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This document is a comment on a review paper titled "Could Selenium Supplementation Prevent COVID-19? A Comprehensive Review of Available Studies." The authors of the comment are experienced selenium researchers who take issue with the assessments made in the review. They argue that the review is not comprehensive and fails to include important studies that support the association between selenium and COVID-19 outcomes. The authors also address specific criticisms made by the reviewers regarding their own work and highlight the importance of further research into the role of selenium in COVID-19. [Extracted from the article]

Iodine supply is crucial during pregnancy to ensure that the proper thyroid function of mother and baby support fetal brain development. Little is known about iodine status or its dietary determinants in pregnant women in the Republic of Cyprus. We therefore recruited 128 pregnant women at their first-trimester ultrasound scan to a cross-sectional study. We collected spot-urine samples for the measurement of urinary iodine concentration (UIC, µg/l) and creatinine concentration (Creat, g/l), the latter of which allows us to correct for urine dilution and to compute the iodine-to-creatinine ratio (UI/Creat). Women completed a FFQ and a general questionnaire. We used a General Linear model to explore associations between maternal and dietary characteristics with UI/Creat. The median UIC (105 µg/l) indicated iodine deficiency according to the WHO criterion (threshold for adequacy = 150 µg/l), and the UI/Creat was also low at 107 µg/g. Only 32 % (n 45) of women reported the use of iodine-containing supplements; users had a higher UI/Creat than non-users (131 µg/g v. 118 µg/g), though this difference was NS in the adjusted analysis (P = 0·37). Of the dietary components, only egg intake was significantly associated with a higher UI/Creat in adjusted analyses (P = 0·018); there was no significant association with milk, dairy products or fish intake. Our results suggest that pregnant women in Cyprus have inadequate iodine status and are at risk of mild-to-moderate iodine deficiency. Further research on dietary sources in this population is required. [ABSTRACT FROM AUTHOR]

We begin by arguing that the often used algorithm for the discovery and use of disease risk factors, stepwise logistic regression, is unstable. We then argue that there are other algorithms available that are much more stable and reliable (e.g. the lasso and gradient boosting). We then propose a protocol for the discovery and use of risk factors using lasso or boosting variable selection. We then illustrate the use of the protocol with a set of prostate cancer data and show that it recovers known risk factors. Finally, we use the protocol to identify new and important SNP based risk factors for prostate cancer and further seek evidence for or against the hypothesis of an anticancer function for Selenium in prostate cancer. We find that the anticancer effect may depend on the SNP-SNP interaction and, in particular, which alleles are present. [ABSTRACT FROM AUTHOR]

Breastfeeding mothers often report perceived insufficient milk (PIM) believing their infant is crying too much, which leads to introducing formula and the early abandonment of breastfeeding. We sought to determine if infant crying was associated with reported PIM (yes/no) and number of problems associated with lactation (lactation problem score [LPS] 6‐point Likert scale) before formula introduction. Primiparous breastfeeding mothers were recruited at birth and visited at 1, 2 and 4 weeks. Among those fully breastfeeding at 1 week (N = 230), infant crying variables based on maternal reports were not associated with PIM at 1 week, but LPS was. However, a mother's expectation that her infant would cry more than other infants was associated with increased odds of reporting PIM at 2 and 4 weeks, as were delayed onset of lactation and previous LPS. At 1 week, crying variables (frequency, difficulty in soothing) were associated with LPS along with percent weight change. Delayed onset of lactation, infant care style, number of breastfeeds and previous LPS were longitudinally associated with change in LPS from 1 to 2 weeks and 2 to 4 weeks. Our data suggest that reported infant crying is associated with PIM and LPS in the first 4 weeks of life. Guidance on what to expect in crying behaviour and the impact of infant care style may be beneficial in reducing PIM and LPS in the first month. [ABSTRACT FROM AUTHOR]

Selenium is an essential trace element important for human health. A balanced intake is, however, crucial to maximize the health benefits of selenium. At physiological concentrations, selenium mediates antioxidant, anti‐inflammatory, and pro‐survival actions. However, supra‐nutritional selenium intake was associated with increased diabetes risk leading potentially to endothelial dysfunction, the initiating step in atherosclerosis. High selenium causes apoptosis in cancer cells via endoplasmic reticulum (ER) stress, a mechanism also implicated in endothelial dysfunction. Nonetheless, whether ER stress drives selenium‐induced endothelial dysfunction, remains unknown. Here, we investigated the effects of increasing concentrations of selenium on endothelial cells. High selenite reduced nitric oxide bioavailability and impaired angiogenesis. High selenite also induced ER stress, increased reactive oxygen species (ROS) production, and apoptosis. Pretreatment with the chemical chaperone, 4‐phenylbutyrate, prevented the toxic effects of selenium. Our findings support a model where high selenite leads to endothelial dysfunction through activation of ER stress and increased ROS production. These results highlight the importance of tailoring selenium supplementation to achieve maximal health benefits and suggest that prophylactic use of selenium supplements as antioxidants may entail risk. [ABSTRACT FROM AUTHOR]

Abstract Background A preventive role of selenium on the risk of diabetes has been reported and ascribed to the "insulin-like" activity of selenium and the antioxidant properties of the selenoenzymes. By contrast, data from cross-sectional studies and clinical trials have suggested an adverse effect of high selenium status and selenium supplementation on type-2 diabetes risk. Given these controversial results, we investigated prospectively the relationship between baseline plasma selenium concentration and occurrence of dysglycemia (impaired fasting glucose or type 2 diabetes) in an elderly French cohort. Methods The Epidemiology of Vascular Ageing (EVA) study (n = 1389, 59-71 years) is a 9-year longitudinal study in which, fasting plasma glucose was measured at baseline, 2, 4 and 9 years. Analyses were performed on 1162 participants with complete data. Results At baseline plasma selenium mean levels were 1.08 (0.21) μmol/l in men and 1.10 (0.20) μmol/l in women. During the 9-year follow-up, 127 cases of dysglycemia occurred. A significant interaction was found between plasma selenium and sex. Risk of dysglycemia was significantly lower in men with plasma selenium in the highest tertile (T3:1.19-1.97) compared to those in the lowest tertile (T1:0.18-1.00) [HR = 0.48 (0.25-0.92)], but no significant relationship was observed in women. After controlling for socio-demographic factors, lifestyle factors, cardiovascular diseases, body mass index, hypertension and lipid profile, plasma selenium remained marginally significantly associated with occurrence of dysglycemia in men [T3 vs. T1, HR = 0.50 (0.24-1.04)] and unrelated in women. Conclusions This prospective study suggests a sex-specific protective effect of higher selenium status at baseline on later occurrence of dysglycemia.

Background Mild-to-moderate iodine deficiency, particularly in pregnancy, is prevalent; this is of concern because observational studies have shown negative associations with child neurodevelopment. Although neither the benefits nor the safety of iodine supplementation in pregnancy in areas of mild-to-moderate deficiency are well researched, such supplementation is increasingly being recommended by health authorities in a number of countries. Objectives By reviewing the most recent published data on the effects of iodine supplementation in mildly-to-moderately deficient pregnant women on maternal and infant thyroid function and child cognition, we aimed to determine whether the evidence was sufficient to support recommendations in these areas. Methods A systematic review of randomized controlled trials (RCTs), non-RCT interventions, and observational studies was conducted. To identify relevant articles, we searched the PubMed and Embase databases. We defined mild-to-moderate iodine deficiency as a baseline median urinary iodine concentration (UIC) of 50–149 µg/L. Eligible studies were included in meta-analyses. Results In total, 37 publications were included—10 RCTs, 4 non-RCT interventions, and 23 observational studies. Most studies showed no effect of iodine supplementation on maternal or infant thyroid-stimulating hormone and free thyroxine. Most RCTs found that supplementation reduced maternal thyroglobulin and in 3 RCTs, it prevented or diminished the increase in maternal thyroid volume during pregnancy. Three RCTs addressed child neurodevelopment; only 1 was adequately powered. Meta-analyses of 2 RCTs showed no effect on child cognitive [mean difference (MD): −0.18; 95% CI: −1.22, 0.87], language (MD: 1.28; 95% CI: −0.28, 2.83), or motor scores (MD: 0.28; 95% CI: −1.10, 1.66). Conclusions There is insufficient good-quality evidence to support current recommendations for iodine supplementation in pregnancy in areas of mild-to-moderate deficiency. Well-designed RCTs, with child cognitive outcomes, are needed in pregnant women who are moderately deficient (median UIC < 100 µg/L). Maternal intrathyroidal iodine stores should be considered in future trials by including appropriate measures of preconceptional iodine intake. This review was registered at www.crd.york.ac.uk/prospero as CRD42018100277. [ABSTRACT FROM AUTHOR]

Background: Severe iodine deficiency during pregnancy can cause intellectual disability, presumably through inadequate placental transfer of maternal thyroid hormone to the fetus. The association between mild-to-moderate iodine deficiency and child neurodevelopmental problems is not well understood.Objectives: We investigated the association of maternal iodine status during pregnancy with child attention-deficit hyperactivity disorder (ADHD) and autistic traits.Methods: This was a collaborative study of 3 population-based birth cohorts: Generation R (n = 1634), INfancia y Medio Ambiente (n = 1293), and the Avon Longitudinal Study of Parents and Children (n = 2619). Exclusion criteria were multiple fetuses, fertility treatment, thyroid-interfering medication use, and pre-existing thyroid disease. The mean age of assessment in the cohorts was between 4.4 and 7.7 y for ADHD symptoms and 4.5 and 7.6 y for autistic traits. We studied the association of the urinary iodine-to-creatinine ratio (UI/Creat) <150 μg/g-in all mother-child pairs, and in those with a urinary-iodine measurement at ≤18 weeks and ≤14 weeks of gestation-with the risk of ADHD or a high autistic-trait score (≥93rd percentile cutoff), using logistic regression. The cohort-specific effect estimates were combined by random-effects meta-analyses. We also investigated whether UI/Creat modified the associations of maternal free thyroxine (FT4) or thyroid-stimulating hormone concentrations with ADHD or autistic traits.Results: UI/Creat <150 μg/g was not associated with ADHD (OR: 1.2; 95% CI: 0.7, 2.2; P = 0.56) or with a high autistic-trait score (OR: 0.8; 95% CI: 0.6, 1.1; P = 0.22). UI/Creat <150 μg/g in early pregnancy (i.e., ≤18 weeks or ≤14 weeks of gestation) was not associated with a higher risk of behavioral problems. The association between a higher FT4 and a greater risk of ADHD (OR: 1.3; 95% CI: 1.0, 1.6; P = 0.017) was not modified by iodine status.Conclusions: There is no consistent evidence to support an association of mild-to-moderate iodine deficiency during pregnancy with child ADHD or autistic traits. [ABSTRACT FROM AUTHOR]

Background: Thyroid hormone is essential for optimal fetal brain development. Evidence suggests that both low and high maternal thyroid hormone availability may have adverse effects on child neurodevelopmental outcomes, but the effect on behavioral problems remains unclear. We studied the association of maternal thyrotropin (TSH) and free thyroxine (fT4) concentrations during the first 18 weeks of pregnancy with child attention-deficit hyperactivity disorder (ADHD). Methods: A total of 7669 mother–child pairs with data on maternal thyroid function and child ADHD were selected from three prospective population-based birth cohorts: INfancia y Medio Ambiente (INMA; N = 1073, Spain), Generation R (N = 3812, The Netherlands), and Avon Longitudinal Study of Parents and Children (ALSPAC; N = 2784, United Kingdom). Exclusion criteria were multiple pregnancy, fertility treatment, usage of medication affecting the thyroid, and pre-existing thyroid disease. We used logistic regression models to study the association of maternal thyroid function with the primary outcome, ADHD, assessed via the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria by parents and/or teachers at a median child age of 4.5 to 7.6 years, and with the secondary outcome, an ADHD symptom score above the 90th percentile. Effect modification by gestational age and sex was tested with interaction terms and stratified analyses. Results: Overall, 233 (3%) children met the criteria for ADHD. When analyzed continuously, neither fT4 nor TSH was associated with a higher risk of ADHD (odds ratio [OR] 1.1, 95% confidence interval [CI 1.0–1.3], p = 0.060 and OR 0.9 [CI 0.9–1.1], p = 0.385, respectively) or with high symptom scores. When investigating effect modification by gestational age, a higher fT4 was associated with symptoms above the 90th percentile but only in the first trimester (for fT4 per 1 SD: OR 1.2 [CI 1.0–1.4], p = 0.027). However, these differential effects by gestational age were not consistent. No significant effect modification by sex was observed. Conclusions: We found no clear evidence of an association between maternal thyroid function and child ADHD. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effect of selenium supplementation at different dose levels on changes in HbA1c after 6 months and 2 years in a population of low selenium status. Materials and Methods: The Denmark PRECISE study was a single‐centre, randomized, double‐blinded, placebo‐controlled, multi‐arm, parallel clinical trial with four groups. In total, 491 volunteers aged 60 to 74 years were randomly assigned to treatment with 100, 200 or 300 μg selenium/day as selenium‐enriched yeast or placebo‐yeast. HbA1c measurements were available for 489 participants at baseline, 435 at 6 months, and 369 after 2 years of selenium supplementation. Analyses were performed by intention to treat. Results: The mean (SD) age, plasma‐selenium concentration, and blood HbA1c at baseline were 66.1 (4.1) years, 86.5 (16.3) ng/g and 36.6 (7.0) mmol/mol, respectively. During the initial 6‐month intervention period, mean HbA1c (95% CI) decreased by 1.5 (−2.8 to −0.2) mmol/mol for 100 μg/d of selenium supplementation and by 0.7 (−2.0 to 0.6) mmol/mol for the 200 and 300 μg/d groups compared with placebo (P = 0.16 for homogeneity of changes across the four groups). After 2 years of selenium supplementation, HbA1c had decreased significantly in all treatment groups, with no difference between active treatment and placebo. Conclusions: Selenium supplementation in an elderly European population of low selenium status did not significantly affect HbA1c levels after 2 years. Our findings corroborate a possible U‐shaped response of selenium supplementation on glucose metabolism. [ABSTRACT FROM AUTHOR]

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are examples of autoimmune thyroid disease (AITD), the commonest autoimmune condition. Antibodies to thyroid peroxidase (TPO), the enzyme that catalyses thyroid-hormone production and antibodies to the receptor for the thyroid-stimulating hormone, are characteristic of HT and GD, respectively. It is presently accepted that genetic susceptibility, environmental factors, including nutritional factors and immune disorders contribute to the development of AITD. Aiming to investigate the effect of iodine, iron and selenium in the risk, pathogenesis and treatment of thyroid disease, PubMed and the Cochrane Library were searched for relevant publications to provide a narrative review. Iodine: chronic exposure to excess iodine intake induces autoimmune thyroiditis, partly because highly-iodinated thyroglobulin (Tg) is more immunogenic. The recent introduction of universal salt iodisation can have a similar, although transient, effect. Iron: iron deficiency impairs thyroid metabolism. TPO is a haem enzyme that becomes active only after binding haem. AITD patients are frequently iron-deficient since autoimmune gastritis, which reduces iron absorption and coeliac disease which causes iron loss, are frequent co-morbidities. In two-thirds of women with persistent symptoms of hypothyroidism despite appropriate levothyroxine therapy, restoration of serum ferritin above 100 µg/l ameliorated symptoms. Selenium: selenoproteins are essential to thyroid action. In particular, the glutathione peroxidases remove excessive hydrogen peroxide produced there for the iodination of Tg to form thyroid hormones. There is evidence from observational studies and randomised controlled trials that selenium, probably as selenoproteins, can reduce TPO-antibody concentration, hypothyroidism and postpartum thyroiditis. Appropriate status of iodine, iron and selenium is crucial to thyroid health. [ABSTRACT FROM AUTHOR]