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    The LifeLines Cohort Study: Prevalence and treatment of cardiovascular disease and risk factors

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    AbstractBackgroundThe LifeLines Cohort Study is a large three-generation prospective study and Biobank. Recruitment and data collection started in 2006 and follow-up is planned for 30years. The central aim of LifeLines is to understand healthy ageing in the 21st century. Here, the study design, methods, baseline and major cardiovascular phenotypes of the LifeLines Cohort Study are presented.Methods and resultsBaseline cardiovascular phenotypes were defined in 9700 juvenile (8–18years) and 152,180 adult (≥18years) participants. Cardiovascular disease (CVD) was defined using ICD-10 criteria. At least one cardiovascular risk factor was present in 73% of the adult participants. The prevalence, adjusted for the Dutch population, was determined for risk factors (hypertension (33%), hypercholesterolemia (19%), diabetes (4%), overweight (56%), and current smoking (19%)) and CVD (myocardial infarction (1.8%), heart failure (1.0%), and atrial fibrillation (1.3%)). Overall CVD prevalence increased with age from 9% in participants<65years to 28% in participants≥65years. Of the participants with hypertension, hypercholesterolemia and diabetes, respectively 75%, 96% and 41% did not receive preventive pharmacotherapy.ConclusionsThe contemporary LifeLines Cohort Study provides researchers with unique and novel opportunities to study environmental, phenotypic, and genetic risk factors for CVD and is expected to improve our knowledge on healthy ageing. In this contemporary Western cohort we identified a remarkable high percentage of untreated CVD risk factors suggesting that not all opportunities to reduce the CVD burden are utilised

    Radiative neutron capture: Hauser Feshbach vs. statistical resonances

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    AbstractThe radiative neutron capture rates for isotopes of astrophysical interest are commonly calculated on the basis of the statistical Hauser Feshbach (HF) reaction model, leading to smooth and monotonically varying temperature-dependent Maxwellian-averaged cross sections (MACS). The HF approximation is known to be valid if the number of resonances in the compound system is relatively high. However, such a condition is hardly fulfilled for keV neutrons captured on light or exotic neutron-rich nuclei. For this reason, a different procedure is proposed here, based on the generation of statistical resonances. This novel technique, called the “High Fidelity Resonance” (HFR) method is shown to provide similar results as the HF approach for nuclei with a high level density but to deviate and be more realistic than HF predictions for light and neutron-rich nuclei or at relatively low sub-keV energies. The MACS derived with the HFR method are systematically compared with the traditional HF calculations for some 3300 neutron-rich nuclei and shown to give rise to significantly larger predictions with respect to the HF approach at energies of astrophysical relevance. For this reason, the HF approach should not be applied to light or neutron-rich nuclei. The Doppler broadening of the generated resonances is also studied and found to have a negligible impact on the calculated MACS

    The relief of dry eye signs and symptoms using a combination of lubricants, lid hygiene and ocular nutraceuticals

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    AbstractPurposeTo determine the combined effect of TheraTears® Lubricant Eye Drops, TheraTears® SteriLid Eyelid Cleanser, and TheraTears® Nutrition on dry eye signs and symptoms.MethodsThis prospective study enrolled 28 dry eye participants. Participants were instructed to use the Lubricant Eye Drops at least 2–4× a day, SteriLid 1–2× a day, and Nutrition 3 gel caps once a day. Participants were followed up at baseline, 1 month and 3 months. Outcome variables were the Ocular Surface Disease Index (OSDI), Symptom Assessment iN Dry Eye (SANDE) questionnaire, non-invasive tear break-up time (NIBUT), osmolarity, number of meibomian glands blocked (#MG blocked), meibum quality, eyelid margin features, Schirmer's test, tear film lipid layer thickness (LLT), meniscus height, corneal and conjunctival staining.ResultsTwenty participants (mean age=43, from 23 to 66, 17F, 3M) completed the study. Participants reported having used, on average, the Lubricant Eye Drop 2.4×/day, the SteriLid 1.1×/day, and the Nutrition 3 gel caps 1×/day. There was a significant change over time (p<0.05) for OSDI (−21.2 points), SANDE (−32.4 points), NIBUT (+0.43s), eyelid margin features (−1.1 grade), meibum quality (−1.0 grade), and #MG blocked (−4.0 glands).ConclusionBy using a combination of TheraTears® Lubricant Eye Drop, SteriLid, and Nutrition, patients experience significant relief in both dry eye symptoms and signs

    One pot four component sequential synthesis of hexahydroquinoline derivatives in aqueous media via enaminone intermediates: A green protocol

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    AbstractA convenient green chemistry method through one pot four component tandem synthesis of hexahydroquinoline via enaminone intermediate using dimedone, ammonium acetate, aryl aldehydes and malononitrile has been described in aqueous media without the use of any external catalyst. The excess of ammonium acetate used acts as a reagent as well as catalyst. The incorporation of water as solvent along with eradication of external catalyst renders the protocol to comply with the green chemistry aspects. Shorter reaction time, high atom economy, easy work up and purification of products by non-chromatographic method are the crucial features of this methodology. The crystal structure of hexahydroquinoline basically shaped by chromatographic free selective reaction was determined by single crystal X-ray diffraction analysis

    Synthesis and mesomorphic properties of new heterocyclic liquid crystals with Central Ester–Chalcone linkages

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    AbstractA series of new calamitic liquid crystals, 4-[3-(pyridin-4-yl)prop-2-enoyl]phenyl 4-alkyloxybenzoates, comprising a pyridyl core, ester–chalcone central linkage and terminal alkyloxy chain were synthesized and characterized. This series consists of four members that differ by the length of the alkyloxy chain (CnH2n+1O, where n=10, 12, 14, 16). The structures of the title compounds were elucidated using spectroscopic and spectrometric techniques, such as FT-IR, NMR (1H and 13C) and EI-MS. The mesomorphic properties were studied using differential scanning calorimetry and optical polarizing microscopy. The decyloxy-containing compound was found to be non-mesogenic, whilst the compounds containing n-dodecyloxy to n-hexadecyloxy chains exhibited an enantiotropic smectic A phase with a fan-shaped texture. From the structure–property relationship study, it was proposed that the number of carbons in the alkyloxy chain must be at least 12 (n≥12) to generate the smectic phase in the corresponding substituted ArCOOArCOCHCHC5H4N compounds

    Environmental exogenous factors and facial dermatitis: A case control study

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    AbstractBackground/objectiveFacial dermatitis is common and the roles different exogenous factors play between facial and nonfacial dermatitis is unknown. The study aim was to investigate the etiology and self-reported exogenous aggravation factors in facial dermatitis.MethodsThere were 89 facial dermatitis patients patch tested in a tertiary hospital during a 1-year period, and 112 patients with nonfacial dermatitis tested in the same period who served as a control. Association of exogenous factors was investigated by multivariate analyses.ResultsOf the cases of facial dermatitis, 30.3% were confirmed allergic contact dermatitis, which was higher than that (23.2%) in controls. Cosmetic allergy was much more common in facial than nonfacial allergic contact dermatitis (96.3% vs. 19.2%); 51.9% of facial allergic contact dermatitis cases were caused by facial creams; 6.7% of facial dermatitis were irritant contact dermatitis, compared with 2.7% for controls; 9.0% of cases were seasonal facial dermatitis. The positive patch test reactions to at least one standard allergen were 65.2% in facial dermatitis and 58.0% in controls. Self-reported exogenous aggravation factors in facial dermatitis were spicy food ingestion (24.7%), low moisture (22.5%), sunlight (19.1%), alcohol ingestion (15.7%), seafood ingestion (14.6%), beef or lamb ingestion (12.4%), and high humidity (5.6%). Multivariate logistic regression analysis adjusting for sex, age, disease duration, atopic diathesis, and contact allergy showed that more patients reported aggravation by sunlight exposure (p = 0.008), ingestion of spicy food (p = 0.025), or alcohol (p = 0.044).ConclusionsContact factors play an important role in facial dermatitis. Aggravation by sunlight exposure, ingestion of spicy food, or alcohol are more reported in facial dermatitis compared with nonfacial dermatitis

    Novel isochroman-triazoles and thiadiazole hybrids: Design, synthesis and antimicrobial activity

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    AbstractIn this study, new isochroman-triazole (6a–e) and thiadiazole (7a–e) conjugates were obtained by heterocyclization of isochromanyl thiosemicarbazides (5a–e) under basic and acidic catalysis respectively. The latter were obtained by the treatment of corresponding acetohydrazide (4) with suitably substituted phenylisothiocyanates. The acetohydrazide (4) is accessible from methyl 2-(6,7,8-trimethoxy-1-methyl-3,4-dihydro-1H-isochromen-1-yl)acetate (3) obtainable by oxa-Pictet–Spengler reaction of 2-(3,4,5-trimethoxyphenyl)ethanol (2) with methyl acetoacetate in the presence of p-TsOH. The isochromanyl triazoles (6a–e) and isochromanyl thiadiazoles (7a–e) were screened for their in vitro antibacterial activity against four bacterial strains and were found to exhibit moderate to good activity toward the tested microorganisms, compared to ampicillin, the standard drug. In vitro antifungal activity was also determined against four fungal strains using fluconazole as standard and the most active compounds were identified in each case

    MTRR rs326119 polymorphism is associated with plasma concentrations of homocysteine and cobalamin, but not with congenital heart disease or coronary atherosclerosis in Brazilian patients

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    AbstractBackgroundDifferences in the distribution of the MTRR rs326119 polymorphism (c.56+781 A>C) between patients with congenital heart disease (CHD) and controls have been described in Chinese individuals. The association is thought to be due to deregulation of homocysteine-cobalamin pathways. This has not been replicated in other populations. The primary objective of this study was to assess the influence of the MTRR rs326119 polymorphism on biochemical parameters of vitamin B12 metabolism, coronary lesions, and congenital heart disease in Brazilian subjects.MethodsWe selected 722 patients with CHD, 1432 patients who underwent coronary angiography, and 156 blood donors. Genotyping for the MTRR polymorphism was evaluated by high-resolution melting analysis, and biochemical tests of vitamin B12 metabolism were measured.ResultsSubjects carrying the AC or CC genotypes had higher homocysteine concentrations (9.7±0.4μmol/L and 10.1±0.6μmol/L) and lower cobalamin concentrations (260.5±13.3pmol/L and 275.6±19.9pmol/L) compared with the subjects carrying the AA genotype (8.7±0.5μmol/L and 304.8±14.7pmol/L), respectively. A multiple linear regression model also identified a significant association between the number of C variant alleles with the concentrations of homocysteine and cobalamin. Nonetheless, the allelic and genotypic distributions for MTRR rs326119 were not associated with CHD or coronary atherosclerosis in the studied samples.ConclusionOur findings indicate that the MTRR rs326119 variant might be a genetic marker associated with homocysteine and cobalamin concentrations, but not a strong risk factor for CHD or coronary atherosclerosis in the Brazilian population

    Redox imbalance and mitochondrial abnormalities in the diabetic lung

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    AbstractAlthough the lung is one of the least studied organs in diabetes, increasing evidence indicates that it is an inevitable target of diabetic complications. Nevertheless, the underlying biochemical mechanisms of lung injury in diabetes remain largely unexplored. Given that redox imbalance, oxidative stress, and mitochondrial dysfunction have been implicated in diabetic tissue injury, we set out to investigate mechanisms of lung injury in diabetes. The objective of this study was to evaluate NADH/NAD+ redox status, oxidative stress, and mitochondrial abnormalities in the diabetic lung. Using STZ induced diabetes in rat as a model, we measured redox-imbalance related parameters including aldose reductase activity, level of poly ADP ribose polymerase (PAPR-1), NAD+ content, NADPH content, reduced form of glutathione (GSH), and glucose 6-phophate dehydrogenase (G6PD) activity. For assessment of mitochondrial abnormalities in the diabetic lung, we measured the activities of mitochondrial electron transport chain complexes I to IV and complex V as well as dihydrolipoamide dehydrogenase (DLDH) content and activity. We also measured the protein content of NAD+ dependent enzymes such as sirtuin3 (sirt3) and NAD(P)H: quinone oxidoreductase 1 (NQO1). Our results demonstrate that NADH/NAD+ redox imbalance occurs in the diabetic lung. This redox imbalance upregulates the activities of complexes I to IV, but not complex V; and this upregulation is likely the source of increased mitochondrial ROS production, oxidative stress, and cell death in the diabetic lung. These results, together with the findings that the protein contents of DLDH, sirt3, and NQO1 all are decreased in the diabetic lung, demonstrate that redox imbalance, mitochondrial abnormality, and oxidative stress contribute to lung injury in diabetes

    Data on the role of accessible surface area on osmolytes-induced protein stabilization

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    AbstractThis paper describes data related to the research article “Testing the dependence of stabilizing effect of osmolytes on the fractional increase in the accessible surface area on thermal and chemical denaturations of proteins” [1]. Heat- and guanidinium chloride (GdmCl)-induced denaturation of three disulfide free proteins (bovine cytochrome c (b-cyt-c), myoglobin (Mb) and barstar) in the presence of different concentrations of methylamines (sarcosine, glycine-betaine (GB) and trimethylamine-N-oxide (TMAO)) was monitored by [ϴ]222, the mean residue ellipticity at 222nm at pH 7.0. Methylamines belong to a class of osmolytes known to protect proteins from deleterious effect of urea. This paper includes comprehensive thermodynamic data obtained from the heat- and GdmCl-induced denaturations of barstar, b-cyt-c and Mb

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