Search Results (35)

Background: Although erythropoiesis-stimulating agent (ESA) therapy is fundamental for correcting anemia, excessive ESA administration is associated with increased risks. This study aimed to investigate the impact of the erythropoietin resistance index (ERI) on clinical outcomes in a population-based cohort of hemodialysis (HD) patients. Methods: This retrospective study analyzed datasets from patients who underwent periodic HD quality assessments and their claims data. Overall, we included 35,913 patients. Participants were divided into quartiles based on the ERI during the 6-month assessment period: Q1, Q2, Q3, and Q4 groups. Results: The 5-year survival rates were 68.8% (Q1), 67.8% (Q2), 66.9% (Q3), and 60.2% (Q4) (p < 0.001). Multivariable analysis showed the same trends as the univariable analysis. Additionally, a spline curve using the multivariable model indicated that the increased ERI was linked to all-cause mortality. However, cardiovascular events were not associated with ERI quartiles in Cox regression analyses. Subgroup analysis revealed that in most subgroups, the all-cause mortality was significantly higher in those with a high ERI than in those with a low ERI. Further analysis using the balanced cohort, which attenuated baseline characteristic differences, confirmed that the high mortality in those with a high ERI was maintained. Conclusions: Our population-based cohort study reveals an association between the ERI and all-cause mortality in HD patients. Full article

The relationship between telomere shortening and patients with chronic kidney disease (CKD) has recently been investigated. Although most patients respond adequately to erythropoiesis-stimulating agents (ESAs), approximately 10% do not, and this is referred to as ESA resistance. The aim of our study was to investigate the relationship between telomere shortening and erythropoietin resistance in patients with CKD on hemodialysis. This cross-sectional, comparative, analytical, and observational study was conducted in patients of both sexes over 18 years of age diagnosed with CKD. Two groups of patients were identified. The first group consisted of 40 patients receiving erythropoiesis-stimulating agents with erythropoietin resistance. The second group consisted of 40 patients with the same characteristics but without erythropoietin resistance. Telomere length was measured by real-time PCR. Eighty patients were included in the study. Mean hemoglobin levels were lower in the erythropoietin resistance group (8.8 ± 1.67 vs. 11.95 ± 1.81, p = 0.001). Differences were observed in hematocrit and albumin levels, which were lower in patients with erythropoietin resistance, while PTH levels were higher in this group (788 ± 538.47 vs. 535.65 ± 603.06, p = 0.001). A significant difference in telomere length (T/S) was observed between the two groups, with shorter telomere length in the erythropoietin resistance group (0.45 ± 0.04 vs. 0.56 ± 0.03, p = 0.01). Telomere shortening may be associated with anemia and erythropoietin resistance in patients with CKD undergoing hemodialysis. This relationship suggests the need to explore whether telomere length recovery improves the response to ESAs. Full article

Background/Objectives: Renal anemia is one of the major complications associated with chronic kidney disease (CKD). Erythropoietin-stimulating agents (ESAs) are commonly used; however, some patients exhibit resistance. Hypoxia-inducible factor prolyl-hydroxylase inhibitors (HIF-PHIs) have emerged as a novel treatment for renal anemia, enhancing erythropoiesis and iron metabolism. Methods: We retrospectively analyzed laboratory data related to erythropoiesis from 105 patients with CKD before and after treatment with HIF-PHI or ESA. The dialysis initiation and mortality rates were also assessed over a median follow-up of 614 days. Results: HIF-PHI and ESA significantly increased the hemoglobin levels within 6 months of treatment (9.5 ± 1.0 to 10.7 ± 1.1, p < 0.01, and 9.9 ± 1.5 to 10.7 ± 1.2 g/dL, p < 0.01, respectively). The HIF-PHI group demonstrated a significant decrease in red cell distribution width (14.5 ± 1.9% to 13.8 ± 1.4%, p < 0.01), suggesting improved erythropoiesis, and exhibited a lower cumulative incidence of outcomes. The aged-adjusted multivariate analysis confirmed the independent association between HIF-PHI treatment and reduced risk of cumulative outcome (p = 0.042). Conclusions: HIF-PHIs can serve as an alternative to ESA for managing renal anemia in CKD, improving both hematological parameters and long-term outcomes. Full article

The gut dysbiosis present in chronic kidney disease (CKD) has been associated with anemia. Factors such as the accumulation of gut-derived uremic toxins, increased gut barrier permeability-induced inflammation, and a reduced intestinal production of short-chain fatty acids (SCFAs), all associated with changes in the intestinal microbiota composition in CKD, may lead to the development or worsening of anemia in renal patients. Understanding and addressing these mechanisms related to gut dysbiosis in CKD patients can help to delay the development of anemia and improve its control in this population. One approach is to avoid or reduce the use of drugs linked to gut dysbiosis in CKD, such as phosphate binders, oral iron supplementation, antibiotics, and others, unless they are indispensable. Another approach involves introducing dietary changes that promote a healthier microbiota and/or using prebiotics, probiotics, or symbiotics to improve gut dysbiosis in this setting. These measures can increase the presence of SCFA-producing saccharolytic bacteria and reduce proteolytic bacteria, thereby lowering the production of gut-derived uremic toxins and inflammation. By ameliorating CKD-related gut dysbiosis, these strategies can also improve the control of renal anemia and enhance the response to erythropoiesis-stimulating agents (ESAs) in ESA-resistant patients. In this review, we have explored the relationship between gut dysbiosis in CKD and renal anemia and propose feasible solutions, both those already known and potential future treatments. Full article

Background/Objectives: Besides a multitude of consequences patients on chronic renal replacement therapy have, anemia is one of the most prominent factors making a significant number of patients dependent on erythropoiesis-stimulating agent (ESA) therapy. The aim of this study was to examine the relationship between the levels of a broad spectrum of thrombo-inflammatory and oxidative stress-related biomarkers and the presence and level of ESA hyporesponsiveness in patients undergoing regular chronic hemodialysis. Methods: This cross-sectional study included 96 patients treated with chronic hemodialysis. Levels of several thrombo-inflammatory and oxidative stress-related biomarkers, as well as demographic, clinical, and laboratory analyses, were collected and analyzed based on the calculated value of the ESA-hyporesponsiveness index (EHRI). Results: In the analyzed sample, 58 patients received ESAs. Of all the investigated parameters, only body mass index (BMI), level of plasminogen activator inhibitor-1, and level of L-type fatty acid binding protein (L-FABP) were observed as significant predictors of EHRI. A significant diagnostic potential for ESA resistance has been observed in BMI and L-FABP between ESA-resistant and ESA-non-resistant groups of patients (p = 0.004, area under the curve 0.763 and p = 0.014, area under the curve 0.712, respectively) with the cut-off values of 25.46 kg/m² and 5355.24 ng/mL, respectively. Having a BMI of 25.46 kg/m² or less and an L-FABP level higher than 5355.24 ng/mL were observed as significant predictors of ESA resistance (odds ratio 9.857 and 6.125, respectively). Conclusions: EHRI was positively predicted by low BMI and high levels of plasminogen activator inhibitor-1 and L-FABP. High levels of L-FABP and low BMI have been observed as strong predictors of ESA resistance. Full article

In cold regions with high daily temperature gradients (>20 °C), the durability of cement-stabilized macadam (CSM) base materials is poor and prone to cracking. To effectively reduce the cracking of semi-rigid base layers in cold regions with high daily temperature gradients and extend fatigue life, this study focused on cracking and fatigue characteristics of CSM with a 10% commercial early strength agent (ESA) added by the external mixing method under different curing conditions. The ESA was manufactured by Jiangsu Subote New Materials Co., Ltd. (Nanjing, China). The curing conditions were divided into variable temperature (0–20 °C) and standard temperature (20 °C). CSM curing was carried out through a programmable curing box. The research results indicated that the variable temperature curing conditions reduced the strength and fatigue resistance of CSM and accelerated the modulus attenuation rate of CSM. At the same time, the drying shrinkage of CSM was greater. The temperature shrinkage coefficient and strain of CSM under variable temperature conditions were smaller than those under standard temperature conditions. The effect of variable temperature conditions on the cracking and durability of CSM could not be ignored in cold regions. Compared to standard temperature curing conditions, the indirect tensile strength of CSM reduced by 31.04% under variable temperature conditions, the coefficient of variation increased by 2.97 times, and the discrete type significantly increased. Compared with CSM without ESA, the dry and temperature shrinkage strains of CSM with 10% ESA were reduced by 24.65% and 26.10%, respectively. At a stress level of 0.6, compared to standard temperature curing conditions, the fatigue life of CSM decreased by 97.19% under variable temperature conditions. Under variable temperature conditions, the fatigue life of CSM with 10% ESA increased by 196 times compared to 0% ESA. Adding ESA enhanced the anti-shrinkage cracking, strength, and durability of CSM under variable temperatures. ESA incorporation effectively compensated for the weakened characteristics of CSM under variable temperature conditions. The study proposed a practical approach for boosting the durability of CSM in cold environments. Full article

Optical instrumentation used in space normally employs optical coatings. Future interplanetary space missions will be characterized by ever longer stays in environmental conditions where low energy protons represent one of the main types of radiation impacting the coating longevity and performance. To ensure the reliability of coated optics, environmental resistance tests should be accurately planned to be representative for a mission. To this end, the existing standards for coating tests and the test results interpretation have been constantly improved. In this study, we analyze the relevant standards of the European Space Agency (ESA) and of the Chinese Space Agency (CSA) for testing coated optics for interplanetary missions, and in particular for the missions at the Lagrange points. We focus in particular on the applicability of these standards and hence on their possible refinement when specifically implemented to the optical thin films and coatings. We proceed with the development of a methodology for reliable interpretation of the proton irradiation tests for the optical coatings for interplanetary missions, first briefly overviewing the existing tools which allow for space environment simulation and hence deriving the test conditions for the Lagrange points. Furthermore, we apply the approach to testing of aluminum oxide optical coatings for applications in the visible spectral range, concluding on the representativeness of the proposed approach and on possible refinement of the existing standards for coating tests when they are specifically developed for optical applications. Full article

The exploration of ecological security patterns (ESPs) can help people find those areas that are in urgent need of restoration, which is an effective way to realize ecological protection. It is of utmost significance for promoting regional sustainable development to construct ESP and put forward sub-regional optimization suggestions based on the supply and demand ratio of ecosystem services (ESs). In this paper, we assessed the level of supply and demand for five ESs based on multi-source data in 2020 with the help of InVEST, ArcGIS, and IUEMS. Based on the results of supply and demand, we calculated the supply and demand ratio of ESs and extracted the ecological source areas (ESAs) on this basis. Then, we used the Linkage Mapper tool to construct the ESP based on the principle of the minimum cumulative resistance (MCR) model and circuit theory in the Chengdu–Chongqing economic circle (CCEC). Our results indicated that there were apparent spatial differences in the supply and demand of five ESs. There were 35 ESAs in the ESP network, covering an area of about 7914 km², and most of their land use types were woodland. The CCEC was interconnected by a network of 91 ecological corridors (ECs), spanning a total length of approximately 10,701 km. From the ECs, we extracted 29 ecological pinch points (EPPs) and 16 ecological barrier points (EBPs), which each accounted for about 0.3% of the planned area of the CCEC. Finally, we divided the ecological spaces into four types and put forward the corresponding optimization suggestions. Among them, the proportion of ecological restoration area was 7.7%, which was located in Chengdu City, northwest of the study area. The findings of this paper can give some theoretical guidance and serve as a reference for making decisions in the pursuit of ecological civilization in this region. Full article

Placed in a sulfate-rich environment, concrete reacts with sulfate ions, influencing the long-term durability of reinforced concrete (RC) structures. This external sulfate attack (ESA) degrades the cement paste through complex and coupled physicochemical mechanisms that can lead to severe mechanical damage. In common practice, RC structures are generally exposed to sulfate at an early age. This early exposition can affect ESA mechanisms that are generally studied on pre-cured specimens. Moreover, current efforts for sustainable concrete construction focus on replacing clinker with supplementary cementitious materials, requiring a 90-day curing period, which contradicts real-life scenarios. Considering all these factors, the objective of this study is to explore ESA effects at an early age on cement-blended paste samples using various low-carbon formulations. The characterization techniques used demonstrated that the reference mix (100% CEM I) exhibits the weakest resistance to sulfate, leading to complete deterioration after 90 weeks of exposure. This is evident through the highest mass gain, expansion, cracking, formation of ettringite and gypsum, and sulfate consumption from the attacking solution. Conversely, the ternary mix, consisting of CEM I, slag, and metakaolin, demonstrates the highest resistance throughout the entire 120 weeks of exposure. All the blended pastes performed well in the sulfate environment despite being exposed at an early age. It can be recommended to substitute clinker with a limited quantity of metakaolin, along with blast furnace slag, as it is the most effective substitute for clinker, outperforming other combinations. Full article

The objective of this study was to characterize Cronobacter spp. and related organisms isolated from powder dairy products intended for consumption by adults and older adults using whole-genome sequencing (WGS), and to identify genes and traits that encode antibiotic resistance and virulence. Virulence (VGs) and antibiotic resistance genes (ARGs) were detected with the Comprehensive Antibiotic Resistance Database (CARD) platform, ResFinder, and MOB-suite tools. Susceptibility testing was performed using disk diffusion. Five presumptive strains of Cronobacter spp. were identified by MALDI–TOF MS and ribosomal MLST. Three C. sakazakii strains were of the clinical pathovar ST1, one was ST31, and the remaining isolate was C. malonaticus ST60. In addition, Franconibacter helveticus ST345 was identified. The C. sakazakii ST1 strains were further distinguished using core genome MLST based on 2831 loci. Moreover, 100% of the strains were resistant to cefalotin, 75% to ampicillin, and 50% to amikacin. The C. sakazakii ST1 strains were multiresistant (MDR) to four antibiotics. Additionally, all the strains adhered to the N1E-115 cell line, and two invaded it. Eighteen ARGs mainly involved in antibiotic target alteration and antibiotic efflux were detected. Thirty VGs were detected and clustered as flagellar proteins, outer membrane proteins, chemotaxis, hemolysins, and genes involved in metabolism and stress. The pESA3, pSP291-1, and pCMA1 plasmids were detected, and the prevalent mobile genetic elements (MGEs) were ISEsa1, ISEc52, and IS26. The isolates of C. sakazakii and C. malonaticus exhibited multiresistance to antibiotics, harbored genes encoding various antibiotic resistance proteins, and various virulence factors. Consequently, these contaminated powdered dairy products pose a risk to the health of hypersensitive adults. Full article

The study of anaemia is a well-developed discipline where the concepts of precision medicine have, in part, been researched extensively. This review discusses the treatment of erythropoietin (EPO) deficiency anaemia and resistance in cases of chronic kidney disease (CKD). Traditionally, erythropoietin-stimulating agents (ESAs) and iron supplementation have been used to manage anaemia in cases of CKD. However, these treatments pose potential risks, including cardiovascular and thromboembolic events. Newer treatments have emerged to address these risks, such as slow-release and low-dosage intravenous iron, oral iron supplementation, and erythropoietin–iron combination therapy. Another novel approach is the use of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). This review highlights the need for precision medicine targeting the genetic components of EPO deficiency anaemia in CKD and discusses individual variability in genes such as the erythropoietin gene (EPO), the interleukin-β gene (IL-β), and the hypoxia-inducible factor gene (HIF). Pharmacogenetic testing aims to provide targeted therapies and interventions that are tailored to the specific characteristics of an individual, thus optimising treatment outcomes and minimising resistance and adverse effects. This article concludes by suggesting that receptor modification has the potential to revolutionise the treatment outcomes of patients with erythropoietin deficiency anaemia through the integration of the mentioned approach. Full article

In this work, the features of the phase composition, structures, and properties of coatings obtained on a high-speed steel substrate (steel R6M5) were studied. The coatings were prepared using the ESA method (electro-spark alloying). Electrode materials prepared through self-propagating high-temperature synthesis (SHS) based on (Ti-B-Fe)_xAlN with the addition of nanosized AlN particles in the amount of x = 0.5, 10, 15 wt % were used as electrodes. The structure, phase composition, and physical and mechanical properties of the SHS electrode materials are reported. It was found that the coatings inherited the structure of the SHS electrode material and formed two characteristic zones for x = 0 and three zones for x = 5, 10, 15. The surface hardness of the substrate made of the high-speed steel R6M5 with the developed coatings was found to increase up to five times compared to the uncoated substrate. It was found that the wear resistance of the samples with the coating was four to six times higher than that of uncoated samples. Full article

Shikimate is a valuable chiral precursor for synthesizing oseltamivir (Tamiflu^®) and other chemicals. High production of shikimate via microbial fermentation has attracted increasing attention to overcome the unstable and expensive supply of shikimate extracted from plant resources. The current cost of microbial production of shikimate via engineered strains is still unsatisfactory, and thus more metabolic strategies need to be investigated to further increase the production efficiency. In this study, we first constructed a shikimate E. coli producer through the application of the non-phosphoenolpyruvate: carbohydrate phosphotransferase system (non-PTS) glucose uptake pathway, the attenuation of the shikimate degradation metabolism, and the introduction of a mutant of feedback-resistant 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase. Inspired by the natural presence of bifunctional 3-dehydroquinate dehydratase (DHD)-shikimate dehydrogenase (SDH) enzyme in plants, we then designed an artificial fusion protein of DHD-SDH to decrease the accumulation of the byproduct 3-dehydroshikimate (DHS). Subsequently, a repressed shikimate kinase (SK) mutant was selected to promote shikimate accumulation without the supplementation of expensive aromatic substances. Furthermore, EsaR-based quorum sensing (QS) circuits were employed to regulate the metabolic flux distribution between cell growth and product synthesis. The final engineered strain dSA10 produced 60.31 g/L shikimate with a yield of 0.30 g/g glucose in a 5 L bioreactor. Full article

Background and Objectives: Iron deficiency and anemia characterize patients on chronic hemodialysis (HD). Available intravenous iron agents, such as ferric gluconate (FG) and ferric carboxymaltose (FCM), vary in dosing regimens and safety profiles. The aim of the present study was to analyze the modification of the iron status, the correction of anemia, and the economic implications after the shift from FG to FCM therapy in chronic HD patients. We evaluated, during the study, the variations in iron metabolism, assessing ferritin and transferrin saturation, erythropoietin-stimulating agent (ESA) doses and the number of administrations, the effects on anemic status, and consequent costs. Materials and Methods: A retrospective study was performed with a follow-up period of 24 months, enrolling forty-two HD patients. The enrolment phase started in January 2015, when patients were treated with iv FG, and continued until December 2015, when FG was discontinued, and, after a wash-out period, the same patients were treated with FCM. Results: The iron switch reduced the administered dose of ESA by 1610.500 UI (31% of reduction; p < 0.001) during the entire study period and reduced the erythropoietin resistance index (ERI) (10.1 ± 0.4 vs. 14.8 ± 0.5; p < 0.0001). The FCM group had the highest percentage of patients who did not require ESA treatment during the study period. The FCM patients were characterized by higher levels of iron (p = 0.04), ferritin (p < 0.001), and TSAT levels (p < 0.001) compared to the FG patients. The annual cost during FG infusion was estimated at EUR 105,390.2, while one year of treatment with FCM had a total cost of EUR 84,180.7 (a difference of EUR 21,209.51 (20%), saving EUR 42.1 per patient/month (p < 0.0001). Conclusions: FCM was a more effective treatment option than FG, reducing ESA dose requirements, increasing Hb levels, and improving iron status. The reduced ESA doses and the decreased number of patients needing ESA were the main factors for reducing overall costs. Full article

Although the double-layer pavement structure with a top layer of stone mastic asphalt concrete (SMAC) and a bottom layer of epoxy asphalt concrete (EAC) has been confirmed to have excellent overall performance in the laboratory, there is a lack of comparison and verification in practical projects. Hence, the utilization of the SMAC + EAC structure in this steel bridge deck pavement (SBDP) practical project and the clarification of its service performance are of significant importance for facilitating the promotion and application of this novel structure. This study relied on an SBDP reconstruction project in Ningbo, China. Indoor performance tests were used to determine the appropriate material compositions for SMAC and EAC. Subsequently, both ERS and SMAC + EAC pavement structures were paved in the project, and the service conditions of the different pavements after one year of operation were tested and compared. The results indicated that the epoxy SBS asphalt (ESA) binder prepared by substituting SBS-modified asphalt binder for the base binder, exhibited improved mechanical strength and toughness. The variation of modifier content significantly affected the high-temperature stability, low-temperature crack resistance, and moisture damage resistance of epoxy SBS asphalt concrete (ESAC) and high-viscosity SBS asphalt concrete (HSAC), while the gradation mainly influenced the skid resistance. The optimal contents of modifiers in ESA and HAS binders were finalized at 45 wt% and 11 wt%. After one year of operation on the trial road, the pavement performance of the SMAC + EAC structure had significant advantages over the ERS system, with all lanes having an SBDP quality index (SDPQI) above 90 and an excellent service condition. The successful application of the SMAC + EAC structure validated its applicability and feasibility in SBDP, which provided strong evidence for the further promotion of this structure. Full article