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The concentration of sodium ions can cause severe imbalances (high pressure on blood vessels, swelling of the muscular tissues, and misfunctioning of the whole nervous system) to the human body when its limits are uncontrolled. Thus, it is necessary to determine the amount of sodium ions present in the blood. Electrochemical sensing is an efficient methodology for detecting lower concentrations of ions even with fewer samples. Calixarenes are one of the supramolecules with a distinctive structure that has a predominant ability to complex with alkali metals. Thus, calixarenes are widely used in the detection of sodium (Na + ) ions. Herein, 4- tert -butylcalix[4]arene, the simplest and cheapest calixarene, is used to deduce sodium ion concentration by electrochemical sensing approach. The sensitivity of the 4- tert -butylcalix[4]arene/GCE was 0.35269 μA M -1 and the limit of detection was 0.1 ± 0.06 μM, the lowest range of detection reported for sodium ions through differential pulse voltammetry, which is an accurate analysis. This is because calixarenes can interact with sodium ions efficiently through the hydrophilic OH groups at the lower rim of the calixarene structure. The interaction of Na + ions with phenolic OH was confirmed by proton NMR titration against NaOH. 4- tert -Butylcalix[4]arene/GCE is adequately selective against various interfering metal ions, and it can also detect sodium ions with high accuracy (recovery range = 99.25-100.01%) in bovine serums.

Enhancing early-stage breast cancer detection requires integrating additional screening methods with current diagnostic imaging. Omics screening, using easily collectible serum samples, could serve as an initial step. Alongside biomarker identification capabilities, omics analysis allows for a comprehensive analysis of prevalent histological types-DCIS and IDC. Employing metabolomics, metallomics, and machine learning, could yield accurate screening models with valuable insights into organism responses. Serum samples of confirmed breast cancer patients were utilized to analyze metabolite and metal ion profiles, using two distinct analysis methods, proton NMR for metabolomics and ICP-OES for metallomics. The resulting responses were then subjected to discriminant analysis, progression biomarker exploration, examination of correlations between patients' metabolites and metal ions, and the impact of age and menopause status. Measured NMR spectra and metabolite relative integrals were used to achieve statistically significant discrimination through MVA between breast cancer and control groups. The analysis identified 24 metabolites and 4 metal ions crucial for discrimination. Furthermore, four metabolites were associated with disease progression. Additionally, there were important correlations and relationships between metabolite relative integrals, metal ion concentrations, and age/menopausal status subgroups. Quantified relative integrals allowed for discrimination between studied subgroups, validated with a holdout set. Feature importance and statistical analysis for metabolomics and metallomics extracted a set of common entities which in combination provides valuable insights into ongoing molecular disturbances and disease progression., (© 2024. The Author(s).)

Micronutrient deficiencies and excesses are closely related to developing and treating depression. Traditional and effective antidepressants include tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and lithium. There is no consensus on the fluctuation of zinc (Zn 2+ ), magnesium (Mg 2+ ), calcium (Ca 2+ ), copper (Cu 2+ ), iron (Fe 2+ ), and manganese (Mn 2+ ) ion levels in depressed individuals before and after therapy. In order to determine whether there were changes in blood and cerebrospinal fluid (CSF) levels of these ions in depressed patients compared with healthy controls and depressed patients treated with TCAs, SSRIs, or lithium, we applied a systematic review and meta-analysis. Using the Stata 17.0 software, we performed a systematic review and meta-analysis of the changes in ion levels in human samples from healthy controls, depressive patients, and patients treated with TCAs, SSRIs, and lithium, respectively. By searching the PubMed, EMBASE, Google Scholar, Web of Science, China National Knowledge Infrastructure (CNKI), and WAN FANG databases, 75 published analyzable papers were chosen. In the blood, the levels of Zn 2+ and Mg 2+ in depressed patients had decreased while the Ca 2+ and Cu 2+ levels had increased compared to healthy controls, Fe 2+ and Mn 2+ levels have not significantly changed. After treatment with SSRIs, the levels of Zn 2+ and Ca 2+ in depressed patients increased while Cu 2+ levels decreased. Mg 2+ and Ca 2+ levels were increased in depressed patients after Lithium treatment. The findings of the meta-analysis revealed that micronutrient levels were closely associated with the onset of depression and prompted more research into the underlying mechanisms as well as the pathophysiological and therapeutic implications., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aimed to investigate the long-term serum metal ion levels of patients who received metal-on-metal hip resurfacing arthroplasty (MoM HRA). We conducted a retrospective study of 99 patients (110 hips) from March 2006 to May 2017 who underwent MoM HRA. The Harris Hip Score (HHS) and the University of California at Los Angeles (UCLA) activity score were measured, and the patients underwent clinical and radiological management. Serum levels of cobalt (Co), chromium (Cr), and molybdenum (Mo) were measured using inductively coupled plasma mass spectrometry (ICPMS) at 1, 6, and 12 months, and each year follow-up after prosthesis implantation. Patients were followed up from 1 to 156 months, with a mean of 98 months. No complications occurred. Metal ion analysis revealed significantly elevated levels compared to preoperative levels. The metal ions levels increased and reached a peak after surgery, and then the levels began to decline gradually. Approximately 84-108 months after surgery, the metal ion levels increased again to approximately peak levels. Then, up to 156 months after surgery, the metal ions levels will drop approximately to preoperative levels. The serum levels of Cr in women were higher than those in men, with the difference being statistically significant. Patients with a body mass index (BMI) of ≥24.9 kg/m2 Co levels were significantly higher than those of normal-weight patients. The serum levels of metal ions showed no significant differences between the prostheses. The use of the MoM HRA was clinically effective, and the Co, Cr, and Mo levels increased significantly after HRA; however, upon long-term follow-up, serum metal ion levels tended to decrease to preoperative levels. Longer follow-up periods and larger study samples are needed to establish the long-term outcome of patients undergoing HRA with MoM bearings. Level IV, Therapeutic Study.

Background: There is a gap of knowledge regarding cerebrospinal fluid (CSF) ion concentrations in normal and pathological states, particularly during the neonatal period. We aim to compare CSF ion concentrations in newborns with different causes of neonatal-onset epilepsy (NOE) and acute symptomatic seizures (ASS) and controls, to examine their usefulness for diagnostic purposes., Methods: A descriptive retrospective study was conducted from January 2019 to June 2020 in a tertiary hospital. We analyzed CSF K + , Na + , Cl -, and Ca 2+ concentrations in frozen samples from patients with neonatal seizures (NS) secondary to NOE and ASS (neonatal arterial ischemic stroke [NAIS] and hypoxic-ischemic encephalopathy). As the control group, we selected CSF samples from newborns who had undergone CSF analysis as part of the diagnostic workup and in whom central nervous system infections had been ruled out, without signs of dehydration, gastroenteritis, or history of seizures., Results: Sixty-eight newborns were included, 16 with NOE, 13 with ASS, and 39 without NS (control group). In comparison with the control group, [K + ] CSF was lower in patients with KCNQ2-related epilepsy (P = 0.007), other causes of NOE (P = 0.010), and NAIS (P = 0.002). Changes in [Na + ] CSF , [Cl - ] CSF , and [Ca 2+ ] CSF were less consistent among subgroups., Conclusions: Here we report for the first time ionic imbalances in the CSF of neonates with NOE and NAIS. No differences were observed between newborns with different causes of NS. Further studies should be undertaken to investigate the physiopathology behind these changes and their impact on biological function., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The evaluation of the natural history prevalence of adverse local tissue reactions (ALTRs) using MRI has focused only on metal-on-metal (MoM) bearing surfaces without comparison to nonMoM bearing surfaces., Questions/purposes: To determine (1) the longitudinal changes and differences in blood metal ion levels in patients with hip resurfacing arthroplasty (HRA), ceramic-on-ceramic (CoC) THA, and metal-on-polyethylene (MoP) THA compared with those undergoing ceramic-on-polyethylene (CoP) THA; (2) how the longitudinal change of synovial reaction classification in patients with HRA, CoC THA, and MoP THA compares with those undergoing CoP THA, and whether there is an association between the presence of an ALTR or metallosis on MRI with corresponding patient-reported outcomes, or the presence of capsular dehiscence; and (3) differences in blood metal ion levels between patients undergoing HRA with an ALTR or metallosis on MRI and those with HRA without these conditions., Methods: Between March 2014 and February 2019, 22,723 patients underwent primary HRA and THA at one center. Patients received an HRA based on their desired athletic level after surgery and the presence of normal acetabular and proximal femoral bone morphology without osteopenia or osteoporosis. Two percent (342 of 22,723) of patients were contacted to participate, and 71% (243 of 342 hips in 206 patients) were enrolled for analysis at baseline. The patients underwent arthroplasty for degenerative joint disease, and 25 patients withdrew over the course of the study. We included patients who were more than 1 year postarthroplasty. All participants had an MRI examination and blood serum ion testing and completed a Hip Disability and Osteoarthritis Outcome Score survey annually for four years (baseline, year 1, year 2, year 3). Morphologic and susceptibility-reduced MR images were evaluated by a single radiologist not involved in the care of patients for the presence and classification of synovitis (Gwet AC1: 0.65 to 0.97), synovial thickness, and volume (coefficient of repeatability: 1.8 cm3). Linear mixed-effects models were used to compare the mean synovial thickness, synovial volume, and Hip Disability and Osteoarthritis Outcome Score subscales between bearing surfaces at each timepoint and within each bearing surface over time. Marginal Cox proportional hazards models were used to compare the time to and the risk of developing ALTR only, metallosis only, and ALTR or metallosis between bearing surfaces. All models were adjusted for age, sex, BMI, and length of implantation based on known confounders for hip arthroplasty. Adjustment for multiple comparisons was performed using the Dunnett-Hsu method., Results: Patients with unilateral HRA had higher cobalt and chromium serum ion levels (baseline: 1.8 ± 0.8 ppb, year 1: 2.0 ± 1.5 ppb, year 2: 2.1 ± 1.2 ppb, year 3: 1.6 ± 0.7 ppb) than those with unilateral CoP bearings (baseline: 0.0 ± 0.1 ppb, year 1: 0.1 ± 0.3 ppb, year 2: 0.0 ± 0.2 ppb, year 3: 0.0 ± 0.0 ppb) at all timepoints (p < 0.001 for each time point). More patients who received an HRA developed ALTR or metallosis on MRI than did patients with CoP bearings (hazard ratio 4.8 [95% confidence interval 1.2 to 18.4]; p = 0.02). There was no association between the longitudinal change of synovial reaction to ALTR or metallosis on MRI with patient-reported outcomes. In addition, there was no association between the presence of dehiscence at baseline and the subsequent development of ALTR or metallosis, as seen on MRI. There were elevated cobalt (4.7 ± 3.5 ppb) and chromium (4.7 ± 2.6 ppb) serum levels in patients with unilateral HRA who had an ALTR or metallosis present on MRI at year 1 compared with patients without an ALTR or metallosis on MRI (cobalt: 1.8 ± 1.0 ppb, mean difference 4.7 ppb [95% CI 3.3 to 6.0]; p < 0.001; chromium: 2.3 ± 0.5 ppb, mean difference 3.6 ppb [95% CI 2.2 to 5.0]; p < 0.001) as well as for chromium at year 3 (3.9 ± 2.4 ppb versus 2.2 ± 1.1 ppb, mean difference 1.3 ppb [95% CI 0.3 to 2.4]; p = 0.01)., Conclusion: We found a higher proportion of ALTR or metallosis on MRI in patients with HRA compared with patients with CoP, even when patient self-assessed symptomatology of those with an ALTR or metallosis on MRI was not different than the absence of these features. MRI detected ALTRs in high-function patients, emphasizing that an annual clinical assessment dependent on survey or blood ion testing alone may not detect soft tissue complications. The results of this study are in line with prior consensus recommendations of using MRI as part of a routine follow-up protocol for this patient population., Level of Evidence: Level III, therapeutic study., Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2021 by the Association of Bone and Joint Surgeons.)

The aim of this study was to evaluate the performance, hematological responses and economic indicators of juvenile tambaqui Colossoma macropomum fed different levels of partial replacement of corn by glycerol (0%, 25%, 50%, 75%, and 100%). The experiment was conducted for 90 days in the production of aquatic organisms lab at the Nilton Lins University, Manaus, Brazil, in a completely randomized design, and consisted of four treatments, four repetitions and two sampling times. In total, 240 juveniles were used with initial average weight and standard length of 15.32 ± 1,61 g and 8.03 ± 0.22 cm, respectively. The fish were maintained in twenty 310 L water tanks that had a closed system with no reuse, continuous aeration, siphoning and replacement of water every 48 h. Feeding was twice a day with the experimental diets, which contained 28% crude protein. The following parameters were considered: zootechnical checks (weight gain + survival %), welfare (health) (hepatosomatic index + condition factor + viscerosomatic index), economic (Economic efficiency rate + economic profitability index) and hematology (hematology + metabolites + ions). The results of the study show that diets for juvenile tambaqui can contain up to 50% replacement of corn by glycerol without compromising the fishes' development under the conditions studied., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The metal/metal alloy-based implants and prostheses are in use for over a century, and the rejections, revisions, and metal particle-based toxicities were reported concurrently. Complications developed due to metal ions, metal debris, and organo-metallic particles in orthopedic patients have been a growing concern in recent years. It was reported that local and systemic toxicity caused by such released products from the implants is one of the major reasons for implant rejection and revision. Even though the description of environmental metal toxicants and safety limits for their exposure to humans were well established in the literature, an effort was not adequately performed in the case of implant-based metal toxicology. Since the metal ion concentration in serum acts as a possible indicator of the systemic toxicity, this review summarizes the reported human serum safe limits, toxic limits, and concentration range (μg/L, ppb, etc.) for mild to severe symptoms of six (cardiac, hepatic, neuro, nephron, dermal and endocrine) systemic toxicities for twelve most commonly used metallic implants. It also covers the widely used metal ion quantification techniques and systemic toxicity treatments reported., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021. Published by Elsevier B.V.)

A highly selective and sensitive photoelectrochemical (PEC) detection method has been developed for the analysis of copper (Cu2+) ions using nanoflower-like ZnO@CdS heterojunctions, of which ZnO was first in situ grown onto the indium tin oxide electrodes by a hydrothermal method and then coated with CdS through the chemical bath deposition route. It was discovered that the ZnO@CdS heterojunction so formed could serve as a photosensitive catalyst with improved charge separation for visible-light-driven PEC responses. Enhanced visible-light harvesting of nanocomposites could also be expected with CdS as the visible-light sensitizer. Furthermore, the introduction of Cu2+ ions could cause a rational decrease in the photocurrents of nanocomposites through the specific interaction between CdS and Cu2+ ions. A ZnO@CdS heterojunction-based PEC sensor was thereby developed for the detection of Cu2+ ions in blood in the linear concentrations ranging from 0.50 to 80 nM, with a limit of detection of 0.18 nM. Such a heterojunction-based PEC detection platform constructed using two photocatalytic materials with matched band structures are promising for a wide range of applications for sensing Cu2+ ions in clinical diagnostics, food monitoring, and environmental analysis.

Aims: Dual mobility (DM) implants have been shown to reduce the dislocation rate after total hip arthroplasty (THA), but there remain concerns about the use of cobalt chrome liners inserted into titanium shells. The aim of this study was to assess the clinical outcomes, metal ion levels, and periprosthetic femoral bone mineral density (BMD) at mid-term follow-up in young, active patients receiving a modular DM THA., Methods: This was a prospective study involving patients aged < 65 years, with a BMI of < 35 kg/m 2 , and University of California, Los Angeles activity score of > 6 who underwent primary THA with a modular cobalt chrome acetabular liner, highly cross-linked polyethylene mobile bearing, and a cementless titanium femoral stem. Patient-reported outcome measures, whole blood metal ion levels (μg/l), and periprosthetic femoral BMD were measured at baseline and at one, two, and five years postoperatively. The results two years postoperatively for this cohort have been previously reported., Results: A total of 43 patients were enrolled. At minimum follow-up of five years, 23 (53.4%) returned for clinical and radiological review, 25 (58.1%) had metal ion analysis performed, 19 (44.2%) underwent dual energy x-ray absorptiometry scans, and 25 (58%) completed a pain-drawing questionnaire. The mean modified Harris Hip Scores improved significantly from 54.8 (SD 19) preoperatively to 93.08 (SD 10.5) five years postoperatively (p < 0.001). One patient was revised for aseptic acetabular loosening. The mean cobalt levels increased from 0.065 μg/l (SD 0.03) to 0.08 (SD 0.05) and the mean titanium levels increased from 0.35 (SD 0.13) to 0.78 (SD 0.29). The femoral BMD ratio decreased in Gruen Zone 1 (91.9%) at five years postoperatively compared with the baseline scores at six weeks potoperatively. The femoral BMD ratio was maintained in Gruen zones 2 to 7., Conclusion: The use of a modular DM component and a cementless, tapered femoral stem shows excellent mid-term survivorship with minimal concerns for corrosion and metal ion release in a cohort of young, active patients undergoing primary THA. Cite this article: Bone Joint J  2021;103-B(7 Supple B):73-77.

Background and purpose - Modular-neck hip stems have been identified with corrosion-related problems from the neck-stem junction. We report an ongoing varus deformity of modular-neck hip stems with simultaneous metal ion release observed during a study comparing the migration of modular vs. standard hip stems.Patients and methods - We followed 50 patients with modular and 25 with standard neck stems using radiostereometry (RSA). At 5-year follow-up, we noted a compromised integrity of the modular stem with varus deformity in the neck-stem interface. Changes in head-tip distance as well as whole-blood ion concentration and MRI findings were analyzed. The modular stems were followed further up to 8 years.Results - The head-tip distance decreased continuously by 0.15 mm per year resulting in 1.2 (95% CI 1.0-1.4) mm at 8 years for modular stems, while for the standard stems at 5 years, the decrease was 0.09 (CI 0.0-0.2) mm or 0.02 mm/year. For the modular stems, the reduction in head-tip distance correlated to the increase in whole-blood cobalt concentration at 8 years but not to the MRI grading of tissue reactions. At 5 years, cobalt levels were 4.9 µg/L for modular stems and at 8 years 4.8 µg/L, whereas for standard stems this was 1.0 µg/L. After 8 years, 9 of 72 stems had been revised for different reasons, but only 1 with obvious adverse local tissue reaction (ALTR).Interpretation - We present a surprisingly large progressive deformation at the modular neck-stem junction, but so far without a definite clinical problem. Even the femoral head seems to show slight compression onto the taper over time. A high rate of revisions for the modular type of this stem has raised general concerns, and it has been recalled from the market.

Study Design: Prospective 2-year study with operative sampling and in-vitro analysis of chromium ions following spinal surgery in children., Objectives: To measure metal ion levels at preoperative, intraoperative, and postoperative times to determine patterns of metal ion release during instrumented spinal surgery., Summary of Background Data: Raised serum metal ion levels are reported following instrumented spinal fusion in adolescent idiopathic scoliosis. The authors noted raised chromium levels in patients receiving implants that did not contain chromium. This prompted further work to establish the source. The electrosurgery tips used were discovered to contain 17% chromium., Methods: Chromium, cobalt, and titanium levels were measured before, during, and after surgery in serum and local intraoperative fluid samples in 11 children undergoing posterior instrumentation for scoliosis. Administered drugs, cell-saver fluids, and intraoperative fluids, both local and intravenous, were investigated to exclude these as sources of chromium ions. An in-vitro study was also performed to elucidate sources of intraoperative chromium ions., Results: High chromium levels were detected in all samples from the wound irrigation fluid prior to insertion of metal implants. Immediate postoperative chromium serum ion levels were also elevated and returned to baseline by day 30. In-vitro sampling of fluids from test models using electrosurgery revealed high levels of chromium ions CONCLUSION.: This finding of high chromium metal ion concentrations in intraoperative and early postoperative samples provides evidence of chromium release during the dissection phase of spinal surgery. This challenges existing beliefs that metal ion release occurs solely due to implants and now implicates the electrosurgery electrode tips as a source of raised chromium ion levels. Thorough irrigation of the operative site after the dissection phase of surgery to both dilute and reduce the intraoperative chromium ion load is suggested. Alternative electrosurgery electrode tips or other methods to coagulate during surgery could be considered., Level of Evidence: 2.

Background: Aerobic blood sample collection and processing results in increased serum pH and decreased ionised calcium (iCa) concentration. This prospective study aimed to determine the effect of pH and storage conditions on measured iCa concentration in serum samples obtained from dogs and cats and establish correction formulas for use in samples obtained aerobically., Methods: Blood samples were collected from 44 dogs and 25 cats; iCa and pH were measured immediately under anaerobic conditions and in samples stored under several aerobic conditions., Results: Measured iCa concentrations were significantly lower in samples stored at all aerobic conditions than in samples handled anaerobically in both dogs and cats (P<0.01 for all). The largest and most clinically significant differences were noted in samples stored at -20°C for 30 days in both dogs (0.48 mmol/l; 95 per cent CI 0.40 to 0.55) and cats (0.40 mmol/l; 95 per cent CI 0.33 to 0.47). Correction formulas (corrected iCa=measured iCa+coefficient × (measured pH-7.41); coefficient=0.597 for dogs, 0.627 for cats) yielded good agreement between the corrected and the actual iCa concentrations., Conclusions: Samples for iCa measurement can be stored at either 4°C or -20°C for 24 hours. Storage at -80°C is recommended for longer storage time periods., Competing Interests: Competing interests: None declared., (© British Veterinary Association 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Ions are ubiquitous biological regulators playing a key role for vital processes in animals and plants. The combined detection of ion concentration and real-time monitoring of small variations with respect to the resting conditions is a multiscale functionality providing important information on health states. This multiscale functionality is still an open challenge for current ion sensing approaches. Here we show multiscale real-time and high-sensitivity ion detection with complementary organic electrochemical transistors amplifiers. The ion-sensing amplifier integrates in the same device both selective ion-to-electron transduction and local signal amplification demonstrating a sensitivity larger than 2300 mV V -1 dec -1 , which overcomes the fundamental limit. It provides both ion detection over a range of five orders of magnitude and real-time monitoring of variations two orders of magnitude lower than the detected concentration, viz. multiscale ion detection. The approach is generally applicable to several transistor technologies and opens opportunities for multifunctional enhanced bioelectronics.

Objectives: We sought to test the strength of correlation between predicted and observed systemic acid-base status based on the Stewart model equations during continuous infusion (CI) furosemide therapy., Design, Setting and Participants: This was a prospective, single-center, observational study conducted in the Surgical ICU of a large academic medical center. Ten critically ill patients who received CI furosemide were included., Main Outcomes and Measures: The primary purpose was to characterize the relationship between changes in serum electrolyte and acid-base status and the excretion of electrolytes in the urine during infusion of CI furosemide in critically ill patients. As a secondary endpoint, we sought to evaluate the predictive application of the Stewart model. Over 72-h, intake and output volumes, electrolyte content of fluids administered, plasma and urine electrolytes, urine pH, and venous blood gases were collected. Predicted and observed changes in acid-based status were compared for each day of diuretic therapy using Spearman's correlation coefficient., Results: The mean (SD) strong ion difference (SID) increased from 45.2 (3.2) at baseline to 49.6 (4.0) after 72 h of continuous infusion furosemide. At Day 1, the mean SID (observed) (SD) was 47.5 (3.5) and the predicted SID was 49.5 (5.8). Day 1 observed plasma SID was positively correlated with the predicted SID (r s  = 0.80, p = 0.01). By Days 2 and 3, the correlations of observed and predicted SID were no longer statistically significant., Conclusions and Relevance: Using the Stewart model, increases in SID as an indicator of metabolic alkalosis due to the chloruretic effects of furosemide were observed. Predicted and observed SID correlated well over the first 24 h of treatment.

The aim of this study was to evaluate the levels of As, Be, Bi, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Se, Tl, V, and Zn, by inductively coupled plasma-mass spectrometry (ICP-MS) in the urine of two groups of patients with two different types of metal-on-metal (MoM) total hip prostheses (ASR DePuy ® , group A, 25 patients; total Met-Met System Lima ® , group B, 28 patients). The determination of metals reflected a steady-state release (group A: 9 years after surgery and group B: 6 years after surgery). The results obtained confirmed the increase of Co and Cr urinary levels in both group when compared with the reference values for the general population adopted by the Italian Society of Reference Values (SIVR). In particular, Co and Cr levels exceeded the threshold values in urine, respectively, of 30 μg and 21 µg, adjusted to creatinine based on the threshold in whole blood of 7 μg/L proposed by the Medicines and Healthcare Products Regulatory Agency (MHRA). Regarding the other investigated metals, significantly higher values were found in Group A than in Group B. These differences could be due to the type of hip prosthesis implanted, the longer period of time since the implantation, as well as many other factors such as diet, age, drug consumption, physical activity, or presence of dental fillings. The continuous monitoring over the years of metal concentrations in patients carrying a prosthesis could be useful to better identify the sources of these metals.

In this study, an electromembrane extraction-dispersive liquid-liquid microextraction (EME-DLLME) was performed using a lab-on-a-disc device. It was used for sample microextraction, preconcentration, and quantitative determination of tricyclic antidepressants as model analytes in biofluids. The disc consisted of six extraction units for six parallel extractions. First, 100 μL of a biofluid was used to extract the analytes by the drop-to-drop EME to clean-up the sample. The extraction then was followed by applying the DLLME method to preconcentrate the analytes and make them ready for being analyzed by gas chromatography (GC). Implementing the EME-DLLME method on a chip device brought some significant advantages over the conventional methods, including saving space, cost, and materials as well as low sample and energy consumption. In the designed device, centrifugal force was used to move the fluids in the disc. Both sample preparation methods were performed on the same disc without manual transference of the donor phases for doing the two methods. Scalable centrifugal force made it possible to adjust the injection speed of the organic solvent into the aqueous solution in the DLLME step by changing the spin speed. Spin speed of 100 rpm was used in dispersion step and spin speed of 3500 rpm was used to sediment organic phase in DLLME step. The proposed device provides effective and reproducible extraction using a low volume of the sample solution. After optimization of the effective parameters, an EME-DLLME followed by GC-MS was performed for determination of amitriptyline and imipramine in saliva, urine, and blood plasma samples. The method provides extraction recoveries and preconcentration factors in the range of 43%-70.8% and 21.5-35.5 respectively. The detection limits less than 0.5 μg L -1 with the relative standard deviations of the analysis which were found in the range of 1.9%-3.5% (n = 5). The method is suitable for drug monitoring and analyzing biofluids containing low levels of the model analytes., 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 © 2020 Elsevier B.V. All rights reserved.)

Background and Aim: Major and trace elements play an important role in human body, and it has been reported that ionomic distribution differ greatly in tumor patients. The aim of the present study was to investigate the effects of cisplatin-based neoadjuvant chemoradiotherapy on the ionomic profile in human plasma as a potential biomarker for the therapeutic effects of cervical cancer., Method: Thirty-seven patients with cervical cancer receiving neoadjuvant chemoradiotherapy were included in this study, pretherapy and post-treatment blood samples were collected and concentrations of 24 ions were analyzed by inductively coupled plasma mass spectrometry (ICP-MS)., Results: The results showed that after cisplatin chemotherapy and radiotherapy, patients' plasma Pt level significantly increased, Na, Mg, P, K, Ca, Se, Cu, Zn, Se, Sr, Ba levels significantly decreased (P < 0.01), and Al, Cu ions were significantly correlated with the treatment effect (P < 0.05). In addition, the pattern of elemental correlations changed dramatically after the neoadjuvant chemoradiotherapy., Conclusion: The results indicated that the plasma ionomic profile may serve as a quick and convenient tool to reflect the therapeutic effect of cisplatin-based chemoradiotherapy in cervical cancer patients, and supplement of certain essential elements may be of great importance for the maintenance of ion homeostasis in human body and for the reduction of adverse effect of chemotherapy and radiotherapy., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Cell membrane potential and inorganic ion distributions are currently viewed from a kinetic electric paradigm, which ignores thermodynamics. The resting membrane potential is viewed as a diffusion potential. The 9 major inorganic ions found in blood plasma (Ca 2+ , Na + , Mg 2+ , K + , H + , Cl - , HCO 3 - , H 2 PO 4 - , and HPO 4 2- ) are distributed unequally across the plasma membrane. This unequal distribution requires the energy of ATP hydrolysis through the action of the Na + -K + ATPase. The cell resting membrane potential in each of 3 different tissues with widely different resting membrane potentials has been shown to be equal to the Nernst equilibrium potential of the most permeant inorganic ion. The energy of the measured distribution of the 9 major inorganic ions between extra- and intracellular phases was essentially equal to the independently measured energy of ATP hydrolysis, showing that the distribution of these 9 major ions was in near-equilibrium with the Δ G ' of ATP. Therefore, thermodynamics does appear to play an essential role in the determination of the cell resting membrane potential and the inorganic ion distribution across the plasma membrane.-Veech, R. L., King, M. T., Pawlosky, R., Bradshaw, P. C., Curtis, W. Relationship between inorganic ion distribution, resting membrane potential, and the Δ G ' of ATP hydrolysis: a new paradigm.

Background and purpose - A risk-stratification algorithm for metal-on-metal hip arthroplasty (MoMHA) patients was devised by US experts to help clinicians make management decisions. However, the proposed algorithm did not cover all potential patient or surgical abnormalities. Therefore we adapted the US risk-stratification algorithm in MoMHA patients revised for adverse reactions to metal debris (ARMD) to determine the variability in the revision threshold, and also whether high-risk patients had inferior outcomes following revision.Patients and methods - We analysed 239 MoMHA revisions for ARMD between 2001 and 2016 from 2 centres with pre-revision blood metal ions and imaging. Patients were stratified (low risk, moderate risk, high risk) using pre-revision factors (implant, radiographic, blood metal ions, cross-sectional imaging) by adapting a published algorithm. The risk categories for each factor were assessed against revision year, revision centre, and post-revision outcomes (re-revision surgery, and any poor outcome).Results - Compared with hips revised before 2012, hips revised from 2012 onwards included more high-risk implants (44% vs. 17% pre-2012), high-risk radiographic features (85% vs. 69% pre-2012), and low-risk metal ions (41% vs. 19% pre-2012). 1 centre more frequently revised patients with high-risk implants (48% vs. 14%) and low-risk blood metal ions (45% vs. 15%) compared with the other. All these comparisons were statistically significant (p < 0.05). With the limited sample size available, implant, radiographic, blood metal ion, and cross-sectional imaging risk groups did not statistically significantly affect the rates of re-revision surgery or frequency of poor outcomes post-revision.Interpretation - When applying the adapted risk-stratification algorithm the threshold for ARMD revision changed over time, presumably due to increasing evidence, patient surveillance, and investigation since 2012. Lower blood metal ion thresholds were used from 2012 for ARMD revisions; however, there was evidence that centres attached different importance to metal ions when managing patients. High-risk patients did not have inferior outcomes following ARMD revision.

For lack of feasible interval values from population differences and potential analytical discrepancies, it is essential to ascertain potassium (K), sodium (Na), chlorine (Cl), calcium (Ca), and phosphorus (P) ions reference intervals within Chinese children to fill the gap. Healthy children ( n  = 1391, 2-<15 years old) were recruited from communities and schools to establish sex- and age-specific serum electrolyte reference intervals of Han children in Changchun, China. Levels of serum K, Na, Cl, Ca, and P were measured using a Hitachi 7600-210 automatic biochemical analyzer. Reference intervals were established according to Clinical and Laboratory Standards Institute EP28-A3c guidelines. Data from five representative hospitals located across Changchun were used to verify pediatric serum electrolyte reference intervals. Values were different from adult reference intervals in China. There were sex-specific differences in Na, Cl, Ca, and P reference intervals in 13-<14 children. Serum Na, Cl, and Ca reference intervals showed stable trends within early age groups but fluctuated in teens. Each serum electrolyte had ≤3 age-specific reference intervals. Five laboratories suggested reference intervals were applicable across Changchun., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2019 Qi Zhou et al.)

Introduction: Metal-on-metal (MoM) hip arthroplasties have shown high clinical failure rates with many patients at risk for a revision and under surveillance for high metal ion concentrations. Implant wear releasing such ions is assumed to be a function of use, i.e. the patient's physical activity. This study aimed to assess whether habitual physical activity levels of MoM patients are correlated with metal ion concentrations and are higher in patients with high (at risk) than in patients with low (safe) metal ion concentrations., Methods: A cohort study was conducted of patients with any type of MoM hip prosthesis. Metal ion concentrations were determined using ICP-MS. Habitual physical activity of subjects was measured in daily living using an acceleration-based activity monitor. Outcome consisted of quantitative and qualitative activity parameters., Results: In total, 62 patients were included. Mean age at surgery was 60.8 ± 9.3 years and follow-up was 6.3 ± 1.4 years. Cobalt concentrations were highly elevated overall (112.4 ± 137.9 nmol/L) and significantly more in bilateral (184.8 ± 106.5 nmol/L) than in unilateral cases (87.8 ± 139.4 nmol/L). No correlations were found between physical activity parameters and metal ion concentrations. Subgroup analysis of patients with low versus high cobalt concentration showed no significant differences in habitual physical activity., Discussion: No correlation was found between physical activity levels and metal ion concentrations. Implant use by normal habitual activities of daily living seems not to influence metal ion concentrations.

Blooms of cyanobacteria, a common event in eutrophic environments, result in the release of potentially toxic substances into the water. The cyanobacterium Radiocystis fernandoi produces microcystin (MC) and other peptides that may disturb homeostasis. This study evaluated the effect of intraperitoneal injections containing the crude extract (CE) of R. fernandoi strain R28 on the gills and kidneys of neotropical fish, Piaractus mesopotamicus, 3, 6 and 24 h post-injection. CE contained MC-RR, MC-YR and minor other oligopeptides. Plasma ions and the activities of the enzymes PP1 and PP2A, Na + /K + -ATPase (NKA), H + -ATPase (HA) and carbonic anhydrase (CA) were determined and morphological changes in both the gills and kidneys were characterized. Compared to controls, the concentration of Na + within the plasma of P. mesopotamicus decreased after treatment with CE 3 h post treatment and increased after 24 h; the concentration of K + decreased after 6 h. The activity of the endogenous PP1 and PP2A was unchanged in the gills and was inhibited in the kidneys 6 h after i.p. injection. In the gills, NKA activity increased after 3 h and decreased 6 h post i.p. exposure. Further, NKA activity did not differ from the controls 24-h post injection. In the kidneys, NKA, HA and CA activities were unaffected by treatment. The mitochondria-rich cell (MRC) density in the gills decreased after 3 h in the filament and 3 and 6 h in the lamellae and was restored to the control levels 24 h post-exposure. Filament epithelial hyperplasia and hypertrophy, lamellar atrophy and rupture of the lamellar epithelium were the most common effects of treatment in the gills. No histopathological changes occurred in the kidneys. This study demonstrates that a single dose of toxic CE from R. fernandoi can cause a transitory ion imbalance in P. mesopotamicus which is related to the changes in MRC levels and NKA activity. Ionic balance was recovered 24 h post i.p. injection, however, morphological changes that occurred in the gills took a longer amount of time to return to normal. To conclude, the effects of components contained within the CE of R. fernandoi may be harmful to P. mesopotamicus. In particular, the recovery of ionic regulation depends on MRC responses and histopathological changes produced by CE may affect gas exchange and other gill functions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Preserved blood cells undergo progressive structural and functional changes that may affect their function, integrity, and viability after transfusion. The impact of transfusion of stored blood on potassium, sodium, or acid-base balance in the recipient may be complex, but information on it is inconsistent. This study therefore sought to determine the changes in the potassium and sodium levels in whole blood stored at 4°C for 28 days and clinical outcomes when such blood are transfused., Methods: Whole blood were taken into double CPDA-1 bags and 50 ml transferred into the satellite bags for the study. Electrolyte concentration determinations were made on each of the blood sample on days 0, 7, 14, 21, and 28 using the Vitalab Selectra Junior chemistry analyser. The remaining blood in the main bags was transfused after the 28-day period, and biochemical analysis carried out on the patients before and after the transfusion. One-way ANOVA was used for the analysis of variance between the weekly ion concentrations and independent sample Mann-Whitney U test for the data obtained from the patients., Results: The mean potassium level of all the samples started with a normal value of 3.45 mmol/L on the first day followed by a sharp rise to 9.40 mmol/L on day 7, 13.40 mmol/L on day 14, 14.60 mmol/L on day 21, and 15.40 mmol/L on day 28. Sodium on the other hand started with a high value of 148.4 mmol/L on day 0 and then reduced to 146.4 mmol/L on day 7, 140.8 mmol/L on day 14, 135.6 mmol/L on day 21, and a low value of 130.8 mmol/L on day 28. No adverse clinical outcomes were seen in patients after they were transfused with the blood., Conclusion: It can be deduced that potassium concentration in refrigerated blood increases, whilst sodium concentration reduces with time and when such blood is transfused, it may not result in any adverse clinical outcome., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Samuel Antwi-Baffour et al.)

Background: Elevated serum levels of chromium and cobalt ions in metal-on-metal (MoM) bearing surfaces is a well-known phenomenon in THA. However, few studies have addressed this issue in complex primary and revision knee arthroplasty using a MoM hinged mechanism, and no study, to our knowledge, has investigated knees with MoM hinges in patients without megaprostheses (tumor prostheses)., Questions/purposes: We analyzed a series of patients who received MoM hinged revision knee prostheses and asked: (1) What are the serum metal ion levels at short-term followup? (2) Is there any correlation between metal ion levels and the Knee Society Score (KSS) at this followup?, Methods: Between 2013 and 2017, we performed 198 revision knee arthroplasties, of which 32 (17.7%) were performed with a latest-generation MoM hinge knee design. In addition, three complex primary TKAs utilizing the same design were included in this study. The device features a metal-on-polyethylene bearing with a MoM hinge. During that period, our general indications for using a hinge were single-stage and two-stage revision surgeries, revisions with large bone defects, and primary TKA with > 20° mechanical malalignment or collateral ligament insufficiency. Of the 35 patients who received this device, 23 patients (65% of the overall group who received this implant; 11 males, 12 females) were available for followup at a median of 28 months (range, 13-61 months), and the remaining 12 (35%) patients were lost to followup. Our rationale for reporting before the more typical 2-year minimum was the finding of elevated serum ion levels with unclear clinical significance. Median age at the time of surgery was 68 years (range, 52-84 years). None of the patients included in the study had other implants with MoM bearings. Serum ion levels of chromium (III) and cobalt were assessed using mass spectrometry. Ion levels > 5 ppb were considered elevated. Clinical outcome was assessed using the original KSS., Results: Median chromium serum level was 6.3 ppb (range, 0.6-31.9 ppb) and median cobalt serum level was 10.5 (range, 1.0-47.5 ppb). Of the 23 patients, 16 had elevated serum ion levels. There was a moderate correlation between KSS and both chromium (p = 0.029, r = 0.445) and cobalt (p = 0.012, r = 0.502) levels., Conclusions: Elevated metal ion levels and radiolucent lines are common after surgery with this MoM hinge design at short-term followup, and we believe this finding is of great concern. Although no patient has yet been revised, these patients will be closely monitored. We recommend that serum ion analysis become a routine part of followup after any hinge TKA in an attempt to better understand the potential consequences of this phenomenon., Level of Evidence: Level IV, therapeutic study.

A droplet-based microfluidic synthesis approach for preparation of ficin capped gold nano clusters (AuNCs) was developed. Well dispersed AuNCs could be procured within 8 min. Upon excitation wavelength at 340 nm, the resultant AuNCs exhibited a strong blue fluorescence with the maximum emission at 450 nm. Due to the aggregation-induced "turn-off" fluorescence mechanism, the synthesized AuNCs as a fluorescent probe displayed high sensitivity and good selectivity for sensing ferric ions. The relative fluorescence intensity versus ferric ions concentration yielded a good linear calibration in the range of 10.0-1000.0 μM (R 2 = 0.998) and the limit of detection was 4.1 μM. Moreover, the possible mechanism for abated fluorescence intensity of AuNCs by adding ferric ions was discussed briefly. Further, the as-prepared fluorescent AuNCs was successfully applied for the detection of serum ferric ions. The results indicated that the droplet-based microfluidic synthesis system could provide a new way for the rapid preparation of AuNCs with good polydispersity and have potential as the sensing probes for the analysis of ferric ions in real biological samples., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The present work aimed to provide a novel chemosensor for ferric ion detection in human serum samples using nano-structured Mg-Al layered double hydroxide intercalated with salicylic acid (Mg-Al LDH-SA) as a sensitive fluorescence probe. The Mg-Al LDH-SA nanomaterial was synthesized and characterized via Fourier transform infrared spectroscopy, X-ray diffraction analysis, field emission scanning electron microscopy, dynamic light scattering and energy dispersive spectroscopy. The synthesized nanomaterial was applied to determine ferric ions by measuring the fluorescence intensity of Mg-Al LDH-SA sol solution at λ em  = 404 nm with excitation at λ ex  = 287 nm. In the presence of ferric ions, the fluorescence intensity decreases owing to the formation of a stable complex between ferric ions and salicylic acid. Several important parameters affecting the analytical signal were studied and optimized. Under optimum conditions, the calibration graph was linear in the concentration range of 0.07-100 μmol L -1 with a corresponding detection limit of 26 nmol L -1 . The intra- and inter-day relative standard deviations (n = 6 and ferric ion concentration; 50 μmol L -1 ) were 3.4% and 4.5%, respectively. The method was successfully employed to assess ferric ion in several human serum samples with relative recovery values between 98.7 and 104.6% for the spiked samples., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this era of global climate change, ocean acidification is becoming a serious threat to the marine ecosystem. Despite this, it remains almost unknown how fish will respond to the co-occurrence of ocean acidification with other conventional environmental perturbations typically salinity fluctuation and high ammonia threat. Therefore, the present work evaluated the interactive effects of elevated pCO 2 , salinity reduction and high environmental ammonia (HEA) on the ecophysiological performance of European sea bass (Dicentrarchus labrax). Fish were progressively acclimated to seawater (32 ppt), to brackish water (10 ppt) and to hyposaline water (2.5 ppt). Following acclimation to different salinities for at least two weeks, fish were exposed to CO 2 -induced water acidification representing present-day (control pCO 2 , 400 μatm, LoCO 2 ) and future (high pCO 2 , 1000 μatm, HiCO 2 ) sea-surface CO 2 level for 3, 7 and 21 days. At the end of each exposure period, fish were challenged with HEA for 6 h (1.18 mM representing 50% of 96 h LC 50 ). Results show that, in response to the individual HiCO 2 exposure, fish within each salinity compensated for blood acidosis. Fish subjected to HiCO 2 were able to maintain ammonia excretion rate (J amm ) within control levels, suggesting that HiCO 2 exposure alone had no impact on J amm at any of the salinities. For 32 and 10 ppt fish, up-regulated expression of Na + /K + -ATPase was evident in all exposure groups (HEA, HiCO 2 and HEA/HiCO 2 co-exposed), whereas Na + /K + /2Cl - co-transporter was up-regulated mainly in HiCO 2 group. Plasma glucose and lactate content were augmented in all exposure conditions for all salinity regimes. During HEA and HEA/HiCO 2 , J amm was inhibited at different time points for all salinities, which resulted in a significant build-up of ammonia in plasma and muscle. Branchial expressions of Rhesus glycoproteins (Rhcg isoforms and Rhbg) were upregulated in response to HiCO 2 as well as HEA at 10 ppt, with a more moderate response in 32 ppt groups. Overall, our findings denote that the adverse effect of single exposures of ocean acidification or HEA is exacerbated when present together, and suggests that fish are more vulnerable to these environmental threats at low salinities., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: The present study investigated the five-year interval changes in pseudotumours and measured serum metal ions at long-term follow-up of a previous report of 28 mm diameter metal-on-metal (MoM) total hip arthroplasty (THA)., Patients and Methods: A total of 72 patients (mean age 46.6 years (37 to 55); 43 men, 29 women; 91 hips) who underwent cementless primary MoM THA with a 28 mm modular head were included. The mean follow-up duration was 20.3 years (18 to 24). All patients had CT scans at a mean 15.1 years (13 to 19) after the index operation and subsequent follow-up at a mean of 20.2 years (18 to 24). Pseudotumour volume, type of mass, and new-onset pseudotumours were evaluated using CT scanning. Clinical outcomes were assessed by Harris Hip Score (HHS) and the presence of groin pain. Serum metal ion (cobalt (Co) and chromium (Cr)) levels were measured at the latest follow-up., Results: At final follow-up, pseudotumours were observed in 26/91 hips (28.6%). There was an increase in volume of the pseudotumour in four hips (15.4%), no change in volume in 21 hips (80.8%), and a decrease in volume in one hip (3.8%). There were no new-onset pseudotumours. There was no significant difference in HHS between patients with and without pseudotumours. At final follow-up, mean serum Co ion levels and median Co:Cr ratios were significantly greater in patients with pseudotumours, but the serum Cr ion levels were not significantly different., Conclusion: At a mean 20 years of follow-up, pseudotumours were observed in 26/91 hips (28.6%) with no new-onset pseudotumours during subsequent follow-up. Most pseudotumours in small-head MoM THA were static in volume and asymptomatic with normal serum metal ion levels. Cite this article: Bone Joint J 2019;101-B:317-324.

Background: Products from metal wear have been identified as a potential cause of adverse local tissue reactions and implant failure in total hip arthroplasty. However, the role of metal ion exposure in patients after total shoulder replacement is unclear. The objective of the present study was to determine in vivo blood metal ion levels of cobalt, chromium, and titanium in patients after anatomic total shoulder arthroplasty (TSA) or reverse TSA., Methods: A consecutive series of patients after anatomic TSA or reverse TSA was evaluated retrospectively. After exclusion of patients with additional metal implants, 40 patients with unilateral anatomic TSA (n = 20) or reverse TSA (n = 20) were available for whole-blood metal ion analysis at a mean follow-up of 28 ± 9.6 months. Twenty-three healthy individuals without metal implants served as a control group., Results: Mean cobalt ion concentrations were 0.18 µg/L (range, 0.1-0.66 µg/L), 0.15 µg/L (range, 0.03-0.48 µg/L), and 0.11 µg/L (range, 0.03-0.19 µg/L), mean chromium ion levels were 0.48 µg/L (range, 0.17-2.41 µg/L), 0.31 µg/L (range, 0.09-1.26 µg/L), and 0.14 µg/L (range, 0.04-0.99 µg/L), and mean titanium ion concentrations were 1.31 µg/L (range, 0.75-4.52 µg/L), 0.84 µg/L (range, 0.1-1.64 µg/L), and 0.62 µg/L (range, 0.32-2.14 µg/L) in the reverse TSA group, the anatomic TSA group, and the control group, respectively., Conclusions: TSA resulted in elevated metal ion levels compared with healthy controls, although overall metal ion concentrations measured in this study were relatively low. The role of local metal ion exposure in patients with total shoulder replacements should be further investigated., (Copyright © 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Waterborne ammonia is an environmental pollutant that is toxic to all aquatic animals. However, ammonia induced toxicity as well as compensatory mechanisms to defend against high environmental ammonia (HEA) are not well documented at present for largemouth bass (Micropterus salmoides), a high value fish for culture and sport fisheries in the United States. To provide primary information on the sensitivity of this species to ammonia toxicity, a 96 h-LC 50 test was conducted. Thereafter, responses at physiological, ion-regulatory and transcript levels were determined to get insights into the underlying adaptive strategies to ammonia toxicity. For this purpose, fish were progressively exposed to HEA (8.31 mg/L representing 25% of 96 h-LC 50 ) for 3, 7, 14, 21 and 28 days. Temporal effects of HEA on oxygen consumption rate (MO 2 ), ammonia and urea dynamics, plasma ions (Na + , Cl - and K + ), branchial Na + /K + -ATPase (NKA) and H + -ATPase activity, muscle water content (MWC), energy store (glycogen, lipid and protein) as well as branchial mRNA expression of Rhesus (Rh) glycoproteins were assessed. Probit analysis showed that 96 h-LC 50 of (total) ammonia (as NH 4 HCO 3 ) at 25 °C and pH 7.8 was 33.24 mg/L. Results from sub-lethal end-points shows that ammonia excretion rate (J amm ) was strongly inhibited after 7 days of HEA, but was unaffected at 3, 14 and 21 days. At 28 days fish were able to increase J amm efficiently and concurrently, plasma ammonia re-established to the basal level. Urea production was increased as evidenced by a considerable elevation of plasma urea, but urea excretion rate remained unaltered. Expression of Rhcg isoform (Rhcg2) mRNA was up-regulated in parallel with restored or increased J amm , suggesting its ammonia excreting role in largemouth bass. Exposure to HEA also displayed pronounced augmentations in NKA activity, exemplified by a rise in plasma [Na + ]. Furthermore, [K + ], [Cl - ] and MWC homeostasis were disrupted followed by recovery to the control levels. H + -ATPase activity was elevated but NKA did not appear to function preferentially as a Na + /NH 4 + -ATPase. From 14 days onwards MO 2 was depressed, potentially an attempt towards minimizing catabolism. Glycogen content in liver and muscle were temporarily depleted, whereas a remarkable increment in protein was evident at the last exposure period. Overall, these data suggest that ammonia induced toxicity can disturb several biological processes in largemouth bass, however, it can adapt to the long-term sub-lethal ammonia concentrations by activating various components of ammonia excretory, ion-regulatory and metabolic pathways., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Testing of whole blood or serum metal ion levels has become an important part of assessing and monitoring the performance of metal-on-metal bearings, both in hip resurfacing arthroplasty and in total hip replacement. The aim of this study was to determine the concordance between 2 laboratories testing cobalt and chromium ion levels in patients with metal-on-metal bearings., Methods: Serum and whole blood samples from patients who had undergone metal-on-metal resurfacing or large-diameter total hip arthroplasty were tested for cobalt and chromium ions in laboratory A (a recognized laboratory) and laboratory B (tasked with testing clinical specimens). Laboratory A performed cobalt and chromium testing on whole blood, and laboratory B performed cobalt testing on whole blood and chromium testing on serum., Results: Samples from 104 patients were tested. Laboratory B reported lower whole blood cobalt levels than laboratory A. Furthermore, laboratory A reported that all patients had elevated whole blood cobalt ion levels compared to the normal reference values for the laboratory, whereas laboratory B reported that 46 patients (44.2%) had whole blood cobalt ion levels within the normal reference range for the laboratory., Conclusion: This comparative study highlights the importance of using a single laboratory for metal ion testing, as values generated from different laboratories may not be directly comparable. With recent literature suggesting that whole blood cobalt levels as low as 1 ppb may be a predictor of adverse reactions to metal debris, accurate clinical measurement needs to be increasingly exact., Competing Interests: None declared., (© 2019 Joule Inc. or its licensors)

Background: Failure to restore femoral offset in metal on polyethylene total hip arthroplasty (THA) causes polyethylene wear and aseptic loosening. To our knowledge, no study to date has investigated the relationship between femoral offset and wear in metal-on-metal (MOM) THA., Aims: In this study, we investigated the relationship between femoral offset and wear by measuring circulating metal ion levels in MOM THA., Methods: In this retrospective study, we identified patients who had undergone MOM THA with the ASR XL system (DePuy International Ltd., Leeds, UK). Femoral offset was measured using anteroposterior radiographs, and circulating metal ion levels (cobalt and chromium) were recorded., Results: In total, 95 patients were included (68 males and 27 females). The mean age at the time of surgery was 64.9. Mean time from surgery to blood sampling was 15.4 months. No statistically significant relationship was found between femoral offset and cobalt (p = 0.313) or chromium (p = 0.401) ions., Conclusion: It is known that failure to restore femoral offset during THA can lead to high rates of wear in metal-on-polyethylene articulations. In our study, no statistically significant relationship was found between femoral offset and serum cobalt or chromium ions. This study adds to the information available to surgeons regarding factors that increase wear in metal-on-metal total hip arthroplasty.

The elements Br, Ca, Cl, Cr, Fe, K, Mg, Na, P, Rb, S, and Zn were investigated in the whole blood samples of Golden Retriever dogs submitted to cell therapy (hASCs). These analyses were performed over 2 years using Neutron Activation Analysis and X-Ray Fluorescence techniques. The results were compared with control and untreated dog's. A significant increase was observed in K blood levels. There was also variation in blood levels of Br, Cr, Fe, Rb, S, and Zn., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Photochromic molecules can respond to external stimulations and undergo reversible conversion between different chemical structures, providing one photochromic molecule with multiple recognition states for targeting compounds. Here we design a facile sensor microchip with only one photochromic molecule (spirooxazine) to discriminate multiplex metal ions. The sensor chip performs in dark, ultraviolet, or visual stimulation, resulting in different molecular states of spirooxazine-metallic coordination and patterned fluorescent signals for analysis. By using this sensor microchip, 11 metal ions are discriminated. Furthermore, mineral water of 16 different brands and metal ions in human serum are distinguished.

Purpose: The aim of this study is to present an algorithm for the evaluation of both symptomatic and asymptomatic patients., Methods: From November 2004 to May 2010, there were performed 296 operations: 245 total hip arthroplasty and 51 resurfacing arthroplasty with the ASR DePuy system. In April 2010, there was the first Medical Device Alert regarding all MoM hip replacements in the UK and in August 2010, DePuy recall started worldwide. In March 2012, we started our recall. All patients were invited to undergo clinical investigation, X-ray evaluations, and blood chrome and cobalt level determination. For a short period of time, there were performed second level exams and subsequently, we carried out MARS MRI hip study to all symptomatic patients and there was evidence of ALVAL lesions., Results: To the patients with ALVAL lesions were proposed surgical hip revision while the others frequent follow-up controls. One hundred patients underwent hip surgical revision., Conclusions: We recommend constant MoM THA patients monitoring and early revision if necessary.

In this study, Mussel-inspired polydopamine (PDA) nanospheres were synthesized via spontaneous oxidative polymerization of dopamine hydrochloride (dopa-HCl) in a deionized water-alcohol mixed solvent at room temperature and atmospheric air, under alkaline condition. Field-emission scanning electron microscopy (FE-SEM) demonstrated production of sphere-like shape with a smooth surface and tunable size, while monodispersity increased by utilizing isopropanol instead of ethanol owing to lower R a values based on Hansen solubility parameter (HSP) theory. Dropwise addition of monomer played an undeniable role in the fabrication of uniform and smaller spheres. The difference of the charge repulsion of constructs in the range of pH led to different dispersive behavior in a variety of solvents, exhibiting versatile applications. The presence of active functional groups on the surface of PDA spheres made them an appropriate option for PDA-assisted biomimetic mineralization of hydroxyapatite (HA), which is the result of the interaction between abundant catecholamine moieties in PDA and Ca +2 ions in simulated body fluid. Bio-adhesive nature of PDA in water and the presence of amino and hydroxyl functional groups support desirable L929 mouse fibroblast cell spreading. The viability of >90% fibroblast cells proved the biocompatibility of polymerized structure. All the achievements indicated that PDA nanospheres provide a biocompatible and bioactive template for green synthesizing hydroxyapatite and the innovative basis for further tissue engineering applications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: This study explored several strategies to improve the performance of literature QSAR models for plasma protein binding (PPB), such as a suitable endpoint transformation, a correct representation of chemicals, more consistency in the dataset, and a reliable definition of the applicability domain., Methods: We retrieved human fraction unbound (Fu) data for 670 compounds from the literature and carefully checked them for consistency. Descriptors were calculated taking account of the ionization state of molecules at physiological pH (7.4), in order to better estimate the affinity of molecules to blood proteins. We used different algorithms and chemical descriptors to explore the most suitable strategy for modeling the endpoint. SMILES (simplified molecular input line entry system)-based string descriptors were also tested with the CORAL software (CORelation And Logic). We did an outlier analysis to establish the models to use (or not to use) in case of well recognized families., Results: Internal validation of the selected models returned Q 2 values close to 0.60. External validation also gave r 2 values always greater than 0.60. The CORAL descriptor based model for √fu was the best, with r 2 0.74 in external validation., Conclusions: Performance in prediction confirmed the robustness of all the derived models and their suitability for real-life purposes, i.e. screening chemicals for their ADMET profiling. Optimization of descriptors can be useful in order to obtain the correct results with a ionized molecule.

Introduction: Dual mobility cups have become the implant of choice for older patients with a high risk of dislocation. However, to our knowledge, no study has explored the possibility of metal ion production with these implants that incorporate a polyethylene-on-metal bearing. This led us to conduct a prospective study to determine whether use of a dual mobility cup is accompanied by increased levels of nickel and chromium in the blood., Hypothesis: Use of a dual mobility cup is accompanied by an increase of nickel and chromium levels in the blood., Methods: Between 2012 and 2015, 16 consecutive patients were enrolled in the study. They underwent primary hip arthroplasty with a ceramic Biolox™ head (CeramTec, Plochingen, Germany), Corail™ titanium alloy stem (DePuy Synthes, Saint Priest, France) and a Novae™ dual mobility cup (SERF, Décines-Charpieu, France) consisting of 19% chromium (Cr) and 13-15% nickel (Ni). Patients who had other potential sources of nickel or chromium in their body (joint implants, dental implants, etc.) were excluded. The blood levels (μg/L) of nickel and chromium were measured preoperatively and at 2 years' follow-up by an independent laboratory (Biomnis) using inductively coupled plasma mass spectrometry. The upper limits set by the laboratory were<0.87μg/L for chromium and<1.0μg/L for nickel. AP and lateral X-rays of the pelvis were taken preoperatively and at each postoperative follow-up visit to look for signs of loosening. The Postel-Merle-d'Aubigné (PMA) score was determined preoperatively and at each postoperative follow-up visit. Surgical revision procedures for any cause were also documented., Results: The mean follow-up was 29 months [13-39]. Preoperatively, blood nickel ion levels were measured in 7 patients; they were below 1μg/L in 6 patients (86%) and at 1.5μg/L in 1 patient (14%). The mean preoperative chromium ion levels (n=7) was 0.2μg/L [0-0.8μg/L]. Postoperatively, all 16 enrolled patients had their blood ion levels checked at a mean follow-up of 29 months. The nickel ion levels averaged 1.69±1.49 [0.2-5.6] (with 4/16 having>2μg/L and 12/16>1μg/L) and the chromium ion levels averaged 0.5±0.11 [0.4-0.7] (with no patients>0.7μg/L). There were no signs of loosening or osteolysis on the follow-up radiographs. The mean PMA score at 2 years was 17.8 [17,18]., Conclusion: We found that dual mobility cups generate increased nickel but not chromium ions in the blood. The levels measured are comparable to those for other orthopedic implants such as spine implants. The clinical consequences of these increased levels are not known. Nevertheless, there were no clinical or radiological signs of loosening, although the follow-up was only 2 years., Level of Evidence: IV, Cohort study., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Silvering has been associated with advancing osmoregulatory ability. Given the demonstrated role of 11-ketotestosterone (11KT) in mediating many of the silvering-related changes, we investigated the role of 11KT in driving this advanced osmoregulatory ability in the New Zealand short-finned eel (Anguilla australis). Yellow (non-migratory) eels with or without 11KT implants and blank-implanted silver (migratory) eels, either held in freshwater or subjected to seawater challenge, were sampled to determine serum [Na + ] and [Cl - ], pituitary prolactin mRNA levels, gill Na + /K + -ATPase activity and gill mRNA levels for Na + /K + -ATPase-α1 subunit and for Na + /K + /2Cl - co-transporter-1α-subunit. Developmental stage and 11KT treatment advanced the eels' osmoregulatory ability. Thus, serum [Na + ] and [Cl - ] were affected by developmental stage and 11KT treatment upon seawater challenge. However, seawater challenge, not 11KT treatment or developmental stage, produced the strongest and the most consistent effects on A. australis osmoregulatory processes, inducing significant effects in all the relevant parameters we measured. In light of our results and in view of the eel's marine ancestry, we contend that A. australis, or freshwater eels in general, are highly tolerant and able to adapt quickly to changing salinities even at the yellow stage, which may preclude a critical need for an advanced osmoregulatory ability at silvering.

Background: A transition ion ratio (TIR) is the ratio of one fragment over another from the same precursor and is frequently monitored in liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for analyte identification. The Clinical and Laboratory Standards Institute (CLSI) C50-A guidelines give a static percent allowable TIR deviation based on the TIR level. Anecdotally, we observed failures of these rules for some of our LC-MS/MS assays. We determined what parameters may affect TIRs in a clinical setting and whether TIR variations may be analyte, matrix, instrument service, and/or concentration dependent., Methods: Data was collected from the validation and selected periods after implementation for urine benzodiazepines (7 analytes) and plasma azole antifungals (6 analytes). TIRs for the calibrators and quality control materials on a Thermo TSQ™ Quantum Ultra from July 2016 to February 2017 for benzodiazepines in urine and Thermo TSQ™ Vantage from May 2016 to Oct 2016 for azoles in serum were monitored., Results: The statistically significant day-to-day TIR shift ranged from 5.7 to 27.0% of the days studies for benzodiazepines and from 5.6 to 27.8% of the days studied for azoles excluding shifts caused by instrument services. Instrument service had significant impact on all benzodiazepines except oxazepam with p-values ranging from 1.79 × 10 -6 to 1.53 × 10 -39 and 4 of the 6 azoles (fluconazole, isavuconazole, voriconazole, and itraconazole) with (p from 7.89 × 10 -3 to 1.98 × 10 -12 ). Lorazepam, α-hydroxyalprazolam, and hydroxyitraconazole showed significant concentration dependent TIR variations., Conclusions: TIR variations may be affected by instrument services, and can be concentration and analyte dependent. Instead of using a static percent deviation rule, establishment of TIR variation criteria for each analyte during test development and validation may provide a more useful tool for analyte identification., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Instability remains one of the main problems after revision hip surgery. The aim of this study was to review the clinical, radiological, and patient-reported outcomes with the use of modular dual-mobility articulation for revision acetabular reconstruction and investigate the risk of fretting corrosion by measuring serum trace metal ion levels., Methods: Sixty consecutive patients with a minimum of 24-month follow-up after the insertion of a modular dual-mobility (Stryker, Mahwah, NJ) cup at the time of revision hip surgery were identified. Follow-up included clinical and radiological patient review and functional outcome measures, and a subset of patients had their metal ion (cobalt and chromium) levels checked., Results: At the most recent follow-up, 5 patients had died, 3 patients have been revised because of ongoing instability, and 3 patients have had revision surgery due to infection. Overall functional outcome (mean Western Ontario and McMaster Universities Osteoarthritis Indexfunction 76, University of California, Los Angeles 5.6, mean Oxford 74.7, Short Form-12 physical 41.6/mental 53.3) and overall pain relief (mean Western Ontario and McMaster Universities Osteoarthritis Index pain score 78.3) scores were good. The mean satisfaction score was 78 of 100. The median serum trace metal chromium and cobalt levels at the most recent follow-up were 0.4 µg/L (range 0.1-6.1 µg/L) and 0.42 µg/L (range 0.21-9.42 µg/L), respectively. The survival with revision as the end point was 90%., Conclusions: Dual-mobility cups with modularity represent an excellent option for the patient having revision hip surgery at high risk of instability. This series presents good patient-reported outcome measures and a low complication and revision rate., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Bone union after spinal fusion surgery with instrumentation has been determined only with imaging studies. We evaluated the usefulness of the serum ionic fluoride (SIF) concentration as a biomarker of the bone union status., Methods: We enrolled 25 patients who underwent spinal surgery in our institution, and we divided patients into three groups with and without instrumentation (G1, G2, and G3). We collected the fasting serum level preoperatively and on day 1 (D1), week 1 (D7), week 2 (D14), month 1 (D30), month 3 (D90), and month 6 (D180) postoperatively, and measured SIF concentrations using the flow injection method with an ion-selective electrode., Results: Although preoperative SIF concentrations were similar among the 3 groups, postoperative SIF concentrations were different among the groups. SIF concentrations in groups with instrumentation (G2 and G3) increased between D14 and D90 postoperatively and decreased at D180 postoperatively. SIF concentrations in the group without instrumentation (G1) decreased between D30 and D180 postoperatively., Conclusions: An SIF concentration that is higher postoperatively than preoperatively may indicate unstable bone union, whereas a lower SIF concentration postoperatively than preoperatively may indicate stable bone union. We concluded that the SIF concentration may be useful for diagnosing bone union., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The main purpose of this study was to investigate the relationship between the electron densities and Na/K ratio which has important role in breast cancer disease. Determinations of sodium and potassium concentrations in blood samples performed with inductive coupled plasma-atomic emission spectrometry. Electron density values of blood samples were determined via ZXCOM. Statistical analyses were performed for electron densities and Na/K ratio including Kolmogorov-Smirnov normality tests, Spearman's rank correlation test and Mann-Whitney U test. It was found that the electron densities significantly differ between control and breast cancer groups. In addition, statistically significant positive correlation was found between the electron density and Na/K ratios in breast cancer group.

The contents of ions in the blood have been compared in three ecological groups of brown trout (parr, mature, and resident) living in rives of the basins of Lake Onega and Lake Ladoga. Brown trout from the Alats-oya (the Ladoga basin, remote from two other rivers belonging to the Onega Lake) is characterized by the lowest concentrations of the Na + , Ca2 + , and Cl - ions in blood. The probable effect of the ion level in blood of brown trout on selection of life strategy is discussed.

We propose an optimized single-step assay of total nitrite and nitrate concentrations based on serum deproteinization by ultrafiltration. After deproteinization, the residual protein concentration was 0.0800±0.0007 mg/ml, which secured necessary transparency of the specimens in contrast to methanol deproteinization. The optimized assay for serum nitrite and nitrate ions is characterized by high reproducibility and accuracy (variation coefficient <7%) and can be recommended for routine use in clinical practice.

This study aims at revealing the effects of the combined treatment of selenium and cadmium on ovary morphology, oxidative stress, and 28 kinds of ion concentrations in laying hens. In this experiment, 128 healthy 31-week-old chickens were selected and divided into four treatment groups, three of which were separately fed the basic diets supplemented with either Se or Cd or both Se and Cd for 90 days, and the remaining group was fed the basic diet and treated as a control. The chickens were sacrificed for collecting ovarian tissues. Morphological structure and ultrastructure analysis of ovaries in the Cd-treated group revealed ovarian damage, with decreased activities of SOD and GPx, along with increased levels of MDA and H 2 O 2 . Cd treatment also resulted in disturbances in ion balance. The concentrations of Ca, Ti, Cu, Zn, and Ba were significantly reduced, while the concentrations of Fe, Mo, and Cd were significantly increased when compared with the control group. Interestingly, the damages caused by cadmium were alleviated in the Se+Cd-treated group. These results indicate that selenium can alleviate cadmium-induced ovarian damages.

In this study, we examined if rainbow trout chronically exposed to acetaminophen (10 and 30 μgL -1 ) showed histological changes that coincided with functional changes in the kidney, gill and liver. Histological changes in the kidney included movement and loss of nuclei, non-uniform nuclei size, non-uniform cytoplasmic staining, and loss of tubule integrity. Histological effects were more severe at the higher concentration and coincided with concentration dependent increases in urine flow rate and increased urinary concentrations of sodium, chloride, potassium, calcium, urea, ammonia, glucose, and protein. Yet, glomerular filtration rate was not altered with acetaminophen exposure. In the gill, filament end swelling, whole filament swelling, and swelling of the lamellae were observed in exposed fish. Lamellar spacing decreased in both exposure groups, but lamellar area decreased only with 30 μgL -1 exposure. At faster swimming speeds, oxygen consumption was limited in acetaminophen exposed fish, and critical swimming speed was also decreased in both exposure groups. The liver showed decreased perisinusoidal spaces at 10 and 30 μgL -1 acetaminophen, and decreased cytoplasmic vacuolation with 30 μgL -1 acetaminophen. A decrease in liver glycogen was also observed at 30 μgL -1 . There was no change in plasma concentrations of sodium, chloride, potassium, calcium, magnesium, and glucose with exposure, suggesting compensation for urinary loss. Indeed, an increase in Na + -K + -ATPase activity in the gills was found with 30 μgL -1 acetaminophen exposure. Chronic exposure of rainbow trout to the environmentally relevant pharmaceutical acetaminophen, alters both histology and function of organs responsible for ion and nutrient homeostasis., (Copyright © 2018 Elsevier B.V. All rights reserved.)