Interference of H-bonding and substituent effects in nitro- and hydroxy-substituted salicylaldehydes

Two intramolecular interactions, i.e., (1) hydrogen bond and (2) substituent effect, were analyzed and compared. For this purpose, the geometry of 4- and 5-X-substituted salicylaldehyde derivatives (X = NO2, H or OH) was optimized by means of B3LYP/6-311 + G(d,p) and MP2/aug-cc-pVDZ methods. The results obtained allowed us to show that substituents (NO2 or OH) in the para or meta position with respect to either OH or CHO in H-bonded systems interact more strongly than in the case of di-substituted species: 4- and 3-nitrophenol or 4- and 3-hydroxybenzaldehyde by ∼31%. The substituent effect due to the intramolecular charge transfer from the para-counter substituent (NO2) to the proton-donating group (OH) is ∼35% greater than for the interaction of para-OH with the proton-accepting group (CHO). The total energy of H-bonding for salicylaldehyde, and its derivatives, is composed of two contributions: ∼80% from the energy of H-bond formation and ∼20% from the energy associated with reorganization of the electron structure of the systems in question

Tracking of fatness during childhood, adolescence and young adulthood: a 7-year follow-up study in Madeira Island, Portugal

Aims: Investigating tracking of fatness from childhood to adolescence, early adolescence to young adulthood and late adolescence to young adulthood. Subjects and methods: Participants from the Madeira Growth Study were followed during an average period of 7.2 years. Height, body mass, skin-folds and circumferences were measured, nine health- and performance-related tests were administered and the Baecke questionnaire was used to assess physical activity. Skeletal maturity was estimated using the TW3 method. Results: The prevalence of overweight plus obesity ranged from 8.2–20.0% at baseline and from 20.4–40.0% at followup, in boys. Corresponding percentages for girls were 10.6– 12.0% and 13.2–18.0%. Inter-age correlations for fatness indicators ranged from 0.43–0.77. BMI, waist circumference and sum of skin-folds at 8, 12 and 16-years old were the main predictors of these variables at 15, 19 and 23-years old, respectively. Strength, muscular endurance and aerobic fitness were negatively related to body fatness. Physical activity and maturation were independently associated with adolescent (15 years) and young adult (19 years) fatness. Conclusions: Over 7.2 years, tracking was moderate-to-high for fatness. Variance was explained by fatness indicators and to a small extent by physical fitness, physical activity and maturation

Diet quality is positively associated with 100% fruit juice consumption in children and adults in the United States: NHANES 2003-2006

<p>Abstract</p> <p>Background</p> <p>One hundred percent fruit juice (100% FJ) has been viewed by some as a sweetened beverage with concerns about its effect on weight. Little regard has been given to the contribution of 100% FJ to diet quality.</p> <p>Methods</p> <p>In this study data from the 2003-2006 National Health and Nutrition Examination Survey were used to examine the association of 100% FJ consumption with diet quality in participants 2-5 years of age (y) (n = 1665), 6-12 y (n = 2446), 13-18 y (n = 3139), and 19+y (n = 8861). Two 24-hour dietary recalls were used to determine usual intake using the National Cancer Institute method. Usual intake, standard errors, and regression analyses (juice independent variable and Healthy Eating Index-2005 [HEI-2005] components were dependent variables), using appropriate covariates, were determined using sample weights.</p> <p>Results</p> <p>The percentage of participants 2-5 y, 6-12 y, 13-18 y, and 19+y that consumed 100% FJ was 71%, 57%, 45%, and 62%, respectively. Usual intake of 100% FJ (ounce [oz]/day) among the four age groups was: 5.8 ± 0.6, 2.6 ± 0.4, 3.7 ± 0.4, and 2.4 ± 0.2 for those in age groups 2-5 y, 6-12 y, 13-18 y, and 19+y, respectively. Consumption of 100% FJ was associated with higher energy intake in 6-12 y, 13-18 y, and 19+y; and higher total, saturated, and discretionary fats in 13-18 y participants. Consumption of 100% FJ was associated with higher total HEI-2005 scores in all age groups (< 0.0001). In 100% FJ consumers, total and whole fruit consumption was higher and intake of added sugars was lower in all age groups.</p> <p>Conclusions</p> <p>Usual intake of 100% FJ consumption exceeded MyPyramid recommendations for children 2-5 y, but was associated with better diet quality in all age groups and should be encouraged in moderation as part of a healthy diet.</p

Multi-Modal Proteomic Analysis of Retinal Protein Expression Alterations in a Rat Model of Diabetic Retinopathy

As a leading cause of adult blindness, diabetic retinopathy is a prevalent and profound complication of diabetes. We have previously reported duration-dependent changes in retinal vascular permeability, apoptosis, and mRNA expression with diabetes in a rat model system. The aim of this study was to identify retinal proteomic alterations associated with functional dysregulation of the diabetic retina to better understand diabetic retinopathy pathogenesis and that could be used as surrogate endpoints in preclinical drug testing studies.A multi-modal proteomic approach of antibody (Luminex)-, electrophoresis (DIGE)-, and LC-MS (iTRAQ)-based quantitation methods was used to maximize coverage of the retinal proteome. Transcriptomic profiling through microarray analysis was included to identify additional targets and assess potential regulation of protein expression changes at the mRNA level. The proteomic approaches proved complementary, with limited overlap in proteomic coverage. Alterations in pro-inflammatory, signaling and crystallin family proteins were confirmed by orthogonal methods in multiple independent animal cohorts. In an independent experiment, insulin replacement therapy normalized the expression of some proteins (Dbi, Anxa5) while other proteins (Cp, Cryba3, Lgals3, Stat3) were only partially normalized and Fgf2 and Crybb2 expression remained elevated.These results expand the understanding of the changes in retinal protein expression occurring with diabetes and their responsiveness to normalization of blood glucose through insulin therapy. These proteins, especially those not normalized by insulin therapy, may also be useful in preclinical drug development studies

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field