The impact of ambient temperature on mortality among the urban population in Skopje, Macedonia during the period 1996–2000

BACKGROUND: This study assesses the relationship between daily numbers of deaths and variations in ambient temperature within the city of Skopje, R. Macedonia. METHODS: The daily number of deaths from all causes, during the period 1996–2000, as well as those deaths from cardiovascular diseases, occurring within the city of Skopje were related to the average daily temperature on the same day using Multiple Regression statistical analyses. Temperature was measured within the regression model as two complementary variables: 'Warm' and 'Cold'. Excess winter mortality was calculated as winter deaths (deaths occurring in December to March) minus the average of non-winter deaths (April to July of the current year and August to November of the previous year). RESULTS: In this study the average daily total of deaths was 7% and 13% greater in the cold when compared to the whole period and warm period respectively. The same relationship was noticed for deaths caused by cardiovascular diseases. The Regression Beta Coefficient (b = -0.19) for the total mortality as a function of the temperature in Skopje during the period 1996–2000 was statistically significant with negative connotation as was the circulatory mortality due to average temperature (statistically significant regression Beta coefficient (b = -0.24)). A measure of this increase is provided, on an annual basis, in the form of the excess winter mortality figure. CONCLUSION: Mortality with in the city of Skopje displayed a marked seasonality, with peaks in the winter and relative troughs in the summer

Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G

Background: The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET families that are upregulated on the surface of virally infected cells and tumours. Two splicing variants of ULBP5/RAET1G have been cloned previously, but not extensively characterised. Methodology/Principal Findings: We pursue a number of approaches to characterise the expression, trafficking, and function of the two isoforms of ULBP5/RAET1G. We show that both transcripts are frequently expressed in cell lines derived from epithelial cancers, and in primary breast cancers. The full-length transcript, RAET1G1, is predicted to encode a molecule with transmembrane and cytoplasmic domains that are unique amongst NKG2D ligands. Using specific anti-RAET1G1 antiserum to stain tissue microarrays we show that RAET1G1 expression is highly restricted in normal tissues. RAET1G1 was expressed at a low level in normal gastrointestinal epithelial cells in a similar pattern to MICA. Both RAET1G1 and MICA showed increased expression in the gut of patients with celiac disease. In contrast to healthy tissues the RAET1G1 antiserum stained a wide variety or different primary tumour sections. Both endogenously expressed and transfected RAET1G1 was mainly found inside the cell, with a minority of the protein reaching the cell surface. Conversely the truncated splicing variant of RAET1G2 was shown to encode a soluble molecule that could be secreted from cells. Secreted RAET1G2 was shown to downregulate NKG2D receptor expression on NK cells and hence may represent a novel tumour immune evasion strategy. Conclusions/Significance: We demonstrate that the expression patterns of ULBP5RAET1G are very similar to the well-characterised NKG2D ligand, MICA. However the two isoforms of ULBP5/RAET1G have very different cellular localisations that are likely to reflect unique functionality

Prevalence of hallux valgus in the general population: a systematic review and meta-analysis

BACKGROUND: Hallux valgus (HV) is a foot deformity commonly seen in medical practice, often accompanied by significant functional disability and foot pain. Despite frequent mention in a diverse body of literature, a precise estimate of the prevalence of HV is difficult to ascertain. The purpose of this systematic review was to investigate prevalence of HV in the overall population and evaluate the influence of age and gender. METHODS: Electronic databases (Medline, Embase, and CINAHL) and reference lists of included papers were searched to June 2009 for papers on HV prevalence without language restriction. MeSH terms and keywords were used relating to HV or bunions, prevalence and various synonyms. Included studies were surveys reporting original data for prevalence of HV or bunions in healthy populations of any age group. Surveys reporting prevalence data grouped with other foot deformities and in specific disease groups (e.g. rheumatoid arthritis, diabetes) were excluded. Two independent investigators quality rated all included papers on the Epidemiological Appraisal Instrument. Data on raw prevalence, population studied and methodology were extracted. Prevalence proportions and the standard error were calculated, and meta-analysis was performed using a random effects model. RESULTS: A total of 78 papers reporting results of 76 surveys (total 496,957 participants) were included and grouped by study population for meta-analysis. Pooled prevalence estimates for HV were 23% in adults aged 18-65 years (CI: 16.3 to 29.6) and 35.7% in elderly people aged over 65 years (CI: 29.5 to 42.0). Prevalence increased with age and was higher in females [30% (CI: 22 to 38)] compared to males [13% (CI: 9 to 17)]. Potential sources of bias were sampling method, study quality and method of HV diagnosis. CONCLUSIONS: Notwithstanding the wide variation in estimates, it is evident that HV is prevalent; more so in females and with increasing age. Methodological quality issues need to be addressed in interpreting reports in the literature and in future research

Prognostic impact of reduced connexin43 expression and gap junction coupling of neoplastic stromal cells in giant cell tumor of bone

Missense mutations of the GJA1 gene encoding the gap junction channel protein connexin43 (Cx43) cause bone malformations resulting in oculodentodigital dysplasia (ODDD), while GJA1 null and ODDD mutant mice develop osteopenia. In this study we investigated Cx43 expression and channel functions in giant cell tumor of bone (GCTB), a locally aggressive osteolytic lesion with uncertain progression. Cx43 protein levels assessed by immunohistochemistry were correlated with GCTB cell types, clinico-radiological stages and progression free survival in tissue microarrays of 89 primary and 34 recurrent GCTB cases. Cx43 expression, phosphorylation, subcellular distribution and gap junction coupling was also investigated and compared between cultured neoplastic GCTB stromal cells and bone marow stromal cells or HDFa fibroblasts as a control. In GCTB tissues, most Cx43 was produced by CD163 negative neoplastic stromal cells and less by CD163 positive reactive monocytes/macrophages or by giant cells. Significantly less Cx43 was detected in alpha-smooth muscle actin positive than alpha-smooth muscle actin negative stromal cells and in osteoclast-rich tumor nests than in the adjacent reactive stroma. Progressively reduced Cx43 production in GCTB was significantly linked to advanced clinico-radiological stages and worse progression free survival. In neoplastic GCTB stromal cell cultures most Cx43 protein was localized in the paranuclear-Golgi region, while it was concentrated in the cell membranes both in bone marrow stromal cells and HDFa fibroblasts. In Western blots, alkaline phosphatase sensitive bands, linked to serine residues (Ser369, Ser372 or Ser373) detected in control cells, were missing in GCTB stromal cells. Defective cell membrane localization of Cx43 channels was in line with the significantly reduced transfer of the 622 Da fluorescing calcein dye between GCTB stromal cells. Our results show that significant downregulation of Cx43 expression and gap junction coupling in neoplastic stromal cells are associated with the clinical progression and worse prognosis in GCTB

A predictive model relating daily fluctuations in summer temperatures and mortality rates

<p>Abstract</p> <p>Background</p> <p>In the context of climate change, an efficient alert system to prevent the risk associated with summer heat is necessary. The authors' objective was to describe the temperature-mortality relationship in France over a 29-year period and to define and validate a combination of temperature factors enabling optimum prediction of the daily fluctuations in summer mortality.</p> <p>Methods</p> <p>The study addressed the daily mortality rates of subjects aged over 55 years, in France as a whole, from 1975 to 2003. The daily minimum and maximum temperatures consisted in the average values recorded by 97 meteorological stations. For each day, a cumulative variable for the maximum temperature over the preceding 10 days was defined.</p> <p>The mortality rate was modelled using a Poisson regression with over-dispersion and a first-order autoregressive structure and with control for long-term and within-summer seasonal trends. The lag effects of temperature were accounted for by including the preceding 5 days. A "backward" method was used to select the most significant climatic variables. The predictive performance of the model was assessed by comparing the observed and predicted daily mortality rates on a validation period (summer 2003), which was distinct from the calibration period (1975–2002) used to estimate the model.</p> <p>Results</p> <p>The temperature indicators explained 76% of the total over-dispersion. The greater part of the daily fluctuations in mortality was explained by the interaction between minimum and maximum temperatures, for a day <it>t </it>and the day preceding it. The prediction of mortality during extreme events was greatly improved by including the cumulative variables for maximum temperature, in interaction with the maximum temperatures. The correlation between the observed and estimated mortality ratios was 0.88 in the final model.</p> <p>Conclusion</p> <p>Although France is a large country with geographic heterogeneity in both mortality and temperatures, a strong correlation between the daily fluctuations in mortality and the temperatures in summer on a national scale was observed. The model provided a satisfactory quantitative prediction of the daily mortality both for the days with usual temperatures and for the days during intense heat episodes. The results may contribute to enhancing the alert system for intense heat waves.</p

High Refractive Index Silicone Gels for Simultaneous Total Internal Reflection Fluorescence and Traction Force Microscopy of Adherent Cells

Substrate rigidity profoundly impacts cellular behaviors such as migration, gene expression, and cell fate. Total Internal Reflection Fluorescence (TIRF) microscopy enables selective visualization of the dynamics of substrate adhesions, vesicle trafficking, and biochemical signaling at the cell-substrate interface. Here we apply high-refractive-index silicone gels to perform TIRF microscopy on substrates with a wide range of physiological elastic moduli and simultaneously measure traction forces exerted by cells on the substrate

Defining Feasibility and Pilot Studies in Preparation for Randomised Controlled Trials: Development of a Conceptual Framework

We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a randomised controlled trial. To develop the framework, we undertook a Delphi survey; ran an open meeting at a trial methodology conference; conducted a review of definitions outside the health research context; consulted experts at an international consensus meeting; and reviewed 27 empirical pilot or feasibility studies. We initially adopted mutually exclusive definitions of pilot and feasibility studies. However, some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions. Their viewpoint was supported by definitions outside the health research context, the use of the terms ‘pilot’ and ‘feasibility’ in the literature, and participants at the international consensus meeting. In our framework, pilot studies are a subset of feasibility studies, rather than the two being mutually exclusive. A feasibility study asks whether something can be done, should we proceed with it, and if so, how. A pilot study asks the same questions but also has a specific design feature: in a pilot study a future study, or part of a future study, is conducted on a smaller scale. We suggest that to facilitate their identification, these studies should be clearly identified using the terms ‘feasibility’ or ‘pilot’ as appropriate. This should include feasibility studies that are largely qualitative; we found these difficult to identify in electronic searches because researchers rarely used the term ‘feasibility’ in the title or abstract of such studies. Investigators should also report appropriate objectives and methods related to feasibility; and give clear confirmation that their study is in preparation for a future randomised controlled trial designed to assess the effect of an intervention

Assessment and prevention of acute health effects of weather conditions in Europe, the PHEWE project: background, objectives, design

<p>Abstract</p> <p>Background</p> <p>The project "Assessment and prevention of acute health effects of weather conditions in Europe" (PHEWE) had the aim of assessing the association between weather conditions and acute health effects, during both warm and cold seasons in 16 European cities with widely differing climatic conditions and to provide information for public health policies.</p> <p>Methods</p> <p>The PHEWE project was a three-year pan-European collaboration between epidemiologists, meteorologists and experts in public health. Meteorological, air pollution and mortality data from 16 cities and hospital admission data from 12 cities were available from 1990 to 2000. The short-term effect on mortality/morbidity was evaluated through city-specific and pooled time series analysis. The interaction between weather and air pollutants was evaluated and health impact assessments were performed to quantify the effect on the different populations. A heat/health watch warning system to predict oppressive weather conditions and alert the population was developed in a subgroup of cities and information on existing prevention policies and of adaptive strategies was gathered.</p> <p>Results</p> <p>Main results were presented in a symposium at the conference of the International Society of Environmental Epidemiology in Paris on September 6^th2006 and will be published as scientific articles. The present article introduces the project and includes a description of the database and the framework of the applied methodology.</p> <p>Conclusion</p> <p>The PHEWE project offers the opportunity to investigate the relationship between temperature and mortality in 16 European cities, representing a wide range of climatic, socio-demographic and cultural characteristics; the use of a standardized methodology allows for direct comparison between cities.</p