023) whereas the least educated (high school only) were more likely to consume “less healthy” choices (p = 0.002). The least educated were less likely to believe in a relationship between diet and health (p<0.001), and more likely to have lower nutritional knowledge compared with their highly educated counterparts (p<0.001). Education differences in beliefs about the relationship between diet and health partly and significantly mediated the association between education and “healthy” takeaway food consumption. Diet- and health-related beliefs and nutritional knowledge partly and significantly mediated the education differences in “less healthy” takeaway food consumption. Conclusions Interventions that target beliefs about the relationship between diet and health, and nutritional knowledge may reduce socioeconomic differences in takeaway food consumption, particularly for “less healthy” options.

Archiving primary data: Solutions for long-term studies

The recent trend for journals to require open access to primary data included in publications has been embraced by many biologists, but has caused apprehension amongst researchers engaged in long-term ecological and evolutionary studies. A worldwide survey of 73 principal investigators (Pls) with long-term studies revealed positive attitudes towards sharing data with the agreement or involvement of the PI, and 93% of PIs have historically shared data. Only 8% were in favor of uncontrolled, open access to primary data while 63% expressed serious concern. We present here their viewpoint on an issue that can have non-trivial scientific consequences. We discuss potential costs of public data archiving and provide possible solutions to meet the needs of journals and researchers.

Removal of organic content from diesel exhaust particles alters cellular responses of primary human bronchial epithelial cells cultured at an air-liquid interface

Background Exposure to air pollutants, including diesel particulate matter, has been linked to adverse respiratory health effects. Inhaled diesel particulate matter contains adsorbed organic compounds. It is not clear whether the adsorbed organics or the residual components are more deleterious to airway cells. Using a physiologically relevant model, we investigated the role of diesel organic content on mediating cellular responses of primary human bronchial epithelial cells (HBECs) cultured at an air-liquid interface (ALI). Methods Primary HBECs were cultured and differentiated at ALI for at least 28 days. To determine which component is most harmful, we compared primary HBEC responses elicited by residual (with organics removed) diesel emissions (DE) to those elicited by neat (unmodified) DE for 30 and 60 minutes at ALI, with cigarette smoke condensate (CSC) as the positive control, and filtered air as negative control. Cell viability (WST-1 cell proliferation assay), inflammation (TNF-α, IL-6 and IL-8 ELISA) and changes in gene expression (qRT-PCR for HO-1, CYP1A1, TNF-α and IL-8 mRNA) were measured. Results Immunofluorescence and cytological staining confirmed the mucociliary phenotype of primary HBECs differentiated at ALI. Neat DE caused a comparable reduction in cell viability at 30 or 60 min exposures, whereas residual DE caused a greater reduction at 60 min. When corrected for cell viability, cytokine protein secretion for TNF-α, IL-6 and IL-8 were maximal with residual DE at 60 min. mRNA expression for HO-1, CYP1A1, TNF-α and IL-8 was not significantly different between exposures. Conclusion This study provides new insights into epithelial cell responses to diesel emissions using a physiologically relevant aerosol exposure model. Both the organic content and residual components of diesel emissions play an important role in determining bronchial epithelial cell response in vitro. Future studies should be directed at testing potentially useful interventions against the adverse health effects of air pollution exposure.

Fine mapping and replication of genetic risk Loci in primary sclerosing cholangitis

Background and aims. Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis of the bile ducts eventually leading to biliary cirrhosis. Recent genetic studies in PSC have identified associations at 2q13, 2q35, 3p21, 4q27, 13q31 and suggestive association at 10p15. The aim of this study was to further characterize and refine the genetic architecture of PSC. Methods. We analyzed previously reported associated SNPs at four of these non-HLA loci and 59 SNPs tagging the IL-2/IL-21 (4q27) and IL2RA (10p15) loci in 992 UK PSC cases and 5162 healthy UK controls. Results. The most associated SNPs identified were rs3197999 (3p21 (MST1), p = 1.9 × 10 -6, OR A vs G = 1.28, 95% CI (1.16-1.42)); rs4147359 (10p15 (IL2RA), p = 2.6 × 10 -4, OR A vs G = 1.20, 95% CI (1.09-1.33)) and rs12511287 (4q27 (IL-2/IL-21), p = 3.0 × 10 -4, OR A vs T = 1.21, 95% CI (1.09-1.35)). In addition, we performed a meta-analysis for selected SNPs using published summary statistics from recent studies. We observed genome-wide significance for rs3197999 (3p21 (MST1), P combined = 3.8 × 10 -12) and rs4147359 (10p15 (IL2RA), P combined = 1.5 × 10 -8). Conclusion. We have for the first time confirmed the association of PSC with genetic variants at 10p15 (IL2RA) locus at genome-wide significance and replicated the associations at MST1 and IL-2/IL-21 loci in a large homogeneous UK population. These results strongly implicate the role of IL-2/IL2RA pathway in PSC and provide further confirmation of MST1 association. © Informa Healthcare.

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis. © 2011 Macmillan Publishers Limited. All rights reserved.

Positive psychological strengths and school engagement in primary school children

A sizeable body of research has investigated the impact of specific character strengths or traits on significant outcomes. Some recent research is beginning to consider the effects of groups of strengths, combined as a higher order variable, and termed covitality. This study investigated the combined influence of four positive character traits: gratitude, optimism, zest and persistence, upon school engagement, within a sample of 112 Australian primary school students. The combined effect of these four traits, in defining covitality as a higher or second order factor within a path analysis, was found to predict relatively higher levels of school engagement and pro-social behaviour.

Telling tales and painting pictures: A narrative inquiry into the professional learning of Northern Territory primary teachers

This thesis narrates the professional learning experiences of seven Northern Territory teachers. It outlines the evolution from traditional professional development in schools to an active, responsive professional learning agenda. With increasing demands on teachers, standardisation and the quest for improved student outcomes, key themes in the re-storied narrative emerge about the definition and role of professional learning in complex conditions, effective teaching, quality programmes, and teacher agency. This thesis contributes to knowledge about the characteristics that teachers value in their professional learning experiences. An Ongoing Professional Enhancement Model (OPE) is proposed, highlighting directions in this field for key stakeholders.

Pathophysiology team teaching: Bioscientist contribution to knowledge integration in a nursing subject

Bioscience content within undergraduate nursing degrees provides foundational knowledge of pathophysiology, anatomy, physiology, microbiology and pharmacology. However, nursing students often find studying the bioscience components of undergraduate nursing program daunting (Friedel & Treagust 2005, Craft et al. 2013). This is related to factors such as the volume of content, degree of difficulty and insufficient linkage between bioscience concepts and nurses' clinical practice. Students who are unable to conceptualise the relevance of bioscience with nursing subjects and subsequent nursing practice may not appreciate the broader importance of bioscience, and hence may adopt a surface approach to learning (Craft et al. 2013). The aim of this study was to develop a model within Nursing Practice in the Context theory subject, to include a bioscientist lecturing to complement the nursing lecturer, in order to explicitly demonstrate links between physiology, pathophysiology and nursing practice.

Arsenic trioxide promotes mitochondrial DNA mutation and cell apoptosis in primary APL cells and NB4 cell line

This study aimed to investigate the effects of arsenic trioxide (As2O3) on the mitochondrial DNA (mtDNA) of acute promyelocytic leukemia (APL) cells. The NB4 cell line was treated with 2.0 μmol/L As2O3in vitro, and the primary APL cells were treated with 2.0 μmol/L As2O3in vitro and 0.16 mg kg-1 d-1 As2O3in vivo. The mitochondrial DNA of all the cells above was amplified by PCR, directly sequenced and analyzed by Sequence Navigatore and Factura software. The apoptosis rates were assayed by flow cytometry. Mitochondrial DNA mutation in the D-loop region was found in NB4 and APL cells before As2O3 use, but the mutation spots were remarkably increased after As2O3 treatment, which was positively correlated to the rates of cellular apoptosis, the correlation coefficient: rNB4-As2O3=0.973818, and rAPL-As2O3=0.934703. The mutation types include transition, transversion, codon insertion or deletion, and the mutation spots in all samples were not constant and regular. It is revealed that As2O3 aggravates mtDNA mutation in the D-loop region of acute promyelocytic leukemia cells both in vitro and in vivo. Mitochondrial DNA might be one of the targets of As2O3 in APL treatment.

Is there a role for pharmacists in multidisciplinary health-care teams at community outreach events for the homeless?

Homelessness is a significant public health problem. It is well-documented that people experiencing homelessness exhibit more serious illnesses and have poorer health than the general population. The provision of services and interventions by health-care professionals, including pharmacists, may make a simple yet important contribution to improved health outcomes in those experiencing homelessness, but evidence of roles and interventions is limited and variable. In Australia, the Queensland University of Technology Health Clinic connects with the homeless community by taking part in community outreach events. This paper provides details of one such event, as well as the roles, interventions and experiences of pharmacists. Participation and inclusion of pharmacists in a multidisciplinary health-care team approach at homeless outreach events should be supported and encouraged.

Patterns of care: Primary research in mental health nursing

The foundation of mental health nursing has historically been grounded in an interpersonal, person-centred process of health care, yet recent evidence suggests that the interactional work of mental health nursing is being eroded. Literature emphasises the importance of person-centred care on consumer outcomes, a model reliant upon the intimate engagement of nurses and consumers. Yet, the arrival of medical interventions in psychiatry has diverted nursing work from the therapeutic nursing role to task-based roles delegated by medicine, distancing nurses from consumers. This study used work sampling methodology to observe the proportion of time nurses working in an inpatient mental health setting engage in specific activities. The observations of this study determined that nurses' time is accounted for 31.65% in direct care, 51.63% in indirect care and 16.71% in service related activities.