The COVID-19 Pandemic, Seasons and the Vitamin D Laboratory Strategy

From the very beginning of the COVID-19 pandemic, the laboratory blood tests and markers are searched as a potential diagnostic tool for this disease and for disease severity assessment. Also from the beginning of the pandemic scientists published reports on the potentially important role of vitamin D on the course of the COVID-19 patients. According to the data there are seasonal fluctuations of COVID-19 severity, where the numbers of newly infected in summertime in contrast to wintertime, are the same or even higher, but there are much less death cases. The different seasonal incidence of infectious diseases has been well known since the Hippocratic period. Vitamin D is a molecule with potent immunomodulatory actions. The effectiveness against various upper respiratory infections is confirmed. Based on the findings of previous research on meta-analysis of interventional studies with vitamin D in respiratory viral infections, based on new COVID-19 observational studies and based on pilot randomized study where vitamin D in COVID-19 patients significantly reduced morbidity and alleviated the course of infection, we emphasize the importance of inclusion of vitamin D routine measurement, before vitamin D treatment in COVID patients becomes a routine. Vitamin D has a small chance of side effects in doses of prevention and therapy. Randomized double blinded clinical trials are needed to finally prove the benefit of supplementation of vitamin D in COVID-19 patients. Until then however, in the COVID pandemic, it is highly ethical to consider and use the current knowledge about the benefits of vitamin D substitution in patients with vitamin D deficiency or insufficienc

Molecular impact of glutathione peroxidases in antioxidant processes

Reaktivni radikali kisika (ROS) stvaraju se tijekom različitih patoloških procesa u povećanim koncentracijama. Oni su uzrok peroksidacije lipida i oksidacije DNA i proteina zbog svoje visoke kemijske reaktivnosti. Međutim, mehanizmi antioksidacijske zaštite, uključujući različite antioksidacijske enzime, sprječavaju oštećenja tkiva i druge komplikacije povezane s ROS. Ovaj je pregled usredotočen na učinke različitih glutation-peroksidaza (GPX) na molekularnu kontrolu toksikološkog djelovanja reaktivnih kisikovih radikala. Nadalje, opisuju se specifična biokemijska svojstva, sinteza i uloga svakog izoenzima glutation-peroksidaze u biološkim procesima. Male molekule koje djeluju kao oponašatelji aktivnog mjesta glutation-peroksidaza mogle bi postati novo sredstvo u liječenju mnogih oboljenja.Reactive oxygen species (ROS) are produced during different pathological processes in increased concentrations. They cause lipid peroxidation and oxidation of DNA and proteins due to their high chemical reactivity. However, antioxidative defense mechanisms, including different antioxidant enzymes, prevent tissue damages and other ROS-related complications. The focus of this review is on effects of different glutathione peroxidases (GPXs) on molecular control of reactive oxygen species toxicology. Furthermore, specific biochemical properties, synthesis and role of each glutathione peroxidase isoenzyme in biological processes are described. Small molecules acting as mimetics of the active site of glutathione peroxidases could become new tools for treatment of many diseases

The comparison of the three assays for determination of fecal calprotectin in inflammatory bowel disease

Fecal calprotectin is a biomarker for monitoring inflammatory bowel disease (IBD) activity. Our aim, therefore, was to evaluate two new assays, the point of care test Quantum Blue and the Liaison Calprotectin with respect to the Calprest, commonly used assay, and to determine their performance for IBD diagnosis. We included 73 prospective patients with IBD. Fecal calprotectin was measured and analysed with the routine Calprest assay and two recently introduced assays, the Quantum Blue and the Liaison Calprotectin. Furthermore, we compared the results by Bland and Altman analysis, and Passing-Bablok regression. We observed no difference in median calprotectin values obtained by the Calprest (94.6 µg/g, 95%CI 66.5 to 166.1) and Liaison assay (101.0 µg/g, 95%CI 48.1 to 180.1) whereas significantly higher concentrations were obtained with the Quantum Blue assay (240.0 µg/g, 95%CI 119.9 to 353.2). The mean absolute and relative difference between the Calprest and Quantum Blue methods was statistically significant (- 162.3 µg/g and - 143.1%). Mean absolute difference between the Calprest and Liaison calprotectin methods was positive (2.2 µg/g). The agreement between assays revealed that Quantum Blue and Calprest have fair agreement with Kappa coefficient of 0.38 (95%CI 0.26 to 0.51). Liaison Calprotectin and Calprest revealed moderate agreement with a weak Kappa coefficient of 0.47 (95%CI 0.32 to 0.62). Clinicians should be aware of these differences between the assays and avoid comparison of their respective results

A Dual Biomarker TK1 Protein and CA125 or HE4-Based Algorithm as a Better Diagnostic Tool than ROMA Index in Early Detection of Ovarian Cancer

Simple Summary Ovarian cancer is one of the most difficult tumors to detect and manage. Usually, it is diagnosed in late stage of the disease which is associated with poor prognosis. Therefore, it is important to detect this cancer in the early stages to improve overall survival. In this study, we determined TK1 protein and TK1 activity levels as well as the biomarkers CA 125, HE4, and the ROMA index. Elevated TK1 protein levels were found in both benign and ovarian tumor (borderline and malignant ovarian cancer) patients. The combination of TK1 protein with CA 125 or HE4 showed higher sensitivity compared to the ROMA index. Therefore, the TK1 protein is a promising serum biomarker that can complement CA 125 or HE4 in the diagnostics of the early stages of ovarian cancer. Background: The early detection of ovarian cancer is presently not effective, and it is crucial to establish biomarkers for the early diagnosis of ovarian cancer to improve the survival of patients. Materials and methods: The aim of this study was to investigate the role of thymidine kinase 1 (TK1) in combination with CA 125 or HE4 to serve as a potential diagnostic biomarkers for ovarian cancer. In this study, a set of 198 serum samples consisting of 134 ovarian tumor patients and 64 healthy age-matched controls were analyzed. The TK1 protein levels in serum samples were determined using the AroCell TK 210 ELISA. Results: A combination of TK1 protein with CA 125 or HE4 showed better performance than either of them alone in the differentiation of early stage ovarian cancer from the healthy control group, but also a significantly better performance than the ROMA index. However, this was not observed using a TK1 activity test in combination with the other markers. Furthermore, the combination of TK1 protein and CA 125 or HE4 could differentiate early stage disease (stage I, II) more efficiently from advanced-stage (stage III, IV) disease (p < 0.0001). Conclusions: The combination of TK1 protein with CA 125 or HE4 increased the potential of detecting ovarian cancer at early stages

Circulating estradiol and its biologically active metabolites in endometriosis and in relation to pain symptoms

ObjectivesEndometriosis (EM) is an estrogen-dominant inflammatory disease linked to infertility that affects women of reproductive age. EM lesions respond to hormonal signals that regulate uterine tissue growth and trigger inflammation and pain. The objective of this study was to evaluate whether estradiol (E2) and its biologically active metabolites are differentially associated with EM given their estrogenic and non-estrogenic actions including proliferative and inflammatory properties.DesignWe performed a retrospective study of 209 EM cases and 115 women without EM.MethodsPain-related outcomes were assessed using surveys with validated scales. Preoperative serum levels of estradiol (E2) and estrone (E1), their 2-, 4- and 16- hydroxylated (OH) and methylated (MeO) derivatives (n=16) were measured by mass spectrometry. We evaluated the associations between estrogen levels and EM anatomic sites, surgical stage, risk of EM, and symptoms reported by women. Spearman correlations established the relationships between circulating steroids.ResultsOf the sixteen estrogens profiled, eleven were detected above quantification limits in most individuals. Steroids were positively correlated, except 2-hydroxy 3MeO-E1 (2OH-3MeO-E1). Higher 2OH-3MeO-E1 was linked to an increased risk of EM (Odd ratio (OR)=1.91 (95%CI 1.09-3.34); P=0.025). Ovarian EM cases displayed enhanced 2-hydroxylation with higher 2MeO-E1 and 2OH-E1 levels (P&lt; 0.009). Abdominal, pelvic and back pain symptoms were also linked to higher 2OH-3MeO-E1 levels (OR=1.86; 95%CI 1.06-3.27; P=0.032).ConclusionsThe 2-hydroxylation pathway emerges as an unfavorable feature of EM, and is associated with ovarian EM and pain related outcomes

Personality Traits in Miners with Past Occupational Elemental Mercury Exposure

In this study, we evaluated the impact of long-term occupational exposure to elemental mercury vapor (Hg(0)) on the personality traits of ex-mercury miners. Study groups included 53 ex-miners previously exposed to Hg(0) and 53 age-matched controls. Miners and controls completed the self-reporting Eysenck Personality Questionnaire and the Emotional States Questionnaire. The relationship between the indices of past occupational exposure and the observed personality traits was evaluated using Pearson’s correlation coefficient and on a subgroup level by machine learning methods (regression trees). The ex-mercury miners were intermittently exposed to Hg(0) for a period of 7–31 years. The means of exposure-cycle urine mercury (U-Hg) concentrations ranged from 20 to 120 μg/L. The results obtained indicate that ex-miners tend to be more introverted and sincere, more depressive, more rigid in expressing their emotions and are likely to have more negative self-concepts than controls, but no correlations were found with the indices of past occupational exposure. Despite certain limitations, results obtained by the regression tree suggest that higher alcohol consumption per se and long-term intermittent, moderate exposure to Hg(0) (exposure cycle mean U-Hg concentrations > 38.7 < 53.5 μg/L) in interaction with alcohol remain a plausible explanation for the depression associated with negative self-concept found in subgroups of ex-mercury miners. This could be one of the reason for the higher risk of suicide among miners of the Idrija Mercury Mine in the last 45 years