Influence of Climate on Emergency Department Visits for Syncope: Role of Air Temperature Variability

BACKGROUND: Syncope is a clinical event characterized by a transient loss of consciousness, estimated to affect 6.2/1000 person-years, resulting in remarkable health care and social costs. Human pathophysiology suggests that heat may promote syncope during standing. We tested the hypothesis that the increase of air temperatures from January to July would be accompanied by an increased rate of syncope resulting in a higher frequency of Emergency Department (ED) visits. We also evaluated the role of maximal temperature variability in affecting ED visits for syncope. METHODOLOGY/PRINCIPAL FINDINGS: We included 770 of 2775 consecutive subjects who were seen for syncope at four EDs between January and July 2004. This period was subdivided into three epochs of similar length: 23 January-31 March, 1 April-31 May and 1 June-31 July. Spectral techniques were used to analyze oscillatory components of day by day maximal temperature and syncope variability and assess their linear relationship. There was no correlation between daily maximum temperatures and number of syncope. ED visits for syncope were lower in June and July when maximal temperature variability declined although the maximal temperatures themselves were higher. Frequency analysis of day by day maximal temperature variability showed a major non-random fluctuation characterized by a ∼23-day period and two minor oscillations with ∼3- and ∼7-day periods. This latter oscillation was correlated with a similar ∼7-day fluctuation in ED visits for syncope. CONCLUSIONS/SIGNIFICANCE: We conclude that ED visits for syncope were not predicted by daily maximal temperature but were associated with increased temperature variability. A ∼7-day rhythm characterized both maximal temperatures and ED visits for syncope variability suggesting that climate changes may have a significant effect on the mode of syncope occurrence

Fibrosis progression in paired liver biopsies from HIV/HCV co-infected patients

BACKGROUND: Chronic hepatitis C is more aggressive during HIV infection. Available data about risk factors of liver fibrosis in HIV/HCV co-infected patients derive from studies based on a single liver biopsy. OBJECTIVES: To evaluate the risk factors of liver fibrosis progression (LFP) and to investigate the role of antiretroviral therapy (ARV) in HIV/HCV patients who underwent paired liver biopsy. PATIENTS AND METHODS: We retrospectively studied 58 patients followed at two Infectious Diseases Departments in Northern Italy during the period 1988-2005. All specimens were double-blinded and centrally examined by two pathologists. LFP was defined when an increase of at least one stage occurred in the second biopsy, according to the Ishak-Knodell classification. RESULTS: In a univariate analysis, serum levels of alanine aminotransferase (ALT) > 150 IU/L at the first biopsy (P = 0.02), and a > 20% decrease in CD4+ cell count between the two biopsies (P = 0.007), were significantly associated with LFP. In multivariate analysis, a > 20% decrease in CD4+ cell count remained independently associated to LFP (Odds Ratio, 3.99; 95% confidence interval, 1.25-12.76; P < 0.02). Analysis of life survival curves confirmed the correlation between CD4+ cell count and LFP. CONCLUSIONS: Our findings highlight that in HIV/HCV coinfected patients, an effective antiretroviral therapy that assures a good immune-virological profile contributes to reducing the risk of LF

life expectancy in italian patients with hereditary angioedema due to c1 inhibitor deficiency

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Endothelin-1 Inhibits Prolyl Hydroxylase Domain 2 to Activate Hypoxia-Inducible Factor-1α in Melanoma Cells

The endothelin B receptor (ET(B)R) promotes tumorigenesis and melanoma progression through activation by endothelin (ET)-1, thus representing a promising therapeutic target. The stability of hypoxia-inducible factor (HIF)-1alpha is essential for melanomagenesis and progression, and is controlled by site-specific hydroxylation carried out by HIF-prolyl hydroxylase domain (PHD) and subsequent proteosomal degradation.Here we found that in melanoma cells ET-1, ET-2, and ET-3 through ET(B)R, enhance the expression and activity of HIF-1alpha and HIF-2alpha that in turn regulate the expression of vascular endothelial growth factor (VEGF) in response to ETs or hypoxia. Under normoxic conditions, ET-1 controls HIF-alpha stability by inhibiting its degradation, as determined by impaired degradation of a reporter gene containing the HIF-1alpha oxygen-dependent degradation domain encompassing the PHD-targeted prolines. In particular, ETs through ET(B)R markedly decrease PHD2 mRNA and protein levels and promoter activity. In addition, activation of phosphatidylinositol 3-kinase (PI3K)-dependent integrin linked kinase (ILK)-AKT-mammalian target of rapamycin (mTOR) pathway is required for ET(B)R-mediated PHD2 inhibition, HIF-1alpha, HIF-2alpha, and VEGF expression. At functional level, PHD2 knockdown does not further increase ETs-induced in vitro tube formation of endothelial cells and melanoma cell invasiveness, demonstrating that these processes are regulated in a PHD2-dependent manner. In human primary and metastatic melanoma tissues as well as in cell lines, that express high levels of HIF-1alpha, ET(B)R expression is associated with low PHD2 levels. In melanoma xenografts, ET(B)R blockade by ET(B)R antagonist results in a concomitant reduction of tumor growth, angiogenesis, HIF-1alpha, and HIF-2alpha expression, and an increase in PHD2 levels.In this study we identified the underlying mechanism by which ET-1, through the regulation of PHD2, controls HIF-1alpha stability and thereby regulates angiogenesis and melanoma cell invasion. These results further indicate that targeting ET(B)R may represent a potential therapeutic treatment of melanoma by impairing HIF-1alpha stability

Frequency domain analyses of Maximal Temperature spontaneous fluctuations (variability), during the three epochs.

<p>Max Temperature Variance is the variance of the values of Maximal Temperature corresponding to each epoch. DO₂₃ , DO₇ and DO₃ are the powers of Max Temperature rhythmic fluctuations with a period of ≈23, ≈7 and ≈3 days, respectively. (%) indicates % of total variance. Other abbreviations as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0022719#pone-0022719-t002" target="_blank">table 2</a>.</p

Modifications of the rate of syncope, in all the patients who presented to ED for syncope and in subpopulations of different age and gender, grouped according to three epochs.

<p>Max Temperature is the mean ± SD of daily Maximal Temperatures. Max Temperature Variability is the mean ± SD of day by day Maximal Temperatures variations in each epoch. Admitted Syncope refers to patients admitted to hospital for syncope. n is the number; ‰ is the number of Syncope ED visits per thousand, in respect to Total ED visits; % is the percentage of Admitted Syncope in respect to Syncope ED visits and of Syncope aged >75 yrs in respect to Syncope ED visits.</p><p>*p<0.05 vs epoch 2 and epoch 1;</p>§<p>p<0.001 vs epoch 2 and epoch 1;</p>#<p>p<0.001 vs epoch 1.</p

Day by day values of maximal and minimal air temperature, heat index and of syncope observed from January 23^rd, 2004 to July 31^st, 2004.

<p>The expected progressive increase of air temperature from January diverged from Emergency Department (ED) visits for syncope which remained stable until May, before decreasing. Maximal and minimal air temperatures fluctuate (temperature variability) on a day by day basis. The temperature variability was lower in June and July compared to the cooler months. Heat index has been computed only for values of maximal temperature >20°C and its spontaneous variability mirrors maximal temperature fluctuations.</p

Frequency domain analysis of maximal air temperature variability (upper panel), of daily Emergency Department (ED) visits for syncope variability (middle panel) and of their relationship (coherence, lower panel).

<p>Broken line is the result of surrogate analysis. A major oscillatory component at 0.04 cycles×day⁻¹ corresponding to a period of 23.2 days could be identified in the power spectrum of maximal air temperature variability. Two other minor oscillatory components were also present at 0.15 and 0.3 cycles×day⁻¹, i.e. characterized by periods of ∼7 and ∼3 days, respectively. A significant non-random fluctuation in the pattern of ED visits for syncope (middle panel) was found at a peak frequency of 0.15 cycles×day⁻¹ (period ∼7 days). As obtained from coherence and surrogate analyses, maximal temperature and syncope ED attendances variability were linearly coupled in a frequency range between 0.15 and 0.20 cycles×day⁻¹ (between 7 and 5 days, respectively). This suggests a potential influence of maximal air temperature oscillations on the pattern of ED visits for syncope.</p