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Size exclusion chromatography (SEC) has become a powerful tool for analysing size variants of biologic drugs in their native form. Modern SEC can be defined by the use of chromatographic columns packed with sub-3 µm particles, allowing an increase in method throughput compared to that of conventional SEC.

Soy, red clover, chaste tree, hop and flax have all been found to contain a wide range of phytoestrogenic compounds, and a large number of dietary supplements contain their extracts as principal ingredients. This study is aimed to evaluate the total polyphenolic content and antioxidant activity of phytoestrogen-containing food and formulated dietary supplements. The HPLC-DPPH method was applied for DPPH free radical scavenging activity testing of various phytoestrogen-containing samples. Polyphenol content and antioxidant activity in dietary supplements were higher than in functional food samples; multiple-botanical-source preparations showed higher polyphenol content and antioxidant activity than the mono-botanical counterparts. Furthermore, the correlation between polyphenol content and anti-oxidant activity was strongly statistically significant, so it might be concluded that antioxidant activity is proportional to the content of these secondary metabolites. The most striking batch-to-batch deviations were represented by one chaste berry-based product (RSD 41.3 %) and one red clover derived product (RSD 57.9 %). The results of this study contribute to a better understanding of the phenolic profile and antioxidant properties of phytoestrogen containing food and dietary supplements.

Background/objectives: Janus kinase inhibitors open new horizons for small-molecule drugs in treating inflammatory bowel disease, with ritlecitinib demonstrating significant efficacy in clinical trials for ulcerative colitis and Crohn's disease. Ritlecitinib, a second-generation JAK3 inhibitor, is a novel therapeutic agent for alopecia areata and other autoimmune conditions., Methods: A new stability-indicating UHPLC-DAD-MS/MS method was developed, validated, and applied for a forced degradation study of ritlecitinib under ICH guidelines., Results: The method demonstrated high specificity, sensitivity (LOD: 0.04 µg/mL; LOQ: 0.14 µg/mL), precision (RSD ≤ 0.15%), and accuracy (99.9-100.3%). Forced degradation studies under acidic, basic, oxidative, thermal, and photolytic conditions revealed four novel degradation products. Basic degradation followed second-order kinetics, while oxidative degradation followed zero-order kinetics., Conclusions: The validated method reliably characterized ritlecitinib's stability and degradation products, providing essential data for optimizing formulation, determining proper storage conditions, anticipating drug-excipient interactions, and ensuring quality control. The eco-friendliness and applicability of the developed forced degradation procedure were evaluated using various green and blue metric tools. Incorporating green analytical principles underscores its potential for sustainable pharmaceutical analysis.

Background: The validity of the self-report questionnaire for hand eczema (HE) among Croatian hairdressers was not investigated previously, leading to uncertainty in the prevalence estimated from self-reported data., Objectives: To (1) investigate the validity of the self-report questionnaire for HE in hairdressing apprentices and (2) examine the differences between apprentices who recognised their HE symptoms and those who did not., Methods: Clinical examination for HE signs on hands and wrists was performed by the Osnabrueck Hand Eczema Severity Index for 408 apprentices at four visits covering the entire schooling period. Self-report HE was based on the Nordic Occupational Skin Questionnaire., Results: Low sensitivity (7%-37%) with high specificity (≥95%) was observed, with both measures improving from baseline to last visit. The severity of HE signs was the only factor associated with the correct identification of HE signs in analyses adjusted for previous HE signs, health-related quality of life, and atopic dermatitis (adjusted odds ratios of 1.58 with 95% confidence interval [1.06-2.35] and 1.74[1.38-2.19] at second and third follow-up visit, respectively)., Conclusions: Self-report questionnaire for HE showed low sensitivity in hairdressing apprentices, especially at the beginning of training and in those with mild symptoms. Further validation studies following questionnaire modifications aimed at adolescent population are advised., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Etrasimod, a novel selective sphingosine-1-phosphate receptor modulator, was recently approved by the U.S. Food and Drug Administration and the European Medicinal Agency for the treatment of moderately to severely active ulcerative colitis in adults. In this research, the forced degradation study as an integral part of drug product and packaging development, which generates data on degradation mechanisms, is published. The development and validation of the stability-indicating method using a superior high-performance liquid chromatography technique coupled with a diode array detector and tandem mass spectrometer was performed to support the forced degradation study and monitor the formation of degradation products. Etrasimod demonstrated good stability under elevated temperature and basic stress conditions, while acidic hydrolysis, oxidative, and photolytic degradation produced eight degradation products. The knowledge of degradation products will be useful in the long-term stability study for establishing the acceptance criteria of etrasimod as a drug substance and dosage form during quality control and stability assessment. The eco-friendliness of the developed forced degradation procedure was evaluated using various greenness appraisal tools. The green metric tools showed that the forced degradation procedure obeys eco-friendly conditions., Competing Interests: 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., (© 2024 The Authors.)

This study evaluates the interaction of toxic elements cadmium (Cd) and lead (Pb) due to exposure from cigarette smoking, essential elements, and steroidogenesis in the maternal-placental-fetal unit. In a cohort of 155 healthy, postpartum women with vaginal term deliveries in clinical hospitals in Zagreb, Croatia, samples of maternal blood/serum and urine, placental tissue, and umbilical cord blood/serum were collected at childbirth. The biomarkers determined were concentrations of Cd, Pb, iron (Fe), zinc (Zn), copper (Cu), and selenium (Se), and steroid hormones progesterone and estradiol in maternal and umbilical cord blood and the placenta. Three study groups were designated based on self-reported data on cigarette smoking habits and confirmed by urine cotinine levels: never smokers ( n = 71), former smokers ( n = 48), and active smokers ( n = 36). Metal(loid)s, steroid hormones, urine cotinine, and creatinine levels were analyzed by ICP-MS, ELISA, GC-MS, and spectrophotometry. Cigarette smoking during pregnancy was associated with increased Cd levels in maternal, placental, and fetal compartments, Pb in the placenta, and with decreased Fe in the placenta. In active smokers, decreased progesterone and estradiol concentrations in cord blood serum were found, while sex steroid hormones did not change in either maternal serum or placenta. This study provides further evidence regarding toxic and essential metal(loid) interactions during prenatal life, and new data on sex steroid disruption in cord serum related to cigarette smoking. The results indicate that umbilical cord sex steroid levels may be a putative early marker of developmental origins of the future burden of disease related to harmful prenatal exposure to cigarette smoke.

Inflammatory bowel disease is a complex disorder characterized by chronic gastrointestinal inflammation. Thus, patients prefer to use herbal dietary supplements containing turmeric, Indian frankincense, green chiretta, and black pepper in an attempt to cope better with their chronic condition. The dietary supplements' dosage forms and herbal ingredients were assessed in terms of the products' physicochemical parameters (weight uniformity, friability, disintegration, rupture test, tablet's breaking force, and powder flowability) in view of the USP-NF requirements. In addition, contaminants such as organic solvents and ethylene oxide were evaluated using gas chromatography. Assessment of gluten via an Enzyme-Linked Immunosorbent Assay was also performed. Most of the products met USP requirements. The high average weight of one multicomponent tablet sample with a high breaking force value can explain the observed negative results of the disintegration test. A total of 26% of samples tested positive for gluten, but the most alarming fact is that the ethylene oxide levels found in two samples were up to 30 times higher than the EU limit. Accordingly, dietary supplement quality control is of fundamental importance., Competing Interests: The authors declare no conflicts of interest.

The aim of this study was to investigate the temporal trends and geographical differences in 90 Sr and stable element (Ba, Ca, Mn, Sr, Pb, Zn) levels in the bones of Croatian and Polish brown bear (Ursus arctos) populations. Experimental data suggest that in the decades after nuclear weapon tests and the Chernobyl accident, 90 Sr bone activity concentrations decreased from 352 to 11 Bq kg -1 in the Croatian bear population (period 1982-2015) and from 831 to 27 Bq kg -1 in Polish bears (period 1962-2020). Calculated effective and ecological half-lives were 9 and 13 years for Croatian bears, and 15 and 31 years for Polish bears, respectively. Different temporal trends were noted in levels of Ba, Mn, Pb and Zn between the two countries with majority of bones having lower Pb, Sr and Zn in Croatian than in Polish bears. Estimated values for the soil-to-bear transfer of 90 Sr were the same order of magnitude in the studied populations. Contrary to this, the estimated transfer of stable Sr was an order of magnitude lower for the Croatian bear population compared to Polish bears. The observed differences in soil-to-bear transfer between stable Sr and 90 Sr found for Croatian bears might suggest the need for careful consideration on the use of stable Sr data as an analogue for 90 Sr. To our knowledge, this is the first study that analysed 90 Sr activity in tissue of brown bears. As such, it provides insight into the fate and behaviour of one of the most relevant anthropogenic radionuclides at the top of the food chain., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In the present study, various procedures have been compared for the determination of lipophilicity, hydrophobicity, and plasma protein binding of curcuminoids, boswellic acids, andrographolides, and piperine as biologically active ingredients of botanicals used in IBD treatment. Our results have shown that IAM-HPLC assay is the most suitable one for lipophilicity determination of all analytes regardless of their class and botanical source. HSA-HPAC and AGP-HPAC assays revealed that all investigated compounds have a higher affinity for HSA which is the most abundant protein in human plasma. The high affinity of biologically active compounds to all biological structures (phospholipids and proteins) admonishes that their small portion is available for therapeutic effects in IBD patients. Our experimental research is complemented by various theoretical approaches based on different algorithms for pharmacokinetic properties prediction. The similarities between experimental and calculated values were evaluated using PCA and CA as a statistical tool. The statistical analysis implies that plasma protein binding is a complex process, and theoretical approaches still cannot fully replace experimental ones.

Since oxidative stress has been linked to several pathological conditions and diseases, drugs with additional antioxidant activity can be beneficial in the treatment of these diseases. Therefore, this study takes a new look at the antioxidant activity of frequently prescribed drugs using the HPLC-DPPH method. The antioxidative activity expressed as the TEAC value of 82 drugs was successfully determined and is discussed in this work. Using the obtained values, the QSAR model was developed to predict the TEAC based on the selected molecular descriptors. The results of QSAR modeling showed that four- and seven-variable models had the best potential for TEAC prediction. Looking at the statistical parameters of each model, the four-variable model was superior to seven-variable. The final model showed good predicting power ( r = 0.927) considering the selected descriptors, implying that it can be used as a fast and economically acceptable evaluation of antioxidative activity. The advantage of such model is its ability to predict the antioxidative activity of a drug regardless of its structural diversity or therapeutic classification.

The aim of the study was to assess the effectiveness of the specific design of a poisoning prevention intervention. This controlled before-after study followed Solomon design for educational interventions using two groups (the educational intervention group and the control group). Participants comprised parents of children attending kindergartens under the jurisdiction of the City of Zagreb and in the vicinity of Zagreb. The intervention group (N = 336) underwent an educational intervention during parents' meetings comprising oral presentation by the Croatian Poison Control Centre (CPCC) and distribution of gift packages containing child-proof locks, flyers, and stickers with the CPCC contact number. After the intervention they more frequently started keeping the CPCC's number by their telephone or in the list of important numbers than parents in the control group, and this association remained significant when tested by generalized estimating equations for binary outcomes, after the adjustment for parents' characteristics (age, gender and educational level), and clustered by kindergartens ( p  < 0.001). This means parents acknowledged the CPCC as an adequate and accessible way for initial management of poisoning incidents.

Introduction: The assessment of circulating miRNAs is challenging and still limited due to their low concentrations, small size and lack of reference values in human biological samples. Pre-amplification of complementary DNAs may facilitate reliable miRNA quantification. The aim of our study was to evaluate the efficacy of pre-amplification as a step to increase the sensitivity of qPCR analysis for five candidate circulating miRNAs presumably related to toxic metals and cigarette smoke exposure: miR-1537, miR-190b, miR-16, miR-21, and miR-146a., Materials and Methods: Candidate miRNAs expression was analysed in plasma samples of 19 mother-newborn pairs. For isolation, transcription, pre-amplification and qPCR quantification kits and protocols by Qiagen (Hilden, Germany) were used. Paired t-test or Wilcoxon rank test were used to compare miRNAs expression levels with and without a pre-amplification step prior to qPCR, separately in maternal and cord plasma. Intraclass correlation (ICC) was calculated as an agreement measure between procedures for each miRNA., Results: Pre-amplification facilitated the detection of all assayed miRNAs with an overall cycle threshold (C T ) improvement of 6.6 ± 0.89 (P < 0.05). Excellent ICCs (> 0.90) were found between data for preamplified and not preamplified miR-16, miR-21 and miR-146a. However, these correlations for low expressed miR-190b were moderate (0.79 in maternal; 0.61 in cord plasma) and poor for miR-1537 (0.49 in maternal; no correlation in cord plasma)., Conclusion: Pre-amplification is a useful, necessary step in the analysis of miR-1537 and miR-190b as a reliable procedure facilitating extracellular miRNA expression detection in human plasma by real-time PCR quantification., Competing Interests: Potential conflict of interest None declared., (Croatian Society of Medical Biochemistry and Laboratory Medicine.)

The effect of maternal smoking as a source of exposure to toxic metals Cd and Pb on superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity, metallothionein (MT), Cd, Pb, Cu, Fe, Mn, Se and Zn concentrations were assessed in maternal and umbilical cord blood and placenta in 74 healthy mother-newborn pairs after term delivery. Sparse discriminant analysis (SDA) was used to identify elements with the strongest impact on the SOD, GPx and MT in the measured compartments, which was then quantified by multiple regression analysis. SOD activity was lower in maternal and cord plasma, and higher in the placenta of smokers compared to non-smokers, whereas GPx activity and MT concentration did not differ between the groups. Although active smoking during pregnancy contributed to higher maternal Cd and Pb concentrations, its contribution to the variability of SOD, GPx or MT after control for other elements identified by SDA was not significant. However, an impaired balance in the antioxidant defence observed in the conditions of relatively low-to-moderate exposure levels to Cd and Pb could contribute to an increased susceptibility of offspring to oxidative stress and risk of disease development later in life. Further study on a larger number of subjects will help to better understand complex interactions between exposure to toxic elements and oxidative stress related to maternal cigarette smoking., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Objective: This pilot study aimed to estimate annual occupational ultraviolet radiation (UVR) exposures based on 5 consecutive months of dosimetry measurements in Croatian construction workers and assess its relationship with the environmental data collected during the same period., Methods: Four male construction industry workers from the vicinity of Zagreb (lat. 45.8° N, alt. 128 m) participated in the study. The study was a part of the GENESIS-UV project, attempting to collect long-term dosimetry data for outdoor occupations across Europe. Workers wore personal dosimeters (model X2012-10, Gigahertz, Tuerkenfeld, Germany) on the left upper arm during working hours in the period from June to October 2017. Median exposure assessment period was 57 working days., Results: Estimates of annual occupational UVR exposure ranged from 76 SED to 976 SED per worker, reflecting large differences in patterns of workers' exposure. Daily UVR doses received by the workers were comparable to the values of other studies at similar latitudes, reaching up to 12 SED in summer months. Measurements of workers with high exposure values (estimated >600 SED/year) showed moderate to high associations with environmental UVR and insolation data (Spearman's correlation coefficient ranging from 0.57 to 0.73)., Conclusions: The results confirmed high occupational exposure of tested Croatian construction workers to solar UVR. However, more data are needed to explain the between-worker variability and develop prediction models with respect to specific work tasks. The use of environmental UVR for predicting long-term exposure should be considered, especially for high exposure tasks., 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.)

The aim of this study was to examine mental health and cognitive functions in older Croatian workers (50-65 years) taking into account their employment status, self-assessed health, and a set of demographic characteristics. We analysed the data collected on 650 older workers (71 % employed) in the Wave 6 of the Survey of Health, Ageing and Retirement in Europe (SHARE). Unemployed workers reported symptoms of loneliness more often than the employed, while in rural areas unemployment was additionally associated with more pronounced symptoms of depression. Feeling of loneliness was also higher in those living without a partner in the household and in those with poorer health. In urban residents symptoms of depression were more severe in women, respondents with higher education, those living without a partner, and those who rated their health as poorer. As for cognitive functions, unemployment significantly predicted poorer subtraction in the rural subsample. Women in general showed less efficient numerical abilities. In the urban subsample poorer numerical abilities were also associated with lower education and living without a partner in the household. Better verbal recall was predicted by higher education and better self-rated memory. Higher scores in verbal fluency were predicted by urban residency and better self-rated health. Our results indicate that the protective factors for good mental health and cognitive functioning in older Croatian workers are being employed, having more education, living with a partner in the household, and being healthier. These findings stress the importance of implementing broader social policy strategies covering employment, education, and health.

Although the incidence of ventilator-associated pneumonia (VAP) is very high, there are still many uncertainties about clinical course of VAP among tracheotomized patients. The goal of the present study was to determine the impact of tracheotomy on VAP incidence and etiology, as well as outcome of VAP patients with tracheotomy. The study was conducted in a 15-bed Surgical and Neurosurgical Intensive Care Unit (ICU), Sestre milosrdnice University Hospital Center in Zagreb, Croatia. The study included all patients undergoing only percutaneous tracheotomy during the study period. According to our data, the incidence of VAP among percutaneous tracheotomized patients was 42%, not considering the time between tracheotomy and VAP onset. However, when only patients developing VAP after tracheotomy were taken into account, the incidence of VAP among tracheotomized patients dropped to 8% only. The most commonly isolated bacterium was Staphylococcus aureus, accounting for 17 (37%) isolates, followed by Haemophilus influenzae, accounting for another 10 (22%) isolates. The development of VAP among percutaneously tracheotomized patients was associated with longer total ICU stay (regardless of whether VAP developed before or after tracheotomy), while total duration of mechanical ventilation and mortality rate remained unaffected.

When studies in meta-analysis include different sets of confounders, simple analyses can cause a bias (omitting confounders that are missing in certain studies) or precision loss (omitting studies with incomplete confounders, i.e. a complete-case meta-analysis). To overcome these types of issues, a previous study proposed modelling the high correlation between partially and fully adjusted regression coefficient estimates in a bivariate meta-analysis. When multiple differently adjusted regression coefficient estimates are available, we propose exploiting such correlations in a graphical model. Compared with a previously suggested bivariate meta-analysis method, such a graphical model approach is likely to reduce the number of parameters in complex missing data settings by omitting the direct relationships between some of the estimates. We propose a structure-learning rule whose justification relies on the missingness pattern being monotone. This rule was tested using epidemiological data from a multi-centre survey. In the analysis of risk factors for early retirement, the method showed a smaller difference from a complete data odds ratio and greater precision than a commonly used complete-case meta-analysis. Three real-world applications with monotone missing patterns are provided, namely, the association between (1) the fibrinogen level and coronary heart disease, (2) the intima media thickness and vascular risk and (3) allergic asthma and depressive episodes. The proposed method allows for the inclusion of published summary data, which makes it particularly suitable for applications involving both microdata and summary data. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Aim: To point out the similarity of Meniere disease and spontaneous intracranial hypotension and difference of their treatment., Methods: A case of a 54-year-old male patient with previously diagnosed Meniere's disease and newly diagnosed spontaneous intracranial hypotension syndrome is presented. Additional neuroradiological examination, Brain contrast-enhanced MRI and MR myelography were used for diagnosis., Results: Due to deterioration of vertigo, hearing loss and tinnitus in the right ear the patient was referred to the additional neuroradiological examination which confirmed the diagnosis of spontaneous intracranial hypotension syndrome. Brain contrast-enhanced MRI showed increased pachymeningeal contrast enhancement, and MR myelography identified the location of CSF leak. The patient was successfully treated conservatively., Conclusion: According to our knowledge this is the fifth case report of Meniere's disease and spontaneous intracranial hypotension coexistence. Both diseases have similar clinical presentation and initial treatment. We suggest procedures of additional examination when the treatment fails and initial diagnosis becomes questionable., (Copyright© by the Medical Assotiation of Zenica-Doboj Canton.)

Muscle (n = 111), liver (n = 111), and kidney cortex (n = 101) samples from brown bears (Ursus arctos) were collected in the 2009 and 2010 hunting seasons in Croatia and analysed for selenium (Se), cadmium (Cd), and total mercury (Hg). The aim was to assess the levels of these elements according to age, sex, and season of collection, and to investigate possible Se/Cd and Se/Hg interactions. Median Se concentrations were 0.139 μg/g in muscle, 0.409 μg/g in liver and 1.75 μg/g wet mass in kidney cortex. Median Cd and Hg were 0.0078 and 0.0018 μg/g in muscle, 1.09 and 0.031 μg/g in liver, and 16.5 and 0.206 μg/g wet mass in the renal cortex, respectively. Se/Cd molar ratios were less than 1 in the kidney cortex, and close to or above 1 in liver and muscle, respectively. Toxic Cd and Hg correlated with Se in all of the studied tissues. Sex differences were found for all three elements (except Se in liver), with females having higher tissue concentration than males. Only Cd showed age-dependence. Bear samples collected in fall had higher Se in muscles, and Hg in muscles and liver compared to samples collected in spring. Element concentrations in brown bear tissues were within the range of previously reported studies. Bear meat is considered a rich source of Se, safe for consumption with regard to its Cd and Hg content. According to the molar ratio and correlation results, we assume that Se binding is not the primary detoxification pathway for Cd and Hg in brown bears.

Background and Study Design: It is well documented that copper (Cu) blood levels are elevated in combination oral contraceptive (COC) users. The aim of this study was to establish the range of Cu increase in OC users compared to nonusers through a systematic literature overview and quantitative data analysis., Results: Twenty-six articles were included in the meta-analysis. The increase in Cu level exponentially decreased in COC users over time, with a rapid decline through the 1960s and 1970s. After controlling for the publication year, use of COC increases the mean serum/plasma Cu level by 0.57 mg/L (95% confidence interval 0.49-0.66 mg/L)., Conclusion: COCs commonly raise serum Cu to levels between 1.5 and 2 mg/L, which are above reference levels. Although these levels are not considered toxic, there are suggestions that such Cu increase could be implicated in oxidative pathophysiological processes in the body. Further research on safety of COCs use, including oxidative-stress-related effects, is warranted., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Der p 1 is the main allergen of house dust mite Dermatophagoides pteronyssinus, which has routinely been detected in residential dust. However, the procedure for extracting Der p 1 from reservoir dust has not been well defined. The aim of this study was to compare Der p 1 mass fractions in dust extracts prepared using the following extraction buffers: phosphate (pH 7.4), borate (pH 8.0), and ammonium bicarbonate (pH 8.0), all with 0.05 % Tween 20. Twenty-eight dust samples were divided into three aliquots and each portion was extracted with one of the three buffers at room temperature. Der p 1 mass fractions were measured in a total of 84 dust extracts using the enzyme immunoassay (range: 0.1 μg g-1 to 7.53 μg g-1). Statistical methods including intraclass correlation showed a high agreement between Der p 1 mass fractions irrespective of the extracting medium. Our results suggest that all three buffers are suitable for the extraction of mite allergens and routine Der p 1 analysis in dust.