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This article deals with the new OECD international VAT/GST Guidelines on place of supply of B2B Services and Intangibles. The Guidelines were approved by the OECD Committee on Fiscal Affairs in January 2014. The aim of the article is to analyse the new Guidelines from an EU law perspective and also from the perspective of how the Guidelines may contribute to reducing the risks of double taxation and unintended non-taxation. [ABSTRACT FROM AUTHOR]

An abstract of the study "The Relationship Between N-Terminal B-Type Natriuretic Peptide and Circulating Markers of Extracellular Cardiac Remodelling in Patients Following Complicated Myocardial Infarction," by S. Orn and colleagues is presented.

An abstract of the article "Incidence, Severity and Timing of Neurological Events After a Major Myocardial Infarction," by J. G. F. Cleland and colleagues, is presented.

An abstract of the article "Circulating markers of inflammation are independently related to markers of extracellular cardiac remodelling in patients following acute myocardial infarction," by C. Manhenke and colleagues is presented.

An abstract of the article "Temporal Changes Between Infarct Size and Ejection Fraction Following Primary PCI Assessed by Cardiac Magnetic Resonance," by S. Orn and colleagues is presented.

An abstract of the article "Left ventricular global strain in patients with acute myocardial infarction treated with thrombolysis predicts viable myocardium," by B. Sjoli and colleagues is presented.

An abstract of a study which investigated the incidence and mortality from cancer of patients who have suffered a myocardial infarction complicated by left ventricular systolic dysfunction (LVSD) or heart failure, is presented.

Zebrafish (Danio rerio) were orally exposed to a mixture of 20 PCBs in three different dose levels (0.008, 0.08, and 0.4 5g of each congener per gram of freeze-dried chironomids). Generally, the PCBs accumulated in a dose-related manner. After 13 weeks of exposure body, liver, and ovary weights, as well as the liver and ovary somatic index, were significantly lower in exposed groups. In addition, the PCB mixture was an effective inducer of hepatic EROD activity. The reproduction study performed with exposed females and unexposed males after 9 weeks revealed that median survival time for larvae was only 7.7 days in the high-dose group as compared with 14 days in controls. Furthermore, egg production was reduced in all three groups exposed. No differences in hatching frequency or median hatching time were recorded. Histologically, females in both the intermediate and high-dose groups contained a reduced number of mature oocytes. The present study demonstrates that the potency of the mixture of selected PCBs induces hepatic EROD activity and has a clearly negative effect on zebrafish reproduction. [ABSTRACT FROM AUTHOR]

Objective: To determine effects of obesity and gender on left ventricular mass in normotensive and hypertensive Thai patients using 320-slice cardiac computed tomography (CT)., Material and Method: Left ventricular mass (LVM) obtained from 320-slice coronary CT angiogram was compared in 597 normotensive subjects (175 men [65 obese] and 422 women [133 obese], aged 55±7 years) and 483 hypertensive patients (180 men [104 obese] and 303 women [170 obese], aged 60±7 years). Obesity in Asian population was defined by body mass index (BMI) ≥ 25 kg/m2 in both genders. LV mass was normalized for body surface area (BSA)and height2.7., Results: The upper normal limit of LVM/ height2.7 developed from 244 (197 women, 47 men) low risk subjects (non-smoking normal-weight adults free from hypertension, diabetes, coronary artery disease & dyslipidemia) was lower than the established criteria for left ventricular hypertrophy (LVH) (31 versus 44 g/m2.7 in women; 36 versus 48 g/m2.7 in men). There is statistical difference between men and women in all groups of analysis. Among both hypertensive and normotensive subjects, the prevalence of LVH and LVM/height2.7 are higher in the obese group than normal-weight group in both genders (LVM/height2.7p<0.001; prevalence of LVH – obese versus normal-weight hypertension: 58% versus 34% in women, 43% versus 14% in men; obese versus normal-weight normotension: 35% versus 16% in women, 40% versus 15% in men). The same differences between obese and normal-weight groups were also present when normalizing LVM for height but not with LVM/BSA. Logistic regression analysis revealed that systolic blood pressure and BMI were the main predictors of LVH in the entire population (p<0.001 in both genders). Equations for predicting LVH in men and women were: Risk of LVH = 1/(l+e-w) where w is as follows: w (men) = 0.02* systolic pressure + 0.25*BMI – 9.86, w (women) = 0.03* systolic pressure + 0.17*BMI – 8.82., Conclusion: Obesity is an independent stimulus to increase LVM in normo-tensive subjects, and its effect is additive in hypertensive patients. Gender and obesity affect LVM and prevalence of LVH.

Objectives: Galectin-3 (Gal-3) is involved in cardiac inflammation and fibrosis, and is in use as a biomarker that indicates increased risk in heart failure. This study examined the relationship between Gal-3 levels and acute and old myocardial infarction (MI) in patients assessed by cardiac magnetic resonance (CMR) imaging., Methods: Group 1 consisted of 38 patients with ST-elevation MI and single-vessel disease treated with primary percutaneous coronary intervention (PCI). Group 2 consisted of 52 patients with prior complicated MI. Twenty-two controls were included. CMR was performed in group 1 at 2 days, 1 week, 2 months and 1 year following PCI and in group 2 at >4 years after MI., Results: Median Gal-3 was elevated in patients compared with controls, group 1: 11.93 ng/ml (IQR 6.34-17.52, p = 0.03), group 2: 12.96 (IQR 6.33-19.29, p = 0.03) and controls: 10.16 (IQR 5.59-14.73). Gal-3 levels did not change during acute MI, and there was no relationship between Gal-3 and infarct size, troponin-T, high-sensitivity C-reactive protein, left-ventricular (LV) volumes or LV ejection fraction (LVEF) in group 1. In group 2, Gal-3 correlated modestly with MI size (r = 0.28, p < 0.05), LV end-diastolic volume index (r = 0.40, p < 0.01), LV end-systolic volume index (r = 0.43, p < 0.01) and LVEF (r = -0.39, p < 0.01)., Conclusion: There was no relationship between Gal-3 levels and acute ischemic myocardial injury. A significant, modest relationship between Gal-3 levels, MI size and LV remodeling was only found in patients with old MI., (© 2016 S. Karger AG, Basel.)

Objective: To compare the sensitivity of sonographic, cholescintigraphic, and computed tomographic examination of acute cholecystitis to the pathology result, which is considered the Gold Standard., Material and Method: A retrospective analytic study was conducted among 412 patients, aged between 15 and 98 years, who underwent cholecystectomy surgeries, and whose pathology results indicated acute cholecystitis between July 2004 and May 2013. The sensitivity and the differences between sensitivity of the three methods were calculated in all patients. Complicated acute cholecystitis cases were analyzed separately., Results: The three methods demonstrated statistically significant differences in sensitivity (p-value = 0.017), with the cholescintigraphy as the most sensitive method (84.2%), followed by computed tomography (67.3%), and sonography (59.8%). Concerning the samples with the pathology result indicating complicated acute cholecystitis, computed tomography was statistically significantly more sensitive than sonography in detecting acute cholecystitis, whether or not the complications were identified (100% and 63.6%, respectively, with p-value = 0.0055). None of the patients with the pathology result of complicated acute cholecystitis case was examined by cholescintigraphy, thus, no calculation was possible. Regarding the ability to detect the complications of acute cholecystitis, computed tomography had a sensitivity of 35.71% (5 in 14 patients), while sonographic examinations could not detect any of the complications., Conclusion: Cholescintigraphy is a more sensitive method than computed tomography and sonography, but the three methods have its own advantages, disadvantages, and limitations, which must be consideredfor each individual patient.

Perfluoroalkyl acids (PFAAs) are persistent organic contaminants that have been detected in wildlife, humans and the environment. Studies have shown that the toxicity of PFAAs is determined by the carbon chain length as well as the attached functional group. The locomotor activity of zebrafish larvae has become widely used for evaluation of chemicals with neurotoxic properties. In the present study the behavioral effects of seven structurally different PFAAs (i.e. TFAA, PFBA, PFOA, PFNA, PFDA, PFBS and PFOS) were evaluated in zebrafish larvae. Exposure to high concentrations of TFAA, PFNA, PFBS and PFOS resulted in distinct changes in behavioral patterns. Based on redundancy analysis, our results demonstrate three main factors affecting zebrafish larval locomotor behavior. The strongest effect on behavior was determined by the carbon chain length and the attached functional group. PFAAs with longer carbon chain length as well as PFAAs with attached sulfonic groups showed larger potential to affect locomotor behavior in zebrafish larvae. Also the concentration of the PFAAs determined the behavior responses. The results of the present study are in agreement with previous studies showing correlations between the chemical structure of PFAAs and the toxicological effects., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: The myocardium exhibits heterogeneous nature due to scarring after Myocardial Infarction (MI). In Cardiac Magnetic Resonance (CMR) imaging, Late Gadolinium (LG) contrast agent enhances the intensity of scarred area in the myocardium., Methods: In this paper, we propose a probability mapping technique using Texture and Intensity features to describe heterogeneous nature of the scarred myocardium in Cardiac Magnetic Resonance (CMR) images after Myocardial Infarction (MI). Scarred tissue and non-scarred tissue are represented with high and low probabilities, respectively. Intermediate values possibly indicate areas where the scarred and healthy tissues are interwoven. The probability map of scarred myocardium is calculated by using a probability function based on Bayes rule. Any set of features can be used in the probability function., Results: In the present study, we demonstrate the use of two different types of features. One is based on the mean intensity of pixel and the other on underlying texture information of the scarred and non-scarred myocardium. Examples of probability maps computed using the mean intensity of pixel and the underlying texture information are presented. We hypothesize that the probability mapping of myocardium offers alternate visualization, possibly showing the details with physiological significance difficult to detect visually in the original CMR image., Conclusion: The probability mapping obtained from the two features provides a way to define different cardiac segments which offer a way to identify areas in the myocardium of diagnostic importance (like core and border areas in scarred myocardium).

Background: Left ventricular (LV) remodeling takes place after acute myocardial infarction (MI), potentially leading to overt heart failure (HF). Enhanced inflammation may contribute to LV remodeling. Our hypothesis was that the immunomodulating effects of intravenous immunoglobulin (IVIg) would be beneficial in patients with impaired myocardial function after MI by reducing myocardial remodeling and improving myocardial function., Methods: Sixty-two patients with acute MI treated by percutaneous coronary intervention, with depressed LV ejection fraction (LVEF) were randomized in a double-blinded fashion to IVIg as induction therapy and thereafter as monthly infusions or placebo for 26 weeks. The primary end point was changes in LVEF from baseline to 6 months as assessed by MRI., Results: Our main findings were: (i) LVEF increased significantly from 38 ± 10 (mean ± SD) to 45 ± 13% after IVIg and from 42 ± 9 to 49 ± 12% after placebo with no difference between the groups. (ii) The scar area decreased significantly by 3% and 5% in the IVIg and placebo group, respectively, with no difference between the groups. (iii) During the induction therapy (baseline to day 5), IVIg induced both inflammatory (e.g., increase in tumor necrosis factor α and monocyte chemoattractant protein-1) and anti-inflammatory (e.g., increase in interleukin-10 and decrease in leukocyte counts) variables, but during maintenance therapy there were no differences in changes of inflammatory mediators between IVIg and placebo., Conclusions: IVIg therapy after ST elevation MI managed by primary PCI does not affect LV remodeling or function. This illustrates the challenges of therapeutic intervention directed against the cytokine network, to prevent post-MI remodeling., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: To evaluate the five years average equivalent dose, the average collective equivalent dose and fatal cancer risk for the radiation workers in Radiology Department at Phramongkutklao Hospital., Material and Method: In the Radiology Department at Phramongkutklao Hospital, occupationally exposed workers are measured by the Division of Radiation Protection Services, Department of Medical Sciences which measures radiation exposures and evaluated doses from external exposures. Individual's doses of external exposure were monitored using film badges. The present study design describes a retrospective survey of occupational exposure in the Radiology Department at Phramongkutklao Hospital 2004-2008., Results: The distribution of radiation workers monitored according to the groups in the years 2004-2008, physicist, technologist and assistant of technologist were the most numerous occupational group (51.13%). Nurse, assistant of nurse and nurse aids constituted 22.73%. About 59.73% of radiation workers in the Radiology Department at Phramongkutklao Hospital received an annual average equivalent dose below 0.02 mSv which defined as recording level and no radiation workers received doses above the International Commission on Radiological Protection (ICRP) Publication 60 recommended dose limit (20 mSv per year). The five years average equivalent dose per radiation worker was 1.098 mSv. Of all occupational groups measurably exposed, the nuclear medicine group received the highest of the five years average equivalent dose, collective equivalent dose and fatal cancer risk. The five years average equivalent dose, collective equivalent dose and fatal cancer risk for the physicist, technologist and assistant of technologist were the highest., Conclusion: Total risk per the whole monitored radiation workers were 3.86 x lW due to receive the five years average collective equivalent dose 0.096 man Sv. These values were estimated from a very small of number of radiation workers.

Results are presented from a validation (with 5 laboratories) of the Fish Sexual Development Test (FSDT) developed to detect endocrine disrupters (EDs) and included in the OECD (Organisation for Economic Co-operation and Development) working program. The aromatase-inhibiting fungicide prochloraz was tested in zebrafish (Danio rerio) and fathead minnow (Pimephales promelas). The fish were exposed during sexual differentiation and development from 0 to 60 days post hatch (dph). After exposure, the vitellogenin (VTG) concentrations were quantified in head/tail homogenate and the sex ratio was determined (defined as female, male, intersex or undifferentiated). NOEC/LOEC and EC(x) designs were compared to optimize the test approach. Results show that both species are highly sensitive to prochloraz during sexual development. They respond by skewing of the sex ratio towards male phenotype and by a VTG decline in females. The NOEC/LOEC approach is preferred because sex ratio is difficult to analyze with a regression model. The mean NOEC/LOEC for prochloraz on the sex ratio was 43.3/134 μg/L and 101/293 μg/L for zebrafish and fathead minnow, respectively. The mean NOEC/LOEC on the decline in female VTG concentration was 65/110 μg/L and ~30/68 μg/L respectively. In conclusion, zebrafish and fathead minnow are suitable species in the FSDT and their sexual differentiation is equally labile to EDs., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Early prediction of infarct size directs therapy in patients with acute myocardial infarction (AMI). Global strain by echocardiography describes myocardial deformation and correlates with infarct size. However, peak strain measures deformation at a single time point, whereas ischemia and necrosis influence deformation throughout the heart cycle. It was hypothesized that the measurement of myocardial deformation throughout the heart cycle by mean strain is a more comprehensive expression of myocardial deformation. The aim of this study was to assess the ability of mean strain to predict infarct size and to identify large infarctions at admission and after revascularization in patients with AMI., Methods: Seventy-six patients with AMI were included. Echocardiographic measurements were performed at admission and after revascularization. Myocardial strain was calculated using speckle-tracking echocardiography. Infarct size was measured using contrast-enhanced magnetic resonance imaging ≥3 months after revascularization., Results: There were significant correlations between infarct size and longitudinal global mean strain, longitudinal global strain, and left ventricular ejection fraction (P < .0001), both at admission and after revascularization. The correlations improved after revascularization. Longitudinal global mean strain had the best correlation with infarct size and the best ability to discriminate between different infarct size categories. At admission, a cutoff value of -7.6 had 89% sensitivity, 88% specificity, and an area under the receiver operating characteristic curve of 0.92 for the identification of large infarctions. Prediction of infarct size improved for all parameters after revascularization., Conclusions: Longitudinal global mean strain provides improved early prediction of infarct size in patients with AMI compared with longitudinal global strain and left ventricular ejection fraction.

Background: We assessed the time profiles and prognostic utility of circulating markers of collagen turnover (CTO) following acute myocardial infarction (MI). In contrast to previous studies, no patient had been pre-treated with inhibitors of the renin-angiotensin-aldosterone system (RAAS) at the time of initial assessment., Methods: Plasma levels of N-terminal fragment of type I collagen (PINP), carboxy-terminal telopeptide of type I collagen (ICTP), N-terminal fragment of type III collagen (PIIINP), matrix metalloproteinase-1(MMP-1) and tissue inhibitor of MMPs type-1 (TIMP-1) were assessed in 233 patients following acute MI. The CTO markers were initially assessed prior to treatment by either captopril or losartan, at a median of 3 days following MI. In addition, blood samples were acquired at 1 month, 1 year and 2 years following MI. Development of heart failure symptoms, all-cause and cardiovascular death were recorded as endpoints during two years of follow-up., Results: With the exception of PIIINP, all CTO markers demonstrated significant longitudinal changes following MI. At baseline, ICTP (p<0.0001) and TIMP-1 (p=0.01) levels were significantly elevated in patients who later died compared with survivors. In multivariable analysis only ICTP reached statistical significance as predictor of all cause death (p=0.048). In patients developing symptoms of heart failure during follow-up, ICTP was the only significantly elevated CTO marker (p<0.01)., Conclusion: The present study supports a prognostic role for ICTP in both the acute and chronic phase following MI., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The cardiac magnetic resonance (CMR) images from a group of patients with myocardial scars and implanted cardioverter-defibrillator (ICD) are divided into a group with low risk of arrhythmias (late incidents) and a group with high risk of arrhythmias (early incidents). Several hundred quantitative features describing sizes, statistics and textures of the segmented and defined areas of the images are computed from manually segmented images in an exploratory analysis. The method used to determine decision regions to discriminate the patients with low risk of arrhythmias from the patient with high risk of arrhythmias is a maximum likelihood estimation based Bayes classifiers described in [1]. The results presented can be interpreted as hypothesis of which features, and combinations of features, that might have discriminative power. A major hypothesis that arises is that there are important textural information in the scarred and non-scarred areas.

Very high levels of a range of pharmaceuticals have been reported recently in the effluent from a wastewater treatment plant near Hyderabad, India. The plant serves approximately 90 manufacturers of bulk drugs that primarily are exported to the world market. Fluoroquinolone antibiotics were found at levels that are highly toxic to various microorganisms. Even though milligram-per-liter levels of drugs targeting human proteins also have been found, it is difficult to conclude whether these levels are sufficiently high to adversely affect fish or amphibians due to the lack of relevant chronic toxicity data for most human pharmaceuticals. To assess potential effects on aquatic vertebrates, tadpoles of Xenopus tropicalis were exposed to three dilutions of effluent (0.2, 0.6, and 2%) over 14 d, starting at developmental stage 51. Additionally, newly fertilized zebrafish (Danio rerio) were exposed to diluted effluent in 96-well plates for up to 144 h postfertilization (hpf). The tadpoles' body lengths, weights, and developmental stages were recorded, whereas a larger number of sublethal and lethal endpoints were studied in the zebrafish. A 40% reduced growth of the exposed tadpoles was demonstrated at the lowest tested effluent concentration (0.2%), indicating potent constituents in the effluent that can adversely affect aquatic vertebrates. The median lethal concentration (LC50) for zebrafish at 144 hpf was between 2.7 and 8.1% in different experiments. Reduced spontaneous movements, pigmentation, and heart rate were recorded within 48 hpf at 8 and 16% effluent concentrations. Treated effluent from a plant that serves as an important link in the global supply chain for bulk drugs is thus shown to cause adverse effects to aquatic vertebrates even at very high dilutions.

Increased circulating chemokines have been reported during acute myocardial infarction and might give prognostic information about future ischemic events. However, data on the chemokine network in relation to infarct size and measures of left ventricular remodeling after successful percutaneous coronary intervention (PCI) are lacking. A total of 42 patients with first-time ST-segment elevation acute myocardial infarction with a single occluded vessel were recruited, and cardiac magnetic resonance was used for serial assessment (2, 7, and 60 days) of infarct size and left ventricular remodeling. The chemokines were analyzed before and after PCI. After PCI, high levels of CCL4, CXCL16, CXCL10, and, in particular, CXCL8 within the first week after PCI correlated positively with the degree of myocardial damage, as reflected by correlations with the maximum troponin T levels and infarct size after 2 months, as assessed by cardiac magnetic resonance, and with impaired myocardial function after 2 months as assessed by cardiac magnetic resonance and neurohormonal methods. In contrast, the plasma levels of CCL3 and CXCL7 during the first week correlated negatively with myocardial dysfunction after 2 months. In conclusion, our findings suggest a role for chemokines in both adaptive and maladaptive responses after myocardial infarction and might support a role for CCL4, CXCL16, CXCL10, and, in particular, CXCL8 in postmyocardial infarction reperfusion and remodeling.

Objective: To evaluate the efficiency of quality control performance for a general x-ray machine between computed radiography (CR) and film method., Material and Method: CR performance as a quality control method for a general x-ray machine was compared to the film method. Two raters independently analyzed the result of quality control from both methods. Economic evaluation was performed by cost-minimization analysis. All data (result for quality control and cost) were collected from Phramongkutklao Hospital from August 2007 to January 2008., Result: Quality control performances of a general x-ray machine by using CR and film method were equivalent. Interobserver agreement for analysis of quality control measurements was almost perfect. Unit cost, test performance time, radiation dose for quality control by CR were less than the film method (p < 0.001)., Conclusion: The performances of quality control of a general x-ray machine done by the CR method are more efficient than the film method. Using the CR method for quality control performance of the general x-ray machines will save cost enormously.

Background: Altered activity of the matrix metalloproteinases (MMP-2 and -9), has been implicated in the left ventricular (LV) remodeling process occurring after myocardial infarction (MI). In the acute phase, a relation between plasma MMP-9 levels and parameters of LV dysfunction has been demonstrated. The relationship in long-term survivors has not been investigated. We studied the relationships of these biochemical markers, and N-terminal pro-B-type natriuretic peptide (N-BNP), with measures of long-term LV remodeling., Methods and Results: Plasma levels of N-BNP, MMP-2, and MMP-9 were measured at randomization, 1 month, 1 year, and > 4 years after complicated AMI. Contrast-enhanced cardiac magnetic resonance (CMR) was performed at 4.4 (+/-0.4) years in 52 clinically stable long-term survivors of the index AMI. We assessed the relationships of plasma N-BNP, MMP-2, and MMP-9 with myocardial scarring, and measures of long-term LV remodeling. Compared with a reference population, N-BNP and MMP-9 levels were increased at all time points from the acute phase until > 4 years after MI. Plasma N-BNP and MMP-9 correlated only in the subacute phase (randomization, mean 3.3 days after MI) days after acute MI (r = 0.38, P = .006). At CMR assessment > or = 4 years, log MMP-9 level was inversely related to LV ejection fraction (P = .002) and nonscarred myocardial mass (P = .008). This relationship was independent of MMP-2. Log N-BNP was related to end diastolic volume index (P = .0002). There was no correlation between log MMP-9 and LV volumes., Conclusion: There is a time-dependent relationship between plasma N-BNP and MMP-9 levels, these peptides correlating only in the acute phase after MI. In long-term follow-up, plasma MMP-9 and N-BNP levels were related to different parameters of LV remodeling. These findings suggest that in long-term survivors of complicated MI, different mechanisms modulate plasma levels of MMP-9 and N-BNP.

Studies of patients with acute myocardial infarction (MI) suggest that anterior transmural infarcts are associated with greater left ventricular (LV) remodeling compared with nontransmural nonanterior infarctions. It is unclear whether this relation also exists in long-term survivors of MI. Cardiac magnetic resonance imaging was used to explore the relation between myocardial scar size, localization, transmurality, and degree of long-term LV remodeling in patients with healed MI. Subjects were recruited from a registry of patients with healed MI who participated in the OPTIMAAL trial. Cardiac magnetic resonance imaging was performed to assess LV mass, volumes, LV ejection fraction, and myocardial scarring, adjusting for myocardial ischemia. Fifty-seven patients (mean age 69 +/- 10 years mean ejection fraction 49 +/- 13%) were studied 4.4 +/- 0.4 years after MI. Anterior scar was found in 19 patients and nonanterior scar in 33, whereas 5 patients did not show myocardial scar. Transmural scar was evident in 36 patients. In the 52 patients with scar, average total scar size was 13 +/- 8% of total LV mass. There was a strong linear relation between scar size and LV end-diastolic volume index (r = 0.81, p <0.0001), end-systolic volume index (r = 0.86, p <0.0001), and LV ejection fraction (r = -0.74, p <0.0001). In multivariate analysis, scar size was the strongest independent predictor of ejection fraction and LV volumes independently of scar localization and transmurality. In conclusion, in the studied cohort, there was a linear relation between scar size and ejection fraction and LV volumes. This relation was independent of scar location and transmurality.

The presence or onset of bundle branch block (BBB) is associated with increased mortality in patients after acute myocardial infarction (AMI). The risk increases with age. We assessed the prognostic power of BBB patterns for predicting clinical outcomes in patients after high-risk AMI. In the OPTIMAAL trial, the effects of losartan versus captopril were compared in 5,477 patients with heart failure and/or evidence of left ventricular dysfunction after MI. The association between clinical outcomes and the presence of left or right BBB at randomization (median 3 days after AMI) or occurring during follow-up (mean 2.7 years) was assessed using Cox regression models. At randomization, 8% of patients (n = 438) showed BBB patterns; 3.7% (n = 203) showed left BBB and 4.3% (n = 235) showed right BBB patterns. In patients with left BBB, there was an increased risk of all-cause death and cardiovascular death. In patients with right BBB, there was increased risk of sudden cardiac death/resuscitated cardiac arrest. During follow-up, another 4.9% (n = 272) developed BBB patterns; 2.8% (n = 153) developed left BBB and 2.17% (n = 119) developed right BBB. Left BBB was associated with increased risk for all-cause death, cardiovascular death, and sudden cardiac death/resuscitated cardiac arrest, whereas right BBB was related to increased risk of sudden cardiac death/resuscitated cardiac arrest. In conclusion, our results confirm and quantify previous observations showing substantially increased mortality in patients with BBB patterns at baseline or occurring soon after AMI.

Juvenile zebrafish (Danio rerio) were exposed to different dilutions (0, 0.67, 2.5, 10, and 50%) of effluent water from a Swedish pulp mill that previously has been reported to be androgenic to fish. Exposure was performed between days 10-38 days post-hatch. Fish were sampled for whole-body vitellogenin concentrations at day 38 post-hatch and for histological examination of gonads at day 60 post-hatch. In fish exposed to the highest concentration of pulp mill effluent, elevated concentrations of vitellogenin were measured. The androgenicity of the pulp mill water was confirmed by the increased number of males recorded at 60 days post-hatch. Image analysis of testes indicated stimulation of spennato genesis. Intersex fish were observed in all exposure groups. An androgenic activity equivalent to 5.6 ng/L dihydroxytestosterone was measured using the yeast androgen screen (YAS) assay. The present study demonstrates that both androgenic and estrogenic effects can be detected when exposing zebrafish during the juvenile period to complex mixtures of chemicals.

The pharmaceutical estrogen 17alpha-ethinylestradiol (EE2) and the anabolic androgen 17beta-trenbolone (Tb) can interfere with the endocrine and reproductive systems of fish. The potency of these chemicals in zebrafish (Danio rerio) and Japanese medaka (Oryzias latipes) was assessed using the core end points vitellogenin (Vtg) concentration at 38 days post-hatch and sex ratio and gonad morphology at 60 days post-hatch. Vtg concentrations were measured in fish whole-body homogenate samples using enzyme-linked immunosorbent assay. Increased Vtg concentration and feminization of fish after exposure to 10 ng/L EE2, as well as masculinization after exposure to 50 ng/L of Tb, were observed in zebrafish. Intersex was observed in medaka exposed to EE2. A decrease in Vtg production after Tb exposure (50 ng/L) was measured in both zebrafish and medaka. Analyses of gonad morphology revealed increased testicular area and sperm percentage in Tb-exposed zebrafish, whereas increased sperm percentage was measured in Tb-exposed medaka. The higher sensitivity of zebrafish compared with medaka to both EE2 and Tb was revealed in the study.

Purpose: The development of left ventricular systolic dysfunction or heart failure following an acute myocardial infarction (MI) is a powerful marker of an adverse prognosis. Recurrent MI could be an important cause of death, either directly or by provoking arrhythmias., Methods: The OPTIMAAL trial randomized 5477 patients with heart failure or evidence of left ventricular dysfunction following acute MI to losartan or captopril. Over a follow-up of 2.7 years, there were 946 deaths. Of the 180 (19%) of these deaths for which autopsy reports were available, acute MI was found in 57% (102 of 180) of the autopsies. By comparison, an endpoints adjudication committee using clinical data attributed death to acute MI in only 29 cases. An acute MI was found at autopsy in 55% (37 of 67) of the deaths that had been classified as due to an arrhythmia and in 81% (21 of 26) of the deaths classified as due to progressive heart failure. Including autopsy diagnoses, the rate of acute MI in patients who died suddenly was independent of the time elapsed since the index MI, but in patients not classified as dying suddenly, there was a time-related decrease in recurrent MI from 78% in the first 30 days to 30% by the end of follow-up. However, only 19% of patients who died underwent autopsy, so recurrent MI may have been substantially more common and perhaps had a different relation to time since the index MI if more patients had undergone autopsy., Conclusions: In patients with evidence of major cardiac dysfunction after MI, recurrent MI found at autopsy is common and has often not been clinically detected.

In a partial life-cycle test, the impact of 17alpha-ethinylestradiol (EE2) and 17alpha-methyltestosterone (MT) on juvenile zebrafish was evaluated by use of vitellogenin measurements and gonadal development. Exposure to EE2 (1-25 ng/l) resulted in a dose-dependent increase in vitellogenin production starting at 2 ng/l. Significant changes in sex ratios in female direction were detected at 1 ng/l, with complete sex reversal taking place after exposure to 2 ng/l. No intersex fish were observed after exposure to EE2. Exposure to MT resulted in decreased vitellogenin concentrations. Complete sex reversal was detected in all MT concentrations used (26-1000 ng/l). A large proportion of intersex fish was observed after exposure to 1000 ng MT/l. The period of gonadal sex reversal in non-exposed zebrafish was also studied. The main morphological features of the transformation of ovaries into testis were observed 4-5 weeks after hatching.

The uptake and elimination of 20 structurally diverse tetra- to heptachlorinated biphenyls were studied in zebrafish (Danio rerio), three-spined stickleback (Gasterosteus aculeatus), and Arctic char (Salvelinus alpinus). The polychlorinated biphenyls (PCBs) were administered to the fish through food, intraperitoneal injection of peanut oil, or intraperitoneal implantation of silicone capsules. The retention of the PCBs in fish exposed through their diet was related with the substitution patterns of the compounds. Ortho-substituted congeners with no unsubstituted meta-para positions had high biomagnification potential. PCBs with low biomagnification all had adjacent vicinal hydrogens, indicating that congeners with this feature may have been metabolically eliminated. The retention characteristics of the PCBs in the diet-exposed and the injected zebrafish were similar. The pattern of congeners in Arctic char indicates that they have a lower capacity to metabolize PCBs compared to three-spined sticklebacks and zebrafish. The levels in the fish exposed to the PCBs through a silastic implant were negatively correlated with the hydrophobicity of the congeners. Most probably congener-specific release rates of the PCBs from the implants mask their retention characteristics. It is suggested that food, mimicking the natural intake route, should be used in PCB exposure studies to validate extrapolations to natural situations.

Nitro musks are a group of nitrated benzenes mainly used by the fragrance industry as a substitute for natural musk. Two of the most common nitro musks, musk xylene and musk ketone, have been detected in water, fish, human adipose tissue, as well as in human breast milk. In this study, female zebrafish were dietary-exposed to musk ketone, prior to spawning with unexposed males. The fish were exposed for 8 weeks at two different dose levels. Accumulation of the compound in the fish as well as reproductive success were studied. Exposed females had reduced body weight and length, as well as reduced liver- and gonad somatic index. The results from the reproduction study showed a dose-dependent reduction in fecundity. Early life-stage mortality was increased and the median survival time was reduced. In addition, an embryo/larvae toxicity test was performed, using newly fertilized zebrafish eggs from unexposed parental fish. Eggs were exposed to a series of different concentrations of musk ketone via the surrounding water. A NOEC value of 10 micrograms/l and a LOEC value of 33 micrograms/l was determined. Conclusively, the present study clearly shows that musk ketone negatively affects reproduction and early life-stage survival in zebrafish.

Zambia is a country with an extensive mining industry with the majority of mines located in the Copperbelt province. Through this region of the country, the Kafue River drains and receives effluent water from mining activities as well as from other industrial point sources. In addition, production of agricultural products and pest control requires use of different pesticides in the area. Information on industrial and agricultural pollution has not been clearly identified in Zambia, and little attention has been paid to pollution control and possible impact of metals, pesticides, and other persistent compounds in the environment. The objective of this study was to introduce and to evaluate a few methodologies based on in situ bioassays for environmental assessment to promote sustainable and environmentally sound water resource management of the Kafue River. The results show that caged threespot tilapia exposed downstream of industrial points sources rapidly bioaccumulate several trace elements, i.e., Cd, Co, Cu, Cr, Ni. These elements also occurred in much higher concentrations in water samples downstream of the industrial area compared with a locality upstream. Furthermore, the use of a semipermeable membrane device (SPMD) for passive absorption of lipophilic pollutants in the water showed relatively high concentration of several pesticides, i.e., DDT with major metabolites, PCB, and dieldrin. The present study shows that only 2 weeks of in situ studies in waters contaminated by pollutants affects in situ exposed fish and that the correlation between water and tissue concentrations was relatively good. Both trace elements and persistent organic pollutants occurred in such high concentrations that they must be considered from ecotoxicological aspects and may affect aquatic animal health.

Zebrafish (Danio rerio) were orally exposed to a mixture of 20 PCBs in three different dose levels (0.008, 0.08, and 0.4 microg of each congener per gram of freeze-dried chironomids). Generally, the PCBs accumulated in a dose-related manner. After 13 weeks of exposure body, liver, and ovary weights, as well as the liver and ovary somatic index, were significantly lower in exposed groups. In addition, the PCB mixture was an effective inducer of hepatic EROD activity. The reproduction study performed with exposed females and unexposed males after 9 weeks revealed that median survival time for larvae was only 7.7 days in the high-dose group as compared with 14 days in controls. Furthermore, egg production was reduced in all three groups exposed. No differences in hatching frequency or median hatching time were recorded. Histologically, females in both the intermediate and high-dose groups contained a reduced number of mature oocytes. The present study demonstrates that the potency of the mixture of selected PCBs induces hepatic EROD activity and has a clearly negative effect on zebrafish reproduction.