3D lung and rib cage reconstruction using low dose CT scans of adolescent idiopathic scoliosis pre and post anterior thoracoscopic correction

Adolescent Idiopathic Scoliosis (AIS) has been associated with reduced pulmonary function believed to be due to a restriction of lung volume by the deformed thoracic cavity. A recent study by our group examined the changes in lung volume pre and post anterior thoracoscopic scoliosis correction using pulmonary function testing (1), however the anatomical changes in ribcage shape and left/right lung volume after thoracoscopic surgery which govern overall respiratory capacity are unknown. The aim of this study was to use 3D rendering from CT scan data to compare lung and ribcage anatomical changes from pre to two years post thoracoscopic anterior scoliosis correction. The study concluded that 3D volumetric reconstruction from CT scans is a powerful means of evaluating changes in pulmonary and thoracic anatomy following surgical AIS correction. Most likely, lung volume changes following thoracoscopic scoliosis correction are multifactorial and affected by changes in height (due to residual growth), ribcage shape, diaphragm positioning, Cobb angle correction in the thoracic spine. Further analysis of the 3D reconstructions will be performed to assess how each of these factors affect lung volume in this patient cohort.

Morphologic and genomic characterisation of the koala Chlamydia pneumoniae strain

Chlamydia pneumoniae is a common human and animal pathogen associated with a wide range of upper and lower respiratory tract infections. In more recent years there has been increasing evidence to suggest a link between C. pneumoniae and chronic diseases in humans, including atherosclerosis, stroke and Alzheimer’s disease. C. pneumoniae human strains show little genetic variation, indicating that the human-derived strain originated from a common ancestor in the recent past. Despite extensive information on the genetics and morphology processes of the human strain, knowledge concerning many other hosts (including marsupials, amphibians, reptiles and equines) remains virtually unexplored. The koala (Phascolarctos cinereus) is a native Australian marsupial under threat due to habitat loss, predation and disease. Koalas are very susceptible to chlamydial infections, most commonly affecting the conjunctiva, urogenital tract and/or respiratory tract. To address this gap in the literature, the present study (i) provides a detailed description of the morphologic and genomic architecture of the C. pneumoniae koala (and human) strain, and shows that the koala strain is microscopically, developmentally and genetically distinct from the C. pneumoniae human strain, and (ii) examines the genetic relationship of geographically diverse C. pneumoniae isolates from human, marsupial, amphibian, reptilian and equine hosts, and identifies two distinct lineages that have arisen from animal-to-human cross species transmissions. Chapter One of this thesis explores the scientific problem and aims of this study, while Chapter Two provides a detailed literature review of the background in this field of work. Chapter Three, the first results chapter, describes the morphology and developmental stages of C. pneumoniae koala isolate LPCoLN, as revealed by fluorescence and transmission electron microscopy. The profile of this isolate, when cultured in HEp-2 human epithelial cells, was quite different to the human AR39 isolate. Koala LPCoLN inclusions were larger; the elementary bodies did not have the characteristic pear-shaped appearance, and the developmental cycle was completed within a shorter period of time (as confirmed by quantitative real-time PCR). These in vitro findings might reflect biological differences between koala LPCoLN and human AR39 in vivo. Chapter Four describes the complete genome sequence of the koala respiratory pathogen, C. pneumoniae LPCoLN. This is the first animal isolate of C. pneumoniae to be fully-sequenced. The genome sequence provides new insights into genomic ‘plasticity’ (organisation), evolution and biology of koala LPCoLN, relative to four complete C. pneumoniae human genomes (AR39, CWL029, J138 and TW183). Koala LPCoLN contains a plasmid that is not shared with any of the human isolates, there is evidence of gene loss in nucleotide salvage pathways, and there are 10 hot spot genomic regions of variation that were previously not identified in the C. pneumoniae human genomes. Sequence (partial-length) from a second, independent, wild koala isolate (EBB) at several gene loci confirmed that the koala LPCoLN isolate was representative of a koala C. pneumoniae strain. The combined sequence data provides evidence that the C. pneumoniae animal (koala LPCoLN) genome is ancestral to the C. pneumoniae human genomes and that human infections may have originated from zoonotic infections. Chapter Five examines key genome components of the five C. pneumoniae genomes in more detail. This analysis reveals genomic features that are shared by and/or contribute to the broad ecological adaptability and evolution of C. pneumoniae. This analysis resulted in the identification of 65 gene sequences for further analysis of intraspecific variation, and revealed some interesting differences, including fragmentation, truncation and gene decay (loss of redundant ancestral traits). This study provides valuable insights into metabolic diversity, adaptation and evolution of C. pneumoniae. Chapter Six utilises a subset of 23 target genes identified from the previous genomic comparisons and makes a significant contribution to our understanding of genetic variability among C. pneumoniae human (11) and animal (6 amphibian, 5 reptilian, 1 equine and 7 marsupial hosts) isolates. It has been shown that the animal isolates are genetically diverse, unlike the human isolates that are virtually clonal. More convincing evidence that C. pneumoniae originated in animals and recently (in the last few hundred thousand years) crossed host species to infect humans is provided in this study. It is proposed that two animal-to-human cross species events have occurred in the context of the results, one evident by the nearly clonal human genotype circulating in the world today, and the other by a more animal-like genotype apparent in Indigenous Australians. Taken together, these data indicate that the C. pneumoniae koala LPCoLN isolate has morphologic and genomic characteristics that are distinct from the human isolates. These differences may affect the survival and activity of the C. pneumoniae koala pathogen in its natural host, in vivo. This study, by utilising the genetic diversity of C. pneumoniae, identified new genetic markers for distinguishing human and animal isolates. However, not all C. pneumoniae isolates were genetically diverse; in fact, several isolates were highly conserved, if not identical in sequence (i.e. Australian marsupials) emphasising that at some stage in the evolution of this pathogen, there has been an adaptation/s to a particular host, providing some stability in the genome. The outcomes of this study by experimental and bioinformatic approaches have significantly enhanced our knowledge of the biology of this pathogen and will advance opportunities for the investigation of novel vaccine targets, antimicrobial therapy, or blocking of pathogenic pathways.

The effect of graded levels of exercise on energy intake and balance in free-living men, consuming their normal diet

Objective: To assess the effect of graded increases in exercised-induced energy expenditure (EE) on appetite, energy intake (EI), total daily EE and body weight in men living in their normal environment and consuming their usual diets. Design: Within-subject, repeated measures design. Six men (mean (s.d.) age 31.0 (5.0) y; weight 75.1 (15.96) kg; height 1.79 (0.10) m; body mass index (BMI) 23.3(2.4) kg/m2), were each studied three times during a 9 day protocol, corresponding to prescriptions of no exercise, (control) (Nex; 0 MJ/day), medium exercise level (Mex; ~1.6 MJ/day) and high exercise level (Hex; ~3.2 MJ/day). On days 1-2 subjects were given a medium fat (MF) maintenance diet (1.6 ´ resting metabolic rate (RMR)). Measurements: On days 3-9 subjects self-recorded dietary intake using a food diary and self-weighed intake. EE was assessed by continual heart rate monitoring, using the modified FLEX method. Subjects' HR (heart rate) was individually calibrated against submaximal VO2 during incremental exercise tests at the beginning and end of each 9 day study period. Respiratory exchange was measured by indirect calorimetry. Subjects completed hourly hunger ratings during waking hours to record subjective sensations of hunger and appetite. Body weight was measured daily. Results: EE amounted to 11.7, 12.9 and 16.8 MJ/day (F(2,10)=48.26; P<0.001 (s.e.d=0.55)) on the Nex, Mex and Hex treatments, respectively. The corresponding values for EI were 11.6, 11.8 and 11.8 MJ/day (F(2,10)=0.10; P=0.910 (s.e.d.=0.10)), respectively. There were no treatment effects on hunger, appetite or body weight, but there was evidence of weight loss on the Hex treatment. Conclusion: Increasing EE did not lead to compensation of EI over 7 days. However, total daily EE tended to decrease over time on the two exercise treatments. Lean men appear able to tolerate a considerable negative energy balance, induced by exercise, over 7 days without invoking compensatory increases in EI.

Differences in post-prandial responses to fat and carbohydrate loads in habitual high and low fat consumers (phenotypes).

The present study investigated metabolic responses to fat and carbohydrate ingestion in lean male individuals consuming an habitual diet high or low in fat. Twelve high-fat phenotypes (HF) and twelve low-fat phenotypes (LF) participated in the study. Energy intake and macronutrient intake variables were assessed using a food frequency questionnaire. Resting (RMR) and postprandial metabolic rate and substrate oxidation (respiratory quotient; RQ) were measured by indirect calorimetry. HF had a significantly higher RMR and higher resting heart rate than LF. These variables remained higher in HF following the macronutrient challenge. In all subjects the carbohydrate load increased metabolic rate and heart rate significantly more than the fat load. Fat oxidation (indicated by a low RQ) was significantly higher in HF than in LF following the fat load; the ability to oxidise a high carbohydrate load did not differ between the groups. Lean male subjects consuming a diet high in fat were associated with increased energy expenditure at rest and a relatively higher fat oxidation in response to a high fat load; these observations may be partly responsible for maintaining energy balance on a high-fat (high-energy) diet. In contrast, a low consumer of fat is associated with relatively lower energy expenditure at rest and lower fat oxidation, which has implications for weight gain if high-fat foods or meals are periodically introduced to the diet.

GIS-based mapping and statistical analysis of air pollution and mortality in Brisbane, Australia

In this thesis, the relationship between air pollution and human health has been investigated utilising Geographic Information System (GIS) as an analysis tool. The research focused on how vehicular air pollution affects human health. The main objective of this study was to analyse the spatial variability of pollutants, taking Brisbane City in Australia as a case study, by the identification of the areas of high concentration of air pollutants and their relationship with the numbers of death caused by air pollutants. A correlation test was performed to establish the relationship between air pollution, number of deaths from respiratory disease, and total distance travelled by road vehicles in Brisbane. GIS was utilized to investigate the spatial distribution of the air pollutants. The main finding of this research is the comparison between spatial and non-spatial analysis approaches, which indicated that correlation analysis and simple buffer analysis of GIS using the average levels of air pollutants from a single monitoring station or by group of few monitoring stations is a relatively simple method for assessing the health effects of air pollution. There was a significant positive correlation between variable under consideration, and the research shows a decreasing trend of concentration of nitrogen dioxide at the Eagle Farm and Springwood sites and an increasing trend at CBD site. Statistical analysis shows that there exists a positive relationship between the level of emission and number of deaths, though the impact is not uniform as certain sections of the population are more vulnerable to exposure. Further statistical tests found that the elderly people of over 75 years age and children between 0-15 years of age are the more vulnerable people exposed to air pollution. A non-spatial approach alone may be insufficient for an appropriate evaluation of the impact of air pollutant variables and their inter-relationships. It is important to evaluate the spatial features of air pollutants before modeling the air pollution-health relationships.

Image acquisition and manipulation protocols for CT-PET fusion to improve the accuracy of gross tumour volume localisation for 3D conformal radiotherapy for lung cancer

Aims: To develop clinical protocols for acquiring PET images, performing CT-PET registration and tumour volume definition based on the PET image data, for radiotherapy for lung cancer patients and then to test these protocols with respect to levels of accuracy and reproducibility. Method: A phantom-based quality assurance study of the processes associated with using registered CT and PET scans for tumour volume definition was conducted to: (1) investigate image acquisition and manipulation techniques for registering and contouring CT and PET images in a radiotherapy treatment planning system, and (2) determine technology-based errors in the registration and contouring processes. The outcomes of the phantom image based quality assurance study were used to determine clinical protocols. Protocols were developed for (1) acquiring patient PET image data for incorporation into the 3DCRT process, particularly for ensuring that the patient is positioned in their treatment position; (2) CT-PET image registration techniques and (3) GTV definition using the PET image data. The developed clinical protocols were tested using retrospective clinical trials to assess levels of inter-user variability which may be attributed to the use of these protocols. A Siemens Somatom Open Sensation 20 slice CT scanner and a Philips Allegro stand-alone PET scanner were used to acquire the images for this research. The Philips Pinnacle3 treatment planning system was used to perform the image registration and contouring of the CT and PET images. Results: Both the attenuation-corrected and transmission images obtained from standard whole-body PET staging clinical scanning protocols were acquired and imported into the treatment planning system for the phantom-based quality assurance study. Protocols for manipulating the PET images in the treatment planning system, particularly for quantifying uptake in volumes of interest and window levels for accurate geometric visualisation were determined. The automatic registration algorithms were found to have sub-voxel levels of accuracy, with transmission scan-based CT-PET registration more accurate than emission scan-based registration of the phantom images. Respiration induced image artifacts were not found to influence registration accuracy while inadequate pre-registration over-lap of the CT and PET images was found to result in large registration errors. A threshold value based on a percentage of the maximum uptake within a volume of interest was found to accurately contour the different features of the phantom despite the lower spatial resolution of the PET images. Appropriate selection of the threshold value is dependant on target-to-background ratios and the presence of respiratory motion. The results from the phantom-based study were used to design, implement and test clinical CT-PET fusion protocols. The patient PET image acquisition protocols enabled patients to be successfully identified and positioned in their radiotherapy treatment position during the acquisition of their whole-body PET staging scan. While automatic registration techniques were found to reduce inter-user variation compared to manual techniques, there was no significant difference in the registration outcomes for transmission or emission scan-based registration of the patient images, using the protocol. Tumour volumes contoured on registered patient CT-PET images using the tested threshold values and viewing windows determined from the phantom study, demonstrated less inter-user variation for the primary tumour volume contours than those contoured using only the patient’s planning CT scans. Conclusions: The developed clinical protocols allow a patient’s whole-body PET staging scan to be incorporated, manipulated and quantified in the treatment planning process to improve the accuracy of gross tumour volume localisation in 3D conformal radiotherapy for lung cancer. Image registration protocols which factor in potential software-based errors combined with adequate user training are recommended to increase the accuracy and reproducibility of registration outcomes. A semi-automated adaptive threshold contouring technique incorporating a PET windowing protocol, accurately defines the geometric edge of a tumour volume using PET image data from a stand alone PET scanner, including 4D target volumes.

The role of the health surveillance program in the Queensland coal mining industry

The Queensland Coal Industry Employees Health Scheme was implemented in 1993 to provide health surveillance for all Queensland coal industry workers. Tt1e government, mining employers and mining unions agreed that the scheme should operate for seven years. At the expiry of the scheme, an assessment of the contribution of health surveillance to meet coal industry needs would be an essential part of determining a future health surveillance program. This research project has analysed the data made available between 1993 and 1998. All current coal industry employees have had at least one health assessment. The project examined how the centralised nature of the Health Scheme benefits industry by identi~)jng key health issues and exploring their dimensions on a scale not possible by corporate based health surveillance programs. There is a body of evidence that indicates that health awareness - on the scale of the individual, the work group and the industry is not a part of the mining industry culture. There is also growing evidence that there is a need for this culture to change and that some change is in progress. One element of this changing culture is a growth in the interest by the individual and the community in information on health status and benchmarks that are reasonably attainable. This interest opens the way for health education which contains personal, community and occupational elements. An important element of such education is the data on mine site health status. This project examined the role of health surveillance in the coal mining industry as a tool for generating the necessary information to promote an interest in health awareness. The Health Scheme Database provides the material for the bulk of the analysis of this project. After a preliminary scan of the data set, more detailed analysis was undertaken on key health and related safety issues that include respiratory disorders, hearing loss and high blood pressure. The data set facilitates control for confounding factors such as age and smoking status. Mines can be benchmarked to identify those mines with effective health management and those with particular challenges. While the study has confirmed the very low prevalence of restrictive airway disease such as pneu"moconiosis, it has demonstrated a need to examine in detail the emergence of obstructive airway disease such as bronchitis and emphysema which may be a consequence of the increasing use of high dust longwall technology. The power of the Health Database's electronic data management is demonstrated by linking the health data to other data sets such as injury data that is collected by the Department of l\1mes and Energy. The analysis examines serious strain -sprain injuries and has identified a marked difference between the underground and open cut sectors of the industry. The analysis also considers productivity and OHS data to examine the extent to which there is correlation between any pairs ofJpese and previously analysed health parameters. This project has demonstrated that the current structure of the Coal Industry Employees Health Scheme has largely delivered to mines and effective health screening process. At the same time, the centralised nature of data collection and analysis has provided to the mines, the unions and the government substantial statistical cross-sectional data upon which strategies to more effectively manage health and relates safety issues can be based.

Characterization of particle number concentrations and PM2.5 in a school : influence of outdoor air pollution on indoor air

Background, Aim and Scope The impact of air pollution on school children’s health is currently one of the key foci of international and national agencies. Of particular concern are ultrafine particles which are emitted in large quantities, contain large concentrations of toxins and are deposited deeply in the respiratory tract. Materials and methods In this study, an intensive sampling campaign of indoor and outdoor airborne particulate matter was carried out in a primary school in February 2006 to investigate indoor and outdoor particle number (PN) and mass concentrations (PM2.5), and particle size distribution, and to evaluate the influence of outdoor air pollution on the indoor air. Results For outdoor PN and PM2.5, early morning and late afternoon peaks were observed on weekdays, which are consistent with traffic rush hours, indicating the predominant effect of vehicular emissions. However, the temporal variations of outdoor PM2.5 and PN concentrations occasionally showed extremely high peaks, mainly due to human activities such as cigarette smoking and the operation of mower near the sampling site. The indoor PM2.5 level was mainly affected by the outdoor PM2.5 (r = 0.68, p<0.01), whereas the indoor PN concentration had some association with outdoor PN values (r = 0.66, p<0.01) even though the indoor PN concentration was occasionally influenced by indoor sources, such as cooking, cleaning and floor polishing activities. Correlation analysis indicated that the outdoor PM2.5 was inversely correlated with the indoor to outdoor PM2.5 ratio (I/O ratio) (r = -0.49, p<0.01), while the indoor PN had a weak correlation with the I/O ratio for PN (r = 0.34, p<0.01). Discussion and Conclusions The results showed that occupancy did not cause any major changes to the modal structure of particle number and size distribution, even though the I/O ratio was different for different size classes. The I/O curves had a maximum value for particles with diameters of 100 – 400 nm under both occupied and unoccupied scenarios, whereas no significant difference in I/O ratio for PM2.5 was observed between occupied and unoccupied conditions. Inspection of the size-resolved I/O ratios in the preschool centre and the classroom suggested that the I/O ratio in the preschool centre was the highest for accumulation mode particles at 600 nm after school hours, whereas the average I/O ratios of both nucleation mode and accumulation mode particles in the classroom were much lower than those of Aitken mode particles. Recommendations and Perspectives The findings obtained in this study are useful for epidemiological studies to estimate the total personal exposure of children, and to develop appropriate control strategies for minimizing the adverse health effects on school children.

Exposure to particle number, surface area and PM concentrations in pizzerias

The aim of this work was to quantify exposure to particles emitted by wood-fired ovens in pizzerias. Overall, 15 microenvironments were chosen and analyzed in a 14-month experimental campaign. Particle number concentration and distribution were measured simultaneously using a Condensation Particle Counter (CPC), a Scanning Mobility Particle Sizer (SMPS), an Aerodynamic Particle Sizer (APS). The surface area and mass distributions and concentrations, as well as the estimation of lung deposition surface area and PM1 were evaluated using the SMPS-APS system with dosimetric models, by taking into account the presence of aggregates on the basis of the Idealized Aggregate (IA) theory. The fraction of inhaled particles deposited in the respiratory system and different fractions of particulate matter were also measured by means of a Nanoparticle Surface Area Monitor (NSAM) and a photometer (DustTrak DRX), respectively. In this way, supplementary data were obtained during the monitoring of trends inside the pizzerias. We found that surface area and PM1 particle concentrations in pizzerias can be very high, especially when compared to other critical microenvironments, such as the transport hubs. During pizza cooking under normal ventilation conditions, concentrations were found up to 74, 70 and 23 times higher than background levels for number, surface area and PM1, respectively. A key parameter is the oven shape factor, defined as the ratio between the size of the face opening in respect

The application of a profluorescent nitroxide probe to detect reactive oxygen species derived from combustion-generated particulate matter

Particulate pollution has been widely recognised as an important risk factor to human health. In addition to increases in respiratory and cardiovascular morbidity associated with exposure to particulate matter (PM), WHO estimates that urban PM causes 0.8 million premature deaths globally and that 1.5 million people die prematurely from exposure to indoor smoke generated from the combustion of solid fuels. Despite the availability of a huge body of research, the underlying toxicological mechanisms by which particles induce adverse health effects are not yet entirely understood. Oxidative stress caused by generation of free radicals and related reactive oxygen species (ROS) at the sites of deposition has been proposed as a mechanism for many of the adverse health outcomes associated with exposure to PM. In addition to particle-induced generation of ROS in lung tissue cells, several recent studies have shown that particles may also contain ROS. As such, they present a direct cause of oxidative stress and related adverse health effects. Cellular responses to oxidative stress have been widely investigated using various cell exposure assays. However, for a rapid screening of the oxidative potential of PM, less time-consuming and less expensive, cell-free assays are needed. The main aim of this research project was to investigate the application of a novel profluorescent nitroxide probe, synthesised at QUT, as a rapid screening assay in assessing the oxidative potential of PM. Considering that this was the first time that a profluorescent nitroxide probe was applied in investigating the oxidative stress potential of PM, the proof of concept regarding the detection of PM–derived ROS by using such probes needed to be demonstrated and a sampling methodology needed to be developed. Sampling through an impinger containing profluorescent nitroxide solution was chosen as a means of particle collection as it allowed particles to react with the profluorescent nitroxide probe during sampling, avoiding in that way any possible chemical changes resulting from delays between the sampling and the analysis of the PM. Among several profluorescent nitroxide probes available at QUT, bis(phenylethynyl)anthracene-nitroxide (BPEAnit) was found to be the most suitable probe, mainly due to relatively long excitation and emission wavelengths (λex= 430 nm; λem= 485 and 513 nm). These wavelengths are long enough to avoid overlap with the background fluorescence coming from light absorbing compounds which may be present in PM (e.g. polycyclic aromatic hydrocarbons and their derivatives). Given that combustion, in general, is one of the major sources of ambient PM, this project aimed at getting an insight into the oxidative stress potential of combustion-generated PM, namely cigarette smoke, diesel exhaust and wood smoke PM. During the course of this research project, it was demonstrated that the BPEAnit probe based assay is sufficiently sensitive and robust enough to be applied as a rapid screening test for PM-derived ROS detection. Considering that for all three aerosol sources (i.e. cigarette smoke, diesel exhaust and wood smoke) the same assay was applied, the results presented in this thesis allow direct comparison of the oxidative potential measured for all three sources of PM. In summary, it was found that there was a substantial difference between the amounts of ROS per unit of PM mass (ROS concentration) for particles emitted by different combustion sources. For example, particles from cigarette smoke were found to have up to 80 times less ROS per unit of mass than particles produced during logwood combustion. For both diesel and wood combustion it has been demonstrated that the type of fuel significantly affects the oxidative potential of the particles emitted. Similarly, the operating conditions of the combustion source were also found to affect the oxidative potential of particulate emissions. Moreover, this project has demonstrated a strong link between semivolatile (i.e. organic) species and ROS and therefore, clearly highlights the importance of semivolatile species in particle-induced toxicity.

Patient education to prevent falls among older hospital inpatients : a randomized controlled trial

Background Falls are a common adverse event during hospitalization of older adults, and few interventions have been shown to prevent then. Methods This study was a 3-group randomized trial to evaluate the efficacy of 2 forms of multimedia patient education compared with usual care for the prevention of in-hospital falls. Older hospital patients (n = 1206) admitted to a mixture of acute (orthopedic, respiratory, and medical) and subacute (geriatric and neurorehabilitation) hospital wards at 2 Australian hospitals were recruited between January 2008 and April 2009. The interventions were a multimedia patient education program based on the health-belief model combined with trained health professional follow-up (complete program), multi-media patient education materials alone (materials only), and usual care (control). Falls data were collected by blinded research assistants by reviewing hospital incident reports, hand searching medical records, and conducting weekly patient interviews. Results Rates of falls per 1000 patient-days did not differ significantly between groups (control, 9.27; materials only, 8.61; and complete program, 7.63). However, there was a significant interaction between the intervention and presence of cognitive impairment. Falls were less frequent among cognitively intact patients in the complete program group (4.01 per 1000 patient-days) than among cognitively intact patients in the materials-only group (8.18 per 1000 patient-days) (adjusted hazard ratio, 0.51; 95% confidence interval, 0.28-0.93]) and control group (8.72 per 1000 patient-days) (adjusted hazard ratio, 0.43; 95% confidence interval, 0.24-0.78). Conclusion Multimedia patient education with trained health professional follow-up reduced falls among patients with intact cognitive function admitted to a range of hospital wards.

Chlamydial infection of immune cells : altered function and implications for disease

Chlamydia trachomatis is an obligate intracellular bacterial pathogen that infects the genital and ocular mucosa of humans, causing infections that can lead to pelvic inflammatory disease, infertility, and blinding trachoma. C. pneumoniae is a respiratory pathogen that is the cause of 12–15% of community-acquired pneumonia. Both chlamydial species were believed to be restricted to the epithelia of the genital, ocular, and respiratory mucosa; however, increasing evidence suggests that both these pathogens can be isolated from peripheral blood of both healthy individuals and patients with inflammatory conditions such as coronary artery disease and asthma. Chlamydia can also be isolated from brain tissues of patients with degenerative neurological disorders such as Alzheimer’s disease and multiple sclerosis, and also from certain lymphomas. An increasing number of in vitro studies suggest that some chlamydial species can infect immune cells, at least at low levels. These infections may alter immune cell function in a way that promotes chlamydial persistence in the host and contributes to the progression of several chronic inflammatory diseases. In this paper, we review the evidence for the growth of Chlamydia in immune cells, particularly monocytes/macrophages and dendritic cells, and describe how infection may affect the function of these cells.

Effects of magnesium stearate on the efficient dispersion of salbutamol sulphate from carrier-based dry powder inhaler formulations

Dry powder inhaler (DPI) formulations is one of the most useful aerosol preparations in which drugs may be formulated as carrier-based interactive mixtures with micronised drug particles (<5 μm) adhered onto the surface of large inert carriers (lactose powders). The addition of magnesium stearate (MgSt) (1-3), was found to increase dispersion of various drugs from DPI formulations. Recently, some active compounds coated with 5% (wt/wt) MgSt using the mechanofusion method showed significant improvements in aerosolization behavior due to the reduction in intrinsic cohesion force (4). Application of MgSt in powder formulations is not new; however, no studies demonstrated the minimum threshold level for this excipient in efficient aerosolization of drug powders from the interactive mixtures. Therefore, this study investigated the role of MgSt concentration on the efficient dispersion of salbutamol sulphate (SS) from DPI formulations.

Development and evaluation of an integrated clinical learning model to inform continuing education for acute care nurses

Background Significant ongoing learning needs for nurses have occurred as a direct result of the continuous introduction of technological innovations and research developments in the healthcare environment. Despite an increased worldwide emphasis on the importance of continuing education, there continues to be an absence of empirical evidence of program and session effectiveness. Few studies determine whether continuing education enhances or develops practice and the relative cost benefits of health professionals’ participation in professional development. The implications for future clinical practice and associated educational approaches to meet the needs of an increasingly diverse multigenerational and multicultural workforce are also not well documented. There is minimal research confirming that continuing education programs contribute to improved patient outcomes, nurses’ earlier detection of patient deterioration or that standards of continuing competence are maintained. Crucially, evidence-based practice is demonstrated and international quality and safety benchmarks are adhered to. An integrated clinical learning model was developed to inform ongoing education for acute care nurses. Educational strategies included the use of integrated learning approaches, interactive teaching concepts and learner-centred pedagogies. A Respiratory Skills Update education (ReSKU) program was used as the content for the educational intervention to inform surgical nurses’ clinical practice in the area of respiratory assessment. The aim of the research was to evaluate the effectiveness of implementing the ReSKU program using teaching and learning strategies, in the context of organisational utility, on improving surgical nurses’ practice in the area of respiratory assessment. The education program aimed to facilitate better awareness, knowledge and understanding of respiratory dysfunction in the postoperative clinical environment. This research was guided by the work of Forneris (2004), who developed a theoretical framework to operationalise a critical thinking process incorporating the complexities of the clinical context. The framework used educational strategies that are learner-centred and participatory. These strategies aimed to engage the clinician in dynamic thinking processes in clinical practice situations guided by coaches and educators. Methods A quasi experimental pre test, post test non–equivalent control group design was used to evaluate the impact of the ReSKU program on the clinical practice of surgical nurses. The research tested the hypothesis that participation in the ReSKU program improves the reported beliefs and attitudes of surgical nurses, increases their knowledge and reported use of respiratory assessment skills. The study was conducted in a 400 bed regional referral public hospital, the central hub of three smaller hospitals, in a health district servicing the coastal and hinterland areas north of Brisbane. The sample included 90 nurses working in the three surgical wards eligible for inclusion in the study. The experimental group consisted of 36 surgical nurses who had chosen to attend the ReSKU program and consented to be part of the study intervention group. The comparison group included the 39 surgical nurses who elected not to attend the ReSKU program, but agreed to participate in the study. Findings One of the most notable findings was that nurses choosing not to participate were older, more experienced and less well educated. The data demonstrated that there was a barrier for training which impacted on educational strategies as this mature aged cohort was less likely to take up educational opportunities. The study demonstrated statistically significant differences between groups regarding reported use of respiratory skills, three months after ReSKU program attendance. Between group data analysis indicated that the intervention group’s reported beliefs and attitudes pertaining to subscale descriptors showed statistically significant differences in three of the six subscales following attendance at the ReSKU program. These subscales included influence on nursing care, educational preparation and clinical development. Findings suggest that the use of an integrated educational model underpinned by a robust theoretical framework is a strong factor in some perceptions of the ReSKU program relating to attitudes and behaviour. There were minimal differences in knowledge between groups across time. Conclusions This study was consistent with contemporary educational approaches using multi-modal, interactive teaching strategies and a robust overarching theoretical framework to support study concepts. The construct of critical thinking in the clinical context, combined with clinical reasoning and purposeful and collective reflection, was a powerful educational strategy to enhance competency and capability in clinicians.