Concordance between health administrative data and survey-derived diagnoses for mood and anxiety disorders.

OBJECTIVE: To assess whether estimates of survey structured interview diagnoses of mood and anxiety disorders were concordant with diagnoses of these disorders obtained from health administrative data. METHODS: All Ontario respondents to the 2012 Canadian Community Health Survey-Mental Health (CCHS-MH) were linked to health administrative databases at ICES (formerly known as the Institute for Clinical Evaluative Sciences). Survey structured interview diagnoses were compared with health administrative data diagnoses obtained using a standardized algorithm. We used modified Poisson regression analyses to assess whether socio-demographic factors were associated with concordance between the two measures. RESULTS: Of the 4157 Ontarians included in our sample, 20.4% had either a structured interview diagnosis (13.9%) or health administrative diagnosis (10.4%) of a mood or anxiety disorder. There was high discordance between measures, with only 19.4% agreement. Migrant status, age, employment, and income were associated with discordance between measures. CONCLUSIONS: Our findings indicate that previous estimates of the 12-month prevalence of mood and anxiety disorders in Ontario may be underestimating the true prevalence, and that population-based surveys and health administrative data may be capturing different groups of people. Understanding the limitations of data commonly used in epidemiologic studies is a key foundation for improving population-based estimates of mental disorders.

Real-Time Dynamics of the Formation of Hydrated Electrons upon Irradiation of Water Clusters with Extreme Ultraviolet Light.

Free electrons in a polar liquid can form a bound state via interaction with the molecular environment. This so-called hydrated electron state in water is of fundamental importance, e.g., in cellular biology or radiation chemistry. Hydrated electrons are highly reactive radicals that can either directly interact with DNA or enzymes, or form highly excited hydrogen (H^{*}) after being captured by protons. Here, we investigate the formation of the hydrated electron in real-time employing extreme ultraviolet femtosecond pulses from a free electron laser, in this way observing the initial steps of the hydration process. Using time-resolved photoelectron spectroscopy we find formation timescales in the low picosecond range and resolve the prominent dynamics of forming excited hydrogen states.

Subtraction of subcutaneous fat to improve the prediction of visceral adiposity: exploring a new anthropometric track in overweight and obese youth.

BACKGROUND: The efficiency of traditional anthropometric measurements such as body mass index (BMI) or waist circumference (Waist C) used to replace biomedical imaging for assessing visceral adipose tissue (VAT) is still highly controversial in youth. HYPOTHESIS AND OBJECTIVES: We evaluated the most accurate model predicting VAT in overweight/obese youth, using various anthropometric measurements and their correlation with different body fat compartments, especially by testing, for the first time in youth, the hypothesis that subtracting the anthropometric measurement the most highly correlated with subcutaneous abdominal adipose tissue (SAAT) and less correlated possible with VAT from an anthropometric abdominal measurement highly correlated with visceral and total abdominal adipose tissue (TAAT), predicts VAT with higher accuracy. SUBJECTS AND METHODS: VAT and SAAT data resulted from magnetic resonance imaging (MRI) analysis performed on 181 boys and girls (7-17 y) from Diabetes & Endocrinology Care Paediatrics Clinic in Luxembourg. Height, weight, abdominal diameters, waist, hip, and thigh circumferences were measured with a view to developing the anthropometric VAT predictive algorithms. RESULTS: In girls, subtracting proximal thigh circumference (Proximal Thigh C), the most closely correlated anthropometric measurement with SAAT, from Waist C, the most closely correlated anthropometric measurement with VAT was instrumental in improving VAT prediction, in comparison with the most accurate single VAT anthropometric surrogate. [Formula: see text] Residual analysis showed a negligible estimation error (5 cm2 ). In boys, Waist C was the best VAT predictor. CONCLUSIONS: Subtraction of abdominal subcutaneous fat is important to predict VAT in overweight/obese girls.

The role of global and regional DNA methylation and histone modifications in glycemic traits and type 2 diabetes: A systematic review.

BACKGROUND: New evidence suggests the potential involvement of epigenetic mechanisms in type 2 diabetes (T2D) as a crucial interface between the effects of genetic predisposition and environmental influences. AIM: To systematically review studies investigating the association between epigenetic marks (DNA methylation and histone modifications) with T2D and glycemic traits (glucose and insulin levels, insulin resistance measured by HOMA-IR). METHOD AND RESULTS: Six bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, PubMed, Cochrane Central and Google Scholar) were screened until 28th August 2015. We included randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined the association between epigenetic marks (global, candidate or genome-wide methylation of DNA and histone modifications) with T2D, glucose and insulin levels and insulin metabolism. Of the initially identified 3879 references, 53 articles, based on 47 unique studies met our inclusion criteria. Overall, data were available on 10,823 participants, with a total of 3358 T2D cases. There was no consistent evidence for an association between global DNA-methylation with T2D, glucose, insulin and insulin resistance. The studies reported epigenetic regulation of several candidate genes for diabetes susceptibility in blood cells, muscle, adipose tissue and placenta to be related with T2D without any general overlap between them. Histone modifications in relation to T2D were reported only in 3 observational studies. CONCLUSIONS AND RELEVANCE: Current evidence supports an association between epigenetic marks and T2D. However, overall evidence is limited, highlighting the need for further larger-scale and prospective investigations to establish whether epigenetic marks may influence the risk of developing T2D.

Effects of moderate beer consumption on health and disease: A consensus document.

A large evidence-based review on the effects of a moderate consumption of beer on human health has been conducted by an international panel of experts who reached a full consensus on the present document. Low-moderate (up to 1 drink per day in women, up to 2 in men), non-bingeing beer consumption, reduces the risk of cardiovascular disease. This effect is similar to that of wine, at comparable alcohol amounts. Epidemiological studies suggest that moderate consumption of either beer or wine may confer greater cardiovascular protection than spirits. Although specific data on beer are not conclusive, observational studies seem to indicate that low-moderate alcohol consumption is associated with a reduced risk of developing neurodegenerative disease. There is no evidence that beer drinking is different from other types of alcoholic beverages in respect to risk for some cancers. Evidence consistently suggests a J-shaped relationship between alcohol consumption (including beer) and all-cause mortality, with lower risk for moderate alcohol consumers than for abstainers or heavy drinkers. Unless they are at high risk for alcohol-related cancers or alcohol dependency, there is no reason to discourage healthy adults who are already regular light-moderate beer consumers from continuing. Consumption of beer, at any dosage, is not recommended for children, adolescents, pregnant women, individuals at risk to develop alcoholism, those with cardiomyopathy, cardiac arrhythmias, depression, liver and pancreatic diseases, or anyone engaged in actions that require concentration, skill or coordination. In conclusion, although heavy and excessive beer consumption exerts deleterious effects on the human body, with increased disease risks on many organs and is associated to significant social problems such as addiction, accidents, violence and crime, data reported in this document show evidence for no harm of moderate beer consumption for major chronic conditions and some benefit against cardiovascular disease.

Short term Heart Rate Variability to predict blood pressure drops due to standing: a pilot study.

BACKGROUND: Standing from a bed or chair may cause a significant lowering of blood pressure (ΔBP), which may have severe consequences such as, for example, falls in older subjects. The goal of this study was to develop a mathematical model to predict the ΔBP due to standing in healthy subjects, based on their Heart Rate Variability, recorded in the 5 minutes before standing. METHODS: Heart Rate Variability was extracted from an electrocardiogram, recorded from 10 healthy subjects during the 5 minutes before standing. The blood pressure value was measured before and after rising. A mathematical model aiming to predict ΔBP based on Heart Rate Variability measurements was developed using a robust multi-linear regression and was validated with the leave-one-subject-out cross-validation technique. RESULTS: The model predicted correctly the ΔBP in 80% of experiments, with an error below the measurement error of sphygmomanometer digital devices (± 4.5 mmHg), a false negative rate of 7.5% and a false positive rate of 10%. The magnitude of the ΔBP was associated with a depressed and less chaotic Heart Rate Variability pattern. CONCLUSIONS: The present study showes that blood pressure lowering due to standing can be predicted by monitoring the Heart Rate Variability in the 5 minutes before standing.

Novel collective autoionization process observed in electron spectra of He clusters.

The ionization dynamics of He nanodroplets irradiated with intense femtosecond extreme ultraviolet pulses of up to 1013 W/cm2 power density have been investigated by photoelectron spectroscopy. Helium droplets were resonantly excited to atomiclike 2p states with a photon energy of 21.4 eV, below the ionization potential (Ip), and directly into the ionization continuum with 42.8 eV photons. While electron emission following direct ionization above Ip is well explained within a model based on a sequence of direct electron emission events, the resonant excitation provides evidence of a new, collective ionization mechanism involving many excited atomiclike 2p states. With increasing power density the direct photoline due to an interatomic Coulombic decay disappears. It indicates that ionization occurs due to energy exchange between at least three excited atoms proceeding on a femtosecond time scale. In agreement with recent theoretical work the novel ionization process is very efficient and it is expected to be important for many other systems.

Risk factors for prehypertension in the community: a prospective analysis from the Western New York Health Study.

BACKGROUND AND AIM: Prehypertension is an increasingly highly prevalent condition in the general population, and is associated with an increased risk for coronary heart disease and stroke. However, evidence from population-based studies of the risk factors for prehypertension is scant. We sought to examine the predictors of progression from normotension to prehypertension in a community-based population from Western New York. METHODS AND RESULTS: A longitudinal analysis, over 6 years of follow-up, among 569 men and women (mean age 51.8 years) who were free of prehypertension, hypertension, cardiovascular disease and diabetes at the baseline examination, in the Western New York Health Study (WNYHS). Incident prehypertension at follow-up was defined as systolic blood pressure of 120-139 mm Hg and/or diastolic blood pressure of 80-89 mm Hg. The cumulative six year incidence of prehypertension was 33.5% (189/564). In bivariate analyses, there were several correlates of incident prehypertension, including age, BMI and waist circumference, impaired fasting glucose (IFG), uric acid, and baseline blood pressure levels. After multivariate adjustment, IFG at baseline [odds ratio (OR): 1.70, 95% CI: 1.07-2.69) and weight gain since age 25 (OR: 1.12, 1.04-1.21 per 10 lb increase)] were the strongest significant predictors of prehypertension at follow-up. Neither baseline waist circumference nor change in BMI were predictor variables in models when they were substituted for weight gain. CONCLUSIONS: Results from this study suggest early dysregulation of glucose metabolism and weight gain over the lifespan may represent important risk factors for prehypertension in the general population.

Functional foods and cardiometabolic diseases* International Task Force for Prevention of Cardiometabolic Diseases.

Mounting evidence supports the hypothesis that functional foods containing physiologically-active components may be healthful. Longitudinal cohort studies have shown that some food classes and dietary patterns are beneficial in primary prevention, and this has led to the identification of putative functional foods. This field, however, is at its very beginning, and additional research is necessary to substantiate the potential health benefit of foods for which the diet-health relationships are not yet scientifically validated. It appears essential, however, that before health claims are made for particular foods, in vivo randomized, double-blind, placebo controlled trials of clinical end-points are necessary to establish clinical efficacy. Since there is need for research work aimed at devising personalized diet based on genetic make-up, it seems more than reasonable the latter be modeled, at present, on the Mediterranean diet, given the large body of evidence of its healthful effects. The Mediterranean diet is a nutritional model whose origins go back to the traditional dietadopted in European countries bordering the Mediterranean sea, namely central and southern Italy, Greece and Spain; these populations have a lower incidence of cardiovascular diseases than the North American ones, whose diet is characterized by high intake of animal fat. The meeting in Naples and this document both aim to focus on the changes in time in these two different models of dietary habits and their fall out on public health.

The population impact of common mental disorders and long-term physical conditions on disability and hospital admission.

BACKGROUND: Long-term physical conditions (LTCs) consume the largest share of healthcare budgets. Although common mental disorders (CMDs) and LTCs often co-occur, the potential impact of improved mental health treatment on severe disability and hospital admissions for physical health problems remains unknown. Method A cross-sectional study of 7403 adults aged 16-95 years living in private households in England was performed. LTCs were ascertained by prompted self-report. CMDs were ascertained by structured clinical interview. Disability was assessed using questions about problems with activities of daily living. Population impact and potential preventive gain were estimated using population-attributable fraction (PAF), and conservative estimates were obtained using 'treated non-cases' as the reference group. RESULTS: Of the respondents, 20.7% reported at least one LTC. The prevalence of CMDs increased with the number of LTCs, but over two-thirds (71.2%) of CMD cases in people with LTCs were untreated. Statistically significant PAFs were found for CMDs and recent hospital admission [13.5%, 95% confidence intervals (CI) 6.6-20.0] and severe disability (31.3%, 95% CI 27.1-35.2) after adjusting for LTCs and other confounders. Only the latter remained significant when using the most conservative estimate of PAF (21.8%, 95% CI 14.0-28.9), and this was reduced only slightly when considering only participants with LTCs (18.5%, 95% CI 7.9-27.9). CONCLUSIONS: Better treatments for CMDs in people with LTCs could achieve almost the same population health gain in terms of reducing severe disability as those targeted at the entire population. Interventions to reduce the prevalence of CMDs among people with LTCs should be part of routine medical care.

The soft X-ray absorption spectrum of the allyl free radical.

The first experimental study of the X-ray absorption spectrum (XAS) of the allyl free radical, CH(2)CHCH(2), is reported. A supersonic He seeded beam of hyperthermal allyl radicals was crossed by a high resolution synchrotron radiation (SR) in the focus of a 3D ion momentum imaging time-of-flight (TOF) spectrometer to investigate the soft X-ray absorption and fragmentation processes. The XAS, recorded as Total-Ion-Yield (TIY), is dominated by C1s electron excitations from either the central carbon atom, C(C), or the two terminal carbon atoms, C(T), to the frontier orbitals, the semi-occupied-molecular-orbital (SOMO) and the lowest-unoccupied-molecular-orbital (LUMO). All of the intense features in the XAS could only be assigned with the aid of ab initio spectral simulation at the Multi-Configuration Self-Consistent-Field (MCSCF) level of theory, this level being required because of the multi-reference nature of the core-excited state wavefunctions of the open shell molecule. The ionization energies (IEs) of the singlet and triplet states of the C1s ionized allyl radical (XPS) were also calculated at the MCSCF level.

Does selenium matter in cardiometabolic disorders? A short review of the evidence.

Selenium is an essential micronutrient in the human diet. It is a constituent of selenoproteins, linked to cysteine, and is involved in the defense against oxidative stress. Few studies suggested a role of selenoproteins in the prevention of chronic degenerative disorders, including Parkinson's and Alzheimer disease, cancer, cardiovascular disease, atherosclerosis, stroke, and infertility. On the other hand, concerns were raised about a possible association of selenium supplementation with increased risk of developing insulin resistance and Type 2 diabetes. The objective of this article is to briefly review the results of the observational (cohort and case-control) studies as well as of the randomized controlled trials of selenium supplementation and risk of metabolic and cardiovascular disorders.

Fasting glucose and treatment outcome in breast and colorectal cancer patients treated with targeted agents: results from a historic cohort.

BACKGROUND: We investigated pretreatment fasting glucose as a predictor of patients' important outcomes in breast and colorectal cancers undergoing targeted therapies. PATIENTS AND METHODS: In a historic cohort of 202 breast and 218 colorectal cancers treated with targeted agents from 1998 to 2009, we used the Kaplan-Meier method and the log-rank test to estimate survival through tertiles of fasting glucose and the Cox proportional hazards model for multivariate analysis stratified by primary site of cancer and including gender, age and body mass index. RESULTS: The median follow-up was 20 months (1-128). At 60 months, 65% of patients in the lowest tertile of fasting glucose did not experiment disease progression compared with 34% in the highest tertile (P=0.001). Seventy-six percent of females in the lowest tertile showed no progression compared with 49% in the top tertiles (P=0.015). In multivariate analysis, fasting glucose was a significant predictor of time to disease progression only in breast cancer patients in the first tertile compared with the third (P=0.017). CONCLUSIONS: We found evidence of a predictive role of pretreatment fasting glucose in the development of resistance in breast cancer patients treated with targeted agents. Prospective studies are warranted to confirm our findings.

Cardiovascular disease prevention in women: a rapidly evolving scenario.

The past decade has witnessed a long overdue recognition of the importance of CVD in women, accompanied by an increasing awareness of gender differences in risk factors, natural history, preventive strategies, treatment, and prognosis of CVD. Reflecting the disease burden and the specific aspects of CVD in women, the American Heart Association has developed women-specific evidence-based guidelines and consensus documents for CVD prevention. The most recent update of these guidelines, published in 2011, is a milestone in the field and shows the rapidly evolving scenario of CVD prevention in women. We discuss some novel aspects of the 2011 update. The new guidelines change the focus from evidence-based to effectiveness-based, with consideration of both benefits and harms/costs of preventive interventions. The guidelines also introduce "ideal cardiovascular health" as the lowest category of risk, which implies the need of communitywide preventive, educational and policy initiatives to promote healthy lifestyles in the general population. Furthermore, the guidelines emphasize long-term overall CVD risk rather than short-term coronary risk. We also address several barriers and open questions in the evaluation and implementation of these guidelines, including how to increase the small proportion of women with ideal cardiovascular health; how to increase implementation and compliance with the recommendations; how to provide effectiveness-based recommendations for lifetime prevention goals based on short-term trials; how to obtain the best possible evidence in women; how to identify subgroups of women with different cardiovascular risk profiles or who may require tailored preventive strategies; and how to adapt current guidelines to international settings, particularly to low- and middle-income countries.

Angular and energy distribution of fragment ions in dissociative double photoionization of acetylene molecules at 39 eV.

The two-body dissociation reactions of the dication, C(2)H(2)(2+), produced by 39.0 eV double photoionization of acetylene molecules, have been studied by coupling photoelectron-photoion-photoion coincidence and ion imaging techniques. The results provide the kinetic energy and angular distributions of product ions. The analysis of the results indicates that the dissociation leading to C(2)H(+)+H(+) products occurs through a metastable dication with a lifetime of 108±22 ns, and a kinetic energy release (KER) distribution exhibiting a maximum at ∼4.3 eV with a full width at half maximum (FWHM) of about 60%. The reaction leading to CH(2)(+)+C(+) occurs in a time shorter than the typical rotational period of the acetylene molecules (of the order of 10(-12) s). The KER distribution of product ions for this reaction, exhibits a maximum at ∼4.5 eV with a FWHM of about 28%. The symmetric dissociation, leading to CH(+)+CH(+), exhibits a KER distribution with a maximum at ∼5.2 eV with a FWHM of 44%. For the first two reactions the angular distributions of ion products also indicate that the double photoionization of acetylene occurs when the neutral molecule is mainly oriented perpendicularly to the light polarization vector.

C-C bond unsaturation degree in monosubstituted ferrocenes for molecular electronics investigated by a combined near-edge x-ray absorption fine structure, x-ray photoemission spectroscopy, and density functional theory approach.

We present the results of an experimental and theoretical investigation of monosubstituted ethyl-, vinyl-, and ethynyl-ferrocene (EtFC, VFC, and EFC) free molecules, obtained by means of synchrotron-radiation based C 1s photoabsorption (NEXAFS) and photoemission (C 1s XPS) spectroscopies, and density functional theory (DFT) calculations. Such a combined study is aimed at elucidating the role played by the C-C bond unsaturation degree of the substituent on the electronic structure of the ferrocene derivatives. Such substituents are required for molecular chemical anchoring onto relevant surfaces when ferrocenes are used for molecular electronics hybrid devices. The high resolution C 1s NEXAFS spectra exhibit distinctive features that depend on the degree of unsaturation of the hydrocarbon substituent. The theoretical approach to consider the NEXAFS spectrum made of three parts allowed to disentangle the specific contribution of the substituent group to the experimental spectrum as a function of its unsaturation degree. C 1s IEs were derived from the experimental data analysis based on the DFT calculated IE values for the different carbon atoms of the substituent and cyclopentadienyl (Cp) rings. Distinctive trends of chemical shifts were observed for the substituent carbon atoms and the substituted atom of the Cp ring along the series of ferrocenes. The calculated IE pattern was rationalized in terms of initial and final state effects influencing the IE value, with special regard to the different mechanism of electron conjugation between the Cp ring and the substituent, namely the σ/π hyperconjugation in EtFC and the π-conjugation in VFC and EFC.

Objective and subjective sleep measures are associated with HbA1c and insulin sensitivity in the general population: Findings from the ORISCAV-LUX-2 study.

AIM: To analyze the association of objective and subjective sleep measures with HbA1c and insulin sensitivity in the general population. METHODS: Using a cross-sectional design, data from 1028 participants in the ORISCAV-LUX-2 study from the general population in Luxembourg were analyzed. Objective sleep measures were assessed using accelerometers whereas subjective measures were assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Sleep measures were defined as predictors, while HbA1c and quantitative insulin sensitivity check index (QUICKI) scores were considered outcomes. Linear and spline regression models were fitted by progressively adjusting for demographic and lifestyle variables in the total sample population as well as by stratified analyses using gender, obesity status, depressive symptoms and diabetes status. RESULTS: In fully adjusted models, total and deep sleep durations were associated with lower HbA1c (mmol/mol) levels, whereas sleep coefficients of variation (%) and poor sleep efficiency, as measured by PSQI scores (units), were associated with higher HbA1c levels. In stratified models, such associations were observed mainly in men, and in subjects who had depressive symptoms, were overweight and no diabetes. In addition, total sleep, deep sleep, coefficients of variation and poor sleep efficiency as measured by PSQI revealed non-linear associations. Similarly, greater insulin sensitivity was associated with longer total sleep time and with PSQI-6 (use of sleep medication). CONCLUSION: Associations were more frequently observed between sleep characteristics and glycaemic control with the use of objective sleep measures. Also, such associations varied within subgroups of the population. Our results highlight the relevance of measuring sleep patterns as key factors in the prevention of diabetes.

Selenium status and blood lipids: the cardiovascular risk in Young Finns study.

BACKGROUND: Concern has been recently raised about possible adverse cardio-metabolic effects of high selenium status, such as increased risks of diabetes and hyperlipidaemia. However, most of the evidence comes from selenium-replete populations such as that of the United States. OBJECTIVES: To examine cross-sectional and longitudinal associations of serum selenium with cardiovascular risk factors in Finland where selenium levels were amongst the lowest in the world until the early 1980s before the implementation of a nationwide selenium fertilization programme. METHODS: Serum selenium was measured in 1235 young Finns aged 3-18 years at baseline in 1980 (prefertilization) and in a subgroup (N = 262) at the 6-year follow-up (1986, postfertilization). During the 27-year follow-up, serum lipids, blood pressure, body mass index and smoking were assessed five times (1980, 1983, 1986, 2001 and 2007). RESULTS: Mean (±SD) serum selenium concentrations were 74.3 ± 14.0 ng mL(-1) in 1980 and 106.6 ± 12.5 ng mL(-1) in 1986 (average increase 32.3 ng mL(-1); 95% CI: 30.3 to 34.3, P < 0.0001). In univariate and multivariable cross-sectional models in 1980 and 1986, increased serum selenium levels were consistently associated with increased total, HDL and Low-density lipoprotein (LDL) cholesterol. However, the average longitudinal changes in lipids were -0.20 mmol L(-1) (95% CI: -0.30 to -0.10, P < 0.0001) for total cholesterol, 0.06 mmol L(-1) (95% CI: 0.03 to 0.10, P < 0.0001) for HDL cholesterol, and -0.23 mmol L(-1) (95% CI: -0.31 to -0.14, P < 0.0001) for LDL cholesterol. Selenium measured in 1986 was not associated with lipids assessed in 2001 and 2007. CONCLUSIONS: Cross-sectional findings from the Young Finns study corroborate positive associations of selenium status with serum lipids. However, longitudinal evidence does not support the causality of this link.

The valence electronic structure and conformational flexibility of epichlorohydrin.

The electronic structure of epichlorohydrin is investigated in the whole valence region by a combined experimental and theoretical study. The issue of controversial assignments of the molecular electronic structure is here addressed. Photoelectron spectra (PES) and Threshold Photoelectron spectra (TPES) of room temperature molecules in the gas phase are recorded. Geometries and energies of the stable conformers due to internal rotation of the C-C-C-Cl dihedral angle, gauche-II (g-II), gauche-I (g-I), and cis, are calculated, and the effect of the conformational flexibility on the photoionization energetics is studied by DFT and 2h-1p Configuration Interaction (CI) methods. Strong breakdown of the Koopmans Theorem (KT) is obtained for the four outermost ionizations, which are further investigated by higher level ab initio calculations. The full assignment of the spectrum is put on a firm basis by the combination of experimental and theoretical results. The orbital composition from correlated calculations is found closer to the DFT orbitals, which are then used to analyze the electronic structure of the molecule. The Highest Occupied Molecular Orbital (HOMO) and HOMO--2 are n(O)/n(Cl) mixed orbitals. The nature of each valence MO is generally preserved in all the conformers, although the magnitude of the n(O)/n(Cl) mixing in HOMO and HOMO--2 varies to some extent with the C-C-C-Cl dihedral angle. The low energy part of the HOMO PE band is predicted to be substantially affected by the conformational flexibility, as experimentally observed in the spectra. The rest of the spectrum is described in terms of the dominant conformer g-II, and a good agreement between experiment and theory is found. The inner-valence PE spectrum is characterized by satellite structures, due to electron correlation effects, which are interpreted by means of 2h-1p CI calculations.

Post-challenge hyperglycaemia, nitric oxide production and endothelial dysfunction: the putative role of asymmetric dimethylarginine (ADMA).

The endothelium is a thin layer of cells at the internal surface of blood vessels in continuous contact with the circulating fluids. The endothelial cells represent the primary barrier for the transport of glucose from the vascular conduits into the interstitial space. Insulin and nitric oxide have an important role in the regulation of glucose transport and metabolism. Hyperglycaemia is the main criteria for the diagnosis of diabetes and is responsible for the micro- and macro-vascular pathology seen in diabetic patients. Recent evidence suggests that post-challenge hyperglycaemia is a better predictor of cardiovascular risk than fasting glucose. Acute glucose elevations have been associated with a reduced endothelial-dependent flow mediated dilation indicating a decrease in nitric oxide production. Post-prandial hyperglycaemic peaks have been directly associated with increased intima media thickness in type 2 diabetic patients indicative of an increased atherosclerotic risk. The increase in intra-cellular glucose concentrations in the endothelial cells induces a hyper-generation of reactive oxygen species via the activation of different pathways (polyol-sorbitol, hexosamine, advanced glycated end products, activation of PKC, asymmetric dimethylarginine (ADMA)). These mechanisms influence the expression of genes and release of signalling and structural molecules involved in several functions (inflammation, angiogenesis, coagulation, vascular tone and permeability, cellular migration, nutrient metabolism). ADMA is considered as a biomarker of endothelial dysfunction and it has been associated with an increased risk of atherosclerosis and cardiovascular diseases. The increased generation of ADMA and reactive oxygen species in subjects with persistent hyperglycaemia could lead to an impairment of nitric oxide synthesis.