Habitual intake of iron, copper, and zinc and the risk of type 2 diabetes in a prospective cohort: The CAVAS (Cardiovascular Disease Association Study).

BACKGROUND AND AIMS: Unlike iron, evidence of the association between dietary copper and zinc intake and type 2 diabetes (T2D) risk is limited. This study aimed to examine the prospective associations of dietary intake of iron (total, plant-based, and animal-based), copper, and zinc with T2D risk among adults aged ≥40 years. METHODS AND RESULTS: For 16,666 participants, dietary intakes (baseline, cumulative average, and most recent) of iron, copper, and zinc were calculated from repeated food frequency questionnaires; a modified Poisson regression model with a robust error estimator was conducted. In men, positive associations between T2D and baseline dietary intake of Cu and Zn, cumulative average dietary intake of Fe (total and animal-based), Cu and Zn, and most recent dietary intake of Fe (total, plant-based, and animal-based), Cu, and Zn [most recent diet: for total Fe, IRR(95%CI) = 1.93 (1.41-2.64); for plant-based Fe, 1.56 (1.15-2.11); for animal-based Fe, 1.44 (1.09-1.90); for Cu, 3.17 (2.33-4.30); for Zn, 2.18 (1.64-2.89)] were observed, where as in women, there were positive associations of only cumulative average dietary Zn intake and most recent dietary intake of plant-based Fe, Cu, and Zn [most recent diet: for plant-based Fe, 1.30 (1.01-1.68); for Cu, 1.62 (1.27-2.08); for Zn, 2.07 (1.61-2.66)]. CONCLUSION: Dietary intakes of iron (total, plant-based, and animal-based), copper, and zinc may be positively associated with T2D risk. These positive associations are predominantly observed in most recent diet and appear to be stronger compared to baseline and cumulative average diet.

Post-marketing surveillance of zinc acetate dihydrate for hypozincemia in Japan.

Zinc is an essential microelement, and its deficit causes various diseases and symptoms. In adults, especially in elderly individuals, zinc shortage can cause symptoms such as taste disorder, dermatitis, and susceptibility to infection. In children, zinc deficiency can lead to growth retardation. In 2017, the indication for zinc acetate dihydrate (NOBELZIN®) was expanded from Wilson's disease to include hypozincemia, leading to wider use of zinc acetate dihydrate. At five years after this broadening of use, we conducted a post-marketing study (PMS) to investigate the utilization, safety, and effectiveness of zinc acetate dihydrate. Over 52 weeks, the overall incidence of adverse drug reactions (ADRs) was 9.4% (87/928). The most common ADR was copper deficiency (2.4%), followed by nausea (1.4%). Among 928 patients, 19 (2%) developed serious ADRs. Of the patients with copper deficiency, 92% were >65 years of age, and all had comorbidities at baseline. Physicians evaluated the effectiveness of zinc acetate dihydrate using three categories: "effective", "not effective", and "indeterminate". The overall efficacy rate was 83.0%. The average serum zinc levels were elevated from 50-60 µg/dL to >90 µg/dL within 12 weeks, and were maintained up to 52 weeks after administration. Among the symptomatic sub-categories, the efficacy rate was highest in pressure ulcer (96.2%; 25/26), followed by in stomatitis (87.5%; 42/48), and taste disorder (87.4%; 181/207). Among pediatric patients with developmental symptoms, an efficacy rate of 66% was achieved. In conclusion, zinc acetate dihydrate has been safely used, and has produced beneficial effects on various diseases and symptoms.

Metal Exposure and Risk of Parkinson Disease: A Systematic Review and Meta-Analysis.

Metal exposure has been suggested as a possible environmental risk factor for Parkinson disease (PD). We searched the PubMed, EMBASE, and Cochrane databases to systematically review the literature on the relationship between metal exposure and PD risk and to examine the overall quality of each study and the exposure assessment method. A total of 83 case-control studies and 5 cohort studies published during the period 1963-July 2021 were included, of which 73 were graded as being of low or moderate overall quality. Investigators in 69 studies adopted self-reported exposure and biomonitoring after disease diagnosis for exposure assessment approaches. The meta-analyses showed that concentrations of copper and iron in serum and concentrations of zinc in either serum or plasma were lower, while concentrations of magnesium in CSF and zinc in hair were higher, among PD cases as compared with controls. Cumulative lead levels in bone were found to be associated with increased risk of PD. We did not find associations between other metals and PD. The current level of evidence for associations between metals and PD risk is limited, as biases from methodological limitations cannot be ruled out. High-quality studies assessing metal levels before disease onset are needed to improve our understanding of the role of metals in the etiology of PD.

Lower-Dose Zinc for Childhood Diarrhea - A Randomized, Multicenter Trial.

BACKGROUND: The World Health Organization recommends 20 mg of zinc per day for 10 to 14 days for children with acute diarrhea; in previous trials, this dosage decreased diarrhea but increased vomiting. METHODS: We randomly assigned 4500 children in India and Tanzania who were 6 to 59 months of age and had acute diarrhea to receive 5 mg, 10 mg, or 20 mg of zinc sulfate for 14 days. The three primary outcomes were a diarrhea duration of more than 5 days and the number of stools (assessed in a noninferiority analysis) and the occurrence of vomiting (assessed in a superiority analysis) within 30 minutes after zinc administration. RESULTS: The percentage of children with diarrhea for more than 5 days was 6.5% in the 20-mg group, 7.7% in the 10-mg group, and 7.2% in the 5-mg group. The difference between the 20-mg and 10-mg groups was 1.2 percentage points (upper boundary of the 98.75% confidence interval [CI], 3.3), and that between the 20-mg and 5-mg groups was 0.7 percentage points (upper boundary of the 98.75% CI, 2.8), both of which were below the noninferiority margin of 4 percentage points. The mean number of diarrheal stools was 10.7 in the 20-mg group, 10.9 in the 10-mg group, and 10.8 in 5-mg group. The difference between the 20-mg and 10-mg groups was 0.3 stools (upper boundary of the 98.75% CI, 1.0), and that between the 20-mg and 5-mg groups was 0.1 stools (upper boundary of the 98.75% CI, 0.8), both of which were below the noninferiority margin (2 stools). Vomiting within 30 minutes after administration occurred in 19.3%, 15.6%, and 13.7% of the patients in the 20-mg, 10-mg, and 5-mg groups, respectively; the risk was significantly lower in the 10-mg group than in the 20-mg group (relative risk, 0.81; 97.5% CI, 0.67 to 0.96) and in the 5-mg group than in the 20-mg group (relative risk, 0.71; 97.5% CI, 0.59 to 0.86). Lower doses were also associated with less vomiting beyond 30 minutes after administration. CONCLUSIONS: Lower doses of zinc had noninferior efficacy for the treatment of diarrhea in children and were associated with less vomiting than the standard 20-mg dose. (Funded by the Bill and Melinda Gates Foundation; ZTDT ClinicalTrials.gov number, NCT03078842.).

Iatrogenic copper deficiency: Risks and cautions with zinc prescribing.

AIMS: Copper deficiency resulting from prescribing zinc in high doses is a rare but life-changing diagnosis that is frequently overlooked. The aim of this study is to gauge how often zinc-induced copper deficiency is missed, to raise awareness of the condition and to stress the need for guidelines for prescribing zinc. METHODS: Suspected cases of zinc-induced copper deficiency were retrospectively obtained by selecting those patients with hyperzincaemia and hypocupraemia from the database of the Scottish Trace Element Laboratory. Case records were reviewed to determine the validity of the suspected diagnosis. RESULTS: After exclusions, 23 instances of high serum zinc and low serum copper concentrations were found. A positive diagnosis of zinc-induced copper deficiency was made in 14 patients, of which 7 (50%) were previously undiagnosed. CONCLUSION: Serum zinc and copper concentrations are rarely measured in patients prescribed zinc and so the vast majority of cases of zinc-induced copper deficiency are likely to be undiagnosed. We recommend the current official advice on the dose and frequency of zinc administration is revised in order to limit, and potentially eradicate, the condition.

Efficacy and safety of supramolecular active zinc in the treatment of scalp psoriasis: a multicentre, randomized, observed-blind, parallel-group, placebo- and active-controlled noninferiority trial.

BACKGROUND: Controlling the relapses of scalp psoriasis is a clinical issue. OBJECTIVES: To evaluate the efficacy and safety of a supramolecular active zinc antidandruff hair conditioner in managing scalp psoriasis (SP). METHODS: This multicentre randomized, observed-blind, parallel-group, placebo- and active-controlled noninferiority trial enrolled 211 patients with SP between October 2018 and June 2019. The participants were randomized 1 : 1 : 1 to the experimental (supramolecular active zinc antidandruff hair conditioner), placebo (supramolecular hydrogel) or positive control (calcipotriol ointment) group. The primary efficacy endpoint was the disease control rate at the end of the fourth week of treatment, measured using the Investigator's Global Assessment score. RESULTS: This study included 70, 70 and 71 participants in the experiment, control and placebo groups, respectively. The disease control rates of SP at the end of week 4 of treatment in the full-analysis set (FAS) were 39%, 25% and 37% in the experimental, placebo and control groups. The margin of superiority between the experimental and placebo groups was > 0 [96% confidence interval (CI) 13.22% (0.43% to ∞)] in the FAS. The experimental group was superior to the placebo group. The noninferiority margin between the experiment and control groups was > -15% [96% CI -1.43% (-14.91% to ∞)] in the FAS. The experimental group was not inferior to the control group. CONCLUSIONS: Supramolecular active zinc antidandruff hair conditioner was helpful for the treatment of SP, and it has good clinical efficacy in maintaining therapeutic effect and assisting in preventing the recurrence of psoriasis.

Severe copper deficiency anemia caused by zinc supplement use.

Copper deficiency is an uncommon condition primarily affecting the hematologic and neurologic systems. We report a unique case of severe anemia in a patient with copper deficiency caused by zinc supplement use.

Zinc supplement use and risk of aggressive prostate cancer: a 30-year follow-up study.

BACKGROUND: Zinc supplementation was hypothesized to have therapeutic potential against prostate cancer, but its influence on prostate cancer incidence especially at high doses is controversial. METHODS: A total of 47,240 men from the Health Professionals Follow-up Study were followed from 1986 to 2016. Men reported their zinc supplement use at baseline and biennially thereafter. Clinical features of prostate cancer included stage, grade, lethal and aggressive (T4 or N1 or M1 or Gleason 8-10) outcome. Multivariable Cox proportional hazards models were used to evaluate the association between zinc supplement use and incidence of prostate cancer. RESULTS: During a median follow-up of 28.3 years, we documented 6,980 incident prostate cancer cases including 1,053 lethal and 1,143 aggressive. Zinc supplement use was not associated with overall, localized, low- and intermediate-grade prostate cancer. However, compared to never-users, men who used supplement zinc more than 75 mg/day were at higher risk for lethal (HR: 1.76, 95% CI: 1.16-2.66, Ptrend = 0.001) and aggressive prostate cancer (HR: 1.80, 95% CI: 1.19-2.73, Ptrend = 0.006). Similarly, men who took supplemental zinc for 15 or more years had a higher risk for lethal (HR: 1.91, 95% CI: 1.28-2.85, Ptrend <0.001) and aggressive prostate cancer (HR: 1.55, 95% CI: 1.03-2.33, Ptrend = 0.004). CONCLUSION: Zinc supplementation of more than 75 mg per day or over 15 years may substantially increase risk of lethal and aggressive prostate cancer. Caution is warranted regarding excessive usage of zinc supplements among adult men.

Heavy Metals in Breast Implant Capsules and Breast Tissue: Findings from the Systemic Symptoms in Women-Biospecimen Analysis Study: Part 2.

BACKGROUND: Breast Implant Illness (BII), as described in recent medical literature and by social media, describes a range of symptoms in patients with breast implants for which there are no physical findings or laboratory results that explain their symptoms. OBJECTIVES: Part 2 of this study aims to determine whether heavy metals are present in the capsules around saline and silicone implants and if there are statistical differences in the type or level of these metals between women with or without symptoms. Demographic data was collected to investigate potential alternate sources of metals: inhaled, absorbed, or ingested. METHODS: A prospective, blinded study enrolled 150 consecutive subjects divided equally into in three cohorts: (A) women with systemic symptoms they attribute to their implants who requested implant removal, (B) women with breast implants requesting removal or exchange who do not have symptoms they attribute to their implants, and (C) women undergoing cosmetic mastopexy who have never had any implanted medical device. Capsule tissue was removed from Cohort A and B for analysis of 22 heavy metals. Additionally, breast tissue was obtained from a control group with no previous exposure to any implanted medical device. RESULTS: The study was performed between 2019-2021. Heavy metal content was compared between the capsule tissue from Cohort A and B. The only statistically significant differences identified in Cohort A were higher levels of arsenic and zinc, and lower levels of cobalt, manganese, silver, and tin. There were no elevated levels or statistically significant differences in the other metals tested between Cohorts A and B. CONCLUSIONS: This study analyzes the metal content in capsules surrounding both saline and silicone breast implants. Heavy metals were also detected in the non-implant control group breast tissue, with some metals at numerically higher levels than either breast implant cohort. Smoking, gluten free diets, dietary supplements, and the presence of tattoos were all identified as statistically significant sources of arsenic and zinc in Cohort A. The risk of heavy metal toxicity should not be used as an indication for total capsulectomy if patients elect to remove their breast implants.

Pregnancy Outcomes in Wilson's Disease Women: Single-Center Case Series.

OBJECTIVES: To evaluate and compare pregnancy outcomes in women with Wilson's disease (WD) undergoing different therapies during pregnancy. MATERIAL AND METHODS: Retrospective review of medication in WD patients during pregnancy and the outcomes. RESULTS: Of 26 pregnancies, zinc was used in 14 (53.8%), D-penicillamine in 4 (15.4%) patients, and 8 (30.8%) were untreated. Spontaneous abortion was observed in 8 (30.8%) pregnancies - untreated patients (4/8 pregnancies), zinc (2/14 pregnancies) and D-penicillamine (2/4 pregnancies) -, healthy outcome in 12 (46.1%) and birth defects in 6 (23.1%). All cases of birth defects occurred in patients using zinc therapy (6/14 pregnancies). CONCLUSIONS: A remarkably high frequency of fetal complications shed lights on the potentially harmful effect of WD drugs during childbearing age. Zinc's safety profile may have to be better evaluated during pregnancy, as all of birth defects occurred with zinc therapy.

Dietary supplements in dermatology: A review of the evidence for zinc, biotin, vitamin D, nicotinamide, and Polypodium.

Dietary supplements are commonly recommended by dermatologists in the treatment of skin, hair, and nail disorders. This review of oral over-the-counter supplement use in dermatology summarizes current evidence for the use of zinc, biotin, vitamin D, nicotinamide, and Polypodium in the management of common dermatologic disorders. Evidence for the safety and efficacy of these supplements is limited. Very few large-scale randomized controlled trials exist for these over-the-counter supplements, particularly biotin and Polypodium. The lack of standardized dosing and standardized outcome measures makes comparison across existing studies challenging, and the lack of adverse events reporting in the majority of studies limits analysis of supplement safety. The most promising evidence exists for the use of nicotinamide in preventing nonmelanoma skin cancers. There is some evidence for the role of vitamin D in decreasing melanoma risk and progression in some individuals and for the photoprotective role of Polypodium, although additional high-quality studies are needed to determine appropriate dosing. Current evidence is insufficient to recommend the use of biotin or zinc supplements in dermatology. Large-scale randomized controlled trials investigating safety and efficacy are needed before widespread incorporation of these oral supplements into the general practice of dermatology.

Prolonged blood coagulation time among occupationally exposed automobile technicians in Abeokuta, Nigeria.

Automobile technicians in resource-poor settings often work in poor environments and are exposed to chemicals that put them at risk of ill health and disease. These chemical exposures could affect blood coagulation, leading to bleeding disorders or thrombosis. The present study is aimed at assessing prothrombin test (PT) and activated partial thromboplastin test (aPTT) values, serum zinc (Zn) and copper (Cu) concentrations, and blood lead level (BLL) among occupationally exposed automobile technicians compared to unexposed controls. A total of 140 consenting participants comprising 70 automobile technicians and 70 unexposed controls were recruited for this case-control study. A 6-mL blood sample was drawn from each participant for estimation of BLL, serum Zn and Cu concentrations, and PT and aPTT values. Blood lead level, and serum Zn and Cu concentrations were determined using atomic absorption spectrophotometry, while PT and aPTT values were determined using Innovin PT and Actin FS Activated PTT reagents on the Sysmex CA-101 coagulation analyser. Data were analysed using t-tests, chi-square tests, and logistic and multiple linear regression analyses with statistical significance set at p < 0.05. The mean BLL, serum Zn concentration, and PT and aPTT values were significantly higher in automobile technicians compared to controls. Binary logistic regression showed that automobile technicians had higher odds of elevated PT value (OR = 21.769; p = 0.000), aPTT value (OR = 1.348; p = 0.018), BLL (OR = 1.261; p = 0.000) and serum Zn concentration (OR = 1.063; p = 0.005) than unexposed controls. Linear regression showed significant positive association of PT value with BLL and with serum Zn concentration. Higher PT and aPTT values reflect prolonged blood coagulation time among automobile technicians, which indicates impairment of extrinsic and intrinsic coagulation pathways associated with work-related exposures.

Zinc Exposure Promotes Commensal-to-Pathogen Transition in Pseudomonas aeruginosa Leading to Mucosal Inflammation and Illness in Mice.

The opportunistic pathogen Pseudomonas aeruginosa (P. aeruginosa) is associated gastrointestinal (GI) inflammation and illness; however, factors motivating commensal-to-pathogen transition are unclear. Excessive zinc intake from supplements is common in humans. Due to the fact that zinc exposure enhances P. aeruginosa colonization in vitro, we hypothesized zinc exposure broadly activates virulence mechanisms, leading to inflammation and illness. P. aeruginosa was treated with excess zinc and growth, expression and secretion of key virulence factors, and biofilm production were determined. Effects on invasion, barrier function, and cytotoxicity were evaluated in Caco-2 cells co-cultured with P. aeruginosa pre-treated with zinc. Effects on colonization, mucosal pathology, inflammation, and illness were evaluated in mice infected with P. aeruginosa pre-treated with zinc. We found the expression and secretion of key virulence factors involved in quorum sensing (QS), motility (type IV pili, flagella), biosurfactants (rhamnolipids), toxins (exotoxin A), zinc homeostasis (CzcR), and biofilm production, were all significantly increased. Zinc exposure significantly increased P. aeruginosa invasion, permeability and cytotoxicity in Caco-2 cells, and enhanced colonization, inflammation, mucosal damage, and illness in mice. Excess zinc exposure has broad effects on key virulence mechanisms promoting commensal-to-pathogen transition of P. aeruginosa and illness in mice, suggesting excess zinc intake may have adverse effects on GI health in humans.

Copper as a Collaborative Partner of Zinc-Induced Neurotoxicity in the Pathogenesis of Vascular Dementia.

Copper is an essential trace element and possesses critical roles in various brain functions. A considerable amount of copper accumulates in the synapse and is secreted in neuronal firings in a manner similar to zinc. Synaptic copper and zinc modulate neuronal transmission and contribute to information processing. It has been established that excess zinc secreted during transient global ischemia plays central roles in ischemia-induced neuronal death and the pathogenesis of vascular dementia. We found that a low concentration of copper exacerbates zinc-induced neurotoxicity, and we have demonstrated the involvement of the endoplasmic reticulum (ER) stress pathway, the stress-activated protein kinases/c-Jun amino-terminal kinases (SAPK/JNK) signaling pathway, and copper-induced reactive oxygen species (ROS) production. On the basis of our results and other studies, we discuss the collaborative roles of copper in zinc-induced neurotoxicity in the synapse and the contribution of copper to the pathogenesis of vascular dementia.

Impact of long-term industrial contamination on the bacterial communities in urban river sediments.

BACKGROUND: The contamination of the aquatic environment of urban rivers with industrial wastewater has affected the abiotic conditions and biological activities of the trophic levels of the ecosystem, particularly sediments. However, most current research about microorganism in urban aquatic environments has focused on indicator bacteria related to feces and organic pollution. Meanwhile, they ignored the interactions among microorganisms. To deeply understand the impact of industrial contamination on microbial community, we study the bacterial community structure and diversity in river sediments under the influence of different types of industrial pollution by Illumina MiSeq high-throughput sequencing technology and conduct a more detailed analysis of microbial community structure through co-occurrence networks. RESULTS: The overall community composition and abundance of individual bacterial groups differed between samples. In addition, redundancy analysis indicated that the structure of the bacterial community in river sediments was influenced by a variety of environmental factors. TN, TP, TOC and metals (Cu, Zn and Cd) were the most important driving factors that determined the bacterial community in urban river sediments (P < 0.01). According to PICRUSt analysis, the bacterial communities in different locations had similar overall functional profiles. It is worth noting that the 15 functional genes related to xenobiotics biodegradation and metabolism were the most abundant in the same location. The non-random assembly patterns of bacterial composition in different types of industrially polluted sediments were determined by a co-occurrence network. Environmental conditions resulting from different industrial pollutants may play an important role in determining their co-occurrence patterns of these bacterial taxa. Among them, the bacterial taxa involved in carbon and nitrogen cycles in module I were relatively abundant, and the bacterial taxa in module II were involved in the repair of metal pollution. CONCLUSIONS: Our data indicate that long-term potential interactions between different types of industrial pollution and taxa collectively affect the structure of the bacterial community in urban river sediments.

Higher Prevalence of Nickel and Palladium Hypersensitivity in Patients with Ulcerative Colitis.

BACKGROUND: The etiology of ulcerative colitis (UC) remains elusive even though many genetic and environmental pathogenic factors have been reported. Aberrant inflammatory responses mediated by specific subsets of T cells have been observed in ulcerative lesions of UC patients. OBJECTIVES: To elucidate the involvement of a delayed-type hypersensitivity reaction in UC, we focused on dental metal hypersensitivity, a T cell-mediated, delayed-type allergic reaction that causes oral contact mucositis and systemic cutaneous inflammation. METHOD: We recruited 65 Japanese UC patients and 22 healthy controls (HC) and used the in vitro lymphocyte stimulation test to quantify their sensitivity to zinc, gold, nickel, and palladium - the metals that have been widely used in dentistry. All subjects were users of metallic dental implants and/or prostheses containing zinc, gold, nickel, and/or palladium as major constituents. RESULTS: Sixty percent of the UC patients were hypersensitive to at least one metal species, whereas 32% of the HC were hypersensitive to only a single metal species. The overall incidence of metal hypersensitivity was significantly higher for UC patients than for HC. Furthermore, a significantly greater proportion of UC patients were hypersensitive to nickel or palladium. The severity of the sensitivity to nickel and palladium was also significantly greater for UC patients than for HC. CONCLUSIONS: This pilot study demonstrates that UC patients have a significantly higher incidence of hypersensitivity to nickel and palladium, suggesting the possible involvement of dental metal hypersensitivity in UC pathogenesis.

Postnatal zinc or paraquat administration increases paraquat or zinc-induced loss of dopaminergic neurons: insight into augmented neurodegeneration.

Epidemiological evidences have shown an association of exposure to pesticides or heavy metals with increased incidences of Parkinson's disease (PD) in humans. Exposure to pesticides or metals during the decisive period of the brain development increases the susceptibility of dopaminergic neurons upon re-exposure in adult rodents. However, the effect of early life exposure to pesticide on the heavy metal-induced neurodegeneration or heavy metal on pesticide-induced neurodegeneration is not yet explored. The current study explored the effect of developmental exposure to zinc (Zn), a metal or paraquat (PQ), a pesticide on the nigrostriatal dopaminergic neurons of rats challenged to Zn or PQ during adulthood. Exposure of Zn or PQ during adulthood alone exhibited marked reduction in motor activities, striatal dopamine and metabolites, glutathione content and number of dopaminergic neurons. However, the levels of lipid peroxidation, protein carbonyls, superoxide dismutase activity, pro-inflammatory cytokines and 4-hydroxynonenal-protein adducts were increased. While the expression of vesicular monoamine transporter-2 and tyrosine hydroxylase were attenuated, dopamine transporter and microglial marker Iba-1 expression, activated microglia, nuclear factor-kappa B activation, mitochondrial cytochrome c release and caspase-3/9 activation were augmented following Zn or PQ exposure. Albeit postnatal alone exposure did not alter any of the studied parameters, the developmental administration of Zn/PQ in re-challenged adult rats produced more pronounced changes in the aforementioned variables as compared with adulthood Zn or PQ alone intoxicated animals. The results demonstrate that postnatal Zn/PQ intoxication dents the oxidative stress, inflammation, cell death and dopamine metabolism and storage regulating machineries, which speed up the toxicant-induced degeneration during adulthood.

Mutualistic Outcomes Across Plant Populations, Microbes, and Environments in the Duckweed Lemna minor.

The picture emerging from the rapidly growing literature on host-associated microbiota is that host traits and fitness often depend on interactive effects of host genotype, microbiota, and abiotic environment. However, testing interactive effects typically requires large, multi-factorial experiments and thus remains challenging in many systems. Furthermore, most studies of plant microbiomes focus on terrestrial hosts and microbes. Aquatic habitats may confer unique properties to microbiomes. We grew different populations of duckweed (Lemna minor), a floating aquatic plant, in three microbial treatments (adding no, "home", or "away" microbes) at two levels of zinc, a common water contaminant in urban areas, and measured both plant and microbial performance. Thus, we simultaneously manipulated plant source population, microbial community, and abiotic environment. We found strong effects of plant source, microbial treatment, and zinc on duckweed and microbial growth, with significant variation among duckweed genotypes and microbial communities. However, we found little evidence of interactive effects: zinc did not alter effects of host genotype or microbial community, and host genotype did not alter effects of microbial communities. Despite strong positive correlations between duckweed and microbe growth, zinc consistently decreased plant growth, but increased microbial growth. Furthermore, as in recent studies of terrestrial plants, microbial interactions altered a duckweed phenotype (frond aggregation). Our results suggest that duckweed source population, associated microbiome, and contaminant environment should all be considered for duckweed applications, such as phytoremediation. Lastly, we propose that duckweed microbes offer a robust experimental system for study of host-microbiota interactions under a range of environmental stresses.

Ability of selenium species to inhibit metal-induced Aß aggregation involved in the development of Alzheimer's disease.

Extracellular accumulation of amyloid beta peptide (Aß) is believed to be one of the main factors responsible for neurodegeneration in Alzheimer's disease (AD). Metals could induce Aß aggregation, by their redox activity or binding properties to amyloid ß fibrils, leading to their accumulation and deposition outside neurons. For this reason, metal chelation may have an acknowledged part to play in AD prevention and treatment. In the current work, the role of different selenium species, including selenium nanoparticles, in Aß aggregation, was studied by evaluating their metal-chelating properties and their ability both to inhibit metal-induced Aß1-42 aggregation fibrils and to disaggregate them once formed. Transition biometals such as Fe(II), Cu(II), and Zn(II) at 50 µM were selected to establish the in vitro models. The DPPH assay was used to determine the antioxidant capacity of the evaluated selenium species. Selenium nanoparticles stabilized with chitosan (Ch-SeNPs) and with both chitosan and chlorogenic acid polyphenol (CGA@ChSeNPs) showed the highest antioxidant properties with EC50 of 0.9 and 0.07 mM, respectively. UV-Vis and d1(UV-Vis) spectra also revealed that selenium species, in particular selenomethionine (SeMet), were able to interact with metals. Regarding Aß1-42 incubation experiments, Fe(II), Cu(II), and Zn(II) induced Aß aggregation, in a similar way to most of the evaluated selenium species. However, Ch-SeNPs produced a high inhibition of metal-induced Aß aggregation, as well as a high disaggregation capacity of Aß fibrils in both the presence and absence of biometals, in addition to reducing the length and width (20% of reduction in the presence of Zn(II)) of the generated Aß fibrils. Graphical abstract.

Effects of magnesium, phosphate and zinc supplementation in ICU patients-Protocol for a systematic review.

BACKGROUND: Depletion of the trace elements magnesium, phosphate and zinc is common in patients admitted to the intensive care unit (ICU). Observational studies have suggested worse outcome in patients with hypomagnesaemia, hypophosphataemia or hypozincaemia, but also inverse associations with worse outcome with too high serum levels. However, it is unclear whether data from randomised clinical trials (RCTs) confirm this. Accordingly, we plan to assess the balance between benefits and harms of supplementation as compared with placebo or no supplementation in adult ICU patients. METHODS: We will conduct a systematic review of RCTs with meta-analysis and trial sequential analysis in accordance with the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement and the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach. We will assess the effects of any supplementation with magnesium, phosphate or zinc vs. placebo or no treatment in adult ICU patients. We will systematically search the Cochrane CENTRAL, Embase, PubMed, and for unpublished trials: ClinicalTrials.gov, the EU clinical Trials Register and the WHO International Clinical Trials Registry Platform. The primary outcomes will be days alive without mechanical ventilation and overall mortality. Secondary outcomes include use for mechanical ventilation, tachy-arrhythmias, use of vasopressors, length of hospital stay and use of renal replacement therapy. DISCUSSION: The benefits and harms of supplementation therapy with magnesium, phosphate and zinc in general ICU patients are unknown. This outlined systematic review will provide data on the evidence, on which future recommendations for supplementation may be founded.