Cardiorespiratory fitness, exercise haemodynamics and birth outcomes: the Coronary Artery Risk Development in Young Adults Study.

OBJECTIVE: Determine associations of cardiorespiratory fitness, exercise systolic blood pressure (SBP) and heart rate recovery (HRR) following a maximal exercise test performed years preceding pregnancy with odds of preterm birth (PTB; <37 weeks' gestation) and small for gestational age (SGA; birthweight <10th percentile) delivery. DESIGN: Prospective, longitudinal. SETTING: Multi-site, observational cohort study initially consisting of 2787 black and white women aged 18-30 at baseline (1985-86) and followed for 25 years (Y25; 2010-2011). POPULATION: 768 nulliparous women at baseline who reported ≥1 live birth by the Y25 exam. METHODS: We used Poisson regression to determine associations of exposures with PTB/SGA. MAIN OUTCOME MEASURES: PTB and/or SGA births. RESULTS: Women with PTB (n = 143) and/or SGA (n = 88) were younger, had completed fewer years of education and were more likely to be black versus women without PTB/SGA (n = 546). Women with PTB/SGA had lower fitness (501 ± 9 versus 535 ± 6 seconds, P < 0.002) and higher submaximal SBP than women without PTB/SGA (144 ± 1 versus 142 ± 1 mmHg, P < 0.04). After adjustment, no exercise test variables were associated with PTB/SGA, though the association with HRR and submaximal SBP approached significance in the subset of women who completed the exercise test <5 years before the index birth. CONCLUSIONS: Neither fitness nor haemodynamic responses to exercise a median of 5 years preceding pregnancy, were associated with PTB/SGA. These findings indicate excess likelihood of PTB/SGA is not detectable by low fitness or exercise haemodynamic responses 5 years preceding pregnancy, but exercise testing, especially HRR and submaximal SBP, may be more useful when conducted closer to the onset of pregnancy. TWEETABLE ABSTRACT: Exercise testing conducted >5 years before pregnancy may not detect women likely to have PTB/SGA.

Genetic polymorphisms associated with smoking behaviour predict the risk of surgery in patients with Crohn's disease.

BACKGROUND: Smoking is a strong environmental factor leading to adverse outcomes in Crohn's disease, but a more benign course in ulcerative colitis. Several single nucleotide polymorphisms (SNPs) are associated with smoking quantity and behaviour. AIM: To assess whether smoking-associated SNPs interact with smoking to influence the clinical course of inflammatory bowel diseases. METHODS: Genetic and prospectively obtained clinical data from 1434 Swiss inflammatory bowel disease cohort patients (821 Crohn's disease and 613 ulcerative colitis) were analysed. Six SNPs associated with smoking quantity and behaviour (rs588765, rs1051730, rs1329650, rs4105144, rs6474412 and rs3733829) were combined to form a risk score (range: 0-12) by adding the number of risk alleles. We calculated multivariate models for smoking, risk of surgery, fistula, Crohn's disease location and ulcerative colitis disease extent. RESULTS: In Crohn's disease patients who smoke, the number of surgeries was associated with the genetic risk score. This translates to a predicted 3.5-fold (95% confidence interval: 2.4- to 5.7-fold, P<.0001) higher number of surgical procedures in smokers with 12 risk alleles than individuals with the lowest risk. Patients with a risk score >7 had a significantly shorter time to first intestinal surgery. The genetic risk score did not predict surgery in ulcerative colitis or occurrence of fistulae in Crohn's disease. SNP rs6265 was associated with ileal disease in Crohn's disease (P<.05) and proctitis in ulcerative colitis (P<.05). CONCLUSIONS: SNPs associated with smoking quantity is associated with an increased risk for surgery in Crohn's disease patients who smoke. Our data provide an example of genetics interacting with the environment to influence the disease course of inflammatory bowel disease.

Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations.

BACKGROUND/OBJECTIVES: Central adiposity measures such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders independently of body mass index (BMI) and are gaining clinically utility. Several studies report genetic variants associated with central adiposity, but most utilize only European ancestry populations. Understanding whether the genetic associations discovered among mainly European descendants are shared with African ancestry populations will help elucidate the biological underpinnings of abdominal fat deposition. SUBJECTS/METHODS: To identify the underlying functional genetic determinants of body fat distribution, we conducted an array-wide association meta-analysis among persons of African ancestry across seven studies/consortia participating in the Population Architecture using Genomics and Epidemiology (PAGE) consortium. We used the Metabochip array, designed for fine-mapping cardiovascular-associated loci, to explore novel array-wide associations with WC and WHR among 15 945 African descendants using all and sex-stratified groups. We further interrogated 17 known WHR regions for African ancestry-specific variants. RESULTS: Of the 17 WHR loci, eight single-nucleotide polymorphisms (SNPs) located in four loci were replicated in the sex-combined or sex-stratified meta-analyses. Two of these eight independently associated with WHR after conditioning on the known variant in European descendants (rs12096179 in TBX15-WARS2 and rs2059092 in ADAMTS9). In the fine-mapping assessment, the putative functional region was reduced across all four loci but to varying degrees (average 40% drop in number of putative SNPs and 20% drop in genomic region). Similar to previous studies, the significant SNPs in the female-stratified analysis were stronger than the significant SNPs from the sex-combined analysis. No novel associations were detected in the array-wide analyses. CONCLUSIONS: Of 17 previously identified loci, four loci replicated in the African ancestry populations of this study. Utilizing different linkage disequilibrium patterns observed between European and African ancestries, we narrowed the suggestive region containing causative variants for all four loci.

Risk factors for exposure to influenza a viruses, including subtype H5 viruses, in Thai free-grazing ducks.

Free-grazing ducks (FGD) have been associated with highly pathogenic avian influenza (HPAI) H5N1 outbreaks and may be a viral reservoir. In July-August 2010, we assessed influenza exposure of Thai FGD and risk factors thereof. Serum from 6254 ducks was analysed with enzyme-linked immunosorbent assay (ELISA) to detect antibodies to influenza A nucleoprotein (NP), and haemagglutinin H5 protein. Eighty-five per cent (5305 ducks) were seropositive for influenza A. Of the NP-seropositive sera tested with H5 assays (n = 1423), 553 (39%) were H5 ELISA positive and 57 (4%) suspect. Twelve per cent (74 of 610) of H5 ELISA-positive/suspect ducks had H5 titres ≥ 1 : 20 by haemagglutination inhibition. Risk factors for influenza A seropositivity include older age, poultry contact, flock visitors and older purchase age. Study flocks had H5 virus exposure as recently as March 2010, but no HPAI H5N1 outbreaks have been identified in Thailand since 2008, highlighting a need for rigorous FGD surveillance.

Changes in procoagulants track longitudinally with insulin resistance: findings from the coronary artery risk development in young adults (CARDIA) study.

AIMS: To examine the association between changes in procoagulants (fibrinogen factors VII and VIII and von Willebrand factor) and the risk of insulin resistance. METHODS: Using data from the Coronary Artery Risk Development in Young Adults study, we followed 2398 black and white adults without diabetes, aged 25-37 years at year 7, to year 20. Levels of fibrinogen factors VII and VIII and von Willebrand factor were divided in tertiles (low/middle/high) at years 7 and 20 and four groups reflecting changes were defined: 'low' (low at years 7 and 20), 'stable' (low/middle at years 7 and 20, but not both low at years 7 and 20), 'high' (high at year 7 and low/middle at year 20; or low/middle at year 7 and high at year 20) and 'highest' (high at years 7 and 20). Linear regression models were used to evaluate 13-year changes (year 20-year 7) in fibrinogen level and factors VII, VIII and von Willebrand change groups in relation to insulin resistance measures. RESULTS: Homeostasis model assessment of insulin resistance (year 20) and changes in log homeostasis model assessment of insulin resistance (year 20-year 7) were significantly associated with the 13-year increase in fibrinogen (P < 0.001). Compared with participants in the low group, those in the high group had significantly higher levels of homeostasis model assessment of insulin resistance (year 20) and changes in homeostasis model assessment of insulin resistance (year 20-year 7) for fibrinogen factor VII and von Willebrand factor (P < 0.017). No significant associations were observed between fibrinogen VIII and insulin resistance measures. CONCLUSIONS: An increase in fibrinogen level and persistently high levels of factor VII and von Willebrand factor are significantly associated with increased risk of insulin resistance. These findings provide new insight into the mechanisms to explain the heightened risk for thrombosis in adults with insulin resistance/diabetes.

Prospective association of serum androgens and sex hormone-binding globulin with subclinical cardiovascular disease in young adult women: the "Coronary Artery Risk Development in Young Adults" women's study.

CONTEXT: The role of endogenous androgens and SHBG in the development of cardiovascular disease in young adult women is unclear. OBJECTIVE: Our objective was to study the prospective association of serum androgens and SHBG with subclinical coronary and carotid disease among young to middle-aged women. DESIGN AND SETTING: This was an ancillary study to the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based multicenter cohort study with 20 yr of follow-up. PARTICIPANTS: Participants included 1629 women with measurements of serum testosterone and SHBG from yr 2, 10, or 16 and subclinical disease assessment at yr 20 (ages 37-52 yr). MAIN OUTCOME MEASURES: Coronary artery calcified plaques (CAC) and carotid artery intima-media thickness (IMT) were assessed at yr 20. The IMT measure incorporated the common carotid arteries, bifurcations, and internal carotid arteries. RESULTS: SHBG (mean of yr 2, 10, and 16) was inversely associated with the presence of CAC (multivariable adjusted odds ratio for women with SHBG levels above the median = 0.59; 95% confidence interval = 0.40-0.87; P = 0.008). SHBG was also inversely associated with the highest quartile of carotid-IMT (odds ratio for women with SHBG levels in the highest quartile = 0.56; 95% confidence interval = 0.37-0.84; P for linear trend across quartiles = 0.005). No associations were observed for total or free testosterone with either CAC or IMT. CONCLUSION: SHBG levels were inversely associated with subclinical cardiovascular disease in young to middle-aged women. The extent to which low SHBG is a risk marker or has its own independent effects on atherosclerosis is yet to be determined.

Longitudinal assessment of fibrinogen in relation to subclinical cardiovascular disease: the CARDIA study.

OBJECTIVE: To examine the strength of the associations of fibrinogen with subclinical atherosclerosis in healthy persons. METHODS: A population-based, prospective, observational study of black and white men and women (Coronary Artery Risk Development in Young Adults [CARDIA]). Fibrinogen levels were measured at year 7 (ages 25-37, n = 2969), and again at year 20 (ages 38-50, n = 2832). Measures of subclinical atherosclerosis (coronary artery calcification [CAC] and carotid intimal-medial thickness [CIMT]) were recorded at year 20. RESULTS: Over the 13-year study interval (1992-1993 to 2005-2006), fibrinogen rose from a mean of 3.32 to 4.05 g L(-1). After adjusting for age, gender and race, fibrinogen was positively associated with greater incidence of CAC and increased CIMT cross-sectionally as well as after 13 years of follow-up (all P-trend < 0.001). After further adjustment for field center, BMI, smoking, education, systolic blood pressure, diabetes, antihypertensive medication use, total and HDL cholesterol, and CRP, significant positive relationships between fibrinogen and incidence of CAC remained for the total cohort longitudinally (P-trend = 0.037), but not cross-sectionally (P-trend = 0.147). CONCLUSION: This 13-year study demonstrates that higher levels of fibrinogen during young adulthood are positively associated with incidence of CAC and increased CIMT in middle-age, but the strength of the association declines with increasing age.

Monochromatic electron photoemission from diamondoid monolayers.

We found monochromatic electron photoemission from large-area self-assembled monolayers of a functionalized diamondoid, [121]tetramantane-6-thiol. Photoelectron spectra of the diamondoid monolayers exhibited a peak at the low-kinetic energy threshold; up to 68% of all emitted electrons were emitted within this single energy peak. The intensity of the emission peak is indicative of diamondoids being negative electron affinity materials. With an energy distribution width of less than 0.5 electron volts, this source of monochromatic electrons may find application in technologies such as electron microscopy, electron beam lithography, and field-emission flat-panel displays.

Changes in risk factors for cardiovascular disease by baseline weight status in young adults who maintain or gain weight over 15 years: the CARDIA study.

OBJECTIVES: To examine whether changes in cardiovascular disease (CVD) risk factors differ by baseline weight status among young adults who maintained or gained weight. DESIGN: Longitudinal cohort study. SUBJECTS: White and African Americans who either maintained (+/-5 pounds; n=488) or gained (>5 pounds; n=2788) weight over 15 years. MEASUREMENTS: Anthropometrics and CVD risk factors were measured at baseline (1985-1986) and follow-up. Participants were classified as normal weight (body mass index (BMI) 18.5-24.9 kg/m2) or overweight (BMI >or=25 kg/m2) at baseline. Multivariable models were stratified by ethnicity and weight change category. RESULTS: Normal weight maintainers tended to have more favorable risk factors at baseline and follow-up than overweight maintainers. Size and direction of 15-year changes in risk factors were similar by weight status, except that in white normal weight maintainers changes in high-density lipoprotein (HDL)-cholesterol (3.3 mg/dl (95% confidence interval (CI): 0.4, 6.3)) and triglycerides (-14.7 mg/dl (-25.8, -3.7)) were more favorable. Weight gain was associated with unfavorable changes in risk factors. Weight gainers normal weight at baseline had less adverse changes in glucose, blood pressure, HDL-cholesterol (whites only) and triglycerides (African Americans only) than overweight gainers. However, normal weight African-American weight gainers had more adverse changes in total (3.1 mg/dl (0.2, 6.1)) and low-density lipoprotein-cholesterol (3.4 mg/dl (0.6, 6.3)). CONCLUSIONS: Baseline weight status does not appear to influence the size or direction of risk factor changes among adults who maintained their weight over 15 years. In contrast, weight gain was associated with changes in some risk factors differentially by baseline weight status.

Dietary intake of n-3, n-6 fatty acids and fish: relationship with hostility in young adults--the CARDIA study.

BACKGROUND: Hostility has been shown to predict both the development and manifestation of coronary disease. Examining the inter-relation of dietary intake of fish and of polyunsaturated (n-3 and n-6) essential fatty acids with hostility may provide additional insights into the cardioprotective effect of dietary fish and polyunsaturated fatty acids. OBJECTIVE: To examine the association of dietary n-3, n-6 fatty acids and fish with level of hostility in a sample of 3581 urban white and black young adults. DESIGN: Cross-sectional observational study as part of an ongoing cohort study. A dietary assessment in 1992-1993 and measurement of hostility and other covariates in 1990-1991 were used in the analysis. RESULTS: The multivariate odds ratios of scoring in the upper quartile of hostility (adjusting for age, sex, race, field center, educational attainment, marital status, body mass index, smoking, alcohol consumption and physical activity) associated with one standard deviation increase in docosahexaenoic acid (DHA, 22:6) intake was 0.90 (95% CI=0.82-0.98; P=0.02). Consumption of any fish rich in n-3 fatty acids, compared to no consumption, was also independently associated with lower odds of high hostility (OR=0.82; 95% CI=0.69-0.97; P=0.02). CONCLUSIONS: These results suggest that high dietary intake of DHA and consumption of fish rich in n-3 fatty acids may be related to lower likelihood of high hostility in young adulthood. The association between dietary n-3 fatty acids and hostile personality merits further research.

Disability after clinical fracture in postmenopausal women with low bone density: the fracture intervention trial (FIT).

Relatively little is known about outcomes following clinical osteoporotic fractures at nonhip, nonvertebral skeletal sites. To address this issue, we prospectively assessed post-fracture disability at multiple skeletal sites in a population of 909 older (aged 55-81 years), community-dwelling women with low femoral neck bone mineral density who had experienced a fracture while enrolled in the Fracture Intervention Trial (FIT). FIT is a randomized, double-masked, placebo-controlled trial that was designed to determine the effect of alendronate on fracture incidence, and the current study was conducted as a secondary analysis of FIT data. Following incident clinical fractures, FIT participants were followed prospectively for assessment of site-specific, fracture-related disability. Measures of disability were self-reported days hospitalized or confined to bed because of the fracture ('bed days') and days of reduced usual activities because of the fracture ('limited activity days'). Of fracture types evaluated, those of the hip resulted in the highest percentage of subjects with any bed days or limited activity days after fracture (94% with any bed days and 100% with any limited activity days), though the mean number of bed days and limited activity days appeared highest after lumbar vertebral fractures (25.8 mean bed days and 158.5 mean limited activity days). Substantial disability also was reported after fractures of thoracic vertebrae, humerus, distal forearm, ankle and foot. Within fracture types, post-fracture disability was highly variable, ranging from none to more than 6 months.

Associations between weight gain and incident hypertension in a bi-ethnic cohort: the Atherosclerosis Risk in Communities Study.

OBJECTIVE: To examine associations between weight gain and changes in blood pressure and the incidence of hypertension in four ethnicity-gender groups. DESIGN: Longitudinal closed cohort studied over an average of 6 y. SUBJECTS: Total of 9309 white and African-American men and women 45-64 y of age who participated in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS: Weight and blood pressure were measured at baseline and after an average of 3 and 6 y of follow-up. Proportional hazard models with weight gain as a time-dependent variable were used to examine the association between weight gain and changes in blood pressure and hypertension. Multivariate models were used with baseline SBP, DBP, age, BMI, height, WHR, smoking, physical activity, education, caloric intake, fat intake and study center as covariates. RESULTS: Weight gain was associated with increases in SBP and DBP in all groups. Hazard ratios for hypertension associated with 1 kg annual weight gain were 1.36 (95% CI, 1.29, 1.45) in white women, 1.12 (95% CI, 1.03, 1.21) in African-American women, 1.35 (95% CI, 1.27, 1.43) in white men and 1.43 (95% CI, 1.27,1.61) in African-American men. CONCLUSION: Weight gain was associated with increased blood pressure and increased incidence of hypertension. The association was weaker among African-American women compared to other ethnicity-gender groups.

Intramolecular 4 + 3 cycloadditions. A theoretical analysis of simple diastereoselectivity in reactions of alkoxyallylic cations and furans.

[reaction--see text] A computational examination (B3LYP/6-31+G*//HF/6-31+G* + ZPVE) of an intramolecular 4 + 3 cycloaddition reaction suggests a stepwise process and the likelihood of reversibility in at least one of the pathways examined.

The cyclization of parent and cyclic hexa-1,3-dien-5-ynes--a combined theoretical and experimental study.

The thermal cycloisomerization of both parent and benzannelated hexa-1,3-dien-5-yne, as well as of carbocyclic 1,3-dien-5-ynes (ring size 7-14), was investigated by using pure density functional theory (DFT) of Becke, Lee, Yang, and Parr (BLYP) in connection with the 6-31G* basis set and the Brueckner doubles coupled-cluster approach [BCCD(T)] with the cc-pVDZ basis set for the parent system. The initial cyclization product is the allenic cyclohexa-1,2,4-triene (isobenzene), while the respective biradical is the transition structure for the enantiomerization of the two allenes. Two consecutive [1,2]-H shifts further transform isobenzene to benzene. For the benzannelated system, the energetics are quite similar and the reaction path is the same with one exception: the intermediate biradical is not a transition state but a minimum which is energetically below isonaphthalene. The cyclization of the carbocyclic 1,3-dien-5-ynes, which follows the same reaction path as the parent system, clearly depends on the ring size. Like the cyclic enediynes, the dienynes were found to cyclize to products with reduced ring strain. This is not possible for the 7- and 8-membered dienynes, as their cyclization products are also highly strained. For 9- to 11-membered carbocycles, all intermediates, transition states, and products lie energetically below the parent system; this indicates a reduced cyclization temperature. All other rings (12- to 14-membered) have higher barriers. Exploratory kinetic experiments on the recently prepared 10- to 14-membered 1,3-dien-5-ynes rings show this tendency, and 10- and 11-membered rings indeed cyclize at lower temperatures.

Molecule-induced alkane homolysis with dioxiranes.

The mechanisms of C-H and C-C bond activations with dimethyldioxirane (DMD) were studied experimentally and computationally at the B3LYP/6-311+G**//B3LYP/6-31G* density functional theory level for the propellanes 3,6-dehydrohomoadamantane (2) and 1,3-dehydroadamantane (3). The sigma(C-C) activation of 3 with DMD (Delta G(*) = 23.9 kcal mol(-1) and Delta G(r) = -5.4 kcal mol(-1)) is the first example of a molecule-induced homolytic C-C bond cleavage. The C-H bond hydroxylation observed for 2 is highly exergonic (Delta G(r) = -74.4 kcal mol(-1)) and follows a concerted pathway (Delta G(*) = 34.8 kcal mol(-1)), in contrast to its endergonic molecule-induced homolysis (Delta G(*) = 28.8 kcal mol(-1) and Delta G(r) = +9.2 kcal mol(-1)). The reactivities of 2 and 3 with CrO(2)Cl(2), which follow a molecule-induced homolytic activation mechanism, parallel the DMD results only for highly reactive 3, but differ considerably for more stable propellanes such as 4-phenyl-3,6-dehydrohomoadamantane (1) and 2.

The rearrangement of the cubane radical cation in solution.

The rearrangement of the cubane radical cation (1*+) was examined both experimentally (anodic as well as (photo)chemical oxidation of cubane 1 in acetonitrile) and computationally at coupled cluster, DFT, and MP2 [BCCD(T)/cc-pVDZ//B3LYP/6-31G* ZPVE as well as BCCD(T)/cc-pVDZ//MP2/6-31G* + ZPVE] levels of theory. The interconversion of the twelve C2v degenerate structures of 1*+ is associated with a sizable activation energy of 1.6 kcalmol(-1). The barriers for the isomerization of 1*- to the cuneane radical cation (2*+) and for the C-C bond fragmentation to the secocubane-4,7-diyl radical cation (10*+) are virtually identical (deltaH0++ = 7.8 and 7.9 kcalmol(-1), respectively). The low-barrier rearrangement of 10*+ to the more stable syn-tricyclooctadiene radical cation 3*+ favors the fragmentation pathway that terminates with the cyclooctatetraene radical cation 6*+. Experimental single-electron transfer (SET) oxidation of cubane in acetonitrile with photoexcited 1,2,4,5-tetracyanobenzene, in combination with back electron transfer to the transient radical cation, also shows that 1*+ preferentially follows a multistep rearrangement to 6*+ through 10*+ and 3*+ rather than through 2*+. This was confirmed by the oxidation of syn-tricyclooctadiene (3), which, like 1, also forms 6 in the SET oxidation/rearrangement/electron-recapture process. In contrast, cuneane (2) is oxidized exclusively to semibullvalene (9) under analogous conditions. The rearrangement of 1*+ to 6*+ via 3*+, which was recently observed spectroscopically upon ionization in a hydrocarbon glass matrix, is also favored in solution.

Halogenation of cubane under phase-transfer conditions: single and double C-H-bond substitution with conservation of the cage structure.

The first highly selective C-H chlorination, bromination, and iodination of cubane (1) utilizing polyhalomethanes as halogen sources under phase-transfer (PT) conditions is described. Isomeric dihalocubanes with all possible combinations of chlorine, bromine, and iodine in ortho, meta, and para positions were also prepared by this method; m-dihalo products form preferentially. Ab initio and density functional theory (DFT) computations were used to rationalize the pronounced differences in the reactions of 1 with halogen (Hal(*)) vs carbon-centered trihalomethyl (Hal(3)C(*)) radicals (Hal = Cl, Br). For Hal(3)C radicals the C-H abstraction pathway is less unfavorable (DeltaG(double dagger)(298) = 21.6 kcal/mol for Cl(3)C(*) and 19.4 kcal/mol for Br(3)C(*) at B3LYP/6-311+G//B3LYP/6-31G) than the fragmentation of the cubane skeleton via S(H)2-attack on one of the carbon atoms of 1 (DeltaG(double dagger)(298) = 33.8 and 35.1 kcal/mol, respectively). In stark contrast, the reaction of 1 with halogen atoms preferentially follows the fragmentation pathway (DeltaG(double dagger)(298) = 2.1 and 7.5 kcal/mol) and C-H abstraction is more unfavorable (DeltaG(double dagger)(298) = 4.6 and 12.0 kcal/mol). Our computational results nicely agree with the behavior of 1 under PT halogenation conditions (where Hal(3)C(*) is involved in the activation step) and under free-radical photohalogenation with Hal(2) (Della, E. W., et al. J. Am. Chem. Soc. 1992, 114, 10730). The incorporation of a second halogen atom preferentially in the meta position of halocubanes demonstrates the control of the regioselectivity by molecular orbital symmetry.

Synthesis of radialene-shaped pyrroles by multiple-anion-capture reactions of 1,3-dianions.

A new multicomponent reaction (multiple-anion-capture reaction) of 1,3-dianions with nitriles and oxalic acid-bis(imidoyl)chlorides is reported. This process allows for an efficient and regioselective synthesis of a variety of radialene-shaped pyrroles which constitute structurally new and interesting heterocyclic systems. The cyclization products can be considered as aza-analogues of the pharmacologically relevant substance class of 3-acetyltetramic acids. A rationalization of the experimental results is given based on quantum chemical computations.

Gender differences in recurrent coronary events; the FINMONICA MI register.

BACKGROUND: Male gender is an established risk factor for first myocardial infarction, but some studies have suggested that among myocardial infarction survivors, women fare worse than men. Therefore, we examined the long-term prognosis of incident myocardial infarction survivors in a large, population-based MI register, addressing gender differences in mortality as well as the number of events and time intervals between recurrent events. METHODS AND RESULTS: Study subjects included 4900 men and women, aged 25-64 years, with definite or probable first myocardial infarctions who were alive 28 days after the onset of symptoms. At first myocardial infarction, women were older and more likely to be hypertensive or diabetic than men, and had a greater proportion of probable vs definite events. After adjustment for age and geographic region, men had 1.74 times the risk of fatal coronary heart disease relative to women (hazard ratio=1.63 and 1.55 for cardiovascular disease and all-cause mortality, respectively) over an average of 5.9 years of follow-up. Number and time intervals between any recurrent event--fatal and non-fatal--did not differ by gender. CONCLUSION: These data suggest that men are far more likely to have a fatal recurrent event than women despite comparable numbers of events.

[Ethics, applied ethics, professional ethics]. / Ethik, angewandte Ethik, Berufsethik.

This study is concerned with "The Familiarity of Basic Rules in Professional Ethics Amongst Nursing Staff Members". Here the codification of norms in professional ethics is understood to be a necessary step on the way to individual nursing ethics. A survey on the study topic showed that there is a lack of familiarity in Germany. Therefore the authors conclude that German nursing has not yet reached this level of individual ethics. As it became clear in the survey that there is a general request for more information, the authors feel bound to demand better coverage of the topic in both basic and further training. The ethics of nursing, however, are applied ethics. In the following discourse first of all the authors will define the term "ethics" and explain the characteristics which are of importance in the present day situation. Secondly, they will ask what "applied ethics" can be against this background. Finally, the authors will discuss what "norms" are as regards professional ethics, how and why they develop and of what relevance they may be with respect to the corresponding ethics applied.