Photodegradable antimicrobial agents − synthesis,photodegradation, and biological evaluation

Multi-drug resistant (MDR) bacteria are already a significant health-care problem and are making the combat of infections quite challenging. Here we report the synthesis of several new compounds containing an ethanolamine moiety, of which two exhibit promising antimicrobial activity (at the 6 μM level). All the compounds are degraded when exposed to light and form inactive products.

The synthesis of several new compounds containing an ethanolamine moiety are reported, of which two exhibit promising antimicrobial activity (at the 6 μM level).     

Variations in relative health inequalities: are they a mathematical artefact?

Background

Substantial research has documented variations in the magnitude of relative socioeconomic differences in health across European countries, and within countries, across different age groups. The aim of this paper is to examine to what extent these variations are determined by differences in the overall rate or prevalence of a health outcome across countries and age-groups in the total population.

Methods

Three surveys (European Social Survey, and two different population census-mortality registry linked longitudinal data) were used. We plotted rates of mortality and prevalence of poor self-rated health against ratios of mortality and morbidity prevalence associated with educational level. We calculated Pearson coefficients to examine the magnitude of correlations.

Results

We found a significant negative correlation between total mortality rates and associated rate ratios of mortality by education in the SEDHA study (r = -0.40, p = 0.04), but not in the HUNT study (r = -0.37, p = 0.06). There was a weaker but significant negative correlation between the prevalence of poor health and associated prevalence ratios by education in the European social survey (r = -0.22, p = 0.00). Correlations increased as underlying prevalence and rates increased, while they were weaker or null at low prevalence or rates.

Conclusion

We found some evidence that the magnitude of relative inequalities in mortality and morbidity is negatively correlated with underlying morbidity prevalence and mortality rates. Although correlations are moderate, underlying morbidity prevalence and mortality rates should be taken into account in the interpretation of variations in relative health inequalities among populations.     

The association between cycling to school and being overweight in Rotterdam (The Netherlands) and Kristiansand (Norway)

Active transportation is a behavior that might contribute to energy balance. However, no clear association between active commuting to school and weight status has been reported in the international literature. Also, new studies indicate that cycling to school might have a greater health potential than walking to school. The purpose of the present study is to assess the potential association between cycling to school and weight status in two European cities, Rotterdam and Kristiansand, where cycling to school remains common. Data from two studies, ENDORSE (Rotterdam) and Youth in Balance (Kristiansand), were used including, respectively, 1361 and 1197 adolescents with mean ages of 14.1 and 14.4 years. The adolescents were categorized as cyclist or non‐cyclist based on questionnaires on the usual mode of transportation to school. A total of 25% and 18% were categorized as overweight, and 35% and 31% were categorized as cyclists, in Rotterdam and Kristiansand, respectively. In multilevel logistic analyses, after adjusting for potential moderators, the odds ratios for cyclists being overweight compared with non‐cyclists were, respectively, 0.63 (95% CI=0.45–0.89) and 0.52 (95% CI=0.34–0.78) in Rotterdam and Kristiansand. The results presented clearly show a negative association between cycling to school and overweight among adolescents both in Rotterdam and in Kristiansand.     

Opioid analgesic effects on subjective well-being in the operating theatre*

Exposure to opioid analgesics due to surgery increases the risk of new persistent opioid use. A mechanistic hypothesis for opioids' abuse liability rests on the belief that, in addition to pain relief, acute opioid treatment improves well-being (e.g. via euphoria) and relieves anxiety. However, opioids do not consistently improve mood in laboratory studies of healthy non-opioid users. This observational study determined how two commonly used opioid analgesics affected patients' subjective well-being in standard clinical practice. Day surgery patients rated how good and how anxious they felt before and after an open-label infusion of remifentanil (n = 159) or oxycodone (n = 110) in the operating theatre before general anaesthesia. One minute after drug injection, patients reported feeling intoxicated (> 6/10 points). Anxiety was reduced after opioids, but this anxiolytic effect was modest (remifentanil Cohen's d = 0.21; oxycodone d = 0.31). There was moderate to strong evidence against a concurrent improvement in well-being (Bayes factors > 6). After remifentanil, ratings of ‘feeling good’ were significantly reduced from pre-drug ratings (d = 0.28). After oxycodone, one in three participants felt better than pre-drug. Exploratory ordered logistic regressions revealed a link between previous opioid exposure and opioid effects on well-being, as only 14 of the 80 opioid-naïve patients reported feeling better after opioid injection. The odds of improved well-being ratings after opioids were higher in patients with previous opioid exposure and highest in patients with > 2 weeks previous opioid use (adjusted OR = 4.4). These data suggest that opioid-induced improvement of well-being is infrequent in opioid-naïve patients. We speculate that peri-operative exposure could increase risk of persistent use by rendering subsequent positive opioid effects on well-being more likely.     

Health inequalities according to educational level in different welfare regimes: a comparison of 23 European countries

The object of this study was to determine whether the magnitude of educational health inequalities varies between European countries with different welfare regimes. The data source is based on the first and second wave of the European Social Survey. The first health indicator describes people's mental and physical health in general, while the second reports cases of any limiting longstanding illness. Educational inequalities in health were measured as the difference in health between people with an average number of years of education and people whose educational years lay one standard deviation below the national average. Moreover, South European welfare regimes had the largest health inequalities, while countries with Bismarckian welfare regimes tended to demonstrate the smallest. Although the other welfare regimes ranked relatively close to each other, the Scandinavian welfare regimes were placed less favourably than the Anglo-Saxon and East European. Thus, this study shows an evident patterning of magnitudes of health inequalities according to features of European welfare regimes. Although the greater distribution of welfare benefits within the Scandinavian countries are likely to have a protective effect for disadvantaged cities in these countries, other factors such as relative deprivation and class-patterned health behaviours might be acting to widen health inequalities.     

Income-related health inequalities in the Nordic countries: examining the role of education, occupational class, and age

Numerous studies have concluded that people's socioeconomic position is related to mortality and morbidity, but that the strength of this association varies considerably both within and between European regions. This has spurred several researchers to more closely examine educational and occupational gradients in health in the Nordic countries to clarify the causes of cross-national differences. However, comparable studies using income as an indicator of socioeconomic position are still lacking. This study uses recent and highly comparable data to fill this gap. The aim of this study is threefold. First, we ask to what extent there is an income gradient in health in the Nordic countries, and to what extent the association differs between these countries. Second and third, we examine whether differences in the attenuation of the income gradient by education and occupational class, and age-specific differences between countries, may act as explanations for differences in the income gradient between the Nordic countries. The data source are three waves of the European Social Survey (ESS, 2002/2004/2006), which included 17,801 people aged 25 and over from Denmark, Finland, Norway, and Sweden. Two subjective health measures (physical/mental self reported health and limiting longstanding illness) were analysed by means of logistic regression. The results show that, in all countries, people reported significantly better health and were less likely to suffer from longstanding illness as they had a higher income. This association is strongest in Norway and Finland and weakest in Denmark. The income gradient in health, but not country differences in this gradient, is partly explained by education and occupational class. Additionally, the strength of the income gradient in health varies between age groups. The relatively high health inequalities between income groups in Norway and Finland are already visible in the youngest age groups. The results imply that the socioeconomic gradient in health will arguably not be strongly reduced in the near future as a result of cohort replacement, as has been suggested in previous studies. Health policy interventions may be particularly important five to ten years prior to retirement and in early adulthood.     

Smoking and the potential for reduction of inequalities in mortality in Europe

Socioeconomic inequalities in health and mortality remain a widely recognized problem. Countries with smaller inequalities in smoking have smaller inequalities in mortality, and smoking plays an important part in the explanation of inequalities in some countries. We identify the potential for reducing inequalities in all-cause and smoking-related mortality in 19 European populations, by applying different scenarios of smoking exposure. Smoking prevalence information and mortality data come from 19 European populations. Prevalence rates are mostly taken from National Health Surveys conducted around the year 2000. Mortality rates are based on country-specific longitudinal or cross-sectional datasets. Relative risks come from the Cancer Prevention Study II. Besides all-cause mortality we analyze several smoking-related cancers and chronic obstructive pulmonary disease/asthma. We use a newly-developed tool to quantify the changes in population health potentially resulting from modifying the population distribution of exposure to smoking. This tool is based on the epidemiological measure of the population attributable fraction, and estimates the impact of scenario-based distributions of smoking on educational inequalities in mortality. The potential reduction of relative inequality in all-cause mortality between those with high and low education amounts up to 26 % for men and 32 % for women. More than half of the relative inequality may be reduced for some causes of death, often in countries of Northern Europe and in Britain. Patterns of potential reduction in inequality differ by country or region and sex, suggesting that the priority given to smoking as an entry-point for tackling health inequalities should differ between countries.     

Activation of muscarinic receptors elicits inotropic responses in ventricular muscle from rats with heart failure through myosin light chain phosphorylation

Background and purpose:

Muscarinic stimulation increases myofilament Ca²⁺ sensitivity with no apparent inotropic response in normal rat myocardium. Increased myofilament Ca²⁺ sensitivity is a molecular mechanism promoting increased contractility in failing cardiac tissue. Thus, muscarinic receptor activation could elicit inotropic responses in ventricular myocardium from rats with heart failure, through increasing phosphorylation of myosin light chain (MLC).

Experimental approach:

Contractile force was measured in left ventricular papillary muscles from male Wistar rats, 6 weeks after left coronary artery ligation or sham surgery. Muscles were also frozen, and MLC-2 phosphorylation level was quantified.

Key results:

Carbachol (10 µmol·L⁻¹) evoked a positive inotropic response only in muscles from rats with heart failure approximating 36% of that elicited by 1 µmol·L⁻¹ isoproterenol (20 ± 1.5% and 56 ± 6.1% above basal respectively). Carbachol-evoked inotropic responses did not correlate with infarction size but did correlate with increased left ventricular end diastolic pressure, heart weight/body weight ratio and lung weight, primary indicators of the severity of heart failure. Only muscarinic receptor antagonists selective for M₂ receptors antagonized carbachol-mediated inotropic effects with the expected potency. Carbachol-evoked inotropic responses and increase in phosphorylated MLC-2 were attenuated by MLC kinase (ML-9) and Rho-kinase inhibition (Y-27632), and inotropic responses were abolished by Pertussis toxin pretreatment.

Conclusion and implications:

In failing ventricular muscle, muscarinic receptor activation, most likely via M₂ receptors, provides inotropic support by increasing MLC phosphorylation and consequently, myofilament Ca²⁺ sensitivity. Enhancement of myofilament Ca²⁺ sensitivity, representing a less energy-demanding mechanism of inotropic support may be particularly advantageous in failing hearts.     

Markers for endothelial activation during open heart surgery

BACKGROUND: Reliable markers for endothelial activation are needed when studying biocompatibility of cardiopulmonary bypass. METHODS: Blood samples from 21 patients undergoing combined valve and coronary artery bypass surgery were collected before anesthesia (T1), after re-transfusion of blood from the heart-lung machine (T2), and on the first postoperative morning (T3). Concentrations of soluble markers were determined using sandwich enzyme-linked immunoadsorbent assay for sICAM-1, sVCAM-1, and sE-selectin. The sera were also used to stimulate human umbilical vein endothelial cells (HUVEC) in culture for 6 hours, in which activation was measured using cell enzyme immunoassay for mICAM-1 and mVCAM-1. RESULTS: The concentrations of sICAM-1 and sVCAM-1 increased during both measurement intervals (p < 0.05). The sICAM-1 T1 was 311.0 ng/mL (range, 271.0 to 350.7 ng/mL); the sICAM-1 T2 was 341.6 ng/mL (range, 322.0 to 422.0 ng/mL), and the sICAM-1 T3 was 400.2 ng/mL (range, 348.0 to 556.4 ng/mL; the sVCAM-1 T1 was 607.5 ng/mL (range, 497.8 to 813.8 ng/mL), the sVCAM-1 T2 was 755.3 ng/mL (range, 660.6 to 834.4 ng/mL), and the sVCAM-1 T3 was 1149.0 ng/mL (946.0 to 1406.0 ng/mL); whereas the sE-selectin increased from T1 to T3 (p < 0.01). Both the mICAM-1 (p < 0.002) and the mVCAM-1 (p < 0.005) increased on the human umbilical vein endothelial cells in culture after stimulation with the patient sera. The amounts of soluble markers in vivo were not correlated with the degree of endothelial activation in vitro, but were correlated with various operative variables including age, medication, and time of aortic cross-clamping. CONCLUSIONS: Endothelial cells were activated during cardiopulmonary bypass. The soluble adhesion molecules sICAM-1, sVCAM-1, and sE-selectin displayed different kinetics, rendering it difficult to determine a simple expression for the degree of endothelial cell activation. Clinically, sVCAM-1 seemed to be the best-suited marker for endothelial cell activation, because it was only associated with aortic cross-clamping and heparin and protamine doses, and it also showed the largest numerical changes.