Rice-based cropping systems in central and eastern India often rely on intensive inputs, leading to soil degradation, nutrient imbalance and reduced system sustainability. Integrating pulses, such as cowpea, after rice is a viable strategy for sustainable intensification to enhance soil fertility and improve resource-use efficiency. However, cowpea yields in marginal and rainfed areas remain low due to inadequate nutrient management, particularly sulphur (S) and zinc (Zn). To address this gap, a field experiment was conducted during the summer season of 2024 at the Post Graduate Research Farm, Gajapati district, Odisha, to assess the effects of edaphic application of sulphur and foliar application of zinc EDTA on the growth, productivity and nutrient uptake of cowpea. The experiment was laid out in a factorial Randomised Block Design with four sulphur levels (0, 10, 20 and 30 kg S/ha) and three foliar zinc levels (0.1%, 0.2% and 0.3%), replicated thrice. Results revealed that both sulphur and zinc significantly influenced growth attributes, physiological parameters, yield components and yield. The application of 30 kg S/ha consistently resulted in the highest plant height, dry matter accumulation, nodule formation, yield attributes, and grain and stover yields. Similarly, foliar zinc EDTA @0.3% at 30 and 50 DAS enhanced physiological efficiency and improved yield and nutrient accumulation. Nutrient content and uptake of S and Zn were highest under a nutrient dose of 30 kg S/ha and 0.3% Zn EDTA than other treatments. Economic analysis confirmed superior net returns and benefit: cost ratio with higher S and Zn application. Overall, the study demonstrates that optimal application of sulphur combined with foliar zinc EDTA substantially enhances cowpea performance and offers a sustainable nutrient management approach under South Odisha conditions.

BackgroundMBLs require zinc ions (Zn²⁺) as essential cofactors for their activity. Previous research has shown that physiological zinc concentrations in human plasma range from approximately 0.8 to 1.2 μg/mL. This study investigated how variations in extracellular zinc concentration within standard culture media impact MBL activity and the resulting MICs of carbapenems.MethodsThe in vitro susceptibility of clinical MBL-producing Escherichia coli and Klebsiella pneumoniae isolates (NDM-1, VIM-1, combinations; n=10), ESBL controls (E. coli ATCC 35218 (TEM-1), K. pneumoniae ATCC 700603 (SHV-18)), and a WT (E. coli ATCC 25922) were evaluated. Zinc-depleted CAMHB was prepared using Chelex-100 resin, and zinc levels were quantified by ICP-MS. Following depletion, the media were reconstituted with standard levels of calcium, magnesium and iron. MICs for carbapenems (meropenem, imipenem, doripenem, ertapenem) and control antibiotics (amikacin, polymyxin B) were determined by broth microdilution (ISO 20776-1) in three parallel media: (i) untreated CAMHB, (ii) zinc-depleted CAMHB and (iii) zinc-depleted CAMHB supplemented with 5 μM Zn²⁺.ResultsICP-MS analysis confirmed that Chelex treatment effectively reduced the intrinsic zinc concentration in CAMHB by over 63% (from 0.964 μg/mL to 0.352 μg/mL). In this zinc-depleted medium, MBL-producing isolates exhibited a significant 2- to 128-fold reduction in carbapenem MICs compared to untreated CAMHB. Crucially, supplementing the zinc-depleted broth with 5 μM Zn²⁺ (1.43 μg/mL) restored carbapenem MICs to levels comparable to, or marginally exceeding, those observed in untreated broth. In contrast, the MICs for MBL-negative isolates (ESBL-producers and WT) and for non-β-lactam antibiotics remained unchanged across all media conditions, confirming the effect was specific to MBL activity. Higher zinc supplementation (>5 mM) yielded no further significant increases in MICs.ConclusionsExtracellular zinc availability is a critical determinant of MBL-mediated carbapenem resistance in vitro. Standard susceptibility testing media may contain supra-physiological concentrations of zinc, resulting in a higher number of false negative susceptibility results in routine clinical testing. Failure to control for zinc can lead to discrepancies in MIC values and misinterpretation of resistance profiles. These findings emphasize the need to standardize zinc concentrations in diagnostic media and to further investigate the clinical relevance of zinc availability at the site of infection.

Calamus erectus Roxb., locally known as Fyakrey in Sikkim, is an underutilized wild fruit species that has significant traditional importance but is poorly scientifically characterized. The present study estimated the nutrient composition, mineral profile, and phytochemicals of its fruits to infer the possible use as a functional food resource. Proximate analysis indicated that the fruit is dominated by carbohydrates (87.69 ± 0.70%), which assigns a very high nutritive value to fruits at 376.88 ± 0.14 Kcal/100 g. Moderate levels of crude protein (3.74 ± 0.56%) and crude fibre (4.99 ± 0.02%), along with lower fat and ash contents, were measured. The mineral profile showed potassium to be the predominant element measured at 160.94 ± 1.56 µg/L, besides moderate amounts of magnesium, sodium, and calcium, and trace levels of iron, copper, manganese, zinc, and molybdenum. The phytochemical evaluation revealed a high total phenolic content of 39.00 ± 1.32 mg GAE/g and good flavonoid content at 22.72 ± 0.21 mg QE/g, thus reflecting strong antioxidant potential. It also contained detectable amounts of ascorbic acid, anthocyanins, and carotenoids. Overall, the above results showed that Calamus erectus is a nutritionally valuable lesser-known fruit and rich in bioactive compounds, thus supporting its possible use as a natural source of energy, dietary fibre, and antioxidants. The present study supports the nutraceutical potential of the species and is relevant in the context of diversified fruits from the Eastern Himalaya.

Zinc levels in patients with lumbar disc herniation: A systematic review and meta-analysis.

Serum trace elements and expression of antioxidant-related genes in the detection of women with ER-positive breast cancer.

Zinc is essential for many physiological processes and its deficiency is highly prevalent worldwide. Its complex homeostasis involves membrane transporters from the SLC39/ZIP and SLC30/ZnT protein families. We conducted a genome-wide association study (GWAS) meta-analysis of urinary zinc levels in three European-ancestry cohorts (N = 10,113), followed by in silico and in vivo studies to elucidate their underlying public health and physiological relevance. We identified eleven genome-wide significant signals with six mapping to SLC39/ZIP and SLC30/ZnT gene regions. The lead signal (rs3008217C>G, p = 2.42E-110) in the SLC30A2 gene region which explained 6.1% of urinary zinc variation strongly colocalized with its expression in kidney tubules. Low phenotypic and genetic correlations between plasma and urinary zinc levels indicated distinct genetic regulation. High urinary zinc correlated with an unfavorable cardiometabolic profile, and Mendelian randomization analyses suggested causal roles for diabetes increasing urinary zinc levels, and elevated urinary zinc increasing stroke risk. Analyzing country-level allele frequencies and zinc deficiency prevalences revealed a 3-fold higher genetic zinc excretion risk in sub-Saharan Africa compared to Europe, significantly correlating with nutritional zinc deficiency prevalence. Although mutations in SLC30A2 are linked to insufficient zinc in human milk, we found no association with common variants using data generated from 387 mothers. Mice experiments showed that dietary zinc deficiency decreased urinary but not plasma zinc levels, and upregulated kidney Slc30a2 expression. This first GWAS on urinary zinc highlights the involvement of zinc transporters in its genetic regulation, as well as its role as a non-invasive biomarker for cardiometabolic diseases.

The association between serum copper-to‑zinc ratio and mortality among older patients in the emergency department: A prospective cohort study in Taiwan.

Abstract This study aims to use different single and combined fertilization treatments, including adding vermicompost and EM biofertilizer to the soil, as well as foliar spraying of gold and silver nanoparticles for the sake of evaluate the response of cabbage plants (hybrid variety Cabbage Top White F1). Vermicompost and bio fertilizer (EM)were applied at a rate of 20L ha −1 . The vegetative parts were sprayed with gold nanoparticles at a concentration of 0.1 mg L −1 and silver nanoparticles at a concentration of 5 mg L −1 , both as individual treatments and in binary, ternary, and quaternary combinations, in addition to a control treatment. Spraying was carried out four times using 400 L ha −1 for each treatment. The experimental units were arranged in a one-way simple experiment using a Randomized Complete Block Design (RCBD) with three replications. The results of Duncan’s multiple range test at the 0.05 level of significance showed the following: The integrated quad-treatment consisting of organic vermicompost, liquid EM biofertilizer, foliar application of gold nanoparticles, and foliar application of silver nanoparticles resulted in the highest concentrations of macronutrients in cabbage (Brassica oleracea) heads, with nitrogen, phosphorus, and potassium levels reaching 1.98%, 0.44%, and 4.42%, respectively. Additionally, this combination recorded superior levels of micronutrients, including iron (380.44 mg kg −1 dry matter), zinc (79.37 mg kg −1 ), copper (166.00 mg kg −1 ), and manganese (43.17 mg kg −1 ), along with detectable concentrations of gold and silver amounting to 0.053 and 0.21 μg kg −1 dry matter, respectively. Moreover, analysis conducted using an amino acid analyzer revealed that the same treatment yielded the highest accumulation of key amino acids in cabbage heads. The recorded values for Tyrosine, Methionine, Cysteine, Arginine, Proline, Histidine, Leucine, and Phenylalanine were 32.98, 36.98, 28.76, 52.63, 29.90, 25.43, 29.65, and 31.24 mg per 100 g, respectively.

Background: Micronutrients and trace elements have been linked to the development of head and neck squamous cell carcinoma (HNSCC). However, the role of these elements in the etiology of HNSCC remains unclear.Purpose: This study was conducted to investigate the association between micronutrient and trace element levels and the risk of HNSCC.Materials and Method: In this case-control study, serum concentrations of iron, selenium, zinc, copper, and calcium were measured in 40 patients with HNSCC and compared to those of 37 healthy subjects. Statistical analysis was conducted using the Mann-Whitney test, Chi-square test, and independent t-test.Results: The mean ages of the case and control groups were 62.80±13.029 and 57.92± 9.367, respectively, with 45% of HNSCC patients and 59.5% of control subjects being male (p= 0.205). Serum concentrations of calcium and copper were higher, and those of selenium, zinc, and iron lower in the case group than in the control group. Adjusted logistic regression showed only copper, calcium, and iron concentrations to be significantly different between the two groups (p= 0.003, p= 0.018, and p= 0.047, respectively).Conclusion: The case group had lower levels of iron, zinc, and selenium, and higher levels of calcium and copper than the control group. Evaluating serum concentrations of these trace metals could be useful for further screening of individuals at high risk.

Evaluation and comparison of the nutritional quality of eggs of different goose breeds: Guidance for consumers and production.

Integrated environmental assessment framework for evaluating and managing nitrogen contamination in complex fractured aquifer systems.

Background Existing research have suggested a significant association between micronutrients and childhood asthma, but the specific causal relationship between micronutrients and childhood asthma remains unclear. Therefore, we aimed to assess the causal relationship between micronutrients and childhood asthma using Mendelian randomization methods. Methods We conducted two-sample Mendelian randomization analyses and multivariable Mendelian randomization analyses using summary statistics from genome-wide association studies (GWAS) of micronutrients (Copper, Calcium, Carotene, Folate, Iron, Magnesium, Potassium, Selenium, Vitamin A, Vitamin B12, Vitamin B6, Vitamin C, Vitamin D, Vitamin E, and Zinc) and childhood asthma among European individuals from the Open GWAS and FinnGen databases. Five Mendelian randomization methods—Inverse Variance Weighted (IVW), Weighted Median, MR-Egger, Simple Mode, and Weighted Mode—were employed to investigate the causal relationship between micronutrients and childhood asthma. Results The IVW method revealed a significant inverse association between zinc and the risk of childhood asthma (OR: 0.002, 95% CI: 0.000-0.153, p = 0.005). Copper (OR: 0.998, 95% CI: 0.947-1.052, p = 0.951), Selenium (OR: 0.967, 95% CI: 0.866-1.079, p = 0.544), Folate (OR: 0.885, 95% CI: 0.603-1.300, p = 0.534), Carotene (OR: 0.849, 95% CI: 0.594-1.215, p = 0.371), Potassium (OR: 1.262, 95% CI: 0.836-1.905, p = 0.268), Vitamin D (OR: 1.237, 95% CI: 0.791-1.934, p = 0.352), Vitamin C (OR: 1.154, 95% CI: 0.759-1.756, p = 0.503), Vitamin B12 (OR: 1.177, 95% CI: 0.754-1.839, p = 0.473), Iron (OR: 0.873, 95% CI: 0.552-1.383, p = 0.563), Vitamin E (OR: 1.082, 95% CI: 0.768-1.524, p = 0.651), Magnesium (OR: 1.190, 95% CI: 0.828-1.712, p = 0.347), Vitamin B6 (OR: 0.928, 95% CI: 0.592-1.456, p = 0.746), Calcium (OR: 1.255, 95% CI: 0.840-1.876, p = 0.268), and Vitamin A (OR: 3.928, 95% CI: 0.001-15166.57, p = 0.745) had no significant causal associations with childhood asthma. The multivariable Mendelian randomization analysis for zinc, Vitamin A, and Vitamin C indicated that zinc is a significant protective factor against childhood asthma (OR: 0.001, 95% CI: 0.000-0.165, p = 0.007). In contrast, Vitamin A and Vitamin C did not show significant causal relationships with childhood asthma when controlling for zinc levels. Conclusion Our study confirms the specific causal relationships between micronutrients and childhood asthma using Mendelian randomization methods.

Two cases of long-term zinc acetate hydrate administration in patients with a zinc deficiency taste disorder with copper deficiency after upper gastrointestinal resection.

ObjectiveADHD, a prevalent neurodevelopmental disorder affecting 5−7% of children and adolescents, is characterized by inattention, hyperactivity, and impulsivity, impacting social and academic functioning. Its complex etiology includes genetic, environmental, and inflammatory factors. In the present research, we aimed to compare serum CRP, TNF-α, IL-6, IFN-γ, TWEAK, neopterin and zinc levels in drug-naive ADHD patients and healthy controls.MethodsThis study included 50 drug-naïve ADHD patients (aged 8−18) and 37 healthy controls. Psychiatric diagnoses were based on DSM-5 criteria. Blood samples were analyzed for inflammatory markers, including CRP, TNF-α, IL-6, IFN-γ, TWEAK, neopterin, and zinc. Statistical analyses were performed using SPSS.ResultsThe study found no significant differences in age, sex, or BMI between individuals with ADHD and the control group. Regarding inflammatory markers, ADHD patients demonstrated significantly lower levels of TWEAK and higher levels of CRP compared to controls. However, no differences were observed in the levels of TNF-α, IL-6, IFN-γ, zinc, or neopterin. When examining ADHD subtypes, it was noted that individuals with the inattentive subtype had markedly lower TWEAK levels and higher CRP levels than the control group.ConclusionThis finding particularly supports that TWEAK levels could be a significant marker both for ADHD and the predominantly inattentive subtype. Additionally, a correlation was identified between IFN-γ levels and psychosomatic symptoms, and this positive correlation suggests that this cytokine may be associated with specific ADHD symptoms. This study highlights the role of neuroinflammatory processes in ADHD and the etiological distinction of the predominantly inattentive ADHD subtype from other subtypes in the literature. Future research should validate these findings through larger and longitudinal studies.

Inorganic arsenical compounds, such as arsenic trioxide (ATO), are toxic environmental contaminants that occur widely in soil, water, and biological systems. Besides, zinc oxide nanoparticles (ZNPs) have been recently incorporated in various industrial and medicinal applications. Thus, their co-existence in the environment could widely occur. This study examined the potential protective activity of gallic acid (GA, 20 mg/kg b. wt) against the harmful impacts of 60-day co-exposure to ATO (8 mg ATO/kg b. wt) and ZNPs (100 mg ZNPs/kg b. wt) on the kidneys of rats. The results indicated that ZNPs and/or ATO exposure resulted in increased serum levels of markers associated with renal damage, an imbalance in electrolytes (sodium, potassium, and calcium), diminished levels of antioxidant enzymes in the kidneys, and an increased malondialdehyde (MDA) concentration. Furthermore, ZNPs and/or ATO co-exposed rats demonstrated markedly increased levels of renal zinc (Zn) and arsenic (As), accompanied by pronounced histopathological alterations, including interstitial nephritis, renal tubular necrosis, and vascular wall thickening. Immunohistochemical analysis revealed that exposure to ZNPs and/or ATO reduced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) while increasing that of heat shock protein 90 (HSP90) in kidney tissues. Co-exposure to ZNPs and ATO produced more pronounced alterations, including increased serum uric acid and creatinine, decreased sodium levels, reduced renal GPx activity, increased MDA content, greater renal accumulation of As and Zn, and diminished Nrf2 expression, compared with individual exposures, suggesting additive toxic effects. However, GA notably reduced renal tissue damage, oxidative stress, and disturbances in renal function and electrolyte balance in rats co-exposed to ZNPs and ATO. Conclusively, the study found that exposure to ZNPs and ATO, especially when combined, was toxic to the kidneys, leading to impaired renal function through increased oxidative stress and disrupted electrolyte balance. However, GA effectively protected kidney health at the administered doses by counteracting these effects through its antioxidant properties and by modulating cellular defense mechanisms involving Nrf2 and HSP90.

Introduction: Dawadawa, a protein-rich fermented condiment from African locust bean (Parkia biglobosa), is widely consumed in Nigeria, but its bioactive compound content and nutritional profile from North-Central regions remain poorly documented. This study represents the first comprehensive characterization of antioxidant activities, nutritional composition, and functional properties of traditionally fermented Dawadawa from North-Central Nigeria (Kogi State), revealing significant location-based differences in quality parameters. Methods: Thirty Dawadawa samples were collected from three local government areas in Kogi State (Anyigba, Dekina, and Ankpa) between June and August 2025. Antioxidant activities were evaluated using DPPH, ABTS, and FRAP assays at an extract concentration of 1.0 mg/mL. Total phenolic, flavonoid, and tannin contents were determined spectrophotometrically using validated standard curves. Proximate composition, amino acid profile, and mineral content were analyzed using AOAC methods. Functional properties, including water absorption capacity, oil absorption capacity, and bulk density, were assessed. Results: Dawadawa extracts exhibited significant antioxidant activities with DPPH radical scavenging capacity of 68.4-79.6%, ABTS radical scavenging of 71.2-82.5%, and FRAP values of 156.3-234.7 µM FE/g. Total phenolic content ranged from 42.8-58.3 mg GAE/g, total flavonoids from 18.4-29.6 mg QE/g, and tannins from 8.4-14.2 mg TAE/g. Strong positive correlations were observed between phenolic content and antioxidant activities (r = 0.82 for DPPH and r = 0.86 for FRAP). Proximate analysis revealed protein content of 35.2-42.7%, crude fat of 12.8-18.4%, crude fiber of 8.4-11.6%, and ash of 4.2-6.8%. Amino acid profiling identified seventeen amino acids with essential amino acid composition meeting FAO/WHO requirements. Mineral analysis showed high levels of calcium (184.6-246.8 mg/100g), iron (12.4-18.7 mg/100g), zinc (3.8-5.6 mg/100g), magnesium (86.4-124.6 mg/100g), and phosphorus (234.8-316.4 mg/100g). Samples from Anyigba demonstrated significantly higher antioxidant activity and bioactive compound content than those from other locations, establishing it as a superior production location. Conclusion: This first comprehensive study of Dawadawa from North-Central Nigeria demonstrates that traditionally fermented products from Kogi State possess substantial antioxidant activities and excellent nutritional composition, confirming their status as functional foods with significant health-promoting potential. The identification of Anyigba as a producer of superior-quality Dawadawa with enhanced antioxidant properties has important implications for quality control, best-practice guidelines for commercial production, and the development of region-specific functional food applications. Keywords: Dawadawa, antioxidant activity, phenolic compounds, nutritional composition, functional food, bioactive compounds, fermented legume, Nigeria, fermented condiments

Background Enfortumab vedotin (EV) is effective for advanced urothelial carcinoma, but cutaneous adverse events (CAEs) remain a major barrier to treatment continuity. Intertriginous eruptions resembling symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) are particularly problematic. Zinc deficiency causes similar dermatoses, suggesting a possible link with EV-induced skin toxicity. Case presentation We retrospectively analyzed 10 EV-treated patients with advanced urothelial carcinoma. Serum zinc levels were measured at the onset of CAEs or dysgeusia, and all patients had subnormal zinc levels (80–130 μg/dL). SDRIFE-like rash occurred in six patients, dry skin in five, and maculopapular rash in four. Patients with SDRIFE-like rash had significantly lower zinc levels than those without (median: 63 μg/dL vs. 70 μg/dL, P = 0.041). Zinc supplementation (100–150 mg/day, 2–4 weeks) was administered in four patients with grade ≥2 skin rash and dysgeusia. Three with SDRIFE-like rash improved within days and resolved within 14 days despite poor response to corticosteroids, whereas dry skin improved only partially and dysgeusia did not improve. Discussion These findings suggest that zinc deficiency may predispose EV-treated patients to SDRIFE-like eruptions by amplifying skin vulnerability typical of zinc-deficient states. Zinc supplementation showed rapid benefit in corticosteroid-refractory cases, pointing to its potential as a supportive adjunct. Conclusion Zinc deficiency may represent a modifiable factor in EV-induced skin toxicity, particularly SDRIFE-like rash. Monitoring zinc status and considering supplementation could help mitigate rash severity and support treatment adherence and continuity, which is critical for patients with advanced urothelial carcinoma receiving EV as one of the last available treatment options.

Pancreatic fibrosis in calves fed a milk replacer with elevated zinc levels.

Background: Trace elements and insulin-like growth factor-I (IGF-I) are critical biochemical regulators of skeletal growth and endocrine function. However, limited data are available regarding their laboratory correlations in pediatric short stature. This study aimed to evaluate the biochemical profiles of calcium, magnesium, zinc, and lead, together with serum IGF-I levels, and to assess their diagnostic significance in children with growth retardation in the Guangzhou region. Methods: A total of 876 children aged 2–12 years were enrolled, including 276 with growth retardation, 300 with short stature, and 300 healthy controls. Serum trace elements and IGF-I concentrations were determined using standardized clinical chemistry assays in a hospital laboratory. Intergroup differences were analyzed using ANOVA, and multivariate logistic regression was employed to identify independent biochemical predictors of growth retardation. Results: Children with growth retardation exhibited significantly lower serum levels of calcium, magnesium, and zinc, and elevated blood lead concentrations compared with controls (P<0.05). IGF-I levels were reduced (109.18 ± 45.08 vs. 111.46 ± 55.44 ng/mL, P=0.012) and correlated positively with calcium, magnesium, and zinc levels. Multivariate analysis identified low calcium, magnesium, zinc, and IGF-I, as well as elevated lead, as independent predictors of growth retardation. Conclusion: Alterations in serum trace elements and IGF-I represent measurable biochemical indicators associated with pediatric growth retardation. Integrating trace element and IGF-I assessments into routine biochemical testing may improve early diagnosis and monitoring of short stature in clinical practice.

The increasing prevalence of type 2 diabetes mellitus (T2DM), largely attributable to poor dietary habits and nutritional imbalances, highlights the need for novel diagnostic and therapeutic approaches. Emerging evidence emphasizes the critical role of trace elements in the pathogenesis and management of T2DM. However, the molecular mechanisms through which zinc and chromium deficiencies contribute to disease progression remain largely unexplored. This study aimed to investigate the role of zinc and chromium in T2DM pathogenesis through a combination of bioinformatics analysis, molecular docking, trace element profiling, and gene expression validation. Relevant genes identified from the literature were analyzed using a bioinformatics pipeline to uncover hub gene networks and regulatory pathways associated with trace element deficiencies. Molecular docking of HUB genes with zinc and chromium enriched compounds were employed to uncover the new therapeutic approach. For experimental validation, serum zinc and chromium levels were measured in fifty T2DM patients and fifteen healthy controls using atomic absorption spectrophotometry. Gene expression profiling of GCK (zinc associated) and GLUT4 (chromium associated) was performed using real time PCR. Bioinformatics analysis revealed that HUB genes affected due to zinc and chromium deficiency were linked to an elevated risk of T2DM. Crucial metabolic pathways was altered due to zinc and chromium deficiency in T2DM.The serum concentration of zinc and chromium were markedly lower in T2DM patients as compared to controls. Level of zinc was significantly lower in T2DM patients with nephropathy and chromium level was significantly were lower in T2DM patients with CVD. Expression of GCK and GLUT4 was reduced by approximately 4-6 folds and 3-4 folds, respectively, in T2DM and its associated complications. The study provide novel insights into the gene-environment interaction driving T2DM and highlight the therapeutic approach of zinc and chromium supplementation in mitigating diseases progression. This study paves the way for future research into personalized nutritional interventions targeting gene expression abnormalities in diabetes management.