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The article discusses the cases of two osteoarthritic patients in Australia who were fitted with articular surface replacement (ASR) XL Acetbular Hip System prostheses that contains chromium and cobalt. It focuses on the revision surgeries performed on the patients despite the use of metal-on-metal bearings to reduce wear at the articulation interface. It explores the withdrawal of ASR implants because of the high failure rate and the increase of cobalt level in the body.

Uptake and toxicity of Ni-Co mixtures in Enchytraeus crypticus were determined after 4 d, 7 d, 10 d, and 14 d exposure. Generally, body concentrations of Ni and Co increased with increasing exposure concentrations. Ni body concentration was significantly reduced in the presence of Co, whereas Ni only marginally affected Co uptake. When expressed as free ion activities, individual toxicity of Ni and Co increased with time, with median lethal concentrations (LC50) decreasing from 78.3 μM and 511 μM at 4 d to 40.4 μM and 393 μM at 14 d, respectively. When expressed as body concentrations, LC50BodyNi remained constant with time whereas LC50BodyCo increased during the first 7 d but remained stable afterwards. As identified by the MIXTOX model, interactions between Ni and Co were mainly antagonistic when based on free ion activities, however, no interaction was observed when based on body concentrations. A process-based model, incorporating exposure time to analyze the mechanisms underlying the dynamic mixture toxicity confirmed the differences in toxicokinetics of the 2 metals. The author's findings suggest that body concentrations, which incorporate bioaccumulation processes, are time-independent and can act as a more constant indicator of metal toxicity. The observed antagonism was mainly caused by competition between Co and Ni for binding sites and subsequent inhibition of Ni uptake. This competitive interaction occurred at the uptake level (toxicokinetics), but not at the target level (toxicodynamics). Environ Toxicol Chem 2014;9999:1-10. © 2014 SETAC [ABSTRACT FROM AUTHOR]

The effects of cobalt on the growth and nutrient balance of mung beans were investigated. Inhibition of seedling growth occurred at 5 μM Co and was associated with chlorosis of the younger leaves. Analysis of nutrient concentrations in root and leaf tissue of mung beans treated with 5 μM Co showed that none of the macronutrients and only two of the micronutrients, Mn and Fe, were significantly affected. The Mn concentration in roots was reduced by 55% and the Fe concentration in the leaves by 80%. Uptake of Fe into roots was not inhibited by Co but transport of Fe to the shoot was greatly reduced. It was shown that the effect of Co on growth was additive to that of Fe deficiency, which argues against Co-induced Fe deficiency as the primary cause of growth inhibition by Co. Rather, it was considered that the high concentrations of Co in the roots and leaves compared with essential micronutrient cations can disrupt a range of metabolic processes due to competitive interactions. Comparison of the toxic effects of Co with those of other toxic trace metals Cd, Cu, Ni and Hg showed that at an applied concentration of 5 μM, there were obvious differences in both the visual symptoms and in nutrient concentrations. The main difference between Co and the other metals was that only Co stimulated the uptake of S into the plant and its transport to the shoots, where the S concentration in the leaves was increased 2-fold. The common feature of all the trace metals examined was the strong inhibition of Fe transport to the shoot. A possible mechanism for the interaction of other trace metals with Fe transport is discussed. [ABSTRACT FROM AUTHOR]

We report two Australian patients with possible cobalt toxicity related to metal-on-metal total hip replacements. Both patients were treated for osteoarthritis with a DePuy ASR (articular surface replacement) XL Acetabular Hip System prosthesis, which contains cobalt and chromium, and which has recently been recalled from the market. [ABSTRACT FROM AUTHOR]

Background: Prosthetic hip-associated cobalt toxicity (PHACT) is an uncommon, but potentially devastating, complication for patients with metal-on-metal hip implants (MoMs). Clinical management of PHACT is poorly defined, with primary intervention being MoM explant followed by chelation therapy. Therapeutic plasma exchange (TPE) in cobalt toxicity has not been previously described. Given that cobalt is predominantly albumin bound, it should theoretically be removed by TPE. Here we report a case of PHACT and our experience using TPE to lower plasma cobalt levels.Case Report: A 61-year-old woman developed deafness, blindness, ambulatory dysfunction, and endocrinopathies after MoM implant. Cobalt levels on admission were greater than 1500 µg/L. In an attempt to rapidly lower cobalt levels before MoM explant, hemodialysis and TPE were performed. Hemodialysis removed negligible amounts of cobalt. One session of TPE temporarily removed approximately two-thirds of measurable cobalt, but levels rebounded to pre-TPE values after 8 hours. It was only after MoM removal that cobalt levels plateaued below 300 µg/L and clinical symptoms improved.Discussion: TPE removed cobalt from a PHACT patient, but a durable decrease in cobalt was only achieved after MoM explant. These findings are comparable to reports where chelation was employed in PHACT patients before MoM explant. The observed rebound phenomenon is likely from rapid equilibration between the immense extravascular tissue source (the MoM) and the intravascular compartment.Conclusion: TPE may serve as adjunctive therapy for PHACT patients whose cobalt levels remain high after explant, especially in patients with renal failure, in whom chelation is contraindicated. [ABSTRACT FROM AUTHOR]

The article presents a case report of an 84-year-old woman with a orthopaedic history who experienced generalized pruritic eczematous rash. She had undergone a metal-on-metal (MoM) right total hip replacement for a fractured femur neck in May 2009. Skin biopsy of the rash revealed urticarial features with no overt histological evidence of a drug eruption. Diagnosis of the patient revealed systemic allergic dermatitis (SAD) caused by cobalt.

Vascular calcification is a strong predictor of cardiovascular events. Essential metals play critical roles in maintaining human health. However, the association of essential metal levels with risk of aortic arch calcification (AoAC) remains unclear. We measured the plasma concentrations of nine essential metals in a cross‐sectional population and evaluated their individual and combined effects on AoAC risk using multiple statistical methods. We also explored the mediating role of fasting glucose. In the logistic regression model, higher quartiles of magnesium and copper were associated with the decreased AoAC risk, while higher quartile of manganese was associated with higher AoAC risk. The least absolute shrinkage and selection operator penalized regression analysis identified magnesium, manganese, calcium, cobalt, and copper as key metals associated with AoAC risk. The weighted quantile sum regression suggested a combined effect of metal mixture. A linear and positive dose–response relationship was found between manganese and AoAC in males. Moreover, blood glucose might mediate a proportion of 9.38% of the association between manganese exposure and AoAC risk. In summary, five essential metal levels were associated with AoAC and showed combined effect. Fasting glucose might play a significant role in mediating manganese exposure‐associated AoAC risk. [ABSTRACT FROM AUTHOR]

Metallosis with subsequent cardiac involvement is a possible long‐term complication of hip arthroplasty. We report the case of a young female referred to our centre for the suspicion of cardiac amyloidosis presenting with low electrocardiogram voltage, left ventricular hypertrophy, pericardial effusion, and global and longitudinal systolic impairment with apical sparing pattern. Her medical history was remarkable for arthroplasty in the context of congenital hip dysplasia. Two years prior to presentation, she underwent revision surgery for prosthesis malfunction, and tissue metallosis was initially documented. At the current presentation, cobalt metallosis was confirmed, as the circulating cobalt and chromium levels were severely elevated. The accurate diagnosis prompted the removal of the cobalt source with extensive tissue debridement and the use of chelating agents. Reversal of the cardiac abnormalities occurred as the circulating cobalt levels returned to normal. [ABSTRACT FROM AUTHOR]

Adverse tissue responses to prostheses wear particles and released ions are important contributors to hip implant failure. In implant-related adverse reactions T-lymphocytes play a prominent role in sustaining the chronic inflammatory response. To further understand the involvement of lymphocytes in metal-on-metal (MoM) implant failure, primary human lymphocytes were isolated and treated with cobalt-chromium (Co-Cr) wear debris and Co ions, individually, and in combination, for 24, 48 and 120 h. There was a significant increase in cell number where debris was present, as measured by the Neutral Red assay. Interleukin-6 (IL-6), interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) secretion levels significantly decreased in the presence of metal particles, as measured by ELISA. Interleukin-2 (IL-2) secretion levels were significantly decreased by both debris and Co ions. Flow cytometry analysis showed that the metal nanoparticles induced a significant increase in apoptosis after 48-h exposure. This investigation showed that prolonged exposure (120 h) to metal debris induces lymphocyte proliferation, suggesting that activation of resting lymphocytes may have occurred. Although cytokine production was affected mainly by metal debris, cobalt toxicity may also modulate IL-2 secretion, and even Co ion concentrations below the MHRA guideline levels (7 ppb) may contribute to the impairment of immune regulation in vivo in patients with MoM implants. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Cobalt toxicity has become a health concern in recent years, due to overexposure resulting in neurological impairments like dementia. With a growing interest in the therapeutic roles of herbs, in toxicity research, it's worth looking into the curative effects of aqueous Prosopis africana seed extract, a plant rich in flavonoids on cobalt‐induced dementia‐like and anxiogenic behaviour. Method: We treated rats with Cobalt (CoCl2) or CoCl2 in combination with aqueous Prosopis africana seed extract (PAE) orally for 14 days. Control rats received distilled water for the same period. Following treatments, behavioral experiments for cognition and anxiety, analysis for oxidative stress, inflammation, histological and immunohistochemical analysis were performed. Result: Results revealed that CoCl2 reduced the exploration time, recognition index in the novel object recognition test, percentage spontaneous alternation in the Y‐maze tests, and reduced open arm entry and duration in elevated plus‐maze. However, treatment with PAE improved these parameters to levels comparable with those of the control group. Furthermore, PAE therapy reduced CoCl2‐induced surge in hydrogen peroxide, malondialdehyde, TNF‐α and IL‐1β levels in brain homogenate, while also increasing superoxide dismutase and reduced reduced‐glutathione activities. CoCl2 exposure resulted in obvious features of neurodegeneration like nuclear disintegration, nuclear shrinkage, and cytoplasmic vacuolations of the cells of the hippocampus and amygdala, with an increased expression of GFAP. The hippocampal and amygdala histology improved after PAE administration, while exacerbated GFAP expressions were attenuated. Conclusion: These findings imply that PAE may be anxiolytic and can help reduce cognitive impairments and hippocampal damage caused by CoCl2 neurotoxicity, via mechanisms that involve attenuation of oxidative stress and neuroinflammation. [ABSTRACT FROM AUTHOR]

Ellagic acid (EA) is a polyphenol extracted from many plants. EA modulates inflammatory mediators via antioxidant mechanisms, such as catalase (CAT) activities, superoxide dismutase (SOD), enhancement, increase in glutathione (GSH), and lipid peroxidation (LPO) suppression. EA has anti‐apoptotic properties that are thought to be mediated by regulating the expression of B‐cell lymphoma 2 (Bcl‐2), Bcl‐2‐associated X protein (Bax), and caspase‐3. In this article, we surveyed the literature dealing with the protective effects of EA against different heavy metals, drugs, and natural toxins. The findings indicated that EA has remarkable protective properties against various toxicants. Its protective effects were mostly mediated via normalizing lipid metabolism, oxidative stress, and inflammatory mediators, for example, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and IL‐1β. The results of this study showed that EA has significant protective effects against a varied range of compounds, either chemical or natural. These effects are mainly mediated via intensifying the antioxidant defense system. However, other mechanisms such as inhibition of inflammatory responses and suppression of apoptosis are important. [ABSTRACT FROM AUTHOR]

Clinical translation of nanoparticles is limited because of their short circulation time, which hampers targeting to prolong therapeutic effects. Angiogenesis is required to regenerate damaged sites under inflammation, and CD11b+ cells turn vasculogenic under hypoxia. As a turning‐point strategy to increase the circulation time, this study explores liposomal targeting of splenic CD11b+ cells, which are gathered in the spleen and move to inflamed sites inherently. Moreover, nano‐hypoxia is strategized as a therapeutic method by loading liposomes with a hypoxic‐mimetic agent (CoCl2) to induce in situ reprogramming of splenic CD11b+ cells upon venous injection. Consequently, the vasculogenic potential of reprogrammed cells accelerates regeneration through inflammation‐responsive homing. Hydrophilic coating of liposomes improves the selectivity of splenic targeting in contrast to fast targeting without coating. Hypoxia chambers and surgical induction of splenic hypoxia are compared to validate the reprogramming effect. The strategy is validated in mouse models of inflamed skin, ischemic hindlimbs, and 70% hepatectomy compared with a conventional approach using bone marrow cells. Intravital multiphoton microscopy, 19F 2D/3D MRI, and microchannel hydrogel chips for 3D tissue culture are used as advanced tools. Overall, nanocarrier change to CD11b+ cells prolong targeting by inducing in situ reprogramming for inflammation‐responsive vasculogenic therapy. [ABSTRACT FROM AUTHOR]

SUMMARY: Hydrogen sulfide (H2S) promotes plant tolerance against various environmental cues, and d‐cysteine desulfhydrase (DCD) is an enzymatic source of H2S to enhance abiotic stress resistance. However, the role of DCD‐mediated H2S production in root growth under abiotic stress remains to be further elucidated. Here, we report that DCD‐mediated H2S production alleviates osmotic stress‐mediated root growth inhibition by promoting auxin homeostasis. Osmotic stress up‐regulated DCD gene transcript and DCD protein levels and thus H2S production in roots. When subjected to osmotic stress, a dcd mutant showed more severe root growth inhibition, whereas the transgenic lines DCDox overexpressing DCD exhibited less sensitivity to osmotic stress in terms of longer root compared to the wild‐type. Moreover, osmotic stress inhibited root growth through repressing auxin signaling, whereas H2S treatment significantly alleviated osmotic stress‐mediated inhibition of auxin. Under osmotic stress, auxin accumulation was increased in DCDox but decreased in dcd mutant. H2S promoted auxin biosynthesis gene expression and auxin efflux carrier PIN‐FORMED 1 (PIN1) protein level under osmotic stress. Taken together, our results reveal that mannitol‐induced DCD and H2S in roots promote auxin homeostasis, contributing to alleviating the inhibition of root growth under osmotic stress. Significance Statement: Hydrogen sulfide (H2S) promotes plant tolerance against various environmental stress resistance. However, the role of H2S in root development under abiotic stress remains to be further elucidated. Here, we report that d‐cysteine desulfhydrase‐mediated H2S accumulation alleviates root growth inhibition under osmotic stress by promoting auxin homeostasis. [ABSTRACT FROM AUTHOR]

This unique study provides information on Cr species and their distribution in periprosthetic tissues of patients with metal‐on‐polyethylene joint implants. Co–Cr–Mo alloy has been widely used in joint replacement and represents a source of metal derived species. In the case of chromium, previous studies on periprosthetic tissues revealed mainly Cr(III) distribution, whereas the potential release of carcinogenic Cr(VI) species has been still a subject of debate. Here, an analytical approach utilizing speciation and fractionation was developed to analyze periprosthetic tissue samples collected from wide range of patients with failed total hip or knee replacements. The results reveal that Cr(III) is mainly released in the form of insoluble CrPO4 and Cr2O3 particles. The highest Cr contents were found in periprosthetic tissues of patients suffering from aseptic loosening and having more Cr‐based implants in the body. Cr species penetrated tissue layers, but their levels decreased with the distance from an implant. The detailed speciation/fractionation study carried out using the set of consecutive periprosthetic tissues of a patient with extensive metallosis showed the presence of trace amounts of free Cr(III), nanoparticles, and metal‐protein complexes, but the majority of Cr still occurred in CrPO4 form. Carcinogenic Cr(VI) species were not detected. Up to date, there is no published human tissue study focused on the detailed speciation of both soluble and insoluble Cr‐based species in the context of failing total hip and knee replacements. [ABSTRACT FROM AUTHOR]

Summary: Prionoplus reticularis larvae ('Huhu grubs'), a traditional food in New Zealand, have been grown commercially. However, no information is available on the composition or safety of the larvae as a food. A proximate analysis (58.7–75.2% moisture, 26.2–30.5% protein, 32.1–58.4% fat, and 1.5–3.2% ash dry weight basis) found that Huhu grubs contain substantial amounts of nutrients. Forty minerals were investigated for four different development stages of wild harvested Huhu grubs (small, medium, and large larvae and pupae). ICP‐MS detected 28 minerals, (11 essential, 13 non‐essential, and four heavy metals). The most abundant minerals were manganese, magnesium, phosphorus, iron, copper, and zinc. The heavy metal content of Huhu grubs was found to be below detection levels for arsenic and vanadium, but cadmium and lead were detectable. The results indicate, on the basis of proximate analysis and mineral content, that moderate consumption of New Zealand wild harvested Huhu is safe and nutritious. [ABSTRACT FROM AUTHOR]

Metal‐on‐polyethylene (MoP) total hip arthroplasty (THA) prostheses are known to release metal debris. Basic science studies suggest that metal implants induce a pro‐inflammatory response that ultimately chemoattracts leukocytes including macrophages and neutrophils to the surgical site. This raises concern of higher risk of infection with these prostheses through the "trojan horse" mechanism by which neutrophils and macrophages transport intracellular pathogens from a remote site. This study compared the infection occurrence between MoP and ceramic‐on‐polyethylene (CoP) implants to determine if a higher infection rate in MoP is present. We reviewed a consecutive series of 6052 CoP and 4550 MoP primary THA patients from 2015 to 2019. The occurrence of periprosthetic joint infection at 2 years was defined according to the 2018 ICM definition. Statistical analysis consisted of descriptive statistics, univariate analysis, and regression modeling. When compared to CoP, MoP patients were older, included more females, had a higher body mass index, and more commonly affected by comorbidities according to Elixhauser's score. Total revisions were higher in the MoP group (3.19% vs. 2.41%) The absolute incidence of PJI was higher in MoP (2.40% vs. 1.64%). When we adjusted for confounding factors, MoP was found independently associated with a higher PJI risk. Despite MoP and CoP both being widely used for primary THA, we found a higher incidence of PJI in MoP patients. The association remained significant when controlled for possible confounders. We hypothesize that leukocyte recruitment to these implants may play a role and should be further investigated. [ABSTRACT FROM AUTHOR]

Humans are continuously exposed to environmental, occupational, consumer and household products, food, and pharmaceutical substances. Luteolin, a flavone from the flavonoids family of compounds, is found in different fruits and vegetables. LUT is a strong anti‐inflammatory (via inhibition of NF‐κB, ERK1/2, MAPK, JNK, IL‐6, IL‐8, and TNF‐α) and antioxidant agent (reducing ROS and enhancement of endogenous antioxidants). LUT can chelate transition metal ions responsible for ROS generation and consequently repress lipoxygenase. It has been proven that NF‐κB, as a commom cellular pathway plays a considerable role in the progression of inflammatory process and stimulates the expression of genes encoding inducible pro‐inflammatory enzymes (iNOS and COX‐2) and cytokines including IL‐1β, IL‐6, and TNF‐α. This review summarizes the available literature discussing LUT and its potential protective role against pharmaceuticals‐, metals‐, and environmental compounds‐induced toxicities. Furthermore, the review explains the involved protective mechanisms, especially inhibition of the NF‐κB pathway. [ABSTRACT FROM AUTHOR]

As a result of climate change, abiotic stresses are the most common cause of crop losses worldwide. Abiotic stresses significantly impair plants' physiological, biochemical, molecular and cellular mechanisms, limiting crop productivity under adverse climate conditions. However, plants can implement essential mechanisms against abiotic stressors to maintain their growth and persistence under such stressful environments. In nature, plants have developed several adaptations and defence mechanisms to mitigate abiotic stress. Moreover, recent research has revealed that signalling molecules like hydrogen sulfide (H2S) play a crucial role in mitigating the adverse effects of environmental stresses in plants by implementing several physiological and biochemical mechanisms. Mainly, H2S helps to implement antioxidant defence systems, and interacts with other molecules like nitric oxide (NO), reactive oxygen species (ROS), phytohormones, etc. These molecules are well‐known as the key players that moderate the adverse effects of abiotic stresses. Currently, little progress has been made in understanding the molecular basis of the protective role of H2S; however, it is imperative to understand the molecular basis using the state‐of‐the‐art CRISPR‐Cas gene‐editing tool. Subsequently, genetic engineering could provide a promising approach to unravelling the molecular basis of stress tolerance mediated by exogenous/endogenous H2S. Here, we review recent advances in understanding the beneficial roles of H2S in conferring multiple abiotic stress tolerance in plants. Further, we also discuss the interaction and crosstalk between H2S and other signal molecules; as well as highlighting some genetic engineering‐based current and future directions. [ABSTRACT FROM AUTHOR]

Simultaneous delivery of therapeutic agents and energy by magnetic nanoparticles (MNPs) at targeted sites can boost cancer therapy and alleviate side effects. To achieve this goal, however, the magnetic fluid hyperthermia (MFH) usually exhibits the unsufficient thermal efficiency due to their narrow magnetization curves. Besides, an inappropriately large administration concentration also causes health deterioration as shown in an animal model. In this study, the core–shell cube that enhances the coercivity and magnetization related to single‐compositional MNPs by elaborately tuning their interface relaxation via the magnetocrystalline and surface anisotropy is developed. Néel and Brownian relaxation can be adjusted by the particles' structures to maximize the hyperthermia efficacy upon an alternating‐magnetic‐field (AMF). Furthermore, temozolomide and lactoferrin‐coated CoFe2O4@Fe3O4 core–shell cubes are rapidly internalized by targeting cancer cells and penetrate into tumor spheroids while subjecting to AMF. The targeted cubes with the capabilities of enhanced coercivity, AMF‐induced drug penetration into tumors, and magnetothermal ablation for cancer therapy display potentials for clinical uses. [ABSTRACT FROM AUTHOR]

We designed a colorimetric chemosensor based on phthalazine ((E)‐9‐((2‐(phthalazin‐1‐yl)hydrazono)methyl)‐2,3,6,7‐tetrahydro‐1H,5H‐pyrido[3,2,1‐ij]quinoline‐8‐ol), denoted HPJ, for detecting Co2+. In the presence of Co2+, HPJ undergoes a colour variation from yellow to dark pink. Analysis of a Job plot and electrospray ionisation‐mass spectra enabled the binding mode of HPJ to Co2+ to be determined as a 1:1 ratio. The detection limit of Co2+ with HPJ was 1.74 μM. In addition, the feasibility of using HPJ in the form of a test strip was confirmed. The sensing process of Co2+ by HPJ was monitored by using a Job plot, proton nuclear magnetic resonance titration, electrospray ionisation‐mass spectrometry and ultraviolet‐visible titration. [ABSTRACT FROM AUTHOR]

Magnetic hyperthermia (HT) using biocompatible ceramics is a ground‐breaking, competent, and safe thermo‐therapeutic strategy for cancer treatment. The magnetic properties of bioceramics, along with their structure and synthesis parameters, are responsible for the controlled heating of malignant tumors and are the key to clinical success. After providing a brief overview of magnetism and its significance in biomedicine, this review deals with materials selection and synthesis methods of bioceramics/glasses used for HT. Relevant research carried out on promising bioceramics for magnetic HT, with a focus on their size, shape, surface functionalization, magnetic field parameters, and in vitro/in vivo properties to optimize cancer therapy, is also discussed. Recent progress in magnetic HT combined with chemotherapy and phototherapy is especially highlighted, with the aim to provide interdisciplinary knowledge to advance further the applications of bioceramics in this field. [ABSTRACT FROM AUTHOR]

Aims: Primary prevention strategies for heart failure (HF) have had limited success, possibly due to a wide range of underlying risk factors (RFs). Systematic evaluations of the prognostic burden and preventive potential across this wide range of risk factors are lacking. We aimed at estimating evidence, prevalence and co‐occurrence for primary prevention and impact on prognosis of RFs for incident HF. Methods and results: We systematically reviewed trials and observational evidence of primary HF prevention across 92 putative aetiologic RFs for HF identified from US and European clinical practice guidelines. We identified 170 885 individuals aged ≥30 years with incident HF from 1997 to 2017, using linked primary and secondary care UK electronic health records (EHR) and rule‐based phenotypes (ICD‐10, Read Version 2, OPCS‐4 procedure and medication codes) for each of 92 RFs. Only 10/92 factors had high quality observational evidence for association with incident HF; 7 had effective randomized controlled trial (RCT)‐based interventions for HF prevention (RCT‐HF), and 6 for cardiovascular disease prevention, but not HF (RCT‐CVD), and the remainder had no RCT‐based preventive interventions (RCT‐0). We were able to map 91/92 risk factors to EHR using 5961 terms, and 88/91 factors were represented by at least one patient. In the 5 years prior to HF diagnosis, 44.3% had ≥4 RFs. By RCT evidence, the most common RCT‐HF RFs were hypertension (48.5%), stable angina (34.9%), unstable angina (16.8%), myocardial infarction (15.8%), and diabetes (15.1%); RCT‐CVD RFs were smoking (46.4%) and obesity (29.9%); and RCT‐0 RFs were atrial arrhythmias (17.2%), cancer (16.5%), heavy alcohol intake (14.9%). Mortality at 1 year varied across all 91 factors (lowest: pregnancy‐related hormonal disorder 4.2%; highest: phaeochromocytoma 73.7%). Among new HF cases, 28.5% had no RCT‐HF RFs and 38.6% had no RCT‐CVD RFs. 15.6% had either no RF or only RCT‐0 RFs. Conclusion: One in six individuals with HF have no recorded RFs or RFs without trials. We provide a systematic map of primary preventive opportunities across a wide range of RFs for HF, demonstrating a high burden of co‐occurrence and the need for trials tackling multiple RFs. [ABSTRACT FROM AUTHOR]

Micronutrients play key roles in numerous metabolic processes in cyanobacteria. However, our understanding of whether the micronutrient cobalt influences the productivity of freshwater systems or the occurrence of cyanobacterial blooms is limited. This study aimed to quantify the concentration of Co necessary for optimal cyanobacterial growth by exposing Microcystis aeruginosa to a range of Co concentrations under culture conditions. Extended exposure to concentrations below ˜0.06 μg · L−1 resulted in notable inhibition of M. aeruginosa growth. A clear negative relationship was observed between Co concentration in solution and intracellular Fe quota of M. aeruginosa, possibly due to decreased transport of Fe at higher Co concentrations. Cyanocobalamin and any Co within the structure of cyanocobalamin appears to be non‐bioavailable to M. aeruginosa, instead they likely rely on the synthesis of a structural variant – pseudocobalamin, which may have implications for the wider algal community as the variants of cobalamin are not necessarily functionally exchangeable. To evaluate the likelihood of Co limitation of cyanobacterial growth under field conditions, a survey of 10 freshwater reservoirs in South‐Eastern Australia was conducted. Four of the ten sites had dissolved Co concentrations below the 0.06 μg · L−1 threshold value. All four of these sites rarely undergo cyanobacterial blooms, strengthening evidence of the potential for Co to limit growth, perhaps either alone or in combination with phosphorus. [ABSTRACT FROM AUTHOR]

Summary: Zinc concentrations in pelagic surface waters are within the range that limits growth in marine phytoplankton cultures. However, the influence of zinc on marine primary production and phytoplankton communities is not straightforward due to largely uncharacterized abilities for some phytoplankton to access zinc species that may not be universally bioavailable and substitute zinc with cobalt or cadmium. We used a quantitative proteomic approach to investigate these strategies and other responses to zinc limitation in the coccolithophore Emiliania huxleyi, a dominant species in low zinc waters. Zinc limitation resulted in the upregulation of metal transport proteins (ZIP, TroA‐like) and COG0523 metallochaperones. Some proteins were uniquely sensitive to growth under replete zinc, substitution of zinc with cobalt, or enhancement of growth with cadmium, and may be useful as biomarkers of zinc stress or substitution in situ. Several proteins specifically upregulated under cobalt‐supported or cadmium‐enhanced growth appear to reflect stress responses, despite titration of these metals to optimal nutritive levels. Relief from zinc limitation by zinc or cadmium resulted in increased expression of a δ‐carbonic anhydrase. Our inability to detect metal binding enzymes that are specifically induced under cobalt‐ or cadmium‐supported growth suggests cambialism is important for zinc substitution in E. huxleyi. [ABSTRACT FROM AUTHOR]

Summary Cobalt can be toxic and the way cells adapt to its presence is largely unknown. Here we carried out a transcriptomic analysis of Escherichia coli exposed to cobalt. A limited number of genes were either up- or downregulated. Upregulated genes include the isc and the nfuA genes encoding Fe/S biogenesis assisting factors, and the rcnA gene encoding a cobalt efflux system. Downregulated genes are implicated in anaerobic metabolism ( narK, nirB, hybO, grcA), metal transport ( feoB, nikA), sulfate/thiosulfate import ( cysP), and one is of unknown function ( yeeE). Cobalt regulation of isc, nfuA, hybO, cysP and yeeE genes was found to involve IscR, a Fe/S transcriptional regulator. Previously, the Suf Fe/S biogenesis machinery was found to be important for cobalt stress adaptation, but suf genes did not show up in the microarray analysis. Therefore, we used qRT-PCR analysis and found that cobalt induced the suf operon expression. Moreover, kinetic analysis of the cobalt-mediated induction of the suf operon expression allowed us to propose that cobalt toxicity is caused first by impaired Fe/S biogenesis, followed by decreased iron bioavailability and eventually oxidative stress. [ABSTRACT FROM AUTHOR]

Lignocellulosic biomass is a highly available and suitable candidate for biogas/biomethane production. However, high concentration of recalcitrant lignin is the major obstacle in successful anaerobic digestion (AD). The main aim of this review is to highlight the applications and challenges of lignocellulosic biomass in AD from the recent reports. Potential approaches to improve instabilities in mesophilic AD process (such as microbial communities' development, co‐digestion, biofilm carrier's addition, and essential nutrients supplement) were also reported. This review goes one more step deeper to discuss the key microbes involved in lignocellulosic biomass degradation. Biofilm carriers provide attached growth systems for microbes in AD and acts as redox mediators to accelerate the biotransformation of recalcitrant pollutants. Addition of nanoparticles (NPs) stimulate Firmicutes, Bacteroidetes, Methanosaeta, Methanobacterium, and Methanosarcina population which further improve biomethanation. The comprehensive study of these proposed strategies and microbial stimulation through additives would make the lignocellulosic biomethanation more feasible. © 2021 Society of Chemical Industry (SCI). [ABSTRACT FROM AUTHOR]

Cobalt is well known for its ability to stimulate erythropoiesis via stabilization of hypoxia‐inducible factors. In sports, this can provide a competitive benefit to athletes, so the World Anti‐Doping Agency prohibits the use of cobalt in any form except its cobalamin vitamers. As of now, cobalt in biological fluids is detected by inductively coupled plasma mass spectrometry (ICP‐MS), a technique which has very limited availability in anti‐doping laboratories. Therefore, a quantitative method based on liquid chromatography–tandem mass spectrometry capable of measuring urinary cobalt in the form of its complex with 2‐(5‐chloro‐2‐pyridylazo)‐5‐diethylaminophenol (5‐Cl‐PADAP) has been developed and validated. A cobalt complex with deuterium‐labeled 5‐Cl‐PADAP was used as internal standard. The method was found linear over the concentration range of 5–500 ng/ml with a combined standard uncertainty less than 10% at 15, 200, and 450 ng/ml. Stability of cobalt ions in urine was investigated over the course of 2 months; the concentration of free Co2+ was observed to decline by approximately 50% but restored upon hydrolysis with hydrochloric acid. Unlike ICP‐MS, this method is practically unaffected by the presence of cyanocobalamin as the latter is resistant to acid hydrolysis. Notwithstanding the lack of formalized threshold concentration of cobalt in urine, it is highly desirable that more anti‐doping laboratories engage in testing for cobalt levels to better understand the prevalence of cobalt misuse in athletes. Given that cobalt salts are inexpensive and easily obtainable, the risk of such abuse should not be underestimated. [ABSTRACT FROM AUTHOR]

A novel reactive fluorescent probe for cobalt ions was prepared based on integration of thiourea functional groups, coumarin, and naphthalimide fluorophores. There was no fluorescence observed for the probe itself, however, in the presence of cobalt ions, catalytic decomposition occurred for the probe and coumarin molecular fragments were produced that emitted blue fluorescence. This enabled the probe to be used as a 'turn on' reagent for detection of cobalt ions. Under physiological pH conditions and in appropriate solvent systems, an obvious fluorescence enhancement for cobalt ions was observed in selective experiments. Competition experiments indicated that cobalt ions could still induce fluorescence enhancement in the presence of other metal ions. Sensitivity experiments showed that the detection limit for cobalt ions was 6.0 nM. Dynamics research demonstrated that the catalytic process was a pseudo‐first‐order reaction and the reaction constant (kobs) was calculated to be 1.49 × 10−2 min−1. In addition, the mechanism of catalytic decomposition could be demonstrated using electrospray ionization mass spectrometry and thin layer chromatography experiments. Cell fluorescence imaging experiments demonstrated that the probe could be used to detect cobalt ions in living HeLa cells. [ABSTRACT FROM AUTHOR]

All‐solid‐state lithium ion batteries (LIB) are currently the most promising technology for next generation electrochemical energy storage. Many efforts have been devoted in the past years to improve performance and safety of these devices. Nevertheless, issues regarding chemical and mechanical stability of the different components still hinder substantial improvements. Pulsed laser deposition (PLD) has proved to be an outstanding technique for the deposition of thin films of materials of interest for the fabrication of LIB. Thanks to its versatility and possible fine tuning of the thin film properties, PLD promises to be a very powerful tool for the fabrication of model systems which would allow to study in detail material properties and mechanisms contributing to LIB degradation. Nevertheless, PLD presents difficulties in the deposition of LIB components, mainly due to the presence of elements with large difference of atomic mass in their chemical composition. In this review, we report the main challenges and solution strategies used for the deposition through PLD of complex oxides thin films for LIB. [ABSTRACT FROM AUTHOR]

The good biocompatibility and corrosion resistance of the bulk CoCrMo alloy has resulted in it being used in the manufacture of implants and load bearing medical devices. These devices, however, can release wear and corrosion products which differ from the composition of the bulk CoCrMo alloy. The physicochemical characteristics of the particles and the associated in vivo reactivity are dictated by the wear mechanisms and electrochemical conditions at the sites of material loss. Debris released from CoCrMo hip bearings, taper junctions, or cement–stem interfaces can, therefore, have different chemical and morphological characteristics, which provide them with different in vivo toxicities. Here, we propose to assess and compare the characteristics of the particles released in vivo from CoCrMo tapers and cement–stem interfaces which have received less attention compared to debris originating from the hip bearings. The study uses state‐of‐art characterization techniques to provide a detailed understanding of the size, morphology, composition, and chemistry of the particles liberated from the wear and corrosion flakes from revised hip replacements, with an enzymatic treatment. The phase analyses identified Cr2O3 nanoparticles released from tapers and cement–stem interfaces, whose composition did not vary with origin or particle morphology. The size distributions showed significantly smaller particles were released from the stems, compared to the particles originating from the corresponding tapers. The investigation demonstrates that the tribocorrosive processes occurring at the taper and stem interfaces both result in Cr2O3 nanoparticle formation. [ABSTRACT FROM AUTHOR]

Proteus mirabilis is a Gram‐negative uropathogen and frequent cause of catheter‐associated urinary tract infection (CAUTI). One important virulence factor is its urease enzyme, which requires nickel to be catalytically active. It is, therefore, hypothesized that nickel import is critical for P. mirabilis urease activity and pathogenesis during infection. P. mirabilis strain HI4320 encodes two putative nickel import systems, designated Nik and Ynt. By disrupting the substrate‐binding proteins from each import system (nikA and yntA), we show that Ynt is the primary nickel importer, while Nik only compensates for loss of Ynt at high nickel concentrations. We further demonstrate that these are the only binding proteins capable of importing nickel for incorporation into the urease enzyme. Loss of either nickel‐binding protein results in a significant fitness defect in a murine model of CAUTI, but YntA is more crucial as the yntA mutant was significantly outcompeted by the nikA mutant. Furthermore, despite the importance of nickel transport for hydrogenase activity, the sole contribution of yntA and nikA to virulence is due to their role in urease activity, as neither mutant exhibited a fitness defect when disrupted in a urease‐negative background. [ABSTRACT FROM AUTHOR]

The replacement of a native hip joint by a metal‐on‐metal prosthesis may induce deleterious inflammatory side effects that are associated with the release of wear particles and metal ions. These events are referred to the adverse reaction to metal debris (ARMD) and the adverse local tissue reaction (ALTR). While wear particles seem involved in ARMD, the role of metal ions in ALTR and their impact on myoblasts, located in the prosthesis vicinity, has not been fully identified. To clarify this issue we investigated, using an in vitro culture system, the effect of cobalt and/or chromium ions (Co2+ and/or Cr3+) on human myoblast proliferation, cellular differentiation, and inflammatory marker expression. Freshly isolated human myoblasts were cultured in media supplemented with graded concentrations of Co2+ and/or Cr3+. Co2+ induced a concentration‐dependent decrease of both myoblast viability and myogenic differentiation while Cr3+ did not. Co2+ or Co2+/Cr3+ also induced the upregulation of ICAM‐1, whereas HLA‐DR expression was unaffected. Moreover, allogenic monocytes induced the synergistic increase of Co2+‐induced ICAM‐1 expression. We also found that Co2+ stabilized HIF‐1α and increased TLR4, tumor necrosis factor‐alpha (TNF‐α), and interleukin 1β (IL‐1β) expression in a dose and time‐dependent manner in human myoblasts. This study showed that Co2+, but not Cr3+, was toxic toward myoblasts and induced, in the surviving cells, expression of inflammatory markers such as ICAM‐1, TLR4, TNF‐α, and IL‐1β. This suggests that Co2+, most efficiently in the presence of monocytes, may be a key inducer of ALTR, which may, if severe and long‐lasting, eventually result in prosthesis loosening. [ABSTRACT FROM AUTHOR]

An increasing concentration of lead (Pb) in urban contaminated soil due to anthropogenic activities has been a global issue threatening human health. The use of urban ornamental plants as phytoremediation of Pb‐contaminated soil is a new choice. In the present experiment, the physiological and biochemical response of five ornamental plants to increase in concentrations of C4H6O4Pb·H2O in the soil were measured to investigate these plans' Pb tolerance strategies and abilities. Our results showed that Pb stress significantly inhibited the growth and the biomass of all the plants. The root activity (RA), net photosynthetic rate (Pn), and chlorophyll (Chl) content in Pb‐stressed leaves were significantly decreased, whereas the leaf proline (Pro), soluble sugar (SS), and membrane stability index (MSI) were remarkable increased compared with those in the control group. By application of all‐subsets regression and linear regression, the reduction in photosynthetic capacity in the five plants is mainly due to the decrease in the leaf Chl content caused by Pb stress. The bioconcentration factor (BCF) in Canna generalis was greater than 1, while in the other plants were lower than 1, suggesting that Canna generalis had the highest Pb accumulation ability. The translocation factor (TF) in all the plants were lower than 1, suggesting that Pb preferentially accumulated in the external part of roots. By calculating the comprehensive evaluation value (CEV), Iris germanica L. was found to be the most sensitive species, and Canna generalis was the most tolerant species, to Pb stress among the five ornamental plants. [ABSTRACT FROM AUTHOR]

Summary: In Saccharomyces cerevisiae, vacuolar H+‐ATPase (V‐ATPase) involved in the regulation of intracellular pH homeostasis has been shown to be important for tolerances to cadmium, cobalt and nickel. However, the molecular mechanism underlying the protective role of V‐ATPase against these metals remains unclear. In this study, we show that cadmium, cobalt and nickel disturbed intracellular pH balance by triggering cytosolic acidification and vacuolar alkalinization, likely via their membrane permeabilizing effects. Since V‐ATPase plays a crucial role in pumping excessive cytosolic protons into the vacuole, the metal‐sensitive phenotypes of the Δvma2 and Δvma3 mutants lacking V‐ATPase activity were supposed to result from highly acidified cytosol. However, we found that the metal‐sensitive phenotypes of these mutants were caused by increased production of reactive oxygen species, likely as a result of decreased expression and activities of manganese superoxide dismutase and catalase. In addition, the loss of V‐ATPase function led to aberrant vacuolar morphology and defective endocytic trafficking. Furthermore, the sensitivities of the Δvma mutants to other chemical compounds (i.e. acetic acid, H2O2, menadione, tunicamycin and cycloheximide) were a consequence of increased endogenous oxidative stress. These findings, therefore, suggest the important role of V‐ATPase in preventing endogenous oxidative stress induced by metals and other chemical compounds. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is an opportunistic pathogen that can cause soft tissue infections but is also a frequent cause of foodborne illnesses. One contributing factor for this food association is its high salt tolerance allowing this organism to survive commonly used food preservation methods. How this resistance is mediated is poorly understood, particularly during long‐term exposure. In this study, we used transposon sequencing (TN‐seq) to understand how the responses to osmotic stressors differ. Our results revealed distinctly different long‐term responses to NaCl, KCl and sucrose stresses. In addition, we identified the DUF2538 domain containing gene SAUSA300_0957 (gene 957) as essential under salt stress. Interestingly, a 957 mutant was less susceptible to oxacillin and showed increased peptidoglycan crosslinking. The salt sensitivity phenotype could be suppressed by amino acid substitutions in the transglycosylase domain of the penicillin‐binding protein Pbp2, and these changes restored the peptidoglycan crosslinking to WT levels. These results indicate that increased crosslinking of the peptidoglycan polymer can be detrimental and highlight a critical role of the bacterial cell wall for osmotic stress resistance. This study will serve as a starting point for future research on osmotic stress response and help develop better strategies to tackle foodborne staphylococcal infections. [ABSTRACT FROM AUTHOR]

Long INterspersed element (LINE‐1, L1) retrotransposons are the most abundant transposable elements in the human genome, constituting approximately 17%. They move by a "copy‐paste" mechanism, involving reverse transcription of an RNA intermediate and insertion of its cDNA copy at a new site in the genome. L1 retrotransposition (L1‐RTP) can cause insertional mutations, alter gene expression, transduce exons, and induce epigenetic dysregulation. L1‐RTP is generally repressed; however, a number of observations collected over about 15 years revealed that it can occur in response to environmental stresses. Moreover, emerging evidence indicates that L1‐RTP can play a role in the onset of several neurological and oncological diseases in humans. In recent years, great attention has been paid to the exposome paradigm, which proposes that health effects of an environmental factor should be evaluated considering both cumulative environmental exposures and the endogenous processes resulting from the biological response. L1‐RTP could be an endogenous process considered for this application. Here, we summarize the current understanding of environmental factors that can affect the retrotransposition of human L1 elements. Evidence indicates that L1‐RTP alteration is triggered by numerous and various environmental stressors, such as chemical agents (heavy metals, carcinogens, oxidants, and drugs), physical agents (ionizing and non‐ionizing radiations), and experiential factors (voluntary exercise, social isolation, maternal care, and environmental light/dark cycles). These data come from in vitro studies on cell lines and in vivo studies on transgenic animals: future investigations should be focused on physiologically relevant models to gain a better understanding of this topic. [ABSTRACT FROM AUTHOR]

Enzyme mimics have been widely used as alternatives to natural enzymes, owing to their high stability and low cost. However, the activity and atom economy of enzyme mimics still need to be improved. Herein, we report the boosting effects of amino acids, peptides and proteins on the peroxidase‐like activity of Co2+. Among 20 amino acids, tryptophan (Trp) enhanced the activity of Co2+ approximately 8 times and was identified as the best stimulator. The study revealed the synergy of amino acids‐based species and HCO3− for efficient catalysis. Co2+ is proposed to bind simultaneously to HCO3− and Trp, and to form a ternary catalyst which facilitates the generation of reactive oxygen species. Based on the selective boosting by Trp, a simple and low‐cost Co2+ sensor with high sensitivity was developed, which showed a linear range of 10–300 μM and a limit of detection of 0.4 μM for Co2+. [ABSTRACT FROM AUTHOR]

Objective: To monitor cobalt concentrations in urine, red blood cells and plasma after chronic parenteral administration of cobalt chloride evaluate these results against the current International Federation of Horseracing Authorities thresholds for detecting cobalt misuse. Design: Eight mares were randomly assigned to four treatment groups, with two mares in each group: Group 1 – control group, Group 2 – 25 milligrams cobalt intravenously as CoCl2 weekly, Group 3 – 50 milligrams cobalt intravenously as CoCl2 weekly, and Group 4 – 25 milligrams cobalt intravenously mid‐week and at the end of the week. Urine and blood samples were collected before each weekly administration so that trough levels were assessed. In the group receiving two doses per week, urine and blood were collected prior to the dose given at the end of each week. Samples were initially collected at time zero then weekly for 10 weeks. Three further collections of urine and blood were made at days 81, 106 and 127. Methods: Urine creatinine measurements to assess horse hydration status were performed by the Jaffe reaction method. Cobalt determinations in plasma, blood and urine were by inductively coupled plasma—mass spectrometry. Haematocrit concentrations, used to calculate red cell cobalt levels, were performed using a microhematocrit centrifuge. Statistical analyses were conducted in Genstat (v17, VSNi). Results: Marked cobalt accumulation was evident with increasing cobalt concentrations for all sample matrices in specimens collected immediately prior to cobalt administration. Correlation between the sample matrices improved when urine cobalt concentration was adjusted for creatinine level. Red cell cobalt levels remained elevated for at least 12 weeks after cessation of administration, consistent with the lifespan of the red cell. There was no significant change in haematocrit concentrations for the duration of the study. Conclusion: The current urine cobalt threshold was only effective at detecting acute cobalt exposure while the plasma cobalt threshold was able to consistently identify chronic high‐level cobalt exposure and potential cobalt misuse. The threshold values legislated for urine cobalt do not correlate with those set for plasma. The acute nature of urinary cobalt excretion provides a relatively small window through which cobalt administration is detected. Plasma and red cell cobalt concentrations can provide a clearer picture of potential cobalt misuse. [ABSTRACT FROM AUTHOR]

Wear particles generated by hip and knee arthroplasties disseminate to the liver and spleen with the highest concentrations observed in subjects who have had a failed arthroplasty. We asked to what extent metallic particles could also disseminate to remote hematopoietic bone marrow. Cored samples of red marrow from the axial skeleton and proximal humerus were obtained postmortem from four males and two females aged 79–92 years. Seven to seventeen years prior to their demise, each subject had undergone successful revision of their arthroplasty for mechanical failure in which an unintended wear condition had generated a large volume of metal particles. The marrow samples were analyzed using stained histological sections and energy dispersive X‐ray analysis. Intracellular metal alloy particles were detected in the bone marrow of the cranium, proximal humerus, sternum, ribs, lumbar vertebrae, and the iliac crest. The components previously revised for mechanical failure were confirmed to be the predominant source of the disseminated wear debris. Particles of either Ti, Ti6Al4V, CoCrMo, FeCrNi alloys, or BaSO4 were identified in 24 of the 25 marrow samples examined. The particles ranged in size from 50 nm (the limit of resolution of our technique) to 6 μm. Metallic wear particles generated by hip and knee arthroplasties can disseminate widely to hematopoietic bone marrow throughout the axial skeleton and proximal humerus, especially in cases with a history of severe wear. The hematopoietic microenvironment is potentially sensitive to metallic degradation products. However, actual medical sequelae from disseminated wear debris is a rare occurrence. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1930–1936, 2019. [ABSTRACT FROM AUTHOR]