Stem cell regulatory gene expression in human adult dental pulp and periodontal ligament cells undergoing odontogenic/osteogenic differentiation

Introduction During development and regeneration, odontogenesis and osteogenesis are initiated by a cascade of signals driven by several master regulatory genes. Methods In this study, we investigated the differential expression of 84 stem cell–related genes in dental pulp cells (DPCs) and periodontal ligament cells (PDLCs) undergoing odontogenic/osteogenic differentiation. Results Our results showed that, although there was considerable overlap, certain genes had more differential expression in PDLCs than in DPCs. CCND2, DLL1, and MME were the major upregulated genes in both PDLCs and DPCs, whereas KRT15 was the only gene significantly downregulated in PDLCs and DPCs in both odontogenic and osteogenic differentiation. Interestingly, a large number of regulatory genes in odontogenic and osteogenic differentiation interact or crosstalk via Notch, Wnt, transforming growth factor β (TGF-β)/bone morphogenic protein (BMP), and cadherin signaling pathways, such as the regulation of APC, DLL1, CCND2, BMP2, and CDH1. Using a rat dental pulp and periodontal defect model, the expression and distribution of both BMP2 and CDH1 have been verified for their spatial localization in dental pulp and periodontal tissue regeneration. Conclusions This study has generated an overview of stem cell–related gene expression in DPCs and PDLCs during odontogenic/osteogenic differentiation and revealed that these genes may interact through the Notch, Wnt, TGF-β/BMP, and cadherin signalling pathways to play a crucial role in determining the fate of dental derived cell and dental tissue regeneration. These findings provided a new insight into the molecular mechanisms of the dental tissue mineralization and regeneration

Persistent chlamydial infections : role in inflammation and challenges for vaccine development.

The development of chlamydial vaccines continues to be a major challenge for researchers. While acute infections are the main target of vaccine development groups, Chlamydia is well known for its ability to establish chronic or persistent infections in its host. To date, little effort has focussed specifically on the challenges of vaccines to successfully combat the chronic or persistent phase of the disease and yet this will be a necessary aspect of any fully successful chlamydial vaccine. This short review specifically examines the phenomenon of chlamydial persistence and the unique challenges that this brings to vaccine development.

Spatial analysis of notified cryptosporidiosis infections in Brisbane, Australia

Purpose: This study explored the spatial distribution of notified cryptosporidiosis cases and identified major socioeconomic factors associated with the transmission of cryptosporidiosis in Brisbane, Australia. Methods: We obtained the computerized data sets on the notified cryptosporidiosis cases and their key socioeconomic factors by statistical local area (SLA) in Brisbane for the period of 1996 to 2004 from the Queensland Department of Health and Australian Bureau of Statistics, respectively. We used spatial empirical Bayes rates smoothing to estimate the spatial distribution of cryptosporidiosis cases. A spatial classification and regression tree (CART) model was developed to explore the relationship between socioeconomic factors and the incidence rates of cryptosporidiosis. Results: Spatial empirical Bayes analysis reveals that the cryptosporidiosis infections were primarily concentrated in the northwest and southeast of Brisbane. A spatial CART model shows that the relative risk for cryptosporidiosis transmission was 2.4 when the value of the social economic index for areas (SEIFA) was over 1028 and the proportion of residents with low educational attainment in an SLA exceeded 8.8%. Conclusions: There was remarkable variation in spatial distribution of cryptosporidiosis infections in Brisbane. Spatial pattern of cryptosporidiosis seems to be associated with SEIFA and the proportion of residents with low education attainment.

A study into the permeability and compressibility of Australian bagasse pulp

This is an experimental study into the permeability and compressibility properties of bagasse pulp pads. Three experimental rigs were custom-built for this project. The experimental work is complemented by modelling work. Both the steady-state and dynamic behaviour of pulp pads are evaluated in the experimental and modelling components of this project. Bagasse, the fibrous residue that remains after sugar is extracted from sugarcane, is normally burnt in Australia to generate steam and electricity for the sugar factory. A study into bagasse pulp was motivated by the possibility of making highly value-added pulp products from bagasse for the financial benefit of sugarcane millers and growers. The bagasse pulp and paper industry is a multibillion dollar industry (1). Bagasse pulp could replace eucalypt pulp which is more widely used in the local production of paper products. An opportunity exists for replacing the large quantity of mainly generic paper products imported to Australia. This includes 949,000 tonnes of generic photocopier papers (2). The use of bagasse pulp for paper manufacture is the main application area of interest for this study. Bagasse contains a large quantity of short parenchyma cells called ‘pith’. Around 30% of the shortest fibres are removed from bagasse prior to pulping. Despite the ‘depithing’ operations in conventional bagasse pulp mills, a large amount of pith remains in the pulp. Amongst Australian paper producers there is a perception that the high quantity of short fibres in bagasse pulp leads to poor filtration behaviour at the wet-end of a paper machine. Bagasse pulp’s poor filtration behaviour reduces paper production rates and consequently revenue when compared to paper production using locally made eucalypt pulp. Pulp filtration can be characterised by two interacting factors; permeability and compressibility. Surprisingly, there has previously been very little rigorous investigation into neither bagasse pulp permeability nor compressibility. Only freeness testing of bagasse pulp has been published in the open literature. As a result, this study has focussed on a detailed investigation of the filtration properties of bagasse pulp pads. As part of this investigation, this study investigated three options for improving the permeability and compressibility properties of Australian bagasse pulp pads. Two options for further pre-treating depithed bagasse prior to pulping were considered. Firstly, bagasse was fractionated based on size. Two bagasse fractions were produced, ‘coarse’ and ‘medium’ bagasse fractions. Secondly, bagasse was collected after being processed on two types of juice extraction technology, i.e. from a sugar mill and from a sugar diffuser. Finally one method of post-treating the bagasse pulp was investigated. The effects of chemical additives, which are known to improve freeness, were also assessed for their effect on pulp pad permeability and compressibility. Pre-treated Australian bagasse pulp samples were compared with several benchmark pulp samples. A sample of commonly used kraft Eucalyptus globulus pulp was obtained. A sample of depithed Argentinean bagasse, which is used for commercial paper production, was also obtained. A sample of Australian bagasse which was depithed as per typical factory operations was also produced for benchmarking purposes. The steady-state pulp pad permeability and compressibility parameters were determined experimentally using two purpose-built experimental rigs. In reality, steady-state conditions do not exist on a paper machine. The permeability changes as the sheet compresses over time. Hence, a dynamic model was developed which uses the experimentally determined steady-state permeability and compressibility parameters as inputs. The filtration model was developed with a view to designing pulp processing equipment that is suitable specifically for bagasse pulp. The predicted results of the dynamic model were compared to experimental data. The effectiveness of a polymeric and microparticle chemical additives for improving the retention of short fibres and increasing the drainage rate of a bagasse pulp slurry was determined in a third purpose-built rig; a modified Dynamic Drainage Jar (DDJ). These chemical additives were then used in the making of a pulp pad, and their effect on the steady-state and dynamic permeability and compressibility of bagasse pulp pads was determined. The most important finding from this investigation was that Australian bagasse pulp was produced with higher permeability than eucalypt pulp, despite a higher overall content of short fibres. It is thought this research outcome could enable Australian paper producers to switch from eucalypt pulp to bagasse pulp without sacrificing paper machine productivity. It is thought that two factors contributed to the high permeability of the bagasse pulp pad. Firstly, thicker cell walls of the bagasse pulp fibres resulted in high fibre stiffness. Secondly, the bagasse pulp had a large proportion of fibres longer than 1.3 mm. These attributes helped to reinforce the pulp pad matrix. The steady-state permeability and compressibility parameters for the eucalypt pulp were consistent with those found by previous workers. It was also found that Australian pulp derived from the ‘coarse’ bagasse fraction had higher steady-state permeability than the ‘medium’ fraction. However, there was no difference between bagasse pulp originating from a diffuser or a mill. The bagasse pre-treatment options investigated in this study were not found to affect the steady-state compressibility parameters of a pulp pad. The dynamic filtration model was found to give predictions that were in good agreement with experimental data for pads made from samples of pretreated bagasse pulp, provided at least some pith was removed prior to pulping. Applying vacuum to a pulp slurry in the modified DDJ dramatically reduced the drainage time. At any level of vacuum, bagasse pulp benefitted from chemical additives as quantified by reduced drainage time and increased retention of short fibres. Using the modified DDJ, it was observed that under specific conditions, a benchmark depithed bagasse pulp drained more rapidly than the ‘coarse’ bagasse pulp. In steady-state permeability and compressibility experiments, the addition of chemical additives improved the pad permeability and compressibility of a benchmark bagasse pulp with a high quantity of short fibres. Importantly, this effect was not observed for the ‘coarse’ bagasse pulp. However, dynamic filtration experiments showed that there was also a small observable improvement in filtration for the ‘medium’ bagasse pulp. The mechanism of bagasse pulp pad consolidation appears to be by fibre realignment. Chemical additives assist to lubricate the consolidation process. This study was complemented by pulp physical and chemical property testing and a microscopy study. In addition to its high pulp pad permeability, ‘coarse’ bagasse pulp often (but not always) had superior physical properties than a benchmark depithed bagasse pulp.

Continuous infusion of ticarcillin-clavulanate for home treatment of serious infections : clinical efficacy, safety, pharmacokinetics and pharmacodynamics

Continuous infusion (CI) ticarcillin–clavulanate is a potential therapeutic improvement over conventional intermittent dosing because the major pharmacodynamic (PD) predictor of efficacy of β-lactams is the time that free drug levels exceed the MIC. This study incorporated a 6-year retrospective arm evaluating efficacy and safety of CI ticarcillin–clavulanate in the home treatment of serious infections and a prospective arm additionally evaluating pharmacokinetics (PK) and PD. In the prospective arm, steady-state serum ticarcillin and clavulanate levels and MIC testing of significant pathogens were performed. One hundred and twelve patients (median age, 56 years) were treated with a CI dose of 9.3–12.4 g/day and mean CI duration of 18.0 days. Infections treated included osteomyelitis (50 patients), septic arthritis (6), cellulitis (17), pulmonary infections (12), febrile neutropenia (7), vascular infections (7), intra-abdominal infections (2), and Gram-negative endocarditis (2); 91/112 (81%) of patients were cured, 14 (13%) had partial response and 7 (6%) failed therapy. Nine patients had PICC line complications and five patients had drug adverse events. Eighteen patients had prospective PK/PD assessment although only four patients had sufficient data for a full PK/PD evaluation (both serum steady-state drug levels and ticarcillin and clavulanate MICs from a bacteriological isolate), as this was difficult to obtain in home-based patients, particularly as serum clavulanate levels were found to deteriorate rapidly on storage. Three of four patients with matched PK/PD assessment had free drug levels exceeding the MIC of the pathogen. Home CI of ticarcillin–clavulanate is a safe, effective, convenient and practical therapy and is a therapeutic advance over traditional intermittent dosing when used in the home setting.

The effect of flocculants on the filtration of bagasse pulp pads

This study examined the effect of flocculants on the filtration parameters of bagasse pulp. In the first phase, flocculants were effective for improving the fiber retention of three different bagasse pulp slurries, based on flocculant system studies using a dynamic drainage jar. In the second phase, pulp pads were formed using these flocculants and the steady-state permeability and compressibility parameters were measured. The results showed that the flocculant system that was effective for a pulp slurry was entirely ineffective in improving pulp pad permeability or compressibility during the second experimental phase for two of the bagasse pulp samples.

Differentially Expressed Protein Profile of Human Dental Pulp Cells in the Early Process of Odontoblast-like Differentiation In Vitro

Dental pulp cells (DPCs) are capable of differentiating into odontoblasts that secrete reparative dentin after pulp injury. The molecular mechanisms governing reparative dentinogenesis are yet to be fully understood. Here we investigated the differential protein profile of human DPCs undergoing odontogenic induction for 7 days. Using two-dimensional differential gel electrophoresis coupled with matrix-assisted laser adsorption ionization time of flight mass spectrometry, 2 3 protein spots related to the early odontogenic differentiation were identified. These proteins included cytoskeleton proteins, nuclear proteins, cell membrane-bound molecules, proteins involved in matrix synthesis, and metabolic enzymes. The expression of four identified proteins, which were heteronuclear ribonuclear proteins C, annexin VI, collagen type VI, and matrilin-2, was confirmed by Western blot and real-time realtime polymerase chain reaction analyses. This study generated a proteome reference map during odontoblast- like differentiation of human DPCs, which will be valuable to better understand the underlying molecular mechanisms in odontoblast-like differentiation.

Pressure filtration of Australian bagasse pulp

A one-dimensional pressure filtration model that can be used to predict the behaviour of bagasse pulp has been developed and verified in this study.The dynamic filtration model uses steady state compressibility parameters determined experimentally by uniaxial loading. The compressibility parameters M and N for depithed bagasse pulp were determined to be in the ranges 3000–8000kPa and 2.5–3.0 units, respectively. The model also incorporates experimentally determined steady state permeability data from separate experiments to predict the pulp concentration and fibre pressure throughout a pulp mat during dynamic filtration. Under steady state conditions, a variable Kozeny factor required different values for the permeability parameters when compared to a constant Kozeny factor. The specific surface area was 25–30% lower and the swelling factor was 20–25% higher when a variable Kozeny factor was used. Excellent agreement between experimental data and the dynamic filtration model was achieved when a variable Kozeny factor was used.

The effect of flocculants, shear, vacuum and depithing on the formation of thin bagasse pulp pads

The effect of bentonite micro-particles and cationic polyacrylamide (CPAM) on the filtration properties of bagasse pulp was investigated under shearing conditions. CPAM improves retention but the bentonite addition level must be optimised for further improvements in retention. A Dynamic Drainage Jar (‘Britt Jar’) was modified to allow bagasse pulp slurry to be subjected to vacuum allowing a thin pulp pad to be formed. Bagasse pulp which had had the majority of the fine fibre removed prior to pulping drained more quickly than a conventional bagasse pulp when vacuum was not applied, however this situation was reversed when vacuum was used. The flocculants continue to improve fibre retention under vacuum and shear conditions but with reduced effectiveness.

Estimating the cost of health care–associated infections : mind your p’s and q’s

Monetary valuations of the economic cost of health care–associated infections (HAIs) are important for decision making and should be estimated accurately. Erroneously high estimates of costs, designed to jolt decision makers into action, may do more harm than good in the struggle to attract funding for infection control. Expectations among policy makers might be raised, and then they are disappointed when the reduction in the number of HAIs does not yield the anticipated cost saving. For this article, we critically review the field and discuss 3 questions. Why measure the cost of an HAI? What outcome should be used to measure the cost of an HAI? What is the best method for making this measurement? The aim is to encourage researchers to collect and then disseminate information that accurately guides decisions about the economic value of expanding or changing current infection control activities.

Time-dependent analysis of length of stay and mortality due urinary tract infections in ten developing countries : INICC findings

Catheter associated urinary tract infections (CAUTI) are a worldwide problem that may lead to increased patient morbidity, cost and mortality.1e3 The literature is divided on whether there are real effects from CAUTI on length of stay or mortality. Platt4 found the costs and mortality risks to be largeyetGraves et al found the opposite.5 A reviewof the published estimates of the extra length of stay showed results between zero and 30 days.6 The differences in estimates may have been caused by the different epidemiological methods applied. Accurately estimating the effects of CAUTI is difficult because it is a time-dependent exposure. This means that standard statistical techniques, such asmatched case-control studies, tend to overestimate the increased hospital stay and mortality risk due to infection. The aim of the study was to estimate excess length of stay andmortality in an intensive care unit (ICU) due to a CAUTI, using a statistical model that accounts for the timing of infection. Data collected from ICU units in lower and middle income countries were used for this analysis.7,8 There has been little research for these settings, hence the need for this paper.

Spatial analysis of notified dengue fever infections

This study aimed to investigate the spatial clustering and dynamic dispersion of dengue incidence in Queensland, Australia. We used Moran’s I statistic to assess the spatial autocorrelation of reported dengue cases. Spatial empirical Bayes smoothing estimates were used to display the spatial distribution of dengue in postal areas throughout Queensland. Local indicators of spatial association (LISA) maps and logistic regression models were used to identify spatial clusters and examine the spatio-temporal patterns of the spread of dengue. The results indicate that the spatial distribution of dengue was clustered during each of the three periods of 1993–1996, 1997–2000 and 2001–2004. The high-incidence clusters of dengue were primarily concentrated in the north of Queensland and low-incidence clusters occurred in the south-east of Queensland. The study concludes that the geographical range of notified dengue cases has significantly expanded in Queensland over recent years.

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.