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Background: The primary goal of this study was to investigate the relationship between body composition and motor coordination performance, and the secondary goal was to determine sex differences in body composition and motor coordination of preschool children., Methods: Forty-eight children (23 boys and 25 girls) underwent assessments for body composition and motor coordination using the Köperkoordinationstest für Kinder (KTK)., Results: Linear regression analysis revealed significant associations between body composition and motor coordination in boys ( p < 0.05) but not in girls. In boys, Body height ( p = 0.01), Total muscle mass ( p = 0.03), Total fat ( p = 0.03), and Total water ( p = 0.02) show statistically significant influence on single-leg jumps. Similar results were obtained for lateral jumps where there was a statistically significant influence of Body height ( p = 0.01), Total muscle mass ( p = 0.03), and Total water ( p = 0.02). Interestingly, predictive variables showed no statistically significant influence on KTK overall score in boys ( p = 0.42) nor in girls ( p = 0.90)., Conclusions: The predictive system of morphological variables demonstrated significance only among boys in this age group and sample. Girls outperformed boys due to early maturation, resulting in better average KTK scores.

Nanotechnology has the potential to provide formulations of antitumor agents with increased selectivity towards cancer tissue thereby decreasing systemic toxicity. This in vivo study evaluated the potential of novel nanoformulation based on poly(lactic- co -glycolic acid) (PLGA) to reduce the cardiotoxic potential of doxorubicin (DOX). In vivo toxicity of PLGADOX was compared with clinically approved non-PEGylated, liposomal nanoformulation of DOX (LipoDOX) and conventional DOX form (ConvDOX). The study was performed using Wistar Han rats of both sexes that were treated intravenously for 28 days with 5 doses of tested substances at intervals of 5 days. Histopathological analyses of heart tissues showed the presence of myofiber necrosis, degeneration processes, myocytolysis, and hemorrhage after treatment with ConvDOX, whereas only myofiber degeneration and hemorrhage were present after the treatment with nanoformulations. All DOX formulations caused an increase in the troponin T with the greatest increase caused by convDOX. qPCR analyses revealed an increase in the expression of inflammatory markers IL-6 and IL-8 after ConvDOX and an increase in IL-8 expression after lipoDOX treatments. The mass spectra imaging (MSI) of heart tissue indicates numerous metabolic and lipidomic changes caused by ConvDOX, while less severe cardiac damages were found after treatment with nanoformulations. In the case of LipoDOX, autophagy and apoptosis were still detectable, whereas PLGADOX induced only detectable mitochondrial toxicity. Cardiotoxic effects were frequently sex-related with the greater risk of cardiotoxicity observed mostly in male rats.

Aim: This study aimed to assess the impact of COVID-19 infection on cardiac surgery outcomes in patients who contracted COVID-19 peri-operatively or had recently recovered from COVID-19., Methods: The study prospectively enrolled 95 patients scheduled for cardiac surgery who had recently recovered from COVID-19. This formed the post-COVID-19 group. The other group consisted of 25 patients who contracted COVID-19 peri-operatively. Patients were followed for all-cause mortality as the primary endpoint and postoperative course complications as the secondary endpoint. Data were compared to a historical cohort of 280 non-COVID-19 patients., Results: The peri-operative COVID-19 group exhibited a significantly higher prevalence of primary outcome all-cause mortality (28%), compared with 4.3% in the controls ( p < 0.01), as well as the secondary composite endpoint (stroke, peri-operative myocardial infarction and pneumonia) (52 vs 13.9%, p < 0.01). The post-COVID-19 group had a higher incidence of acute pulmonary embolism (3.2 vs 0%, p < 0.01) and atrial fibrillation (23.4 vs 11.4%, p < 0.01)., Conclusion: Patients who contracted COVID-19 peri-operatively had an increased rate of mortality and postoperative complications, while cardiac surgery in the recently recovered COVID-19 group was associated with a higher incidence of pulmonary embolism and atrial fibrillation.

Aim/introduction: The study aimed to determine the effectiveness of early antidiabetic therapy in reversing metabolic changes caused by high-fat and high-sucrose diet (HFHSD) in both sexes., Methods: Elderly Sprague-Dawley rats, 45 weeks old, were randomized into four groups: a control group fed on the standard diet (STD), one group fed the HFHSD, and two groups fed the HFHSD along with long-term treatment of either metformin (HFHSD+M) or liraglutide (HFHSD+L). Antidiabetic treatment started 5 weeks after the introduction of the diet and lasted 13 weeks until the animals were 64 weeks old., Results: Unexpectedly, HFHSD-fed animals did not gain weight but underwent significant metabolic changes. Both antidiabetic treatments produced sex-specific effects, but neither prevented the onset of prediabetes nor diabetes., Conclusion: Liraglutide vested benefits to liver and skeletal muscle tissue in males but induced signs of insulin resistance in females., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ivić, Zjalić, Blažetić, Fenrich, Labak, Scitovski, Szűcs, Ducza, Tábi, Bagamery, Szökő, Vuković, Rončević, Mandić, Debeljak, Berecki, Balog, Seres-Bokor, Sztojkov-Ivanov, Hajagos-Tóth, Gajović, Imširović, Bakula, Mahiiovych, Gaspar, Vari and Heffer.)

Background: Approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience treatment resistance to the first-line R-CHOP regimen. ATP binding cassette (ABC) transporters and survivin might play a role in multidrug resistance (MDR) in various tumors. The aim was to investigate if the coexpression of ABC transporters and survivin was associated with R-CHOP treatment response., Methods: The expression of Bcl-2, survivin, P-glycoprotein/ABCB1, MRP1/ABCC1, and BCRP/ABCC2 was analyzed using immunohistochemistry in tumor specimens obtained from patients with DLBCL, and classified according to the treatment response as Remission, Relapsed, and (primary) Refractory groups. All patients received R-CHOP or equivalent treatment., Results: Bcl-2 was in strong positive correlation with clinical parameters and all biomarkers except P-gp/ABCB1. The overexpression of MRP1/ABCC1, survivin, and BCRP/ABCC2 presented as high immunoreactive scores (IRSs) was detected in the Refractory and Relapsed groups ( p < 0.05 vs. Remission), respectively, whereas the IRS of P-gp/ABCB1 was low. Significant correlations were found among either MRP1/ABCC1 and survivin or BCRP/ABCC2 in the Refractory and Relapsed groups, respectively. In multiple linear regression analysis, ECOG status along with MRP1/ABCC1 or survivin and BRCP/ABCG2 was significantly associated with the prediction of the R-CHOP treatment response., Conclusions: DLBCL might harbor certain molecular signatures such as MRP1/ABCC1, survivin, and BCRP/ABCC2 overexpression that can predict resistance to R-CHOP.

Sucralose is widely used as a non-nutritive sweetener (NNS). However, in order to justify its use as a non-nutritive food additive, sucralose would have to be metabolically neutral. The aim of this study was to examine whether sucralose altered the insulin signaling pathway in an in vitro cell model of Parkinson's disease (PD)-the dopaminergic differentiated cell line SH-SY5Y. Cells were exposed to sucralose alone and in combination with either insulin or levodopa. Activation of the insulin signaling pathway was assessed by quantifying protein kinase B (AKT) and glycogen synthase kinase 3 (GSK3), as well as the phosphorylated forms of insulin-like growth factor 1 receptor (IGF1-R). Metabolic effects were assayed using MALDI-TOF MS analysis. In the cell viability test, 2 mM sucralose had a negative effect, and levodopa in all combinations had a positive effect. Sucralose treatment alone suppressed GSK3 and IGF1-R phosphorylation in a dose-dependent manner. This treatment also altered the metabolism of fatty acids and amino acids, especially when combined with insulin and levodopa. Suppression of the insulin signaling pathway and sucralose-induced changes in the metabolic profile could underlie a diet-acquired insulin resistance, previously associated with neurodegeneration, or may be an altered response to insulin or levodopa medical therapy.

Durum wheat landraces represent a genetic resource for the identification and isolation of new valuable genes and alleles, useful to increase the crop adaptability to climate change. Several durum wheat landraces, all denominated "Rogosija", were extensively cultivated in the Western Balkan Peninsula until the first half of the 20th century. Within the conservation program of the Montenegro Plant Gene Bank, these landraces were collected, but without being characterized. The main goal of this study was to estimate the genetic diversity of the "Rogosija collection" consisting of 89 durum accessions, using 17 morphological descriptors and the 25K Illumina single nucleotide polymorphism (SNP) array. The genetic structure analysis of the Rogosija collection showed two distinguished clusters localized in two different Montenegro eco-geographic micro-areas, characterized by continental Mediterranean climate and maritime Mediterranean climate. Data suggest that these clusters could be composed of two different Balkan durum landrace collections evolved in two different eco-geographic micro-areas. Moreover, the origin of Balkan durum landraces is discussed.

Administration of cytotoxic agents like doxorubicin (DOX) is restrained by the effects on different non-targeted/non-cancerous tissues, which instigates the development of nano-enabled drug delivery systems, among others. In this study, imaging mass spectrometry (IMS) was selected to examine the effects of DOX nanoformulations on non-targeted tissues. Chemical alterations induced by liposomal (LPS) and poly (lactic- co -glycolic acid) (PLG) nanoformulations were assessed against the ones induced by the conventional (CNV) formulation. Kidney cryosections of the treated and control Wistar rats were used as a model of the non-targeted tissue and analyzed by MALDI TOF IMS in the 200-1000 Da m / z range. Principal component analysis (PCA) and Volcano plots of the average mass spectra demonstrated a large overlap between treatments. However, the Venn diagram of significant m / z values revealed a nanoformulation-specific fingerprint consisting of 59 m / z values, which set them apart from the CNV formulation characterized by the fingerprint of 22 significant m / z values. Fingerprint m / z values that were putatively annotated by metabolome database search were linked to apoptosis, cell migration and proliferation. In CNV and PLG cases, false discovery rate adjusted ANOVA showed no differences in the spatial distribution of fingerprint m / z values between the histological substructures like glomeruli and convoluted tubules indicating their tissue-nonselective effect. LPS caused the least significant changes in m / z values and some of the LPS-specific fingerprint m / z values were primarily distributed in the glomeruli. The IMS based procedure successfully differentiated the effects of DOX formulations on the model non-targeted tissue, thus indicating the importance of IMS in effective drug development.

Disruption of the alveolar−endothelial barrier caused by inflammation leads to the progression of septic acute lung injury (ALI). In the present study, we investigated the beneficial effects of simvastatin on the endotoxin lipopolysaccharide (LPS)-induced ALI and its related mechanisms. A model of ALI was induced within experimental sepsis developed by intraperitoneal injection of a single non-lethal LPS dose after short-term simvastatin pretreatment (10−40 mg/kg orally). The severity of the lung tissue inflammatory injury was expressed as pulmonary damage scores (PDS). Alveolar epithelial cell apoptosis was confirmed by TUNEL assay (DNA fragmentation) and expressed as an apoptotic index (AI), and immunohistochemically for cleaved caspase-3, cytochrome C, and anti-apoptotic Bcl-xL, an inhibitor of apoptosis, survivin, and transcriptional factor, NF-kB/p65. Severe inflammatory injury of pulmonary parenchyma (PDS 3.33 ± 0.48) was developed after the LPS challenge, whereas simvastatin significantly and dose-dependently protected lung histology after LPS (p < 0.01). Simvastatin in a dose of 40 mg/kg showed the most significant effects in amelioration alveolar epithelial cells apoptosis, demonstrating this as a marked decrease of AI (p < 0.01 vs. LPS), cytochrome C, and cleaved caspase-3 expression. Furthermore, simvastatin significantly enhanced the expression of Bcl-xL and survivin. Finally, the expression of survivin and its regulator NF-kB/p65 in the alveolar epithelium was in strong positive correlation across the groups. Simvastatin could play a protective role against LPS-induced ALI and apoptosis of the alveolar−endothelial barrier. Taken together, these effects were seemingly mediated by inhibition of caspase 3 and cytochrome C, a finding that might be associated with the up-regulation of cell-survival survivin/NF-kB/p65 pathway and Bcl-xL.

The purpose of the study was to compare sex adaptations in hypertrophy, strength and contractile properties of upper and lower-body muscles induced by resistance training (RT). Eighteen RT untrained male (MG) and female (FG) students (aged 24.1 ± 1.7 years, height: 1.75 ± 0.08 m, weight: 70.4 ± 12.3 kg) undervent 7 weeks of biceps curl and squat training (2 days/week, 60-70% repetition maximum, 3-4 sets, 120 s rest intervals, reps until muscular failure). At baseline and final measurement, thickness and cross-section area, one-repetition maximum and tensiomyography parameters (contraction time - Tc and radial displacement - Dm) of elbow flexors (biceps brachii) and knee extensors (4 quadriceps muscles) were evaluated. Although MG tends to display greater absolute strength gains for upper- (p = 0.055) and lower-body (p = 0.098), for relative changes ANCOVA revealed no sex-specific differences for either of the tested variables. Significant hypertrophy was observed for all tested muscles, except for vastus intermedius in FG (p = 0.076). The Dm significantly decreased for biceps brachii (MG by 12%, p < 0.01 and FG by 13.1%, p < 0.01) and rectus femoris (MG by19.2%, p < 0.01 and FG by 12.3%, p < 0.05), while Tc values remain unchanged. These results indicate that initial morphological, functional and contractile alterations following RT are similar for males and females, and that there are no specific sex adaptations either for the upper- or lower-body muscles. The study was registered with ClinicalTrials.gov (NCT04845295)., (© 2021. The Author(s).)

Lipid rafts, membrane microdomains enriched with (glyco)sphingolipids, cholesterol, and select proteins, act as cellular signalosomes. Various methods have been used to separate lipid rafts from bulk (non-raft) membranes, but most often, non-ionic detergent Triton X-100 has been used in their isolation. However, Triton X-100 is a reported disruptor of lipid rafts. Histological evidence confirmed raft disruption by Triton X-100, but remarkably revealed raft stability to treatment with a related polyethylene oxide detergent, Brij O20. We report isolation of detergent-resistant membranes from mouse brain using Brij O20 and its use to determine the distribution of major mammalian brain gangliosides, GM1, GD1a, GD1b and GT1b. A different distribution of gangliosides-classically used as a raft marker-was discovered using Brij O20 versus Triton X-100. Immunohistochemistry and imaging mass spectrometry confirm the results. Use of Brij O20 results in a distinctive membrane distribution of gangliosides that is not all lipid raft associated, but depends on the ganglioside structure. This is the first report of a significant proportion of gangliosides outside raft domains. We also determined the distribution of proteins functionally related to neuroplasticity and known to be affected by ganglioside environment, glutamate receptor subunit 2, amyloid precursor protein and neuroplastin and report the lipid raft populations of these proteins in mouse brain tissue. This work will enable more accurate lipid raft analysis with respect to glycosphingolipid and membrane protein composition and lead to improved resolution of lipid-protein interactions within biological membranes., (© 2021 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Background: It is known that drug shortages represent a major challenge for all stakeholders involved in the process, but there is little evidence regarding insights into patients' awareness and perspectives. This study aimed to investigate the patients-perceived drug shortages experience and their view on outcomes in different European hospital settings. Furthermore, we wanted to explore information preferences on drug shortages., Methods: A retrospective, cross sectional, a mixed method study was conducted in six European hospital settings. One hospital (H) from each of this country agreed to participate: Bosnia and Herzegovina (H-BiH), Croatia (H-CR), Germany (H-GE), Greece (H-GR), Serbia (H-SE) and Poland (H-PO). Recruitment and data collection was conducted over 27 months from November 2017 until January 2020. Overall, we surveyed 607 patients which completed paper-based questionnaire. Questions related to: general information (demographic data), basic knowledge on drug shortages, drug shortages experienced during hospitalization and information preferences on drug shortage. Differences between hospital settings were analyzed using Chi-squared test or Fisher's exact test. For more complex contingency tables, Monte Carlo simulations (N = 2000) were applied for Fisher's test. Post-hoc hospital-wise analyses were performed using Fisher's exact tests. False discovery rate was controlled using the Bonferroni method. Analyses were performed using R: a language and environment for statistical computing (v 3.6.3)., Results: 6 % of patients reported experiences with drug shortages while hospitalized which led to a deterioration of their health. The majority of affected patients were hospitalized at hematology and/or oncology wards in H-BiH, H-PO and H-GE. H-BiH had the highest number of affected patients (18.1 %, N = 19/105, p < 0.001) while the fewest patients were in H-SE (1 %, N = 1/100, p = 0.001). In addition, 82.5 %, (N = 501/607) of respondents wanted to be informed of alternative treatment options if there was a drug shortage without a generic substitute available. Majority of these patients (66.4 %, N = 386/501) prefer to be informed by a healthcare professional., Conclusions: Although drug shortages led to serious medical consequences, our findings show that most of the patients did not perceive shortages as a problem. One possible interpretation is that good hospital management practices by healthcare professionals helped to mitigate the perceived impact of shortages. Our study highlights the importance of a good communication especially between patients and healthcare professionals in whom our patients have the greatest trust., (© 2021. The Author(s).)

Aim: The aim of research was to evaluate the maternal serum concentration of selected endogenous steroid hormones during spontaneous parturition at term and to determinate their association with the need for oxytocin augmentation., Methods: Blood of 108 healthy pregnant women whose parturition started with the regular spontaneous uterine contractions was drawn at the beginning of the labor. Liquid chromatography coupled to the tandem mass spectrometry device was utilized for measurement of sex hormone binding globulin, aldosterone, androstenedione, cortisol, cortisone, corticosterone, dehydroepiandrosterone, dehydroepiandrosteron sulphate, 17-hydroxyprogesterone, progesterone, and testosterone. Mann-Whitney U test, chi-square test, univariate and multivariate logistic regression, and receiver operating characteristic (ROC) analysis were used for the data analysis., Results: Reference ranges of the selected hormones assessed by liquid chromatography coupled to the tandem mass spectrometry in maternal serum were established. Statistically significant differences in the serum concentration of corticosterone, dehydroepiandrosterone, and androstenedione between mothers requiring oxytocin augmentation and the rest of women having spontaneous parturition were found (p = 0.002, p = 0.008, and p = 0.04, respectively). Concentrations were lower in the group of mothers who required oxytocin infusion for progression of labor. ROC analysis showed that all the mothers with dehydroepiandrosterone serum concentration above 21.6 nmol/L have lower chance to use oxytocin infusion for the labor progression ( area under the curve (AUC)  = 0.649, sensitivity = 71.7%, specificity = 59.6%, p = 0.006)., Conclusion: This research provided reference ranges for the selected maternal serum steroid hormones at the beginning of parturition. Association of corticosterone, dehydroepiandrosterone, and androstenedione with the need for the oxytocin infusion usage has been established. Dehydroepiandrosterone could be potential predictor of oxytocin infusion augmentation for progression of the parturition., (© 2021 Japan Society of Obstetrics and Gynecology.)

Tramadol is a commonly used analgesic in intensive care units (ICUs) for acute postoperative pain. Conversion of tramadol into active metabolites may be impaired in inflammatory states. Catechol-O-methyltransferase may influence pain. The aim of the study was to examine differences in the analgesic effect of tramadol between ICU patients with and without signs of systemic inflammation. Forty-three patients were admitted to ICU after a major abdominal surgery. The patients received a dose of 100 mg of tramadol intravenously every 6 hours during the first 24 hours after surgical procedure. Pain scores were measured by the Numeric Rating Scale before and 30 minutes after tramadol administration in awake patients. Systemic inflammation was considered when at least two of the following postoperative parameters were present in the first 24 hours of ICU admission: fever or hypothermia, tachycardia, pCO 2 <4.3 kPa, white blood cells >12000/mm 3 or <4000/mm 3 , or preoperative value of C-reactive protein (CRP) >50 mg/L or/and procalcitonin (PCT) >0.5 mg/L. Catechol-O-methyltransferase was analyzed postoperatively. Fifteen (34.8%) patients met the criteria for systemic inflammation. Tramadol was proven to be an effective analgesic for the treatment of postoperative pain regardless of the presence of systemic inflammation (p<0.05). Lower perception of pain before tramadol application was observed in patients with systemic inflammation, but the difference was not significant. A negative correlation was observed between the preoperative values of CRP and PCT and the analgesic effect of tramadol assessed at the second measurement point (r=-0.358, p=0.03, and r=-0.364, p=0.02, respectively). Catechol-O-methyltransferase variants were not in correlation with pain and opioid consumption. Based on our findings, tramadol is effective in lowering pain scores after major abdominal surgery irrespective of the presence of systemic inflammation.

The aim of this study was to develop and evaluate matrix assisted LASER desorption ionization (MALDI) time-of-flight (TOF) mass spectrometry imaging (MSI) of blood smear. Integrated light microscope and MALDI IT-TOF mass spectrometer, together with a matrix sublimation device, were used for analysis of blood smears coming from healthy male donors. Different blood plasma removal, matrix deposition, and instrumental settings were evaluated using the negative and positive ionization modes while agreement between the light microscopy images and the lateral distributions of cellular marker compounds served as the MSI quality indicator. Red and white blood cells chemical composition was analyzed using the differential m / z expression. Five seconds of exposure to ethanol followed by the 5 min of 9-aminoacridine or α-cyano-4-hydroxycinnamic acid deposition, together with two sets of instrumental settings, were selected for the MALDI TOF MSI experiments. Application of the thin and transparent matrix layers assured good correspondence between the LASER footprints and the preselected regions of interest. Cellular marker m / z signals coincided well with the appropriate cells. A metabolite databases search using the differentially expressed m / z produced hits which were consistent with the respective cell types. This study sets the foundations for application of blood smear MALDI TOF MSI in clinical diagnostics and research.

Introduction: The aim was to evaluate the BD Barricor tubes by comparison with the BD Rapid Serum Tubes (RST) through measuring 25 analytes and monitoring sample stability after 24 hours and 7 days., Materials and Methods: Samples of 52 patients from different hospital departments were examined. Blood was collected in BD RST and BD Barricor tubes (Becton, Dickinson and Company, Franklin Lakes, USA). Analytes were measured by Beckman Coulter AU 480 (Beckman Coulter, Brea, USA), Dimension EXL (Siemens Healthcare Diagnostics, Newark, USA) and ARCHITECT i2000SR (Abbott Diagnostics, Lake Forest, USA). Between-tube comparison for each analyte was performed, along with testing analyte stability after storing samples at 4 °C., Results: BD Barricor tubes showed unacceptable bias compared to BD RST tubes for potassium (K) (- 4.5%) and total protein (4.4%). Analyte stability after 24 hours was acceptable in both tested tubes for most of analytes, except for glucose, aspartate aminotransferase (AST) and lactate dehydrogenase (LD) in BD Barricor and free triiodothyronine in BD RST sample tubes. Analyte stability after 7 days was unacceptable for sodium, K, calcium, creatine kinase isoenzyme MB, AST, LD and troponin I in both samples; additionally for glucose, alkaline phosphatase and albumin in BD Barricor., Conclusion: All analytes, except K and total protein, can be measured interchangeably in BD RST and BD Barricor tubes, applying the same reference intervals. For most of the analytes, sample re-analysis can be performed in both tubes after 24 hours and 7 days, although BD RST tubes show better 7-day analytes stability over BD Barricor tubes., Competing Interests: Potential conflict of interest None declared., (Croatian Society of Medical Biochemistry and Laboratory Medicine.)

Introduction: There is a growing amount of evidence showing the significant analytical bias of steroid hormone immunoassays, but large number of available immunoassays makes conduction of a single comprehensive study of this issue hardly feasible. Aim of this study was to assess the analytical bias of six heterogeneous immunoassays for serum aldosterone, cortisol, dehydroepiandrosterone sulphate (DHEAS), testosterone, 17-hydroxyprogesterone (OHP) and progesterone using the liquid chromatography coupled to the tandem mass spectrometry (LC-MS/MS)., Materials and Methods: This method comparison study included 49 serum samples. Testosterone, DHEAS, progesterone and cortisol immunoassays were performed on the Abbott Architect i2000SR or Alinity i analysers (Abbott Diagnostics, Chicago, USA). DiaSorin's Liaison (DiaSorin, Saluggia, Italy) and DIAsource's ETI-Max 3000 analysers (DIAsource ImmunoAssays, Louvain-La-Neuve, Belgium) were chosen for aldosterone and OHP immunoassay testing, respectively. All immunoassays were evaluated against the LC-MS/MS assay relying on the commercial kit (Chromsystems, Gräfelfing, Germany) and LCMS-8050 analyser (Shimadzu, Kyoto, Japan). Analytical biases were calculated and method comparison was conducted using weighted Deming regression analysis., Results: Depending on the analyte and specific immunoassay, mean relative biases ranged from -31 to + 137%. Except for the cortisol, immunoassays were positively biased. For none of the selected steroids slope and intercept 95% confidence intervals simultaneously contained 0 and 1, respectively., Conclusions: Evaluated immunoassays failed to satisfy requirements for methods' comparability and produced significant analytical biases in respect to the LC-MS/MS assay, especially at low concentrations., Competing Interests: Potential conflict of interest: None declared., (Croatian Society of Medical Biochemistry and Laboratory Medicine.)

Background: Acute pyelonephritis is a severe disease which is sometimes difficult to recognize based on clinical symptoms and routinely available diagnostic tests, especially in young children. The aim of this study was to assess the diagnostic value of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a biomarker of acute pyelonephritis., Methods: In this case-control study we analyzed 134 children (median age 2.5 years) who were admitted to the Pediatric Clinic of University Hospital Centre Osijek, Croatia. Eighty of them had acute pyelonephritis, while 54 children had febrile state of different etiology including cystitis and they represented the control group. uNGAL, white blood cells, C-reactive protein, urinanalysis, urine culture, kidney ultrasound and a dimercaptosuccinic acid scintigraphic scan were done for each child. uNGAL was measured using chemiluminiscent microparticle immunoassay on ARHITECT i1000SR (Abbott Diagnostics, IL, USA)., Results: uNGAL values were significantly higher in children with acute pyelonephritis compared to the control groups (113.6 ng/mL vs. 10.2 ng/mL, p<0.001). A receiver operating characteristic curve comparison was done for tested parameters and encouraging results were obtained for uNGAL (AUC=0.952). A cut-off value of 29.4 ng/mL had 92.5% sensitivity and 90.7% specificity. We showed that uNGAL can also serve in differentiating acute pyelonephritis from cystitis (cut-off 38.5 ng/mL), and for differentiation of cystitis from febrile states with etiology other than urinary tract infection (UTI) (cut-off 20.4 ng/mL)., Conclusions: uNGAL can be a useful diagnostic biomarker in acute pyelonephritis in children, but also in differentiating cystitis from febrile states other than UTI.

The aim of this study was to perform for the first time the intracranial volumetric analysis of cerebrospinal fluid (CSF) and brain parenchyma in the supratentorial and infratentorial space in a 30-year-old female patient with hydranencephaly and macrocephaly. A head scan performed using a 3T magnetic resonance was followed by manual segmentation of the brain parenchyma and CSF on T2 coronal brain sections. The volume of CSF and brain parenchyma was measured separately for the supratentorial and infratentorial space. The total volume of the intracranial space was 3645.5 cm3. In the supratentorial space, the volume of CSF was 3375.2 cm3 and the volume of brain parenchyma was 80.3 cm3. In the infratentorial space, the volume of CSF was 101.3 cm3 and the volume of the brain parenchyma was 88.7 cm3. In the supratentorial space, there was severe malacia of almost all brain parenchyma with no visible remnants of the choroid plexuses. Infratentorial structures of the brainstem and cerebellum were hypoplastic but completely developed. Since our patient had no choroid plexuses in the supratentorial space and no obstruction between dural sinuses and CSF, development of hydrocephalus and macrocephaly cannot be explained by the classic hypothesis of CSF physiology with secretion, unidirectional circulation, and absorption as its basic postulates. However, the origin and turnover of the enormous amount of intracranial CSF volume, at least 10-fold larger than normal, and the mechanisms of macroencephaly development could be elucidated by the new hypothesis of CSF physiology recently published by our research team.

Introduction: Hyperkalemia secondary to beta-adrenergic receptor blockade occurs in 1-5% of patients and is likely to develop with non-cardio-selective beta-blockers., Case Report: We have described hyperkalemia in a patient with angina pectoris receiving propranolol, clinically manifested as weakness, tightness behind the sternum and numbness in the limbs. Laboratory tests showed hyperkalemia (6.6 mmol/L), peaked T wave and a corrected QT interval of 510 ms. After discontinuation of propranolol, decline in potassium level, normalisation of electrocardiographic changes and clinical improvement were achieved. Causal relationship of drug related hyperkalemia has been confirmed as probable/likely according to Naranjo Adverse Drug Reaction Probability Score of 7 and the World Health Organization Uppsala Monitoring Centre Probability Scale., Conclusion: Hyperkalemia can be unpredictable and life-threatening complication of propranolol or a non-selective adrenergic beta blocker treatment, and requires timely identification of cause and implementation of therapeutic measures.

Vitamin K epoxide reductase (VKOR) is a key enzyme in the y-carboxylation of proteins associated with important bodily functions (coagulation, bone metabolism, etc.). This feature is particularly used in warfarin therapy, which blocks the VKOR enzyme and leads to production of dysfunctional coagulation proteins. Genetic factors, particularly vitamin K epoxide reductase complex 1 (VKORC1) gene, have greatest influence on warfarin therapy. The aim of this study was to determine the distribution of VKORC1 1173C > T and VKORC1 -1639G > A polymorphisms, which are most important for warfarin therapy. We investigated 420 unrelated healthy individuals, mostly blood donors, from region of the Eastern Croatia. Both investigated polymorphisms were in perfect linkage disequilibrium (LD) and showed identical results. 151 patients (36%) were homozygous for the wild-type (C/C and G/G), 196 (47%) were heterozygous (C/T and G/A) and 73 (17%) were homozygous for the variant allele (T/T and A/A). Number of normal alleles among individuals was 498 (59.3%), and number of variant alleles was 342 (40.7%). The data obtained are in good agreement with the results of studies in other European populations.

Patients with an autoimmune disease, such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn's disease, ulcerative colitis, uveitis or psoriasis, and treated with the anti-tumour necrosis factor (TNF) alpha inhibitors are at high risk of developing various infections including tuberculosis (TB). Serious infections are the result of the patients' immunocompromised status that is caused by the primary disease itself, as well as by previous immunosuppressive therapy. In order to decrease the risk of developing TB, prior to the introduction of the anti-TNF alpha therapy, all patients should undergo screening for TB. Experiences from the countries that have already implemented recommendations for TB screening show a significant decrease in TB occurrence in the anti-TNF alpha treated patients. The PPD skin test result is considered positive if in duration is of size > or =5 mm. The BCG vaccine applied at birth has no effect on interpretation of PPD test results in adults. The diagnosis of active TB is contraindicated for the introduction of the anti-TNF alpha therapy; first, such patients should receive the TB treatment; and 6 months after the completion of the TB treatment, the introduction of the anti-TNF alpha therapy may be considered. The patients with the diagnosis of the latent TB infection (LTBI) should not immediately start with the anti-TNF alpha therapy, but they should first receive the TB chemoprophylaxis; not earlier than a month upon the introduction of the TB chemoprophylaxis, the anti-TNF alpha therapy may be introduced. The first TB follow-up screening during the anti-TNF alpha therapy is recommended 6 months after the anti-TNF alpha therapy has been introduced and the next one should be scheduled after 12 months.

The control of symptoms in patients with allergic rhinitis and bronchial asthma can not be always attained with hyposensitization. This may be achieved with more success with additional treatment with H1 antagonists of histamine receptors. By hyposensitization statistically significant decrease of the total IgE was achieved. Contrary to this, in cases in which the symptoms could not be controlled with hyposensitization, only antihistamines were additionally administered, no significant decrease of IgE took place. These were, probably, more severe cases in which the symptoms could not be controlled with the hyposensitization only. No significant effect on the values of blood eosinophiles was registered with hyposensitization or additional administration of antihistamines.

Within the fight against smoking a questionnaire was made among schoolchildren of the Secondary Medical School in Zrenjanin in the period from March 1-8, 1988. The anonymous questionnaire dealt both with the schoolchildren's attitude toward smoking and the distribution of this habit among them. It comprised a total of 207 schoolchildren from the I and IV grade. The questions were aimed at the basic facts about smoking: whether they smoke, how many cigarettes they smoke daily and from when, how much pocket-money they get, their opinion about smoking as the social phenomenon and how much they know about harmful effects of smoking. Out of 119 schoolchildren from the I grade 8 were smokers (7 girls and 1 boy) which made 6.7% while out of 88 schoolchildren from the IV grade (83 girls and 5 boys) 46 (52%) were smokers. Which factors contributed to the increase in the number of smokers from I to IV grade, especially when we know that girls accounted for 94%? These facts were discussed in this paper in detail.