Selenium, Selenoproteins, and Heart Failure:Current Knowledge and Future Perspective

PURPOSE OF REVIEW: (Mal-)nutrition of micronutrients, like selenium, has great impact on the human heart and improper micronutrient intake was observed in 30–50% of patients with heart failure. Low selenium levels have been reported in Europe and Asia and thought to be causal for Keshan disease. Selenium is an essential micronutrient that is needed for enzymatic activity of the 25 so-called selenoproteins, which have a broad range of activities. In this review, we aim to summarize the current evidence about selenium in heart failure and to provide insights about the potential mechanisms that can be modulated by selenoproteins. RECENT FINDINGS: Suboptimal selenium levels (<100 μg/L) are prevalent in more than 70% of patients with heart failure and were associated with lower exercise capacity, lower quality of life, and worse prognosis. Small clinical trials assessing selenium supplementation in patients with HF showed improvement of clinical symptoms (NYHA class), left ventricular ejection fraction, and lipid profile, while governmental interventional programs in endemic areas have significantly decreased the incidence of Keshan disease. In addition, several selenoproteins are found impaired in suboptimal selenium conditions, potentially aggravating underlying mechanisms like oxidative stress, inflammation, and thyroid hormone insufficiency. SUMMARY: While the current evidence is not sufficient to advocate selenium supplementation in patients with heart failure, there is a clear need for high level evidence to show whether treatment with selenium has a place in the contemporary treatment of patients with HF to improve meaningful clinical endpoints. GRAPHICAL ABSTRACT: [Figure: see text

Limitations, improvements and alternatives of the silt density index

Reverse osmosis (RO) membrane systems are widely used in the desalination of water. However, flux decline due to fouling phenomena in RO remains a challenge. To minimize fouling, a reliable index is necessary to predict the fouling potential of the RO feed water. The ASTM introduced the silt density index (SDI) as a standard fouling index to measure the fouling potential due to colloidal and suspended particles. For decades, the SDI is worldwide accepted and applied. There are growing doubts about the predictive value of this parameter. In addition there are several deficiencies observed, affecting the accuracy and reproducibility e.g. no correction factor for temperature, nor for variations in membrane resistance, and no linear correlation with the concentration of colloidal/suspended particles. This paper gives an overview of our work on limitations, improvements and alternatives for the SDI. Firstly, the influence of the applied 0.45 μm test membrane on the SDI will be investigated. Variations in SDI values can be attributed to differences in properties of these membranes. In order to quantify the influence of pressure, temperature and membrane resistance on the SDI a mathematical relation was developed between the SDI and the MFI0.45, assuming cake filtration. In addition, also other fouling mechanisms were incorporated in the model using the well-known blocking laws. Based on a cake filtration fouling mechanism and assuming 100% particle retention, the models were used to normalize the experimental SDI values for temperature, pressure and membrane resistance to the SDI+. By applying this normalization, the results of SDI tests carried out under different conditions and/or with different membranes can be compared easily as was proven experimentally in the lab and at a seawater desalination plant. Finally, an alternative filtration index will be introduced, the volume-based SDI_v. The SDI_v compares the initial flow rate to the flow rate after filtering a standard volume of feed water using MF membranes with an average pore size of 0.45 μm. Our experimental results show that SDI_v is independent of the membrane resistance. In that way, it eliminates most of the disadvantages of the SDI and has great potential to replace the SDI in the fiel

A Clinical Tool to Predict Low Serum Selenium in Patients with Worsening Heart Failure

Selenium is an essential micronutrient, and a low selenium concentration (&lt;100 µg/L) is associated with a poorer quality of life and exercise capacity, and an impaired prognosis in patients with worsening heart failure. Measuring selenium concentrations routinely is laborious and costly, and although its clinical utility is yet to be proven, an easy implemented model to predict selenium status is desirable. A stepwise multivariable logistic regression analysis was performed using routinely measured clinical factors. Low selenium was independently predicted by: older age, lower serum albumin, higher N-terminal pro-B-type natriuretic peptide levels, worse kidney function, and the presence of orthopnea and iron deficiency. A 10-points risk-model was developed, and a score of ≥6 points identified &gt;80% of patients with low selenium (sensitivity of 44%, specificity of 80%). Given that selenium and iron overlap in their physiological roles, we evaluated the shared determinants and prognostic associates. Both deficiencies shared similar clinical characteristics, including the model risk factors and, in addition, a low protein intake and high levels of C-reactive protein. Low selenium was associated with a similar or worse prognosis compared to iron deficiency. In conclusion, although it is difficult to exclude low selenium based on clinical characteristics alone, we provide a prediction tool which identifies heart failure patients at higher risk of having a low selenium status.</p

High selenium levels associate with reduced risk of mortality and new onset heart failure:data from PREVEND

AIM: To elucidate the relationship between serum selenium levels and the risk of mortality and new onset heart failure in the general adult population. METHODS AND RESULTS: Selenium was measured in a Dutch cohort and a retrospective analysis of prospectively assessed data was performed. Main outcome measures were all-cause mortality and incidence of new-onset heart failure (HF) separately, and combined as a composite endpoint. Serum selenium was measured in 5973 subjects and mean selenium concentration was 84.6 (±19.5) μg/L. Mean age was 53.6 (±12.1) years and 3103 subjects (52%) were females. Median follow-up period was 8.4 years. Selenium levels associated positively with female sex, higher total cholesterol and glucose concentrations, and associated negatively with incidence of anemia, iron deficiency, current smoking, increasing C-reactive protein levels, and higher body mass index. Univariate analysis on all subjects showed no association of continuous selenium concentrations, per 10 μg/L increase, with the composite endpoint (Hazard Ratio [HR]=0.96, 95% Confidence interval [CI]: 0.87 to 1.06, p = 0.407). However, significant interaction with smoking status was observed. In non-smoking subjects (N=4288), continuous selenium concentrations were independently associated with reduced mortality risk (HR=0.87, 95% CI: 0.79 to 0.96, p = 0.005), lower risk of new-onset HF (HR=0.82, 95% CI: 0.69 to 0.96, p = 0.017), as well as reduced risk of the composite endpoint (HR= 0.86, 95% CI: 0.79 to 0.94, p = 0.001). In smoking subjects, no associations were found. CONCLUSION: Serum selenium was independently associated with multiple indicators of the metabolic syndrome. In addition, high selenium levels were independently associated with reduced mortality and new-onset HF in non-smokers. Well-powered interventional studies are necessary to evaluate the potential benefit of repleting selenium, especially in non-smoking subjects

Vitamin D and Musculoskeletal Status in Nova Scotian Women Who Wear Concealing Clothing

Bone and muscle weakness due to vitamin D deficiency is common among Muslim women who reside in sunny, equatorial countries. The purpose of this study was to determine if living in a northern maritime location additionally disadvantages women who wear concealing clothes. A cross-sectional matched pair design was used to compare women who habitually wore concealing clothing with women who dressed according to western norms. Each premenopausal hijab-wearing woman (n = 11) was matched by age, height, weight and skin tone with a western-dressed woman. Subjects were tested by hand grip dynamometry to assess muscular strength and by quantitative ultrasound at the calcaneus to assess bone status. Nutritional intake was obtained by 24 h recall. Serum 25-hydroxyvitamin D (s-25(OH)D) status was determined in seven matched pairs. The hijab group had lower s-25(OH)D than women who wore western clothes (40 ± 28 vs. 81 ± 32 nmol/L, p= 0.01). Grip strength in the right hand was lower in the hijab-wearing women (p = 0.05) but this appeared to be due to less participation in intense exercise. Bone status did not differ between groups (p= 0.9). Dietary intake of vitamin D was lower in the hijab-wearers (316 ± 353 vs. 601 ± 341 IU/day, p= 0.001). This pilot study suggests that women living in a northern maritime location appear to be at risk for vitamin D insufficiency and therefore should consider taking vitamin D supplements

Micronutrient deficiencies and new-onset atrial fibrillation in a community-based cohort:data from PREVEND

Aim: Malnutrition has been linked to cardiovascular diseases. Both selenium and iron deficiency have been associated with worse prognosis in patients with heart failure (HF). Yet, little is known about the role of micronutrients in the development of atrial fibrillation (AFib). In this study, we aimed to elucidate the association of micronutrient deficiencies with new-onset AFib. Methods: Selenium, magnesium, and iron parameters were measured in a well-characterized prospective cohort study (N = 5452). Selenium deficiency was defined as serum selenium &lt; 70 μg/L, iron deficiency as serum ferritin &lt; 30 μg/L, and magnesium deficiency as plasma magnesium &lt; 0.85 mmol/L. New-onset AFib was the primary outcome. Additionally, we tested for previously reported effect-modifiers where applicable. Results: Selenium, iron, and magnesium deficiency was observed in 1155 (21.2%), 797 (14.6%), and 3600 (66.0%) participants, respectively. During a mean follow-up of 6.2 years, 136 (2.5%) participants developed new-onset AFib. Smoking status significantly interacted with selenium deficiency on outcome (p = 0.079). After multivariable adjustment for components of the CHARGE-AF model, selenium deficiency was associated with new-onset AFib in non-smokers (HR 1.69, 95% CI 1.09–2.64, p = 0.020), but not in smokers (HR 0.78, 95% CI 0.29–2.08, p = 0.619). Magnesium deficiency (HR 1.40, 95% CI 0.93–2.10, p = 0.110) and iron deficiency (HR 0.62, 95% CI 0.25–1.54, p = 0.307) were not significantly associated with new-onset AFib. Conclusion: Selenium deficiency was associated with new-onset AFib in non-smoking participants. Interventional studies that investigate the effects of optimizing micronutrients status in a population at risk are needed to assess causality, especially in those with selenium deficiency. Graphical abstract: Micronutrients deficiencies (selenium, iron, and magnesium) have been associated with cardiovascular diseases and mitochondrial dysfunction in human cardiomyocytes. However, it is not known whether these deficiencies are associated with atrial fibrillation. To investigate this question, we measured all three micronutrients in 5452 apparently healthy individuals. After a mean follow-up of 6.2 years, there were 136 participants who developed atrial fibrillation. Participants with selenium deficiency had a significant increased risk to develop atrial fibrillation, as did the participants with two or more deficiencies. [Figure not available: see fulltext.]</p

Calsequestrin as a risk factor in Graves’ hyperthyroidism and Graves’ ophthalmopathy patients

Background: The pathogenesis of Graves’ ophthalmopathy (GO), Graves’ hyperthyroidism (GH) and the mechanisms for its link to thyroid autoimmunity are poorly understood. Our research focuses on the role of the skeletal muscle calcium binding protein calsequestrin (CASQ1) in thyroid. We measured the concentration of the CASQ1 protein correlating levels with parameters of the eye signs, CASQ1 antibody levels and CASQ1 gene polymorphism rs3838284. Methods: CASQ1 protein was measured by quantitative Western Blotting. The protein concentrations were expressed as pmol/mg total protein by reference to CASQ1 standards. Results: Western blot analysis showed the presence of two forms of CASQ1 in the thyroid. The mean concentration of CASQ1 protein was significantly reduced in patients with Graves’ disease, compared to thyroid from control subjects with multi-nodular goitre or thyroid cancer. Although in patients with GO it was lower than that, compared with patients with GH this difference was not significant. Reduced CASQ1 in Graves’ thyroid correlated with the homozygous genotype of the rs3838284 CASQ1 polymorphism. Conclusions: Decreased CASQ1 in the thyroid of patients with Graves’ disease compared to thyroid from control subjects is not explained but may reflect consumption of the protein during an autoimmune reaction against CASQ1 in the thyroid

Genomic Islands Confer Heavy Metal Resistance in <i>Mucilaginibacter kameinonensis</i> and <i>Mucilaginibacter rubeus</i> Isolated from a Gold/Copper Mine.

Heavy metals (HMs) are compounds that can be hazardous and impair growth of living organisms. Bacteria have evolved the capability not only to cope with heavy metals but also to detoxify polluted environments. Three heavy metal-resistant strains of &lt;i&gt;Mucilaginibacer rubeus&lt;/i&gt; and one of &lt;i&gt;Mucilaginibacter kameinonensis&lt;/i&gt; were isolated from the gold/copper Zijin mining site, Longyan, Fujian, China. These strains were shown to exhibit high resistance to heavy metals with minimal inhibitory concentration reaching up to 3.5 mM Cu &lt;sup&gt;(II)&lt;/sup&gt; , 21 mM Zn &lt;sup&gt;(II)&lt;/sup&gt; , 1.2 mM Cd &lt;sup&gt;(II)&lt;/sup&gt; , and 10.0 mM As &lt;sup&gt;(III)&lt;/sup&gt; . Genomes of the four strains were sequenced by Illumina. Sequence analyses revealed the presence of a high abundance of heavy metal resistance (HMR) determinants. One of the strain, &lt;i&gt;M. rubeus&lt;/i&gt; P2, carried genes encoding 6 putative P &lt;sub&gt;IB-1&lt;/sub&gt; -ATPase, 5 putative P &lt;sub&gt;IB-3&lt;/sub&gt; -ATPase, 4 putative Zn &lt;sup&gt;(II)&lt;/sup&gt; /Cd &lt;sup&gt;(II)&lt;/sup&gt; P &lt;sub&gt;IB-4&lt;/sub&gt; type ATPase, and 16 putative resistance-nodulation-division (RND)-type metal transporter systems. Moreover, the four genomes contained a high abundance of genes coding for putative metal binding chaperones. Analysis of the close vicinity of these HMR determinants uncovered the presence of clusters of genes potentially associated with mobile genetic elements. These loci included genes coding for tyrosine recombinases (integrases) and subunits of mating pore (type 4 secretion system), respectively allowing integration/excision and conjugative transfer of numerous genomic islands. Further in silico analyses revealed that their genetic organization and gene products resemble the &lt;i&gt;Bacteroides&lt;/i&gt; integrative and conjugative element CTnDOT. These results highlight the pivotal role of genomic islands in the acquisition and dissemination of adaptive traits, allowing for rapid adaption of bacteria and colonization of hostile environments

Biomarker and transcriptomics profiles of serum selenium concentrations in patients with heart failure are associated with immunoregulatory processes

Acknowledgements The authors thank Martin Dokter, Jan Koerts and Karin Koerts-Steijn for their excellent technical assistance.Peer reviewedPublisher PD