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Objectives: To determine the association between blood metal mixture and HUA risk., Methods: A cross-sectional study was performed based on the populations from Kailuan cohort trial in China. Inductively coupled plasma mass spectrometry was utilized to detect the blood concentrations of iron (Fe), lead (Pb), calcium (Ca), copper (Cu), magnesium (Mg), zinc (Zn), selenium (Se), and manganese (Mn). Multivariate logistic regression (MLR) models and weighted quantile sum (WQS) regression models were employed to assess the relationships., Results: There were 3706 participants included in this study, and 464 (12.52%) were with HUA. The mean level of uric acid was 485.60 μmol/L in the subjects with HUA, which was remarkably increased compared to those without HUA (293.10 μmol/L). The multivariate-adjusted odds ratios (95% confidence intervals) of HUA were 2.15 (1.40, 3.29) for Pb, 3.42 (2.24, 5.23) for Fe, 1.61 (1.15, 2.25) for Ca, 3.06 (2.04, 4.59) for Mg, and 1.69 (1.26, 2.28) for Zn by comparing the highest and lowest metal quartiles using the single-metal logistic regression model. Meanwhile, the WQS regression models demonstrated a positive association between metal mixtures and HUA risk, to which, Fe, Mg, Pb, and Zn were the major contributors. Pb, Fe, and Zn were still robust in multiple-metal models. Age, gender, weight, smoking, and drinking status could modify these relationships with significant interactions., Conclusions: Co-exposure to Fe, Pb, Ca, Cu, Zn, Mg, Se, and Mn were related to increased HUA risk in Chinese adults, of with, Pb, Fe, and Zn appeared to have greater impacts. These relationships were more obvious in adults aged < 60 years, or women, or overweight, or non-smoking, or drinking with significant interactions. Key Points • Increased Fe, Pb, Mg, Ca, and Zn were related to increased HUA risk in dose-response fashion among Chinese adults. • The metal mixture dominated by Fe, Mg, Pb, and Zn was positively associated with HUA risk. Fe, Pb, and Zn were still robust in MM model. • Such association was stronger showed in adults aged < 60 years, or women, or overweight, or non-smoking, or drinking with significant interactions., Competing Interests: Declarations. Ethical approval and consent to participate: This study was approved by the Ethics Committee of the Kailuan Medical Group and the Chinese Academy of Medical Sciences (Approval No. 2018ZX10715005). All participants were signed informed consent. Consent for publication: All the authors have read and approved the final manuscript. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: Meta-analyses show increased copper (Cu) levels in major depression disorder. However, the association of Cu biomarkers with clinical classification in other mental health disorders has not been fully explored., Methods: To this aim, we compared an extensive panel of Cu biomarkers, composed of Cu, ceruloplasmin (Cp) Cp activity, Cp specific activity, Cu not bound to ceruloplasmin (non-Cp Cu, also known as 'free' copper) in 171 consecutive patients affected by psychiatric disorders and in 61 healthy controls (HC) using MANOVA adjusting for the effect of sex and age, and studied their association with the clinical scale outcomes at psychiatric examination, namely Global Assessment of Functioning, Clinical Global Impression, and Brief Psychiatric Rating Scale., Results: individuals with psychiatric disorders were classified as 109 patients affected by mood spectrum disorders (MSD), 20 patients with schizophrenia spectrum disorders (SSD), and 42 with personality disorders (PD). Cu and non-Cp Cu were increased in psychiatric individuals than in HC, which also differed among the patients stratified per the clinical classification, being higher in the MSD individuals. The analysis stratified for sex revealed that women from the patient group, and specifically from the MSD group, had increased levels of Cu and non-Cp Cu than healthy women, while no difference was revealed in men. A logistic regression model considering the effect of sex and age revealed that non-Cp Cu could explain 26 % increased odds of having MSD per µmol/L unit increase (OR = 1.26; p = 0.0008; 95 % CI 1.099-1.436), that reached 40 % when considering only women. This result was driven by non-Cp Cu that correctly classified 64.1 % MSD (70 % in women) individuals vs. HC in a decision tree model, with values higher than 2.1 µmol/L which could distinguish the majority of MSD patients (86.3 % MSD vs. 13.7 % HC in women). None of the biological variables under study correlated with outcomes of the clinical scales, substances, or alcohol abuse., Conclusion: Current results suggest mild Cu toxicity in women with MSD, as revealed by a value of non-Cp Cu higher than 2.1 µmol/L, which can be further investigated to assess its potential diagnostic accuracy in bigger and longitudinal cohorts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Objective: This study aims to establish the correlation between shifts in serum trace element (TE) levels and the progression of osteoarthritis (OA), while also exploring the underlying causal relationship between these variables., Methods: An investigation was conducted, which included a systematic review, a meta-analysis of observational studies, and a two-sample Mendelian randomization (MR) study., Results: This meta-analysis revealed significant differences in serum levels of copper, manganese, cadmium, and selenium between OA patients and healthy controls, after adjusting for heterogeneity. Specifically, significant disparities were observed for copper (SMD 0.118 [95 % CI: 0.061 ∼ 0.175], P < 0.001), manganese (SMD -0.180 [95 % CI: -0.326 ∼ -0.034], P = 0.016), cadmium (SMD 0.227 [95 % CI: 0.131 ∼ 0.322], P < 0.001), and selenium (SMD -0.138 [95 % CI: -0.209 ∼ -0.068], P < 0.001), while zinc levels did not show a significant difference (SMD -0.02 [95 % CI: -0.077 ∼ 0.038], P = 0.503). Further, MR analysis suggested a causal link between genetically predicted serum copper level changes and OA development, but not for other TEs., Conclusion: The study suggests that there is an association between the occurrence of OA and variations in serum levels of copper, manganese, cadmium, and selenium. Elevated serum copper may play a pivotal role. Further research is needed to explore the therapeutic potential of TE level modulation in OA management., Competing Interests: Declaration of Competing Interest The authors declare no competing interests or any commercial or financial relationships that could be perceived as a potential conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Studies on essential trace elements in the context of Alzheimer's disease (AD) concluded that Cu, Fe and Zn interact with amyloid-β, accelerating plaque formation in the brain. Additionally, Cu and Fe in the vicinity of plaques produce reactive oxygen species (ROS) resulting in oxidative stress, whereas Zn plays a role in the antioxidant defence as a co-factor for antioxidants. In this work, the Cu, Fe and Zn concentrations and isotope ratios were determined in whole blood, blood serum and cerebrospinal fluid of 10 patients diagnosed with AD and 8 control individuals, using tandem (ICP-MS/MS) and multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS), respectively. In whole blood and blood serum of AD patients, a heavier Cu isotopic composition was observed (significant for whole blood only) compared to controls. Albumin levels in cerebrospinal fluid tend to increase with age, which could indicate an increased leakiness of the blood-brain barrier. In cerebrospinal fluid, a large variability was observed for the Cu and Fe isotope ratios, potentially resulting from that leakiness at the blood-brain barrier. Therefore, potential effects of AD on the concentration and isotopic composition of essential elements in cerebrospinal fluid related to amyloid-β formation could be hidden. Finally, in blood serum, Zn, urea and creatinine concentrations showed an increase with age and showed a significant difference between sexes., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Zinc deficiency causes dysgeusia and dermatitis as well as anemia. As approximately half of dialysis patients have zinc deficiency, zinc supplementation should be considered in case of erythropoiesis-stimulating agent (ESA)-hyporesponsive anemia. We report a case of a chronic dialysis patient with copper deficiency anemia caused by standard-dose zinc supplementation. The patient was a 70-year-old woman who had received maintenance hemodialysis for 8 years due to diabetic nephropathy. She had been treated with weekly administration of darbepoetin 30 μg for renal anemia, which resulted in Hb 12 to 14 g/dL. She had no dysgeusia. When zinc deficiency (44 μg/dL) had been identified 4 months earlier, 50 mg daily zinc acetate hydrate (Nobelzin®), which is the standard dose, was started. Unexpectedly, her anemia progressed slowly with macrocytosis together with granulocytopenia. Her platelet count did not decrease at that time. Laboratory tests revealed a marked decrease of serum copper (< 4 μg/dL) and ceruloplasmin (< 2 mg/dL), although serum zinc was within the normal limit (125 μg/dL). We discontinued zinc acetate and started copper supplementation including cocoa for 1 month. Her anemia and granulocytopenia were dramatically restored coincident with the increase in both serum copper and ceruloplasmin. Copper supplementation also improved her iron status as assessed by transferrin saturation and ferritin. Clinicians should monitor both zinc and copper status in anemic dialysis patients during zinc supplementation, as both are important to drive normal hematopoiesis., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interests. Ethical approval and consent to participate: The ethical committee of Kitano Hospital approved this case report. Consent for publication: Informed consent was obtained from the patient in this case report., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Aim: The etiology of telogen effluvium (TE) includes situations that may cause physiological stress, surgical trauma, inflammatory, infectious, iatrogenic causes, medications and nutritional deficiencies. TE has been associated with iron deficiency, vitamin B12 deficiency and thyroid diseases. In recent years, the use of over-the-counter food supplements containing vitamins and minerals such as biotin, vitamin D, zinc (Zn), copper (Cu) and selenium (Se) has been increasing in TE patients. The aim of this study is to investigate whether there are differences in nutritional status, vitamin and mineral levels by comparing individuals with TE and a control group., Materials and Methods: This case-control study included 90 female patients diagnosed with chronic telogen effluvium (CTE), and 90 female controls volunteered to participate in the study who consulted for reasons other than TE. Both groups aged 18 and over and applied to dermatology polyclinic between 01.09.2022 and 01.09.2023. A detailed anamnesis was taken from all patients, a hair pull test was performed, and TE was diagnosed after a dermoscopic examination was performed on all areas of the scalp. Then, serum vitamin D, Zn, Cu, Se levels and biotin levels in serum and urine were measured. Hemoglobin (Hb), ferritin, vitamin B12 and thyroid function tests were retrospectively scanned from the hospital database., Results: It was determined that Zn levels were significantly lower in CTE patients than in controls. Se levels were found to be significantly higher in patients than in controls. There was no difference in Hb, ferritin, vitamin B12, thyroid function tests, vitamin D, Cu levels, serum and urine biotin levels between the two groups. Zn, Cu/Zn and Se levels were found to have statistically significant diagnostic performance in predicting the diagnosis of CTE. Cu/Zn ratio and Se value were found to be significant predictors of CTE., Conclusion: This study shows us that nutritional deficiencies are not as common as thought in patients diagnosed with TE. Other causes that may cause TE should be investigated by a detailed anamnesis and a good physical examination. After all, tests for suspected conditions should be performed and individualized treatment options should be created for each patient., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Copper (Cu), an essential trace element in the metabolism of mammals, plays a central role in various metabolic processes. However, overdosing can lead to severe symptoms and even fatalities. Chronic Cu intoxication continues to be a problem in grazing and domestic animals, with sheep being particularly sensitive. There are few comparative studies on its impact on South American camelids (SACs). Therefore, this work presents the results of literature research combined with a case report on a 3-year-old female vicuña (Vicugna vicugna) presented to the clinic from a zoological garden in northern Germany. The animal showed reduced food intake, recumbency, bruxism, icteric mucous membranes and sclera. Auscultation revealed atony of the third compartment and the digestive tract. Similar to cases described in the literature, the animal showed rapid deterioration of its condition with unspecific symptoms of liver failure and rapid death. However, in contrast to descriptions in sheep, clinical icterus has not been previously reported in cases of other SACs. Laboratory findings from EDTA and serum samples revealed neutrophilia with a left shift, hypoproteinaemia, lymphopaenia, azotaemia, elevated levels of creatine kinase (CK), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH) in the serum. Hyperbilirubinaemia and significantly elevated serum and liver Cu levels were observed. Subsequent blood samples from the remaining vicuñas and alpacas in the same enclosure showed no remarkable abnormalities. To the best of the authors' knowledge, this case report represents the first documented case of Cu intoxication specifically in vicuñas., (© 2024. The Author(s).)

The present study is conducted to know the serum lead, copper, iron, and zinc levels, in parallel to hematological parameters, in battery smelting workers to assess lead toxicity. Battery smelting is known to expose workers to high levels of lead, which can have significant negative health effects. Blood samples from 150 participants, including 75 battery smelting workers and 75 controls, were analyzed for metal concentrations and hematological indices. The results revealed significantly elevated levels of lead in the serum of battery smelting workers as compared to control group. Elevated lead levels were also correlated with significantly decreased hemoglobin levels and hematocrit values, manifesting potential anemia in these workers. In addition, disarrangements in serum copper, iron, and zinc levels were also observed, proposing a possible interaction between lead exposure and the metabolism of these essential metals. These findings highlight the need for regular monitoring of battery smelting facilities and environment and to take improved protective measures to prevent lead toxicity and its associated hematological disturbances. This study aims to analyze the effect of occupational lead exposure on blood levels of lead, zinc, iron, and copper in battery workers compared to normal subjects and evaluate their blood counts., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Wound healing is a complex, highly regulated process that is important in sustaining the skin barrier function. The etiologic relation of specific metals is not adequately described for chronic non-healing wounds. The aim of this study was to estimate heavy and trace metals in chronic non-healing wound and their association with wound healing . The levels of zinc, selenium, copper, magnesium, chromium, cadmium, iron, and lead were estimated in serum of chronic non-healing wound patients using atomic absorption spectrophotometry. The tests were carried out in 50 patients with chronic non-healing wound and thirty healthy volunteers as control. The serum levels of elements namely zinc, selenium, copper, magnesium, and chromium were significantly reduced in chronic non-healing wounds ( P  < .001) as compared to control. Lead and cadmium levels had shown the significantly increasing trend in chronic non-healing wound cases ( P  < .001). The present study demonstrated a significant decrease in serum, levels of selenium, zinc, copper, magnesium, iron, and chromium levels in patients with chronic non-healing wound indicating an association between these elements and wound healing. To summarize the findings of our research, hence trace elements were decreasing in chronic non-healing wound patients suggesting their role in wound healing., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Magnesium (Mg), iron (Fe), copper (Cu), and zinc (Zn) are indispensable elements in children's growth and development. However, epidemiological evidence regarding essential elements and their mixed exposure to behavior problems remains in its infancy. The objective of the present study was to evaluate the association between essential elements and the manifestation of behavior problems, with an additional focus on the implications of their mixture. An electronic medical records review was performed among 4122 subjects aged 6-18 years who underwent examinations at Children's Hospital, Zhejiang University School of Medicine, between January 2019 and July 2022. The concentrations of essential elements were measured by atomic absorption spectrometry, and behavior problems were assessed by using the Conners' Parent Rating Scale (CPRS). A total of 895 (21.7%) children and adolescents were identified as having behavior problems. For single exposure, inversely linear dose-response relationships were identified between continuous Mg and Zn levels and the prevalence of behavior problems, and the prevalence ratios (PRs) in the categorical lowest tertile were 1.28 (95% confidence interval, CI: 1.07-1.54) for Mg and 1.31 (95% CI: 1.05-1.63) for Zn compared to the highest tertile. For mixture exposure, an inverse association between essential elements and behavior problems was also found, mainly contributed by Mg (posterior inclusion probability, PIP = 0.854). Whole blood levels of Mg and Zn were significantly inversely associated with behavior problems. The findings highlight the pivotal role of essential elements in behavior problems and emphasize the importance of maintaining adequate levels of essential elements during children's maturation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The link between exposure to a particular heavy metal or metalloid and the development of anemia is well established. However, the association between combined exposure to multiple heavy metal(loid)s and anemia in children is still lacking in evidence. In this study, a total of 266 children aged 3 to 7 were recruited from Guiyu, China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure blood heavy metal(loid) concentrations. Blood cell count, hemoglobin (HGB), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), hematocrit (HCT), and red blood cell distribution width (RDW) were measured by an automated hematology analyzer. Erythrocyte-related parameters were negatively correlated with the Cu and Cu/Zn ratios and positively correlated with Cr, Ni, Zn, and Se by Spearman correlation analysis. Only blood Cu level was negatively correlated with HGB [β = -2.74, (95% Cl: -4.49, -0.995)], MCH [β = -0.505, (95% Cl: -0.785, -0.226)], MCV [β = -1.024, (95% Cl: -1.767, -0.281)], and MCHC [β = -2.137, (95% Cl: -3.54, -0.734)] by multiple linear regression analysis. The Bayesian Kernel Machine Regression (BKMR) model analysis indicated a negative correlation between the combined exposure to Cu, Zn, Pb, and Cr and MCH and MCV. The single-factor analysis showed a considerable statistical difference only with Cu on MCV, MCH, and HGB. Furthermore, the interaction analysis highlighted the interdependent effects of Cu and Zn, Pb and Zn, and Cr and Zn on MCH and MCV levels. Additionally, the oxidation and/or antioxidation reactions may play a significant role in the development of metal(loid)-induced anemia risk. It is crucial to investigate the effects of co-exposure to multiple heavy metal(loid) elements on anemia, especially the interrelationships and mechanisms among them., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: Opinion of Ethics Committee of Jinan University: National Natural Science Foundation of China—Huo Xia professor from our educational institution submitted an application for the 2023 National Natural Science Foundation of China project titled “6PPD-quinone affects cognitive development by disturbing gut microbiota-immunity-brain axis in children”. The Medical Ethics Committee of Jinan University has reviewed the project and confirmed that its research content and methods comply with the Declaration of Helsinki, medical ethics and moral standards, and the laws and regulations of our country. The project has been approved to apply for the National Natural Science Foundation of China in 2023. Consent to participate: Informed consent was obtained from all individual participants included in the study. Written informed consent was obtained from the parents. Consent for publication: The authors agree to publish this manuscript. The authors are stating that all data included in the manuscript will be available and transparent for interested users., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Chronic prostatitis (CP) is one of the general diseases in urological practice, with category III prostatitis being particularly prevalent. The trace metal abnormalities might be a primary cause of prostatitis, however, their specific roles in category III prostatitis remain largely unexplored., Method: In total, 42 expressed prostatic secretion (EPS) samples from IIIa prostatitis patients, 42 from IIIb prostatitis patients, and 45 from controls were collected, along with 42 serum samples from IIIa prostatitis patients, 45 from IIIb prostatitis patients, and 50 from controls for analysis in this study. To investigate the diagnostic potential of trace metals in category III prostatitis, we analyzed the concentration of zinc (Zn), copper (Cu), calcium (Ca) and magnesium (Mg) in EPS and serum of patients with category III prostatitis and healthy controls using a flame atomic absorption spectrometer (FAAS)., Results: The Results showed that the concentrations of Zn, Ca and Mg in both serum and EPS samples of all subjects with category III prostatitis were significantly different compared to controls (all P < 0.05), while Cu levels were significantly altered in all EPS samples (P < 0.000). In the category of IIIa prostatitis group, the levels of Zn, Ca, Mg in EPS, as well as Ca in serum were significantly reduced (all P < 0.000), whereas the serum Zn level was markedly elevated (P < 0.000). In the category IIIb prostatitis group, the EPS levels of Zn, Ca, Mg were decreased significantly (all P < 0.05), and the levels of serum Ca, Mg were markedly decreased (all P < 0.000), however, the EPS Cu level increased significantly (P < 0.05). Moreover, receiver operating characteristic (ROC) analysis showed that the levels of Mg and Zn/Mg in EPS had better diagnostic value for category IIIa prostatitis (Area Under the ROC Curve(AUC) = 0.796, 0.791, respectively, all P < 0.0001); while Cu and Cu/Ca levels exhibited better diagnostic value for category IIIb prostatitis (AUC = 0.880, 0.901, respectively, all P < 0.0001)., Conclusion: Summarily, there are significant abnormalities in the concentrations of Cu, Mg, Ca, and Zn in EPS and serum samples of patients with category III prostatitis. The levels of Mg, Cu, Zn/Mg, Cu/Ca in EPS may serve as potential diagnostic markers for category III prostatitis., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the the Guilin Medical University Ethics and Anthropology Committee (Number: GLMC202001011), and written informed consent was obtained from the patient. Consent for publication: Not applicable. Clinical trial number: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Epidural-related maternal fever (ERMF) heightens the risk of intrapartum fever, whereas effective prevention and treatment in clinical practice are currently lacking. Rapid and sensitive screening tools for ERMF are urgently needed to advance relevant research. In response to this challenge, we devise and craft porous Co 3 O 4 /CuO hollow polyhedral nanocages with p-p heterojunctions derived from metal-organic frameworks. We employ these p-p heterojunctions in conjunction with high-throughput mass spectrometry to conduct metabolic analysis of substantial plasma samples, with only about 0.03 μL per sample. Leveraging these p-p heterojunctions, metabolic signals from complex plasma can be amplified, with great reproducibility. By harnessing the power of machine learning on these metabolic signals, we are able to achieve advanced warning of ERMF with an area under the curve (AUC) of 0.887-0.975 by the differentially metabolic analysis of plasma samples collected upon admission. Furthermore, we can accurately diagnose ERMF with an AUC of 0.850-1.000 by analyzing plasma samples collected at the time of delivery from individuals who have received epidural analgesia. These breakthroughs offer invaluable insights for clinical decision making during labor and have the potential to significantly reduce the incidence of ERMF.

Background: Impaired cognitive function following exposure to heavy metals has emerged as a significant global health concern. Nevertheless, the impact of combined exposure to multiple heavy metals on cognitive impairment remains unclear., Objective: This study aimed to explore the association between multiple heavy metals exposure and cognitive function to provide theoretical evidence to guide prevention strategies., Methods: The blood levels of lead (Pb), cadmium (Cd), mercury (Hg), selenium (Se), copper (Cu) and zinc (Zn) and the results of the cognitive function tests were extracted from 811 elderly Americans who completed the NHANES between 2011 and 2014. Quantile regression (QR), restricted cubic splines (RCS), and Bayesian kernel machine regression (BKMR) were used to explore the individual and joint association between heavy metals exposure and performance in 4 standardized cognitive tests; Item Response Theory (IRT), Delayed Recall Test (DRT), Animal Fluency Test (AFT) and Digit Symbol Substitution Test (DSST)., Results: A negative association was noted between Cd levels and IRT (p = 0.048, 95%CI: -2.7, -0.1). Se concentrations ranging between 2.197 µg/L (95%CI: 0.004, 0.15) to 2.29 µg/L (95%CI: 2.56, 7.64) (log 10 Se) was postively associated with DSST (p = 0.001 ). Cu was negatively associated with DSST (p = 0.049, 95%CI: -37.75, -0.09), while Zn was positively associated with IRT (p = 0.022, 95%CI: 0.55, 11.73). Exposure to the 6 heavy metals combined showed a positive linear association with IRT, DRT, and a negative linear association with DSST. An interaction between Cd and the other heavy metals (excepted for Pb)., Conclusion: Exposure to Pb, Cd, Hg, Se, Cu, and Zn was associated with cognitive function. Joint exposure to the 6 heavy metals showed a positive linear association with IRT, DRT, contrarily, a negative linear association with DSST., Competing Interests: Declarations Ethics approval and consent to participate The NHANES database is publicly available and has been approved by the Institutional Review Board of the National Center for Health Statistics (NCHS). All participants provided written informed consent during their participation in the national survey conducted in the United States. Ethical review and approval were waived for this study as it involved secondary analysis and did not necessitate additional institutional review board approval. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Highlight Pb, Cd, Hg, Se, Cu, and Zn were significantly associated with cognitive function.An interaction between Cd and the other heavy metals (excepted for Pb).Exposure to the 6 heavy metals combined showed a positive linear association with IRT, DRT and a negative linear association with DSST., (© 2024. The Author(s).)

Background: Nutritional metals (NM) are essential for neurodevelopment and cognitive performance during growth. Nevertheless, epidemiological evidence regarding the associations between NM and brain function remains understudied, particularly among adolescents. Therefore, the objective of this pilot study was to examine the effects of NM biomarkers such as iron (Fe), selenium (Se), zinc (Zn), magnesium (Mg), and copper (Cu) on neurobehavioral functions among a group of rural Bangladeshi adolescents. Methodology: We conducted a cross-sectional study involving 105 adolescents aged 13-17 from Araihazar, Bangladesh. Cognitive function was assessed using the computer-based Behavioral Assessment and Research System (BARS), focusing attention, memory, and executive function, and blood NM levels (Fe, Se, Zn, Mg, and Cu) were measured. Associations between individual minerals, NM composite scores, and cognition were analyzed using multiple linear regressions. Results: This study included 47 boys and 58 girls with an average age of 15 years. Fe levels were correlated with Continuous Performance Test (CPT) latency (r = -0.42, p < 0.05) and Se levels correlated with Match-to-Sample (MTS) correct count (r = 0.32, p < 0.01). Linear regressions showed that Se was associated with MTS correct count (b = 0.02, 95%CI: 0.01, -0.04), reflecting visual memory, and Fe was associated with CPT latency (b = -0.68, 95%CI: -1.11, -0.26), reflecting improved attention. The same BARS measures were also significantly associated with the 3-NM composite score. Conclusions: Our findings suggest that NM, particularly Fe, Se, and NM mixtures, could play a crucial role in brain development and neurocognitive function during adolescence. Further studies will help design national public health policies and strategies to address and mitigate brain health deficiencies among adolescents.

Objectives: While some metals have been reported as carcinogens or potential carcinogens, only few modern-standard datasets including a large number of elements are available. The present analysis established a first trace elements spectrum by relating the concentration of metals and trace elements in the serum of sarcoma patients with survival data., Methods: Patients with sarcoma and controls were retrospectively selected from the International Sarcoma Kindred Study database (ISKS). As part of the ISKS study, blood samples were prospectively collected at the Leon Bérard Cancer Center from February 2012 to July 2019. Stable specimens and copper isotopes ( 65 Cu/ 63 Cu) were analyzed using Triple Quadrupole Inductively Coupled Plasma Mass Spectrometer (ICP-MS) and the Multicollector MC-ICP-MS Nu Plasma HR 500. Wilcoxon rank sum test, log-rank test, and multivariate Cox regression models were used for statistics., Results: In total, 151 patients and 59 healthy controls were included. At the time of blood sample collection, 62% of patients had locally advanced or metastatic disease. Copper (Cu), copper/zinc (Cu/Zn) and potassium/rubidium (K/Rb) ratio were significantly higher in patients compared to controls and were also significantly higher in patients with advanced compared to early-stage sarcoma. Whereas S and Se were significantly correlated in patients, no correlation was observed in controls. Importantly, levels of K, Rb, Se, Fe, P, Si, S, δ 65 Cu, Cu, S/Se and Cu/Zn ratio were independently associated with overall survival., Conclusions: These results depict the metallomic spectrum in sarcoma and highlight substantial variation associated with survival, enhancing our understanding of sarcoma's biology., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: A dual filtration-based method for determination of serum labile bound copper (LBC) and LBC fraction (LBC/total copper) was developed. Reduced total copper, elevated LBC, and elevated LBC fraction have been reported in Wilson disease (WD)., Methods: To evaluate the diagnostic performance of these markers, samples were obtained from 21 WD treatment-naïve (WD-TN, no WD treatment or <28 days of treatment) patients, 46 WD standard-of-care-treated (WD-SOC) patients, along with 246 patients representing other potential disorders of copper status. These were then compared to 213 reference interval population patients., Results: Receiver operating characteristic curves for the reference population vs WD-TN yielded areas under the curve for total copper, LBC, and LBC fraction, of 0.99, 0.81, and 0.98, respectively. Using Youden cutoffs, sensitivity/specificity for WD-TN was 95%/97% for total copper, 71%/85% for LBC, and 95%/94% for LBC fraction. LBC values, but not total copper and LBC fraction, differed substantially between WD-TN and WD-SOC cohorts.We propose a dual model wherein total copper and LBC fraction results must agree to be classified as a "positive" or "negative" result for WD. This correctly classified 19/21 WD-TN patients as positive, and 194/213 reference interval patients as negative. The remaining "indeterminate" patients (representing approximately 9% of the reference and the WD-TN populations) exhibited conflicting total copper and LBC fraction results. When indeterminate results are excluded, this model exhibited apparent 100% sensitivity/specificity., Conclusions: Agreement of total serum copper and LBC fraction classification may constitute an effective "rule-in" and "rule-out" assessment for WD-TN patients., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

It is unclear whether blood concentrations of copper (Cu), magnesium (Mg), and calcium (Ca) influence skeletal muscle mass and strength in children. We aimed to explore the associations between plasma Cu, Mg, and Ca and skeletal muscle indicators in Chinese children. A total of 452 children aged 6 to 9 years old were recruited for this cross-sectional study. Whole body lean soft tissue mass (WLSTM), trunk lean soft tissue mass (TLSTM), and appendicular skeletal muscle mass (ASMM) were measured using dual-energy X-ray absorptiometry. Parameters of these indicators divided by Height 2 (Ht 2 ) and Weight (Wt) at the corresponding sites were calculated. Handgrip strength was also measured. Parameters of skeletal muscle indicators and handgrip strength that were below the sex-specific 20th percentile were considered low levels. Plasma concentrations of Cu, Mg, and Ca were measured using ICP-MS. After adjusting for several potential covariates, among the total subjects, for every one standard deviation increase in Cu concentrations, there was a 0.939% decrease in WLSTM/Wt, a 0.415% decrease in TLSTM/Wt, and a 0.47% decrease in ASMM/Wt. For every one standard deviation increase in Cu concentrations, there was a higher odd (OR: 1.36, 95%CI 1.06, 1.75) of low WLSTM/Wt, TLSTM/Wt (OR: 1.33, 95%CI 1.03, 1.71), ASMM/Ht 2 (OR: 1.32, 95%CI 1.02, 1.69), as well as ASMM/Wt (OR: 1.56, 95%CI 1.23, 1.99). No significant associations were found between Mg, Ca, and most skeletal muscle indicators. Higher plasma Cu concentrations were adversely associated with skeletal muscle indicators at multiple sites in Chinese children., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Context: Copper deficiency myelopathy (CDM) is a rare disease that can present with spastic quadriparesis and sensory ataxia. As a result, it can precisely mimic cervical spondylitic myelopathy (CSM). Copper deficiency may be seen following gastric bypass surgery, malabsorption syndromes such as celiac disease, and with excessive exogenous zinc intake. We present a systematic review of the literature for CDM and an illustrative case., Purpose: Provide a systematic review of CDM to highlight the importance of recognizing the consideration of CDM in patients presenting to a spine surgeon with myelopathy that progress despite adequate surgical decompression, or myelopathy concomitant with cytopenia, thus requiring further workup., Study Design/setting: Retrospective medical record review and systematic review of the literature., Patient Sample: PubMed and Ovid-Embase database search was conducted in July 2022., Outcome Measures: Self-reported measures include PRISMA flow diagram for retrospective review; Physiological measures include retrospective review of MRI imaging of cervical spine; alternate demographic and laboratory value data extracted via literature review., Methods: A PubMed and Ovid-Embase database search was conducted in July 2022 searching for "copper deficiency myelopathy (MeSH)" from 2000 to 2022 via PRISMA guidelines. Following title and abstract review, the following data was extracted from full text: age, sex, etiology, hematological values upon presentation (mean corpuscular volume, white blood count, platelet count, and hemoglobin level), metal serum studies (serum copper, ceruloplasmin, and zinc), 24-hour collection of copper and zinc, and distinct radiographic findings on MRI., Results: A total of 116 studies were included in this review which contained 198 cases of copper deficiency myelopathy. The mean age was 53.57±14.14 years, with the majority being females (63.8%). The most common etiology was prior gastric surgery (n=55, 36.2 %) followed by excessive zinc consumption from the use of zinc denture cream (n=39, 19.9%). The mean serum copper was 15.67±17.84 (normal=80.0-155.0) mcg/dL and mean ceruloplasmin was 6.43±5.25 (normal=16-45) mg/dL. In spite of appropriate treatment with copper supplementation, only 47 cases (24%) reported improvement in neurological status, and only 10 (5.1%) recovered to baseline. A hyperintense T2 signal abnormality resembling an inverted "v" in the dorsal columns was the most common radiographic abnormality., Conclusion: Pertinent risk factors for copper deficiency myelopathy include prior upper gastrointestinal surgery, zinc excess, and malabsorption. Characteristic laboratory and imaging findings include cytopenia, low serum copper and ceruloplasmin, and distinct inverted "v" T2 signal hyperintensity in the dorsal columns. The neurologic deterioration with copper deficiency will progress in spite of decompressive surgery, and can be devastating and irreversible even with copper supplementation, reinforcing the importance of early detection. We thus recommend patients with myelopathy presenting with a history of gastric bypass, malabsorption syndromes, excessive zinc exposure, cytopenia, or imaging resembling an inverted "v" shaped hyperintense T2 MRI signal in the dorsal columns, should first undergo blood tests for copper, ceruloplasmin, and B12 levels prior to surgical consideration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Illicit drug use has become a global issue, posing significant health, socioeconomic, and cultural risks. The study examined essential trace metals: selenium, zinc, and copper in blood concentrations, as well as in serum and scalp hair samples, from 240 male drug-abuse subjects/patients aged 18-45, categorized into three age groups. The study compared 45 healthy subjects of the same age group using an acid digestion method supported by a microwave oven during sample preparation. The technique of atomic absorption spectrometry was employed to identify essential and toxic elements, utilizing certified reference materials for accuracy. According to a recent study, plasma zinc and selenium concentrations in drug abusers are lower than those in referent subjects, potentially increasing vulnerability to infection due to poor nutritional status or other contaminants., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This phase 1/2 study aimed to evaluate the safety and preliminary efficacy of combining disulfiram and copper (DSF/Cu) with radiation therapy (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM)., Methods and Materials: Patients received standard RT and TMZ with DSF (250-375 mg/d) and Cu, followed by adjuvant TMZ plus DSF (500 mg/d) and Cu. Pharmacokinetic analyses determined drug concentrations in plasma and tumors using high-performance liquid chromatography-mass spectrometry., Results: Thirty-three patients, with a median follow-up of 26.0 months, were treated, including 12 IDH-mutant, 9 NF1-mutant, 3 BRAF-mutant, and 9 other IDH-wild-type cases. In the phase 1 arm, 18 patients were treated; dose-limiting toxicity probabilities were 10% (95% CI, 3%-29%) at 250 mg/d and 21% (95% CI, 7%-42%) at 375 mg/d. The phase 2 arm treated 15 additional patients at 250 mg/d. No significant difference in overall survival or progression-free survival was noted between IDH- and NF1-mutant cohorts compared with institutional counterparts treated without DSF/Cu. However, extended remission occurred in 3 BRAF-mutant patients. Diethyl-dithiocarbamate-copper, the proposed active metabolite of DSF/Cu, was detected in plasma but not in tumors., Conclusions: The maximum tolerated dose of DSF with RT and TMZ is 375 mg/d. DSF/Cu showed limited clinical efficacy for most patients. However, promising efficacy was observed in BRAF-mutant GBM, warranting further investigation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Copper is an essential trace element obtained from food. There is a paucity of observational or prospective studies that have investigated the relationship between copper and melanoma risk. Copper serves as a cofactor for pivotal enzymes involved in mitochondrial respiration, antioxidant defense, and neurotransmitter synthesis. Undoubtedly, copper plays an indispensable role in the initiation and progression of tumors, particularly melanoma; however, further investigations are warranted to elucidate the underlying mechanisms linking copper and melanoma risk. Given the availability of dietary copper and serum copper data in the NHANES database, we conducted an investigation into the association between dietary copper intake and serum copper levels with melanoma risk. We enrolled 26,401 individuals with dietary copper data in the 2007-2018 NHANES database. To mitigate confounding variables, a propensity score matching (PSM) was performed. To assess the association between dietary copper intake and melanoma risk, we employed a multivariate logistic regression analysis before and after PSM. The restricted cubic spline analysis was utilized to determine whether there is a non-linear relationship between dietary copper intake and melanoma risk, with subgroup analysis conducted to determine beneficiaries. Then, those with blood copper data from the enrolled population with dietary copper intake were screened out, and subsequently, multivariate logistic regression models were subsequently constructed to investigate the association between serum copper levels and melanoma risk after PSM. Mendelian analysis was further utilized to validate the results of the NHANES database using serum copper as the exposure factor and melanoma as the outcome variable. The study found that melanoma risk was associated with dietary copper intake before and after PSM, demonstrated by multiple logistic regression. The relationship between dietary copper intake and melanoma risk was non-linear, with a reduced risk observed above approximately 2.5 mg/day, as shown by the RCS. The evidence suggests that an increased intake of copper is linked to a decreased risk of melanoma. To clarify the mechanism behind the increased risk of melanoma due to higher dietary copper intake, we analyzed the population data from the NHANES database on serum copper and dietary copper intake. Our results indicated that there is no causal relationship between serum copper and melanoma risk. Mendelian randomization analysis of multi-database data sources confirmed the conclusion of the NHANES database analysis. Dietary copper is a protective factor against melanoma, and serum copper or blood copper is not associated with melanoma risk. This suggests that serum or blood copper is not responsible for the protective effect of dietary copper intake on melanoma risk, and the mechanisms need to be further investigated., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The role of copper in the etiology of metabolic syndrome (MetS) is uncertain. We evaluated associations of plasma copper concentrations with MetS and its components in a cross-sectional study of 198 children ages 7-12 years and 378 adult parents from eight Mesoamerican countries. In children, the outcome was a metabolic risk score based on waist circumference, insulin resistance, mean arterial pressure (MAP), and blood lipids. In adults, we defined MetS per Adult Treatment Panel III criteria. Plasma copper was not significantly related to MetS in children or adults; however, children with copper above the median had a MAP score 0.04 (95% CI, 0.002, 0.08; P = 0.04) adjusted units higher and a HDL-cholesterol score 0.07 (95% CI, - 0.13, - 0.003; P = 0.04) adjusted units lower than those with lower copper concentrations. In adults, copper was positively related to abdominal obesity. Longitudinal studies to confirm the deleterious role of copper on MetS components are warranted., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Various vitamins and minerals have been implicated in the aetiology of depression., Objective: To estimate the effects of micronutrient exposures on major depressive disorder (MDD) and recurrent depression (rMDD) using Mendelian randomisation (MR), a method using genetic data to estimate causal effects given certain assumptions., Methods: We undertook a comprehensive bidirectional MR study of multiple micronutrient exposures on MDD and rMDD. Summary statistics were obtained from the Psychiatric Genomics Consortium (PGC) genome-wide association studies (GWASs) of MDD (cases = 116,209; controls = 314,566) and rMDD (cases = 17,451; controls = 62,482)., Results: None of the micronutrients with available genetic instruments were strongly associated with MDD or rMDD using traditional MR methods. However, using methods to increase analytical power by accounting for genetically correlated variants (e.g., cIVW) highlighted five micronutrients with possible causal effects. Point estimates for rMDD were the largest magnitude, with three micronutrients suggestive of a protective effect: serum iron (OR cIVW 0.90 per SD increase; 95% CI 0.85-0.95; p = 0.0003); erythrocyte copper (OR cIVW 0.97; 95% CI 0.95-0.99; p = 0.0004); and 25(OH) vitamin D (OR cIVW 0.81; 0.66-0.99; p = 0.04). Apparent adverse effects of increased selenium on the risk of MDD (OR cIVW 1.03; 95% CI 1.02-1.05; p = 0.0003) and rMDD (OR cIVW 1.08; 95% CI 1.00-1.08; p = 0.06), and serum magnesium on rMDD (OR cIVW 1.21; 1.01-1.44; p = 0.04); were less consistent between methods and may be driven by pleiotropy., Conclusions: Our results suggest weak evidence for a protective effect of iron, copper and 25(OH)D on major depressive outcomes, with mixed evidence for selenium and magnesium. There was no evidence to support a causal effect of any other micronutrients on MDD or rMDD, although genetic instruments were lacking, with insufficient power to detect small but important effects. Future micronutrient supplementation trials should ensure ample statistical power given modest causal effect estimates and consider potential risks of supplementation, as some micronutrient effect estimates suggested potential harm in excess.

Objective: Lung adenocarcinoma (LA), the most prevalent type of lung cancer, is associated with a high mortality rate, especially among patients with cancer previously infected with coronavirus disease (COVID-19). Therefore, this study aimed to explore the mechanisms by which COVID-19 exacerbates LA progression in a clinical setting., Methods: The experiment involved collecting serum samples from three groups: a healthy control group (Con, n = 20), a lung adenocarcinoma group (LA, n = 30), and a group of lung adenocarcinoma patients with first-time COVID-19 infection (C-LA, n = 58). Metabolites were analyzed using liquid chromatography-mass spectrometry, and differentially expressed metabolites were identified through bioinformatics analysis. The concentrations of glutathione (GSH), reactive oxygen species (ROS), and copper ions (Cu 2+ ) in the serum of patients in the Con and C-LA groups were measured. Mitochondrial morphological changes in monocytes and lymphocytes were observed using electron microscopy., Results: Metabolomic analysis revealed 142 distinct metabolites, among which glutamine (Gln) expression was significantly decreased in the C-LA group. Compared to the Con group, the C-LA group showed a significant decrease in GSH and a notable increase in ROS and Cu 2+ . Further research revealed that the mitochondria of monocytes and lymphocytes in the C-LA group exhibited corresponding alterations indicative of cuproptosis., Conclusions: SARS-CoV-2 infection may reduce Gln levels, leading to reduced GSH levels, copper overload, and increased death of immune cells, which may further exacerbate rapid tumor development. Thus, glutamine regulation plays an important role in LA progression in patients with COVID-19 and represents a potential therapeutic target., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the relationship and potential pathways between metal(loid) exposure and the risk of polycystic ovary syndrome (PCOS) in women of childbearing age., Methods: This case-control study included 200 patients with PCOS (cases) and 896 non-PCOS controls with the age of 25-37 years. The concentrations of 29 metal(loid)s in the follicular fluid (FF) and clinical indicators in the serum were measured in all participants. Logistic regression analysis and mediation analysis were conducted to evaluate the associations between metal(loid) exposure and PCOS risk and investigate the possible roles of clinical indicators, respectively., Results: Logistic regression analysis revealed an association between high copper levels in FF and increased PCOS risk (highest vs. lowest quartile: adjusted odds ratio = 2.94, 95% confidence interval: 1.83-4.72). A high luteinizing hormone/follicle-stimulating hormone ratio and elevated levels of testosterone and anti-Müllerian hormone (AMH) were strongly associated with increased PCOS risk induced by high copper exposure. The mediation analysis indicated a mediating effect of AMH in the association between copper exposure and PCOS risk., Conclusion: Copper may affect PCOS risk through the hypothalamic-pituitary-ovarian axis, mediated by AMH. Copper exposure and internal AMH levels are important indicators for early warning of PCOS development., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Background: Vitamin D deficiency is prevalent worldwide and associated with worse outcomes in various lung diseases. This study examines the association between vitamin D deficiency and pulmonary function in healthy young adults., Methods: This prospective cohort study (2017-2019) explored the impact of vitamin D deficiency on pulmonary function in a community-based young adult population. Pulmonary function was assessed via spirometry, with serum 25-hydroxyvitamin D [25(OH)D] and urinary copper levels quantified. Multivariate regression was used to estimate the relationship between vitamin D levels and lung function, with mediation analysis evaluating copper's role., Results: The study included 1034 participants, average age 33.45 years, 41.93 % male. The median 25(OH)D level was 19.20 ng/mL (Interquartile Range: 13.48-24.90 ng/mL). Over half (54.74 %) had 25(OH)D levels below 20 ng/mL. Higher 25(OH)D levels were associated with better forced vital capacity (FVC) and forced expiratory volume in one second (FEV₁). Trends suggested subgroup differences, but these were not statistically significant, indicating a consistent effect of 25(OH)D on pulmonary function across groups. SEM analysis suggested urinary copper as a mediator between 25(OH)D levels and FVC., Conclusion: Vitamin D deficiency is significantly associated with reduced pulmonary function in young adults in Taiwan., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Vitiligo is a dermatological disease characterized by loss of melanocytes, causing non-scaly white macules on the skin. Zinc, copper, and selenium are important micronutrients that play a role in the normal functioning of the body and have been found to potentially aid in vitiligo treatment, although the relationship between their serum levels and vitiligo is not yet fully understood. This is a systematic review aimed at assessing the levels of serum zinc, copper, and selenium and their association with vitiligo. This review was performed following the Preferred Reporting Items of the systematic Review and Meta-Analysis (PRISMA) checklist and Cochrane guidelines. A comprehensive literature search was conducted on PubMed, Google Scholar and 41 studies published between 1970 and 2022 including 3353 vitiligo cases and 10,638 controls were included in the meta-analysis conducted from August 2022 till September 2023. The quality of the studies was assessed using the National Heart Lung and Blood Institute Study Quality Assessment tool, and the risk of bias was represented using the RobVis tool. The statistical analysis was performed using Review Manager (RevMan) Version 5.4. This meta-analysis indicate a significant decline in serum zinc levels (Z = 4.97; P < 0.0001; SMD = - 0.86; 95% CI - 1.19 to - 0.52) in vitiligo group with high statistical heterogeneity (Tau2 = 0.74; Chi2 = 513.95, d.f. = 26 [P < 0.00001]; I2 = 95%). Similarly for serum copper levels there was decline (Z = 2.43; P < 0.0001; SMD = - 0.50; 95% confidence interval [CI] - 0.91 to - 0.10) in vitiligo group and high statistical heterogeneity (Tau2 = 0.92; Chi2 = 475.10, d.f. = 22 [P < 0.00001]; I2 = 95%). On the other hand, there was a increase of serum selenium levels in the vitiligo group (Z = 0.56; P < 0.0001; SMD = 0.23; 95% confidence interval [CI], 0.58 to 1.04) and the results reveals high statistical heterogeneity among studies (Tau2 = 1.93; Chi2 = 406.44, d.f. = 11 [P < 0.00001]; I2 = 97%) in vitiligo patients compared to healthy controls. Publication bias was not found for the studies analysed. This study analyses the association of serum micronutrient levels and vitiligo among patients and controls from published research along with sub-group analysis specific to Asian populations using a meta-analysis. Low serum levels of Zinc and copper and high selenium levels are associated with Vitiligo., (© 2024. The Author(s).)

Objective: The objective of this study is to analyze oxidative stress markers Total Oxidant Status (TOS) and total Antioxidant Status (TAS), assess antioxidant levels (vitamin C, E), and evaluate co-factor element profiles zinc (Zn), copper (Cu), iron (Fe) in the serum of Iraqi gastric cancer patients. By elucidating these relationships, the research aims to enhance knowledge on oxidative stress, dietary factors, and potential therapeutic approaches for managing nutritional imbalances in this cohort., Methods: The study included 60 gastric cancer patients and 60 matched controls. Blood samples were collected and serum was extracted for analysis of TOS, TAS, Vitamin C, Vitamin E, copper, zinc, and iron levels. Measurements were conducted using spectrophotometry and ELISA kits from various companies. Statistical analysis was performed with IBM SPSS 25.0, presenting results as means ± SD, and differences between groups were assessed via independent samples t-test at p < 0.05 and p ≤ 0.01., Results: The study results indicated statistically significant differences between gastric cancer patients and controls in various biomarkers, with all comparisons showing p-values less than 0.001. This suggests strong evidence for the observed differences between the two groups in (TOS), (TAS), vitamins C and E, Cu, Zn, and  Fe levels. These relationships underscore the intricate connections among biomarkers in gastric cancer pathophysiology., Conclusion: The study underscores the intricate relationship between oxidative stress, antioxidant depletion, and micronutrient imbalances in gastric cancer. These findings offer valuable insights into the disease's pathophysiology, indicating potential diagnostic biomarkers. Further research is warranted to unravel underlying mechanisms and explore clinical applications for early gastric cancer diagnosis.

Objective: To investigate the value of relative exchangeable copper (REC) in diagnosing Wilson's disease (WD) and to determine its significance in the differentiation of Traditional Chinese Medicine (TCM) syndrome., Methods: A total of 78 patients with WD were recruited on the same day of the medical visit, and among them, 32 were suffering from non-WD (N-WD) and 37 were heterozygous ATP7B carriers (HC) enrolled as controls. Molecular genetic testing was performed for diagnosing WD and HC. Additionally, REC levels in different TCM syndromes were investigated. The correlation between REC and serum ceruloplasmin (Cp), serum copper oxidase (CO), and 24-h urinary copper was analyzed using the Global Assessment Scale and Unified Wilson's Disease Rating Scale and the significance of REC in WD diagnosis was investigated. Resting-state functional magnetic resonance imaging was used to assess the clinical symptoms of WD and analyze its severity in different TCM syndromes., Results: REC determination helped in significantly distinguishing patients with N-WD or HC from those with WD with a cut-off of 21.15%. Furthermore, the comparative analysis of REC ratios among different TCM syndromes showed markedly high REC levels in the dampness-heat internal accumulation syndrome group. Additionally, the seed-based functional connectivity value from the putamen to the cerebellum was significantly correlated with TCM syndromes., Conclusion: REC level is a high-quality biomarker for diagnosing WD that effectively reflects disease severity and plays an essential role in deciding on treatment strategies and prognosis. Furthermore, REC levels are closely related to TCM syndromes in WD; thus, it is a potential objective quantitative indicator for distinguishing TCM syndromes in WD.

Purpose: Some studies showed the possible role of copper intake on bone mineral density (BMD) in adults or the elderly, but the association remained uncertain in children and adolescents. Our research explored the association between copper intake and BMD in individuals aged 8-19 years from the National Health and Nutrition Examination Survey (NHANES) 2011-2016., Methods: In the present study, 6,965 individuals aged 8-19 (mean age 13.18 ± 3.38 years) were enrolled from the NHANES 2011-2016. Copper intake was evaluated by averaging two 24-hour copper dietary intake recalls. Multivariate linear regression analyses were used to explore the association between copper intake and total BMD, subtotal BMD, and total spine BMD in children and adolescents. Stratified analyses and interaction tests were performed by age, gender, and race., Results: Participants of the higher quartile of copper intake were more likely to be older, men, Non-Hispanic White, and Other Hispanic. They have higher values of poverty income ratio (PIR), serum phosphorus, blood urea nitrogen, serum vitamin D, and BMD and lower values of body mass index (BMI), cholesterol, total protein, and serum cotinine. In the fully adjusted model, we found positive associations between copper intake and total BMD (β = 0.013, 95CI: 0.006, 0.019)), subtotal BMD (β = 0.020, 95CI: 0.015, 0.024), and total spine BMD (β = 0.014, 95CI: 0.009, 0.019). Stratified analyses showed that the association was stronger in men, individuals aged 14-19, Non-Hispanic White, and Other Hispanic., Conclusions: Our study suggests that copper intake is positively associated with BMD in U.S. children and adolescents. The study emphasizes the role of copper intake on bone health in the early stages of life. However, more investigations are needed to verify our findings and their underlying mechanisms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Quantitative susceptibility mapping (QSM) is a post-processing technique that creates brain susceptibility maps reflecting metal burden through tissue magnetic susceptibility. We assessed topographic differences in magnetic susceptibility between participants with and without Wilson's disease (WD), correlating these findings with clinical severity, brain volume, and biofluid copper and iron indices., Methods: A total of 43 patients with WD and 20 unaffected controls, were recruited. QSM images were derived from a 3T MRI scanner. Clinical severity was defined using the minimal Unified Wilson's Disease Rating Scale (M-UWDRS) and Montreal Cognitive Assessment scoring. Differences in magnetic susceptibilities between groups were evaluated using general linear regression models, adjusting for age and sex. Correlations between the susceptibilities and clinical scores were analyzed using Spearman's method., Results: In age- and sex-adjusted analyses, magnetic susceptibility values were increased in WD patients compared with controls, including caudate nucleus, putamen, globus pallidus, and substantia nigra (all p < 0.01). Putaminal susceptibility was greater with an initial neuropsychiatric presentation (n = 25) than with initial hepatic dysfunction (n = 18; p = 0.04). Susceptibility changes correlated negatively with regional brain volume in almost all topographic regions. Serum ferritin, but not serum copper or ceruloplasmin, correlated positively with magnetic susceptibility level in the caudate nucleus (p = 0.04), putamen (p = 0.04) and the hippocampus (p = 0.03). The dominance of magnetic susceptibility in cortical over subcortical regions correlated with M-UWDRS scores (p < 0.01)., Conclusion: The magnetic susceptibility changes could serve as a surrogate marker for patients with WD., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Micronutrient deficiencies associated with malnutrition in patients with inflammatory bowel disease (IBD) can lead to complications including anemia, coagulopathy, poor wound healing, and colorectal cancer. This study aimed to investigate micronutrient deficiencies (copper, vitamins A, B 9 , E, and K) in IBD patients and highlight associated symptoms to aid in the recognition of micronutrient deficiencies., Methods: A retrospective electronic chart review was performed on adults diagnosed with Crohn's disease or ulcerative colitis hospitalized at a tertiary care center for IBD flare between January 2013 and June 2017. Patients with serum or whole blood micronutrient levels were included. Pregnant and incarcerated patients were excluded., Results: A total of 611 IBD patients (440 Crohn's disease, 171 ulcerative colitis) met the inclusion criteria. Micronutrients were assessed in a subset of IBD patients (copper: 12.3%, A: 10.1%, B 9  : 95.9%, E: 10.3%, and K: 4.6%). Overall, 10.1% of patients had micronutrient deficiencies. The proportion of patients with copper, A, B 9 , E, and K deficiencies were 25.4, 53.3, 1.9, 23.7, and 29.4% for Crohn's disease and 50, 52.9, 1.2, 43.8, and 18.2% for ulcerative colitis, respectively. The most common symptoms or historical features associated with micronutrient deficiency were anemia (copper, B 9 ), muscle weakness (copper, E) thrombocytopenia, fatigue (copper, B 9 ), diarrhea (B 9 ), dry skin, hyperkeratosis, pruritus, significant weight loss, elevated C-reactive protein (A), bleeding, and osteoporosis (K)., Conclusion: Micronutrient deficiencies are common in IBD patients, yet they are not routinely assessed. Copper, vitamins A, E, and K deficiencies are particularly underrecognized. Associated historical features should raise suspicion and prompt assessment and treatment., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: Wilson's disease (WD) in children and adolescents is predominantly asymptomatic or oligo-symptomatic. The symptoms are nonspecific and difficult to distinguish from other hepatic or neuropsychiatric disorders. In this study, we present the experience of a pediatric referral center for WD diagnosis and treatment., Patients and Methods: We retrospectively analyzed clinical and laboratory data from 99 patients with WD of Sardinian origin, including physical examination, laboratory biochemical testing, liver biopsy, and genetic analysis., Results: Patients were prevalently oligo-symptomatic or asymptomatic. The median age of diagnosis was 8.78 years. Ceruloplasmin values were lower than normal values in all analyzed patients. Twenty-four-hour urinary copper levels were higher than 40 μg/24-h in 92/96 patients. In all analyzed patients with the exception of one, liver copper was higher than 250 μg/g of dry weight but all had >75 μg/g of dry weight. Statistical analysis showed correlation between the age at diagnosis, serum copper, and 24-h urinary copper. Correlation was also found between serum copper and 24-h urinary copper. Molecular analysis of ATP7B gene allowed complete characterization in all the analyzed patients., Conclusion: A high index of clinical suspicion and biochemical tests including liver tests, serum ceruloplasmin, and basal 24-h urinary copper excretion and genotype determination are key to WD diagnosis. The long experience that a referral center for WD possesses is an important factor in making WD diagnosis a more accurate process. Studies in animal models on WD could be used as a guide to further investigate the molecular mechanisms that regulate copper metabolism and influence the natural history of WD., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Aims: Previous studies have investigated the relationship between heart failure (HF) and levels of zinc and copper, but conflicting results have been reported. This meta-analysis aims to clarify the role of zinc and copper in HF progression by examining the associations between HF and concentrations of these minerals., Methods and Results: We utilized STATA 12.0 software to calculate the standard mean difference (SMD) and 95% confidence interval (CI) for serum zinc and copper levels in patients with HF compared with healthy controls (HCs). The meta-analysis indicated a lower serum zinc level in patients with HF compared with HCs, using a random effects model (SMD = -0.77; 95% CI: -1.01, -0.54; I 2  = 61.9%, the P-value for Q test = 0.002). Additionally, the meta-analysis showed an increased serum copper level in patients with HF compared with HCs, using a random effects model (SMD = 0.66; 95% CI: 0.09, 1.23; I 2  = 93.8%, the P-value for Q test < 0.001). Meta-regression analysis indicated that publication year, age, and gender were not responsible for heterogeneity across studies., Conclusions: This meta-analysis demonstrates that patients with HF have lower serum zinc and higher copper concentrations compared with healthy subjects. However, the potential of zinc supplementation as a therapy for HF should be approached with caution. The heterogeneity among the included studies was found to be high. It is recommended that further well-designed large sample studies be conducted to validate these findings., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The association between the serum essential metal elements (magnesium, iron, copper, zinc, and calcium) and thyroid nodules is still inconsistent. The current study aims to investigate the relationship of metal elements with thyroid nodules and their malignant tendency. A total of 6480 Chinese euthyroid adults were included in our study. We collect basic information through questionnaires and medical checkups. We diagnose thyroid nodules by ultrasound and detect serum trace metal concentrations by using an automatic biochemical analyzer. Binary and multinomial logistic regressions were used to investigate the associations. As a result, we found that serum copper concentrations were positively associated with thyroid nodules in the second, third, and fourth quartiles, compared to the first quartile (P = 0.024, P = 0.016, P = 0.032) in women and P for trend is 0.038. There is a significant sex-specific association between copper concentrations and thyroid nodules (P for interaction = 0.009). The results of the multinomial logistic regression analyses indicate high serum calcium and magnesium concentrations emerged as consistent risk factors for thyroid nodules in both genders, whereas low zinc was a sex-specific factor. We also observed significant sex interactions in the relationships of magnesium (P for interaction = 0.043) with thyroid nodules with malignant tendency among participants with thyroid nodules. In conclusion, our study suggests that gender is an important factor when studying the association between serum metals and thyroid nodules. The imbalance of selected metal elements (calcium, copper, zinc, and magnesium) may relate to thyroid nodules and their malignant tendency, and future prospective studies are needed to further confirm the associations., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Copper functions as an essential micronutrient influencing diverse metabolic processes in mammals, encompassing oxidative stress responses, lipid metabolism, and participation in enzymatic reactions. However, the impact of serum copper on non-alcoholic fatty liver disease (NAFLD) remains controversial. Our aim was to explore the precise correlation between serum copper and NAFLD in a large-scale population-based study. A total of 1377 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 were included in our study. The diagnosis of NAFLD and its progress to advanced liver fibrosis were based on serological indexes. One-way ANOVA, Kruskal-Wallis H test, and Chi-square test were used to access variations between quartiles groups of serum copper. We conducted multivariate-adjusted logistic regression models and subgroup analyses to investigate the association between serum copper and NAFLD, along with several metabolic diseases. Among the 1377 participants, 661 were diagnosed with NAFLD, and 141 of whom were classified into advanced liver fibrosis. Higher serum copper levels (≥ 21.00 μmol/L) were associated with an increased incidence of NAFLD (odds ratio (OR) = 2.07 (1.38-3.10), p < 0.001), as well as advanced liver fibrosis (OR = 2.40 (1.17-5.19), p = 0.025). Moreover, serum copper exhibited a positive correlation with hypertension, overweight, and abdominal obesity, all of which have been identified as risk factors of NAFLD. Additionally, female participants, under the age of 60, and with a higher body mass index (BMI) (> 24.9 kg/m 2 ) emerged as the most vulnerable subgroup concerning the relationship between serum copper and NAFLD. In the U.S. population, a notable association has been identified, linking elevated serum copper to an increased susceptibility for both the onset and progression of NAFLD, along with several metabolic disorders associated with NAFLD. The adverse effects of excess copper warrant attention in the context of public health considerations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Trace elements (TEs) play a crucial role in metabolism through their biochemical and catalytic effects, and alterations in their levels have been observed in various malignancies. Given that chemotherapy is a common treatment for cancer, it is important to understand how it may affect the levels of TEs in the body. By investigating changes in TEs levels before and after chemotherapy, this study aims to provide insights into the potential impact of chemotherapy on TEs levels in cancer patients. In the present study, analyses were performed on the serum level of some elements including Zn, Cu, Cd, and Se in 69 patients with leukemia, lymphoma, prostate and breast cancers before and after three courses of chemotherapy. The serum TEs were measured by atomic absorption spectroscopy. The serum Zn levels in patients with leukemia, lymphoma, and breast cancer significantly decreased after chemotherapy (P < 0.05). Significant reductions were also observed in the post-chemotherapy serum level of Cd in patients with prostate (P = 0.020) and breast cancer (P = 0.013). Moreover, the Se serum level significantly decreased after chemotherapy compared to before it in the breast cancer patients (P < 0.001). In contrast, the serum level of Cu was higher before than after chemotherapy in all the patients, but no significant difference was found (P > 0.05). The results show that chemotherapy can alter the level of TEs. The assessment of TEs in cancer patients may provide information about the side effects of chemotherapy as well as the use of appropriate strategies to better manage the clinical conditions of patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study was to assess the individual effects of serum copper levels and environmental tobacco exposure and their joint effects on the risk of overweight and obesity among children and adolescents of 6 to 19 year olds. We analyzed cross-sectional data from 1849 children and adolescents participating in the National Health and Nutrition Examination Survey (NHANES) collected between 2011 and 2016. Environmental tobacco exposure was determined by cotinine levels. The serum copper level was divided into < median group and ≥ median groups according to the median of 109.81 µg/dL. The outcome was overweight/obese in children and adolescents. Weighted multinomial multivariate logistic regression models were used to assess the association of serum copper and cotinine levels, with the risk of overweight/obesity, and the joint effects on the risk of overweight and obesity among children and adolescents. The subgroup analyses based on age, gender, and household smoking status were conducted. Among 1849 children and adolescents, 332 children and adolescents had overweight BMI, and 450 children and adolescents had obese BMI. Higher serum copper levels were associated with the risk of obesity in children and adolescents (odds ratio (OR) 2.96, 95% confidence interval (CI) 1.39-6.31, P = 0.006). A positive association between increasing levels of cotinine levels and the risk of overweight (OR 1.83, 95% CI 1.16-2.87, P = 0.010) and obesity (OR 2.56, 95% CI 1.03-6.40, P = 0.044) in children and adolescents was observed. A remarkable association was found between higher serum copper in combination with higher cotinine levels and the risk of overweight (OR 3.23, 95% CI 1.19-8.83, P = 0.023) and obesity (OR 8.76, 95% CI 2.14-35.87, P = 0.003) in children and adolescents. The subgroup analyses revealed positive associations between high serum copper levels in combination with high cotinine levels and overweight and obesity in children and adolescents aged ≥ 12 years, of female sex, and without smoking family members. There may exist a joint effect of serum copper levels and environmental tobacco exposure on overweight/obesity among children and adolescents. These findings offer an insight that early weight control and reduction of tobacco exposure and the detection of serum copper levels may be important in reducing the risk of obesity in children., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Wilson disease (WD) is a rare genetic disorder characterized by copper overload, primarily affecting the liver and brain, and the organ damage is believed to be caused by non-ceruloplasmin-bound copper (NCC). Accurate and early diagnosis is important for prognosis. Recently, a method for the measurement of NCC, exchangeable serum copper (CuEXC), was developed and shown to be a promising marker of WD, especially as the fraction of total copper, relative exchangeable copper (REC). This study aimed to validate the CuEXC extraction method and establish reference intervals for CuEXC and REC, as well as to examine short- and long-term stability of CuEXC in serum samples. The adult reference interval for CuEXC was 0.61-1.62 µmol/L and for REC 3.0-9.7 % based on 120 blood donors. Based on 88 children, the reference intervals for CuEXC was 0.45-1.16 µmol/L. The intervals for REC were 1.8-5.8 % for children <10 years and 2.3-8.5 % for children ≥10 years. Regarding stability, CuEXC increased following a logarithmic scale in uncentrifuged serum and exceeded the permissible difference of 10 % after 4 h. With long-term freezing at -20 °C, CuEXC was stable for 1.7 months. In conclusion, reference intervals for CuEXC and REC were established and confirmed to be substantially lower in children. Accurate reference intervals are important to ensure timely diagnosis of WD. Finally, our findings on stability have important implications and highlight the need for standardization of the pre-analytical handling of CuEXC samples in order to obtain comparable results within and between laboratories both for clinical and research use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Trace elements, including zinc (Zn) and copper (Cu), although toxic at higher concentrations are known to play important roles in the maintenance of human health and neurodevelopment. Few epidemiological studies have investigated the association between prenatal or early postnatal Cu and Zn levels and child neurodevelopment. The aim of this research is to assess the association between child neurodevelopment at 18 months of age and cord blood and breast milk concentrations of Cu and Zn in Italian mother-child pairs enrolled in the Italian Northern Adriatic Cohort II (NAC-II), a part of the "Public health impact of long-term, low-level, mixed element exposure in susceptible population strata" project PHIME., Methods: The study population consisted of 632 children, and their mothers, born within the NAC-II, who were tested with the Bayley Scales of Infant and Toddler Development third edition (BSID-III) at age 18 months. Cu and Zn concentrations were measured in cord blood and breast milk samples. Only children born at term (≥37 gestational week), who completed the BSID-III test and had at least 1 measure of Cu and Zn concentrations were included in the analysis. Information about socio-demographics and lifestyles were collected through questionnaires at different phases of follow-up. Cu and Zn concentrations were log 2 transformed because of their skewed distribution. Multiple linear regression models were performed to study the association between each BSID-III composite score (cognitive, motor and language) and each metal concentration. Separate models were applied for each biological sample. The β coefficient (β) and its 95% confidence interval (95% CI) were estimated. Stratified analyses by child's sex were also conducted., Results: The mean ± standard deviation (SD) of cognitive, motor and language composite scores were respectively: 106 ± 8, 101 ± 5 and 97 ± 8. The mean ± SD of Cu and Zn concentrations (ng/g) were respectively 699.2 ± 129.0 and 2538 ± 589 in cord blood and 607 ± 498 and 3226 ± 1428 in breast milk. No association between metal concentration and cognitive composite score was found. A higher motor composite score was associated with higher Cu concentrations in cord blood (β = 4.31 95% CI 2.03; 6.59). No associations were found between language composite score and metal concentrations. The effect of Cu cord blood concentration on motor composite score was confirmed when stratified by sex: males (β = 5.49 95% CI 2.15; 8.36) and females (β = 3.11; 95% CI 0.00; 6.22). A direct association, in females only, was found between language composite score and Cu concentration in cord blood (β = 5.60 95% CI 0.63; 10.57) and in breast milk (β = 3.04 95% CI 1.06; 5.03), respectively., Conclusion: The results from this cohort study showed a strong direct association between prenatal Cu levels and child motor neurodevelopment at 18 months. However, for generalizability, future research on the effects of Zn and Cu on neurodevelopment should include a larger range of early-life concentration of trace elements., Competing Interests: Declaration of competing interest The authors declare no conflict of interest, (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Mineral are intimately related to human health and disease, and detection of mineral content in the body is of great significance for the diagnosis and prevention of diseases. In this study, we validated the method developed to detect magnesium (Mg), copper (Cu), iron (Fe), zinc (Zn), and selenium (Se) levels in dried blood spots (DBS). In accordance with the requirements of the guidelines for the Bioanalytical Method Validation Guidance for Industry, we evaluate the linearity, sensitivity, precision, accuracy and selectivity of the developed methods. In addition, Mg, Cu, Fe, Zn and Se were quantified in 195 older adults using DBS technique, and its accuracy was assessed by comparing the results to those detected by inductively coupled plasma-mass spectrometry (ICP-MS). The method has excellent sensitivity and linear range to cover the concentration range of mineral elements in the general population with the required precision, accuracy and selectivity. The correlation coefficients of Mg, Cu, Fe, Zn and Se levels in blood detected by the DBS technique and ICP-MS were 0.638, 0.823, 0.463, 0.728 and 0.751, respectively (all P < 0.05), which indicated that there was a strong correlation between the detection results of the two methods. More than 95 % of the sample results in the Bland-Altman consistency test were within the acceptable limits of agreement (LOA) range, indicating that they had good consistency. DBS technique has good accuracy and reliability in detecting blood mineral levels in the elderly, suggesting potential in the quantification of mineral level in blood., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Guowei Huang reports financial support was provided by Ministry of Science and Technology of the People's Republic of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Neutral bis(amino acidato)copper(II) [Cu(aa) 2 ] coordination compounds are the physiological species of copper(II) amino acid compounds in blood plasma taking the form of bis(l-histidinato)copper(II) and mixed ternary copper(II)-l-histidine complexes, preferably with l-glutamine, l-threonine, l-asparagine, and l-cysteine. These amino acids have three functional groups that can bind metal ions: the common α-amino and carboxylate groups and a side-chain polar group. In Cu(aa) 2 , two coordinating groups per amino acid bind to copper(II) in-plane, while the third group can bind apically, which yields many possibilities for axial and planar bonds, that is, for bidentate and tridentate binding. So far, the experimental studies of physiological Cu(aa) 2 compounds in solutions have not specified their complete geometries. This paper provides a brief review of my group's research on structural properties of physiological Cu(aa) 2 calculated using the density functional theory (DFT) to locate low-energy conformers that can coexist in aqueous solutions. These DFT investigations have revealed high conformational flexibility of ternary Cu(aa) 2 compounds for tridentate or bidentate chelation, which may explain copper(II) exchange reactions in the plasma and inform the development of small multifunctional copper(II)-binding drugs with several possible copper(II)-binding groups. Furthermore, our prediction of metal ion affinities for Cu 2+ binding with amino-acid ligands in low-energy conformers with different coordination modes of five physiological Cu(aa) 2 in aqueous solution supports the findings of their abundance in human plasma obtained with chemical speciation modelling., (© 2024 Jasmina Sabolović, published by Sciendo.)

Background: Previous studies have highlighted that copper supplementation at 200% of the recommended daily dietary allowance modified vascular contraction and relaxation through increased reactive oxygen species (ROS) and prostaglandin formation, which modified the antioxidant status of middle-aged Wistar rats., Methods: In this study, young (1 month old) male Wistar rats ( n /group = 10) received a diet supplemented with 6.45 mg copper/kg (100% of daily recommendation-Group A) for 8 weeks. The experimental group received 12.9 mg copper/kg of diet (200% of the daily recommendation-Group B)., Results: Experimental supplementation with 200% copper modified the copper concentration in the blood (1.21-fold, p = 0.04), liver (1.15-fold, p = 0.032), and kidneys (1.23-fold, p = 0.045), potentiated the ROS formation in the aortic rings, and enhanced the sensitivity of the aortic rings to the vasodilator acetylcholine. We observed an increased participation of nitric oxide (NO) derived from inducible NO synthase (iNOS) in vascular contraction and a decreased net effect of vasodilator prostanoids derived from cyclooxygenase-2 in vascular relaxation. In rat kidneys, the concentrations of potassium (1.08-fold, p = 0.001) and iron (1.13-fold, p = 0.046) were higher, while, calcium (0.88-fold, p = 0.001) and chromium (0.77-fold, p = 0.005) concentrations were lower. In the rat liver, magnesium (1.06-fold, p = 0.012) was higher. No differences were observed in the concentrations of sodium, zinc, manganese, selenium, cobalt, molybdenum, and vanadium. The antioxidant activity of water- and lipid-soluble compounds; total antioxidant status in the blood; and superoxide dismutase, catalase, and malondialdehyde levels in the heart did not change., Conclusions: In young rats, prolonged supplementation with 200% copper had a lesser effect than anticipated on oxidative stress and vascular reactivity. Detailed data on the status of trace elements and their interactions in patients of different age groups are strongly required for effective nutritional and therapeutic intervention.

Objective: To establish a method for the simultaneous determination of 22 elements, including beryllium, vanadium, chromium, manganese, iron, calcium, magnesium, barium, cobalt, cadmium, copper, zinc, arsenic, selenium, titanium, strontium, nickel, molybdenum, tin, antimony, thallium and lead, in whole blood by inductively coupled plasma mass spectrometry (ICP-MS) . Methods: In September 2023, the analysis conditions were determined by optimizing the detection mode of the instrument, the pretreatment mode and the dilution factor of the samples, etc. Whole blood samples were diluted with a mixture of 0.1% nitric acid and 0.05% triton X-100, and centrifuged at 2000 r/min by high-speed centrifuge for 2 min. The supernatant was taken into inductively coupled plasma mass spectrometer to determine the content of 22 elements, and the detection limit and precision of the method were analyzed. Results: The 22 elements had a good linear relationship in their respective measurement ranges ( r =0.9991-0.9999), the detection limit ranged from 0.003 μg/L to 0.012 mg/L. The intra-batch precision ranged from 0.5% to 7.2%, the inter-batch precision ranged from 0.4% to 9.4%, and the average recoveries ranged from 80.6% to 114.9%. Conclusion: ICP-MS method has a good effect on the determination of 22 elements in whole blood. The method is fast and simple, and can be used for clinical detection of multiple elements in whole blood.

Background: Wilson disease (WD) is an autosomal recessive inherited disease caused by ATP7B variants and characterized by copper metabolism defects. However, children with WD are often asymptomatic, making the clinical diagnosis difficult. Therefore, more accurate methods are required for clinical diagnosis. The objective of this study was to highlight the phenotypic and genetic characteristics of children with WD in northeast China., Methods: We retrospectively analyzed the clinical data and gene sequencing results of 65 children with WD from January 1, 2014, to December 31, 2022, at the Shengjing Hospital of China Medical University. All data refer to the time of diagnosis before treatment., Results: The median age at diagnosis was 5 years (range 1.2-15 years). In 50 cases (50/65, 76.9%) patients, routine physical examinations revealed only abnormal liver function. However, they had a significantly negative (p < 0.05) Kayser-Fleischer ring (KF). Children with acute liver failure had significantly increased 24 h urinary copper excretion (p < 0.05). We detected 46 genetic variants of ATP7B, including seven novel variants. The most frequent variant was p.R778L with an allele frequency of 38.7%. Phenotype-genotype correlation analysis suggested that p.R778L was significantly associated with lower serum ceruloplasmin levels and higher zinc levels (p < 0.05). The loss-of-function (LOF) variant was associated with significantly lower albumin levels (p < 0.05)., Conclusion: Most children with WD are asymptomatic, which makes early diagnosis of WD difficult. Therefore, clinical and laboratory characteristics as well as genetic testing are essential. p.R778L is the most frequent variant of ATP7B in China and may play an important role in lowering serum ceruloplasmin levels., (© 2024. The Author(s).)

Copper is an essential element in the diet of mammals, including humans. It plays an important role in the physiological regulation of various enzymes and is consequently involved in several biological processes such as angiogenesis, oxidative stress regulation, neuromodulation, and erythropoiesis. Copper is essential for facilitating the transfer of iron from cells to the bloodstream, which is necessary for proper absorption of dietary iron and the distribution of iron throughout the body. In particular, patients with end-stage renal failure who require renal replacement therapy are at increased risk for disorders of copper metabolism. Many studies on hemodialysis, peritoneal dialysis, and kidney transplant patients have focused on serum copper levels. Some reported mild deficiency, while others reported elevated levels or even toxicity. In some cases, it has been reported that alterations in copper metabolism lead to an increased risk of cardiovascular disease, malnutrition, anemia, or mielopathy. The aim of this review is to evaluate the role of copper in patients undergoing hemodialysis and its potential clinical implications.

Background: Wilson disease is an autosomal recessive disorder owing to defective copper metabolism which causes abnormal accumulation of copper and damage to the liver, brain, kidneys and other organs., Aim: To describe the clinical features, laboratory investigations and outcome of Wilson disease in children., Methods: A retrospective observational study was conducted in the paediatric department of a tertiary- care hospital in South India by reviewing medical records between January 2018 and March 2023. The diagnosis of Wilson disease was confirmed by the presence of low serum ceruloplasmin and/or high urine copper excretion in combination with clinical and ophthalmological features., Results: A total of 32 cases were analysed. The mean (SD) age at presentation was 110 (36) months with a M:F ratio of 1.6:1. Isolated hepatic involvement was seen in 19 (60%) patients while 13 (40%) patients had a neurological presentation, either as an isolated entity or in combination with hepatic manifestations. Low serum ceruloplasmin levels were detected in 31 (96%) patients. Urine copper levels were elevated in all patients. Twenty-one patients were commenced on D penicillamine while 11 patients were treated with a combination chelation therapy with zinc. Eighteen patients (56%) were on regular follow-up., Conclusion: The clinical presentation of Wilson disease in children is diverse, varying from the more common hepatic or neurological manifestations to the less common atypical forms of the disease. Diagnosis is based on clinical and ophthalmological features in combination with biochemical abnormalities in the form of low ceruloplasmin and high urinary copper. The majority of patients can be medically managed with chelation therapy.

Background and Aims: Few studies have focused on the outcomes of Wilson's disease (WD) diagnosed before age of 5 years. This study aimed to summarize the clinical features of early diagnosed WD and analyse treatment outcomes and the risk factors associated with treatment failure., Methods: A total of 139 children confirmed with WD before 5 years were enrolled in this study. Only patients with follow-up over 1 year were analysed with Kaplan-Meier survival analysis. The composite outcomes included death, progression to liver failure or acute hepatitis, development of renal or neurological symptoms and persistent elevation of alanine aminotransferase (ALT). The treatment failure was defined as occurrence of at least one of above outcomes., Results: Among 139 WD patients at diagnosis, two (1.4%) WD patients presented with symptomatic liver disease, whereas 137 (98.6%) were phenotypically asymptomatic, including 135 with elevated ALT and 2 with normal liver function. Median serum ceruloplasmin (Cp) was 3.1 mg/dL, and urinary copper excretion was 87.4 μg/24-h. There were 71 variants identified in the the copper-transporting ATPase beta gene, and 29 were loss of function (LOF). 51 patients with LOF variant were younger at diagnosis and had lower Cp than 88 patients without LOF. Among 93 patients with over 1 year of follow-up, 19 (20.4%) received zinc monotherapy, and 74 (79.6%) received a zinc/D-penicillamine combination therapy. 14 (15.1%) patients underwent treatment failure, and its occurrence was associated with poor compliance (p < .01)., Conclusions: Cp is a reliable biomarker for early diagnosis, and zinc monotherapy is an effective treatment for WD during early childhood. Good treatment compliance is critical to achieve a favourable outcome., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: It is widely known that sex differences have a significant impact on patients with major depressive disorder (MDD). This study aims to evaluate the sex-related connection between serum trace elements and changes in neurometabolism in the anterior cingulate cortex (ACC) of MDD patients., Methods: 109 untreated MDD patients and 59 healthy controls underwent proton magnetic resonance spectroscopy ( 1 H-MRS) under resting conditions. We measured metabolic ratios in the ACC from both sides. Additionally, venous blood samples were taken from all participants to detect calcium (Ca), phosphorus, magnesium (Mg), copper (Cu), ceruloplasmin (CER), zinc (Zn), and iron (Fe) levels. We performed association and interaction analyses to explore the connections between the disease and gender., Results: In individuals with MDD, the Cu/Zn ratio increased, while the levels of Mg, CER, Zn and Fe decreased. Male MDD patients had lower Cu levels, while female patients had an increased Cu/Zn ratio. We observed significant gender differences in Cu, CER and the Cu/Zn ratio in MDD. Male patients showed a reduced N-acetyl aspartate (NAA)/phosphocreatine + creatine (PCr + Cr) ratio in the left ACC. The NAA/PCr + Cr ratio decreased in the right ACC in patients with MDD. In the left ACC of male MDD patients, the Cu/Zn ratio was inversely related to the NAA/PCr + Cr ratio, and Fe levels were negatively associated with the GPC + PC/PCr + Cr ratio., Conclusions: Our findings highlight gender-specific changes in Cu homeostasis among male MDD patients. The Cu/Zn ratio and Fe levels in male MDD patients were significantly linked to neurometabolic alterations in the ACC., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)