Large difference but high correlation between creatinine and cystatin C estimated glomerular filtration rate in Mesoamerican sugarcane cutters

Objectives To explore the relationship between creatinine and cystatin C based estimated glomerular filtration rate (eGFR) in actively working sugarcane cutters. Methods This cohort study included 458 sugarcane cutters from Nicaragua and El Salvador. Serum samples were taken before and at end of harvest seasons and analysed for creatinine and cystatin C. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas were used to calculate eGFRs based on creatinine (eGFR cr), cystatin C (eGFR cys) and both creatinine and cystatin C (eGFR crcys) at each time point. Bland-Altman plots and paired t-tests were used to compare the difference between eGFR cr and eGFR cys, and the difference in eGFRs between before and at end of the harvest seasons. Results The mean eGFR cr was higher than eGFR cys in both cohorts; absolute difference 22 mL/min/1.73 m 2 (95% CI 21 to 23) in Nicaragua and 13 mL/min/1.73 m 2 (95% CI 11 to 15) in El Salvador. Correlations between eGFR cr and eGFR cys were high, with r=0.69, 0.77 and 0.67 in Nicaragua at pre-harvest, end-harvest and cross-harvest, and r=0.89, 0.89 and 0.49 in El Salvador. Conclusions Creatinine increases among heat-stressed workers reflect reduced glomerular filtration as estimated using eGFR cys, a marker independent of muscle mass and metabolism. The discrepancy between eGFR cr and eGFR cys may indicate reduced glomerular filtration of larger molecules and/or systemic bias in CKD-EPI performance in this population

Polyunsaturated fatty acids in plasma at 8 years and subsequent allergic disease

Background: Polyunsaturated fatty acids (PUFAs) are hypothesized to modulate the risk of allergic disease. However, evidence from previous studies is inconclusive, and limited longitudinal data exist using circulating biomarkers of PUFA intake and metabolism. Objective: We aimed to investigate associations between n-3 and n-6 PUFAs at age 8 years and asthma, rhinitis, and aeroallergen sensitization at age 16 years. Methods: Proportions of n-3 PUFAs (very long-chain n-3 [VLC n-3; sum of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid] anda-linolenic acid) and n-6PUFAs (linoleic acid and arachidonic acid [AA]) in blood samples at age 8 years weremeasured for 940 children fromthe prospective Swedish birth cohort BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiology). Allergic disease phenotypes were defined by using questionnaires and IgE measures at the ages of 8 and 16 years. Logistic regression was used to examine potential associations. Results: A higher proportion of total VLC n-3 PUFAs in plasma at age 8 years was associated with a reduced risk of prevalent asthma, rhinitis, and aeroallergen sensitization at age 16 years and with incidence of asthma between 8 and 16 years (adjusted odds ratio, 0.67; 95% CI, 0.47-0.94). AA was associated with a reduced risk of asthma, aeroallergen sensitization, and allergic rhinitis. The findings were most evident for allergic phenotypes of asthma and rhinitis. Additionally, AA was associated with an increased probability of asthma and rhinitis remission between 8 and 16 years of age. Conclusion: Higher proportions of certain VLC n-3 and very long-chain n-6 PUFAs in plasma phospholipids at age 8 years were associated with a reduced risk of allergic disease at age 16 years

Contributions of Amino Acid Side Chains to the Kinetics and Thermodynamics of the Bivalent Binding of Protein L to Ig κ Light Chain †

ABSTRACT: Protein L is a bacterial surface protein with 4-5 immunoglobulin (Ig)-binding domains (B1-B5), each of which appears to have two binding sites for Ig, corresponding to the two edges of its β-sheet. To verify these sites biochemically and to probe their relative contributions to the protein L-Ig κ light chain (κ) interaction, we compared the binding of PLW (the Y47W mutant of the B1 domain) to that of mutants designed to disrupt binding to sites 1 and 2, using gel filtration, BIAcore surface plasmon resonance, fluorescence titration, and solid-phase radioimmunoassays. Gel filtration experiments show that PLW binds κ both in 1:1 complexes and multivalently, consistent with two binding sites. Covalent dimers of the A20C and V51C mutants of PLW were prepared to eliminate site 1 and site 2 binding, respectively; both the A20C and V51C dimers bind κ in 1:1 complexes and multivalently, indicating that neither site 1 nor site 2 is solely responsible for κ binding. The A20R mutant was designed computationally to eliminate site 1 binding while preserving site 2 binding; consistent with this design, the A20R mutant binds κ in 1:1 complexes but not multivalently. To probe the contributions of amino acid side chains to binding, we prepared 75 point mutants spanning nearly every residue of PLW; BIAcore studies of these mutants revealed two binding-energy “hot spots ” consistent with sites 1 and 2. These data indicate that PLW binds κ at both sites with similar affinities (high nanomolar), with the strongest contributions to the binding energ

The Dalton quantum chemistry program system

Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree–Fock, Kohn–Sham, multiconfigurational self-consistent-field, Møller–Plesset, configuration-interaction, and coupled-cluster levels of theory. Apart from the total energy, a wide variety of molecular properties may be calculated using these electronic-structure models. Molecular gradients and Hessians are available for geometry optimizations, molecular dynamics, and vibrational studies, whereas magnetic resonance and optical activity can be studied in a gauge-origin-invariant manner. Frequency-dependent molecular properties can be calculated using linear, quadratic, and cubic response theory. A large number of singlet and triplet perturbation operators are available for the study of one-, two-, and three-photon processes. Environmental effects may be included using various dielectric-medium and quantum-mechanics/molecular-mechanics models. Large molecules may be studied using linear-scaling and massively parallel algorithms. Dalton is distributed at no cost from http://www.daltonprogram.org for a number of UNIX platforms.ISSN:1759-0876ISSN:1759-088