Analysing Seasonal Health Data

Seasonal patterns have been found in a remarkable range of health conditions, including birth defects, respiratory infections and cardiovascular disease. Accurately estimating the size and timing of seasonal peaks in disease incidence is an aid to understanding the causes and possibly to developing interventions. With global warming increasing the intensity of seasonal weather patterns around the world, a review of the methods for estimating seasonal effects on health is timely. This is the first book on statistical methods for seasonal data written for a health audience. It describes methods for a range of outcomes (including continuous, count and binomial data) and demonstrates appropriate techniques for summarising and modelling these data. It has a practical focus and uses interesting examples to motivate and illustrate the methods. The statistical procedures and example data sets are available in an R package called ‘season’. Adrian Barnett is a senior research fellow at Queensland University of Technology, Australia. Annette Dobson is a Professor of Biostatistics at The University of Queensland, Australia. Both are experienced medical statisticians with a commitment to statistical education and have previously collaborated in research in the methodological developments and applications of biostatistics, especially to time series data. Among other projects, they worked together on revising the well-known textbook "An Introduction to Generalized Linear Models," third edition, Chapman Hall/CRC, 2008. In their new book they share their knowledge of statistical methods for examining seasonal patterns in health.

FGFR2 as a molecular target in endometrial cancer

Although molecularly targeted therapies have been effective in some cancer types, no targeted therapy is approved for use in endometrial cancer. The recent identification of activating mutations in fibroblast growth factor receptor 2 (FGFR2) in endometrial tumors has generated a new avenue for the development of targeted therapeutic agents. The majority of the mutations identified are identical to germline mutations in FGFR2 and FGFR3 that cause craniosynostosis and hypochondroplasia syndromes and result in both ligand-independent and ligand-dependent receptor activation. Mutations that predominantly occur in the endometrioid subtype of endometrial cancer, are mutually exclusive with KRAS mutation, but occur in the presence of PTEN abrogation. In vitro studies have shown that endometrial cancer cell lines with activating FGFR2 mutations are selectively sensitive to a pan-FGFR inhibitor, PD173074. Several agents with activity against FGFRs are currently in clinical trials. Investigation of these agents in endometrial cancer patients with activating FGFR2 mutations is warranted.

Transforming the future of treatment for ovarian cancer

As for many other cancers, metastasis is the leading cause of death of patients with ovarian cancer. Vigorous basic and clinical research is being performed to initiate more efficacious treatment strategies to improve the poor outcome of women with this cancer. Current treatment for ovarian cancer includes advanced cyto-reductive surgery and traditional platinum and taxane combined chemotherapy. Clinical trials using novel cytotoxic reagents and tyrosine kinase inhibitors have also been progressing. In parallel, the application of robust unbiased high throughput research platforms using transcriptomic and proteomic approaches has identified that not only individual cell signalling pathways, but a network of molecular pathways, play an important role in the biology of ovarian cancer. Furthermore, intensive genomic and epigenetic analyses have also revealed single nucleotide polymorphisms associated with risk and/or aetiology of this cancer including patient response to treatment. Taken together, these approaches, that are advancing our understanding, will have an impact on the generation of new therapeutic approaches and strategies for improving the outcome and quality of life of patients with ovarian cancer in the near future.

γ-radiation-induced γH2AX formation occurs preferentially in actively transcribing euchromatic loci

The central dogma in radiation biology is that nuclear DNA is the critical target with respect to radiosensitivity. In accordance with the theoretical expectations, and in the absence of a conclusive model, the general consensus in the field has been to view chromatin as a homogeneous template for DNA damage and repair. This paradigm has been called into question by recent findings indicating a disparity in γ-irradiation-induced γH2AX foci formation in euchromatin and heterochromatin. Here, we have extended those studies and provide evidence that γH2AX foci form preferentially in actively transcribing euchromatin following γ-irradiation.

ERK-1/2 and p38 in the Regulation of Hypertrophic Changes of Normal Articular Cartilage Chondrocytes Induced by Osteoarthritic Subchondral Osteoblasts

Objective. Previous studies have shown the influence of subchondral bone osteoblasts (SBOs) on phenotypical changes of articular cartilage chondrocytes (ACCs) during the development of osteoarthritis (OA). The molecular mechanisms involved during this process remain elusive, in particular, the signal transduction pathways. The aim of this study was to investigate the in vitro effects of OA SBOs on the phenotypical changes in normal ACCs and to unveil the potential involvement of MAPK signaling pathways during this process. Methods. Normal and arthritic cartilage and bone samples were collected for isolation of ACCs and SBOs. Direct and indirect coculture models were applied to study chondrocyte hypertrophy under the influence of OA SBOs. MAPKs in the regulation of the cell–cell interactions were monitored by phosphorylated antibodies and relevant inhibitors. Results. OA SBOs led to increased hypertrophic gene expression and matrix calcification in ACCs by means of both direct and indirect cell–cell interactions. In this study, we demonstrated for the first time that OA SBOs suppressed p38 phosphorylation and induced ERK-1/2 signal phosphorylation in cocultured ACCs. The ERK-1/2 pathway inhibitor PD98059 significantly attenuated the hypertrophic changes induced by conditioned medium from OA SBOs, and the p38 inhibitor SB203580 resulted in the up-regulation of hypertrophic genes in ACCs. Conclusion. The findings of this study suggest that the pathologic interaction of OA SBOs and ACCs is mediated via the activation of ERK-1/2 phosphorylation and deactivation of p38 phosphorylation, resulting in hypertrophic differentiation of ACCs.

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.

Periodontal regeneration and mesenchymal stem cells

The ultimate goal of periodontal therapy is to regenerate periodontal supporting tissues, but this is hard to achieve as the results of periodontal techniques for regeneration are clinically unpredictable. Stem cells owing to their plasticity and proliferation potential provides a new paradigm for periodontal regeneration. Stem cells from mesenchyme can self renew and generate new dental tissues (including dentin and cementum), alveolar bone and periodontal ligament, and thus they have great potential in periodontal regeneration. This chapter presents an insight into mesenchymal stem cells and their potential use in periodontal regeneration. In this chapter the cellular and molecular biology in periodontal regeneration will be introduced, followed by a range of conventional surgical procedures for periodontal regeneration will be discussed. Mesenchymal stem cells applied in regenerated periodontal tissue and their biological characterizations in vitro will be also introduced. Lastly, the use of mesenchymal stem cell to repair periodontal tissues in large animal models will be also reviewed.

Effect of magnesium depletion and potassium and chlorothiazide on intracellular pH in the rat, studied by 31P NMR

1. Both dietary magnesium depletion and potassium depletion (confirmed by tissue analysis) were induced in rats which were then compared with rats treated with chlorothiazide (250 mg/kg diet) and rats on a control synthetic diet. 2. Brain and muscle intracellular pH was measured by using a surface coil and [31P]-NMR to measure the chemical shift of inorganic phosphate. pH was also measured in isolated perfused hearts from control and magnesium-deficient rats. Intracellular magnesium status was assessed by measuring the chemical shift of β-ATP in brain. 3. There was no evidence for magnesium deficiency in the chlorothiazide-treated rats on tissue analysis or on chemical shift of β-ATP in brain. Both magnesium and potassium deficiency, but not chlorothiazide treatment, were associated with an extracellular alkalosis. 4. Magnesium deficiency led to an intracellular alkalosis in brain, muscle and heart. Chlorothiazide treatment led to an alkalosis in brain. Potassium deficiency was associated with a normal intracellular pH in brain and muscle. 5. Magnesium depletion and chlorothiazide treatment produce intracellular alkalosis by unknown mechanism(s).

Institutional problems of the emerging scientific community in Iran

This article attempts to explore the concept of scientific community at the macro-national level in the context of Iran. Institutionalisation of science and its professional growth has been constrained by several factors. The article first conceptualises the notion of science community as found in the literature in the context of Iran, and attempts to map through some indicators. The main focus, however, lies in mapping some institutional problems through empirical research. This was undertaken in 2002–04 in order to analyse the structure of the scientific community in Iran in the ‘exact sciences’ (mathematics, physics, chemistry, biology and earth sciences). The empirical work was done in two complementary perspectives: through a questionnaire and statistical analysis of it, and through semistructured interviews with the researchers. There are number of problems confronting scientists in Iran. Facilities provided by institutions is one of the major problems of research. Another is the tenuous cooperation among scientists. This is reported by most of the researchers, who deplore the lack of cooperation among their group. Relationships are mostly with the Ph.D. students and only marginally with colleagues. Our research shows that the more brilliant the scientists, the more frustrated they are from scientific institutions in Iran. Medium-range researchers seem to be much happier about the scientific institution to which they belong than the brighter scholars. The scientific institutions in Iran seem to be built for the needs of the former rather than the latter. These institutions seem not to play a positive role in the case of the best scientists. On the whole, many ingredients of the scientific community, at least at its inception, are present among Iranian scientists: the strong desire for scientific achievement in spite of personal, institutional and economic problems.

Expression of chondromodulin-1 in the temporomandibular joint condylar cartilage and disc

BACKGROUND: The temporomandibular joint (TMJ) cartilage consists of condylar cartilage and disc and undergoes continuous remodeling throughout post-natal life. To maintain the integrity of the TMJ cartilage, anti-angiogenic factors play an important role during the remodeling process. In this study, we investigated the expression of the anti-angiogenic factor, chondromodulin- 1 (ChM-1), in TMJ cartilage and evaluate its potential role in TMJ remodeling. METHODS: Eight TMJ specimens were collected from six 4-month-old Japanese white rabbits. Safranin-O staining was performed to determine proteoglycan content. ChM-1 expression in TMJ condylar cartilage and disc was determined by immunohistochemistry. Three human perforated disc tissue samples were collected for investigation of ChM-1 and vascular endothelial growth factor (VEGF) distribution in perforated TMJ disc. RESULTS: Safranin-O stained weakly in TMJ compared with tibial articular and epiphyseal cartilage. In TMJ, ChM-1 was expressed in the proliferative and hypertrophic zone of condylar cartilage and chondrocyte-like cells in the disc. No expression of ChM-1 was observed in osteoblasts and subchondral bone. ChM-1 and VEGF were both similarly expressed in perforated disc tissues. CONCLUSIONS: ChM-1 may play a role in the regulation of TMJ remodeling by preventing blood vessel invasion of the cartilage, thereby maintaining condylar cartilage and disc integrity.

Overview of mesenchymal stem cells

Stem cells are unprogrammed cells which possess plasticity and self renewal capability. The term of stem cell was first used to describe cells committed to give rise to germline cells, and to describe proposed progenitor cells of the blood system [1]. A unique feature of stem cell is to remain quiescent in vivo in an uncommitted state. They serve as reservoir or natural support system to replenish cells lost due to disease, injury or aging. When triggered by appropriate signals these cells divide and may become specialized, committed cells; however being able to control this differentiation process still remains one of the biggest challenge in stem cell research [2]. The cell division of stem cells is a distinct aspect of their biology, since this division may be either symmetric or asymmetric. Symmetric division takes place when the stem cells divides and forms two new daughter cells. Asymmetric division is thought to take place only under certain conditions where stem cells divides and gives rise to a daughter cell which remains primitive and does not proliferate, and one committed progenitor cell, which heads down a path of differentiation. Asymmetric division of stem cells helps reparative process, and also ensures that the stem cells pool does not decrease, whereas symmetric division is responsible for stem cells undergoing self renewal and proliferation. The factors which prompt the stem cells to undergo asymmetric division are, however, not well understood, but it is clear that the delicate balance between the self renewal and differentiation is what maintains tissue homeostasis.

The effect of various pH, ionic strength and temperature on papain hydrolysis of salivary film

Stimulated human whole saliva (WS) was used to study the dynamics of papain hydrolysis at defined pH, ionic strength and temperature with the view of reducing an acquired pellicle. A quartz crystal microbalance with dissipation (QCM-D) was used to monitor the changes in frequency due to enzyme hydrolysis of WS films and the hydrolytic parameters were calculated using an empirical model. The morphological and conformational changes of the salivary films before and after enzymatic hydrolysis were characterized by atomic force microscopy (AFM) imaging and grazing angle infrared spectroscopy (GA-FTIR) spectra, respectively. The characteristics of papain hydrolysis of WS films were pH-, ionic strength- and temperature-dependent. The WS films were partially removed by the action of enzyme, resulting thinner and smoother surfaces. The IR data suggested that hydrolysis-induced deformation did not occur onto the remnants salivary films. The processes of papain hydrolysis of WS films can be controlled by properly regulating pH, ionic strength and temperature.