The Influence of Sevelamer Hydrochloride and Calcium Carbonate on Markers of Inflammation and Oxidative Stress in Hemodialysis at Six Months of Follow-Up

Patients with end-stage renal disease (ESRD) present alterations in mineral and bone metabolism. Hyperphosphatemia in ESRD is considered an independent risk factor for cardiovascular disease (CVD), increasing morbidity, and mortality. Sevelamer hydrochloride is a calcium-free, non-absorbable phosphate-chelating polymer. Calcium carbonate chelator is helpful in controlling serum phosphate levels. There is insufficient information on the influence of sevelamer hydrochloride and calcium carbonate on the behavior of oxidative stress (OS) markers and inflammation in patients on hemodialysis (HD). A randomized open clinical trial was carried out on patients to evaluate sevelamer hydrochloride and calcium carbonate influence at 6 months of study follow-up. Levels of oxidants (LPO, NO, and 8-isoprostanes), antioxidants (SOD and TAC), oxidative DNA damage (8-OHdG and hOGG1), pro-inflammatory cytokines (IL-6 and TNF-α), and inflammation markers (ferritin and C-reactive protein) were measured with colorimetric and ELISA methods. We found a significant increase in oxidants LPO and NO, and antioxidants SOD and TAC, and downregulation of IL-6 and TNF-α. Ferritin decrease at 6 months follow-up in the sevelamer hydrochloride group. Increase in C-reactive protein was found in the group of patients treated with calcium carbonate. In conclusion, we found an oxidative state imbalance with increase in LPO and NO oxidants. The activity of the antioxidant enzymes (SOD and TAC) was also found to increase, suggesting a compensatory effect in the face of increase in oxidants. The same phenomenon was observed with increase in the oxidative damage marker to DNA and the increase in the DNA repair enzyme, suggesting a compensatory effect. Pro-inflammatory cytokines were predominantly downregulated by TNF-α in the group that ingested sevelamer hydrochloride in the final determination at 6 months of follow-up. Serum ferritin levels decreased significantly at the end of follow-up in patients on HD in the sevelamer hydrochloride group. The management of hyperphosphatemia with sevelamer hydrochloride appears to have obvious anti-inflammatory and antioxidant benefits.

Computational Compensatory Mutation Discovery Approach: Predicting a PARP1 Variant Rescue Mutation

The prediction of protein mutations that affect function may be exploited for multiple uses. In the context of disease variants, the prediction of compensatory mutations that reestablish functional phenotypes could aid in the development of genetic therapies. In this work, we present an integrated approach that combines coevolutionary analysis and molecular dynamics (MD) simulations to discover functional compensatory mutations. This approach is employed to investigate possible rescue mutations of a poly(ADP-ribose) polymerase 1 (PARP1) variant, PARP1 V762A, associated with lung cancer and follicular lymphoma. MD simulations show PARP1 V762A exhibits noticeable changes in structural and dynamical behavior compared with wild type PARP1. Our integrated approach predicts A755E as a possible compensatory mutation based on coevolutionary information, and molecular simulations indicate that the PARP1 A755E/V762A double mutant exhibits similar structural and dynamical behavior to WT PARP1. Our methodology can be broadly applied to a large number of systems where SNPs have been identified as connected to disease and can shed light on the biophysical effects of such changes as well as provide a way to discover potential mutants that could restore wild type-like functionality. This can in turn be further utilized in the design of molecular therapeutics that aim to mimic such compensatory effect.

Bank business models, negative policy rates, and prudential regulation

Using data from Italian banks over the period 2011–2017, we study how negative interest rate policy and prudential regulation impact on bank business models. We report four key findings. First, banks shifted into retail- and market-oriented business models. Second, high- and low-deposit banks reduced loans and increased security/liquid assets; only market-oriented banks expanded lending. Third, interest rate income compression induced by negative rates has been substantial for the Italian banking system as a whole, although retail banks seem to have suffered less. Fourth, non-interest incomes played a compensatory effect. The portfolio reshuffling, as we observed for wholesale and retail banks (less lending and more securities/liquid assets), is related to the goal of reducing risk exposures and, in turn, the connected capital absorption required by prudential regulation.

Compensatory Changes in the Anterior Segment and Vascular System of the Eye in Myopic Children After Orthokeratology

Purpose: To analyze changes in the anterior segment, retinal vessel density, and choroidal thickness (ChT) after orthokeratology (Ortho-K).Methods: Myopic children were enrolled from Ruijin Hospital, Shanghai, China. Ortho-K lenses and single-vision spectacles were fitted for myopia correction. Ocular measurements were taken at baseline and 6 months, including axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), white to white (WTW), ChT, macular vessel density (MVD), and optic disc vessel density (OVD).Results: Seventy-six patients were enrolled in this study, including 40 in the Ortho-K group and 36 in the control group. At baseline, no parameters between the two groups were statistically different. After 6 months, changes in CCT and ACD decreased in the Ortho-K group compared with those in the control group (p < 0.05); LT and ChT in the Ortho-K group were thicker than those in the control group (p < 0.05), while there was no difference in MVD and OVD compared with those in the control group (p > 0.05). There were moderate positive correlations between ChT and LT and between ChT and OVD in the Ortho-K group (p < 0.05).Conclusion: The changes in the anterior and posterior segments of the eye after Ortho-K lens wearing suggest that the human eye has a powerful compensatory effect on the imposed defocus.

TREM2 and CD163 ameliorate microglia-mediated inflammatory environment in the aging brain

Aging declines cognitive functions, especially learning and memory. Microglia-mediated neuroinflammation occurs in age-related neurodegenerative diseases. Our study obtained the expression profile of GSE11882 from the Gene Expression Omnibus database and used microarray data to explore the expression of age-related genes in the hippocampus. A total of 120 differentially expressed genes (DEGs) were screened out and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was constructed. In Cytoscape software, 18 key genes were identified by the plugin cytoHubba. Two genes with positive impact on cognition during aging were teased out, including triggering receptor expressed on myeloid cells 2 (TREM2) and scavenger receptor (CD163). Finally, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) verified that the mRNA expression of two genes was significantly up-regulated in the Aged group. Moreover, the inflammatory factor IL-1β and IL-6 significantly increased. The up-regulation of TREM2 and CD163 may exert a compensatory effect on neurodegeneration by mitigating the inflammatory environment in the aging brain.

The Effect of the Mobile Subtalar Joint on Calcaneal and Supramalleolar Osteotomies

Background: The mobile subtalar joint (STJ) may compensate for supra- and inframalleolar deformities and counteract the effect of realigning calcaneal or distal tibial osteotomies. The purpose of this study was to evaluate the compensatory effect of the mobile STJ after supramalleolar osteotomy (SMOT) and calcaneus osteotomy (COT) and whether the extent of the compensation correlates with STJ shape and orientation. Methods: In 10 human lower leg cadavers without evidence of deformity or prior trauma 700 Newton load were applied as a simulated standing pose. The center of force (COF) migration, maximum pressure (Pmax), and the area loaded were measured with high-resolution sensors in the ankle before and after 10-mm varus/valgus sliding COT and 10-degree varus / valgus SMOT. A computed tomographic evaluation of subtalar anatomy was conducted to correlate posterior facet curvature, its varus/valgus orientation in the coronal plane, and the effect on COF, Pmax, and area loaded. Results: The COF migration was significant for both varus and valgus SMOTs (varus SMOT: 1.78 mm, P = .0029; valgus SMOT: 1.85 mm, P = .0018) but not for COT (varus COT: 0.45 mm, P = .85; valgus COT: 1.15 mm, P = .11). Pmax and area loaded changed but not significantly. The radius of the posterior STJ surface showed a moderate correlation (varus SMOT: r = 0.61, P = .063; valgus SMOT: r = 0.28, P = .43, varus COT: r = −0.61, P = .063; valgus COT: r = 0.13, P = .38) and the axis a weak inverse correlation (varus SMOT: r = −0.51, P = .013; valgus SMOT: r = 0.58, P = .079; varus COT: r = −0.51, P = .14; valgus COT: r = 0.38, P = .28) with the COF migration after the osteotomies. Conclusion: The compensatory capacity of a mobile STJ is relatively small but appears to limit the effect of COT more than SMOT. The COT is less effective in influencing ankle joint pressure for realignment purposes than SMOT in mobile STJ and clinically more consistent in stiff STJ. Correlations are moderate to weak, whereas the curvature more than orientation of posterior facet inversely correlates with osteotomy’s effects. Level of Evidence: IV (biomechanical cadaver study).

The effect of different sowing dates on dry matter and nitrogen dynamics for winter wheat: an experimental simulation study

Background Timely sowing is an important agronomic measure to ensure the normal germination, stable seedling establishment, and yield formation for winter wheat (Triticum aestivum L.). Delayed sowing frequently occurs in the current multi-cropping system and mechanized production of this crop. However, the ways in which different sowing dates affect yield and its potential mechanism is still unknown in the middle-lower Yangtze River Basin. We sought to provide a theoretical basis for these mechanisms to improve regional wheat production. Methods We investigated the wheat’s yield differences in a two-year field study under different sowing dates and took into account related growth characteristics including meteorological conditions, growth period, tillers, dry matter accumulation (DMA), and nitrogen accumulation (NA). We used the logistic curve model to simulate DMA and NA dynamics of single stem wheat under different sowing dates. We then analyzed and compared wheat accumulation for different sowing dates. Results Our results showed that grain yield declined by 0.97 ± 0.22% with each one-day change (either early or delayed) in sowing beyond the normal sowing date. The yield loss could be explained by the inhibition of crop growth, yield components, biomass and nitrogen (N) production. The negative effects of delayed sowing were caused by environmental limitations including adverse weather factors such as low temperature during vegetative growth, shortened duration of various phases of crop development, and increased temperature during the grain-filling period. The grain yield gap decreased between the late and normal sowing periods owing to a compensatory effect between the highest average rates (Vt) and the rapid accumulation period (T) of DMA and NA for single stem wheat. The grain yield was maintained at 6,000 kg ha−1 or more when the ratio of DMA at the mature-to-jointing stage (MD/JD) and the ratio of NA at the mature-to-jointing stage (MN/JN) was 4.06 (P < 0.01) and 2.49 (P < 0.05), respectively. The compensatory effect did not prevent the impact caused by delayed sowing, which caused biomass and N production to decrease. Physiological development reached a maximal accumulation rate (Tm) of NA earlier than DMA.