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Increased mortality rate for patients with mental disorders and their shorter lifespan compared to the general public is stated by numerous authors. Services on the Clinic for mental disorders 'Dr Laza Lazarević' were reorganized, by introducing intensive care units - level two, i.e. contemporary intensive care of patients was introduced, only without life support. Primary objective of the research was to determine if the introduction of intensive care to the Clinic led to a statistically significant change in the number of fatal outcomes of hospitalized patients. The research was designed as a cross-sectional study and it included 62 patients that have died while being hospitalized at the Clinic for mental disorders 'Dr Laza Lazarević' in Belgrade, in 2011 and 2012. Data were collected by retrospective insight in the histories of illnesses and treatment protocols of the Clinic and institutes for pathology and forensic medicine of the Faculty of Medicine in Belgrade. Obtained data were statistically analysed with Student's T-test and ANOVA test, with a significance level of 0.05. Statistically significant difference was determined in fatalities in 2011 compared to 2012 with p = 0.007, and there were significantly less fatalities in 2012. Statistically significant difference in frequency of fatal outcomes when comparing 2011 to 2012 was determined only when comparing the ward of previous intensive care on one side with the newly established psychiatric intensive care units - level two on the other. High level of significance was determined with p = 0.005. New organizational concept introduced in 2012 has led to more efficient twenty-four-hour care and monitoring of hospitalized patients, suppression of accompanying somatic illnesses which altogether led to a significant reduction of fatal outcomes.

Postulate of our research issue is based on the argumentation the correlation diffuse damage of neuronical and non neuronical subcortical structures weakened vascularization during the longer premorbid period with the clinical manifestation of cognitive dysfunction. The main aim of our researching is argumentation the atrophy subcortical brains structures and connection with cognitive dysfunction by the extent to the demented and brain mnestic deterioration. Research was carried out in the two researched groups of patients treated in hospital, A and B, that controlled themselves as well. Both groups consisted of 40 patients both sexes aged 50 to 70 years. Results of our research confirmed that cognitive functioning was damaged to all patients with determined subcortical brain, s ischemia and reduction of the neuronical and non neuronical subcortical structures diagnosed by the visualised imaging diagnostic methods. Dysfunction of cognition according to difficulty is the reciprocal psychometric confirmed scope of subcortical atrophy, or the reduction of the brain, s structures.

Until now, a lot of research has been carried out which significantly helped in understanding and solving the problem of obesity. Despite this, there has been an upward in obesity trend at the global level. The role of laboratory diagnostics in the field of obesity is of great importance to doctors for establishing a diagnosis and monitoring the effects of therapy. Determining biochemical parameters also contributes to practical usefulness in the prevention of this disease, and prevention of consequent complications. Routinely available biochemical analyses are usually used to diagnose and monitor the effects of obesity therapy. The initial association related to laboratory analyses refers to parameters of lipid status, but there are a variety of routine laboratory parameters that can help in understanding and monitoring obesity from different angles. Timely and adequate management of obesity is also of interest from an economic aspect. For this reason, the topic of this research is to summarize the latest aspects of the concept of obesity, specifically from the point of view of biochemistry and laboratory diagnostics. Taking into account the complexity of this disease, it is important to point out the future perspectives and challenges that inevitably arise before both laboratory professionals and healthcare providers in general.

Background/Aim. Patients in intensive care units (ICUs) often exhibit disturbances in the concentration of thyroid hormones (THs), even if they had no previous thyroid disorders. The aim of the study was to determine whether there is a correlation between THs and the survival rate in the ICU and whether these hormones have predictive capability for mortality rate assessment. Methods. The study included 41 patients (23 women and 18 men) divided into two groups: survivors (70.7%) and non-survivors (29.3%). In peripheral blood samples taken within the first 24 hrs after ICU admission, TH levels were measured: triiodothyronine (T3), thyroxine (T4), free T3 (FT3), free T4 (FT4), and thyroid stimulating hormone (TSH), as well as procalcitonin (PCT). The Sequential Organ Failure Assessment Score (SOFAS) was calculated for each patient. Results. A statistically significant difference between the study groups (survivor vs. non-survivor patients, p < 0.05) was found for PCT, SOFAS, T3, T4, and FT4. The area under the receiver operating characteristic (ROC) curve (AUC) – (AUROC) for the SOFAS was 0.991 [95% confidence interval (CI): 0.898–1.000, p < 0.001], for T3 was 0.727 (95% CI: 0.566–0.854, p = 0.0097), for T4 was 0.793 (95% CI: 0.638–0.903, p = 0.0008), for FT3 was 0.707 (95% CI: 0.544–0.8389, p = 0.0299), and for FT4 was 0.795 (95% CI: 0.640–0.904, p = 0.0005). Compared to other parameters, T3 had higher sensitivity (91.67%), FT4 had higher specificity (93.10%), while SOFAS had both the highest sensitivity (91.67%) and specificity (96.55%) in relation to all other tested parameters. Multiple linear regression analysis showed that FT4 and T4 were significant predictors of survival time (β = -0.362, p = 0.012 and β = -0.356, p = 0.014, respectively). Conclusion. Among all examined THs, only FT4 and T4 showed strong predictive potential for assessing mortality in ICU patients. This study has highlighted the significance of assessing THs levels in critically ill patients. This is crucial because it opens the possibility of implementing specific therapies to rectify issues stemming from hormonal deficiencies.

Background: Surgical stress and pain result in activation of hypothalamus-pituitary-adrenal axis. The aim of this study was to establish the effects of postoperative pain and various modalities of analgesic administration on salivary and serum cortisol levels, as well as to establish the validity of salivary cortisol as a stress indicator in surgical patients. Methods: A randomized controlled trial involved 60 patients scheduled for elective abdominal aortic aneurysm surgery. Patients were randomly divided into two groups depending on the model of postoperative analgesia. The first group (MI - morphine intermittently) included patients given morphine doses 0.1 mg/kg/6h s.c. intermittently. The second group (MPCA - morphine patient-controlled analgesia) included patients who received morphine via the PCA system - intravenous administration of morphine adjusted to a dose of 1 mg per shot and a lockout interval of 6 minutes. Results: The intensity of pain did not significantly vary until the hour 10 post-surgery. However, in the period from hour 10 to hour 18 post-surgery, higher intensity of pain was reported in group MPCA (P < 0.05). Hemodynamic instability was more prevalent in the MI group (40.0% vs 6.7%, P = 0.0048). Serum cortisol levels were almost identical in both groups (MI 509.4 nmol/L vs MPCA 511.0 nmol/L, P = 0.1473). Higher values of salivary cortisol were recorded in group MPCA; however, the difference was not statistically significant (47.1 nmol/L vs 116.3 nmol/L, P = 0.0970). Conclusion: Our study confirmed that salivary cortisol is a more sensitive stress biomarker in surgical patients as compared to blood cortisol.

Background/Aim: Pruritus is an unpleasant sensation that provokes the desire to scratch. It is one of the most common reasons why patients consult a dermatologist. Aim of this study was to determine the association of chronic pruritus with skin and systemic diseases, as well as the age and sex distribution in the studied population. Methods: The cross-sectional study included 120 patients of both sexes who, in the period from January 2017 to January 2021, received outpatient and inpatient treatment at the Skin and Venereal Diseases Clinic of the University Clinical Centre of the Republic of Srpska diagnosed with pruritus. Through the Clinical Information System insight was gained into the medical history and other documentation of the subjects from which data were taken on the age and sex of the subjects, onset, course and duration of pruritus, daily or seasonal variations in intensity, as well as the presence of associated skin and systemic diseases. Results: Out of a total of 120 subjects, a larger number (53.3 %) of subjects with chronic pruritus were male, and 46.7 % were female, the difference was statistically significant (p < 0.05). The analysis of the distribution of subjects according to their age revealed that the largest number of subjects (62.6 %) was over 65 years of age, while 38.4 % of subjects were under 65 years of age. The difference in the age structure was statistically significant (p < 0.05). In subjects older than 65 years pruritus was most frequently (47.3 %) associated with diabetes and in subjects under 65 years of age with skin diseases and conditions. The difference was statistically significant (p < 0.05). Conclusion: In people aged over 65 years, pruritus was most frequently associated with systemic diseases (diabetes mellitus) and in people aged under 65 years with dermatological diseases (Dermatitis atopica).

Background: The investigation of the prevalence of the IgG and the IgM isotypes of anticardiolipin (aCL) and antib2glycoprotein I (ab2gpI) Abs in healthy Serbian middleaged subjects was the main goal of our study. In addition, we analyzed the potential associations of above-mentioned Abs with serum proteins and lipids/lipoproteins. Methods: Forty healthy subjects were included in our study. Obesity (BMI 30 kg/m2) was present in 8/40 (20%) subjects. Titers of analyzed Abs were measured by ELISA. Results: The prevalence of IgG and IgM ab2gpI Abs was 5% and 12.5%, respectively, while the prevalence of IgM aCL was 10%. The IgG ab2gpI Abs were significantly different between subjects with normal triglycerides levels and those with hypertriglyceridemia (Mann-Whitney, P = 0.014). The significant difference in hsCRP concentrations was observed between subjects with the increased levels of the IgM isotype of aCL Abs and those with normal IgM aCL values (Mann-Whitney, P = 0.028). Conclusions: Dyslipidemia and BMI ≥30 were associated with aPL Abs and therefore, the correction of BMI and lipid status might be beneficial in reduction or elimination of predisposing factors that might trigger thrombotic events in otherwise healthy middle-aged subjects. Larger national study is necessary to confirm our findings.

Erlotinib is an antineoplastic drug used in the treatment of non-small cell lung cancer and pancreatic cancer. It is a potent, selective inhibitor of tyrosine kinase, a receptor for epidermal growth factor receptor (EGFR). Cutaneous side effects such as acneiform eruption, xerosis, telangiectasia, hair and nail changes are common. A case of a 70-year-old patient who developed unusual cutaneous side effects after 6 years of treatment with erlotinib was presented.

Background/Aim. Custodiol® is a hyperpolarizing cardioplegic solution which has been used in our national cardiac surgical practice exclusively for the heart transplant surgery. Owing to its numerous advantages over the standard depolarizing solutions, Custodiol® became cardioplegic solution of choice for all other cardiac surgical procedures in many cardio-surgical centers. This study evaluated myocardial protection by Custodiol® compared to modified St. Thomas cardioplegic solution in coronary artery bypass surgery. Methods. In a prospective four-month study, 110 consecutive adult patients who underwent primary isolated elective on-pump coronary artery bypass grafting (CABG) were randomized into the Custodiol® group (n = 54) and the St. Thomas groupa (n = 50), based on the type of administered cardioplegia; six patients were excluded. Cardiac protection was achieved as antegrade cold crystalloid cardioplegia by one of the solutions. Myocardial preservation was assessed through following outcomes: spontaneous rhythm restoration post cross-clamp, and postpoperative cardiac specific enzymes level, ejection fraction (EF) change, inotropic support, myocardial infarction (MI), atrial fibrillation (AF), and death. Results. Preoperative and intraoperative characteristics of patients in both groups were similar except for a considerably longer cross-clamp time in the Custodiol® group (49.1 ± 19.0 vs. 41.0 ± 12.9 minutes; p = 0.022). The Custodiol® group exhibited a higher rate of return to spontaneous rhythm compared to the St. Thomas group (31.5% vs. 20.0%, respectively; p = 0.267), lower rates of AF (20.4% vs. 28%, respectively; p = 0.496), MI (1.8% vs. 10.0%, respectively; p = 0.075) and inotropic support (9.0% vs. 12.0%, respectively; p = 0.651), albeit not statistically significant. There was an insignificant difference in peak value of troponin I between the Custodiol® and Thee St. Thomas group (5.0 ± 3.92 μg/L vs. 4.5 ± 3.39 μg/L, respectively; p = 0.755) and creatine kinase-MB (26.9 ± 15.4 μg/L vs. 28.5 ± 24.2 μg/L, respectively; p = 0.646) 6 hours post-surgery. EF reduction was comparable (0.81% vs. 1.26%; p = 0.891). There were no deaths in both groups. Conclusions. Custodiol® and modified St.Thomas cardioplegic solution have comparable cardioprotective effects in CABG surgery. The trends of less frequent MI, AF and ino-tropic support, despite the longer cross-clamp time in the Custodiol® group may suggest that its benefits could be ascertained in a larger study.

Background: Some observational studies indicate an association of 25-hydroxy vitamin D (25(OH)D) insufficiency and atherogenic cholesterol concentrations. The aim of this study was to investigate relationship between 25(OH)D concentrations and lipid parameters in end stage renal disease (ESRD) patients, separately for predialysis, hemodialysis and peritoneal dialysis patients. Methods: We have adjusted 25(OH)D concentrations for seasonal variability with cosinor analysis, and performed all further analysis using these corrected 25(OH)D concentrations. Concentrations of 25(OH)D and the lipid parameters were determined in 214 ESRD patients and 50 control group participants. The analysis included the measurement of 25(OH)D by HPLC, apolipoprotein (Apo) AI, ApoB and Lp(a) by nephelometry, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) by spectrophotometry and manually calculated ApoB/ApoAI and LDL-C/HDL-C ratio. Results: ESRD patients with adjusted 25(OH)D concentrations of 50 nmol/L had significantly higher TC (P = 0.005) and ApoAI (P = 0.049). Significantly higher HDLC (P = 0.011) and ApoAI (P = 0.020) were found in hemodialysis patients with the 25(OH)D concentrations of 50 nmol/L. The other analyzed lipid parameters differed significantly between predialysis, hemodialysis and peritoneal dialysis patients with 25(OH)D concentrations of < 50 nmol/L. Conclusions: Our study indicate the significant relationship between 25(OH)D repletion and optimal concentrations of lipid parameters in ESRD patients. Further research is necessary to explain whether joint evaluation of vitamin D status and lipid abnormalities could improve cardiovascular outcome in ESRD patients.

Analysis of the take-off and landing distance of a single tractor propelled aircraft LASTA is presented in this paper. The purpose of the analysis is to enable certification of the LASTA aircraft according to civil regulations CS-23. The paper presents the approximated method for calculating take-off and landing distance and compares it with the flight test results. Good agreement between these two results is obtained.

Medical biochemistry is the usual name for clinical biochemistry or clinical chemistry in Serbia, and medical biochemist is the official name for the clinical chemist (or clinical biochemist). This is the largest sub-discipline of the laboratory medicine in Serbia. It includes all aspects of clinical chemistry, and also laboratory hematology with coagulation, immunology, etc. Medical biochemistry laboratories in Serbia and medical biochemists as a profession are part of Health Care System and their activities are regulated through: the Health Care Law and rules issued by the Chamber of Medical Biochemists of Serbia. The first continuous and organized education for Medical Biochemists (Clinical Chemists) in Serbia dates from 1945, when the Department of Medical Biochemistry was established at the Pharmaceutical Faculty in Belgrade. In 1987 at the same Faculty a five years undergraduate study program was established, educating Medical Biochemists under a special program. Since the academic year 2006/2007 the new five year undergraduate (according to Bologna Declaration) and four-year postgraduate program according to EC4 European Syllabus for Postgraduate Training in Clinical Chemistry and Laboratory Medicine has been established. The Ministry of Education and Ministry of Public Health accredited these programs. There are four requirements for practicing medical biochemistry in the Health Care System: University Diploma of the Faculty of Pharmacy (Study of Medical Biochemistry), successful completion of the professional exam at the Ministry of Health after completion of one additional year of obligatory practical training in the medical biochemistry laboratories, membership in the Serbian Chamber of Medical Biochemists and licence for skilled work issued by the Serbian Chamber of Medical Biochemists. In order to present laboratory medical biochemistry practice in Serbia this paper will be focused on the following: Serbian national legislation, healthcare services organization, sub-disciplines of laboratory medicine and medical biochemistry as the most significant, education in medical biochemistry, conditions for professional practice in medical biochemistry, continuous quality improvement, and accreditation. Serbian healthcare is based on fundamental principles of universal health coverage and solidarity between all citizens.

Background: Until now, a proper biomarker(s) to evaluate sarcoidosis activity has not been recognized. The aims of this study were to evaluate the sensitivity and specificity of the two biomarkers of sarcoidosis activity already in use (serum angiotensin converting enzyme - ACE and serum chitotriosidase) in a population of 430 sarcoidosis patients. The activities of these markers were also analyzed in a group of 264 healthy controls. Methods: Four hundred and thirty biopsy positive sarcoidosis patients were divided into groups with active and inactive disease, and groups with acute or chronic disease. In a subgroup of 55 sarcoidosis patients, activity was also assessed by F-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) scanning. Both serum chitotriosidase and ACE levels showed non-normal distribution, so nonparametric tests were used in statistical analysis. Results: Serum chitotriosidase activities were almost 6 times higher in patients with active sarcoidosis than in healthy controls and inactive disease. A serum chitotriosidase value of 100 nmol/mL/h had the sensitivity of 82.5% and specificity of 70.0%. A serum ACE activity cutoff value of 32.0 U/L had the sensitivity of 66.0% and the specificity of 54%. A statistically significant correlation was obtained between the focal granulomatous activity detected on 18F-FDG PET/CT and serum chitotriosidase levels, but no such correlation was found with ACE. The levels of serum chitotriosidase activity significantly correlated with the disease duration (P< 0.0001). Also, serum chitotriosidase significantly correlated with clinical outcome status (COS) categories (p = 0.272, P = 0.001). Conclusions: Serum chitotriosidase proved to be a reliable biomarker of sarcoidosis activity and disease chronicity.

The essential oils of genus Seseli are known for their beneficial biological activities and could present novel targets in the development of safe and effective preparations of plant products. The objective was to test the essential oils of different parts of Seseli rigidum from two natural habitats for potential genotoxic and antigenotoxic activities against H202-induced DNA damage in human whole blood cells in vitro, by the comet assay. The essential oil analysis showed a high falcarinol content in oil from the root, while oils of the fruit and aerial parts contained α-pinene as the main compound. Genotoxicity was not detected at any of the concentrations of the essential oils from the three parts of the plant from localities I and II. Although the antioxidant activity (established by the FRAP and DPPH tests) of the investigated oils was low, all oils demonstrated a strong antigenotoxic effect against H2O2-induced damage post-treatment, when the oils were applied after the oxidant. Based on the lack of pretreatment activity and the post-treatment reduction in DNA damage, the antigenotoxic effect of S. rigidum essential oils was probably based on the stimulation of DNA repair mechanisms. Environmental conditions did not affect the antigenotoxic properties of the oils. In conclusion, our results revealed the antigenotoxic properties of S. rigidum essential oils and appropriate and safe doses with beneficial effects under the described conditions. [Projekat Ministarstva nauke Republike Srbije, br. OI 173034, 173021]

Head and neck cancers (HNC) are a heterogeneous group of diseases. Histopathological, these are head and neck squamous cell carcinoma (HNSCC) epithelium of the skin, mucosa of the upper aerodigestive tract, pharynx and larynx. HNSCC is the fifth leading cause of cancer worldwide. The most important risk factors are alcohol and smoking. In the recent years, the studies have been conducted in order to prove the role of HPV in HNSCC carcinogenesis. The prevalence of HPV in HNSCC is 30%. HPV is often detected in biological materials of males. People with HPV positive HNSCC respond better to treatment and have a better treatment outcome than patients with no proven HPV. In the future, HPV should be the marker that will influence the choice of therapy in patients with HNSCC, but also the factor that will indicate the outcome of this malignancy in the human population.

Simultaneous influence of corrosion, static and dynamic loads on the elements of aircraft structures influence to a large extent their mechanical properties and the foreseen length of their service. The paper presents the influence of corrosion on physical and mechanical properties of the test bars made from materials for a wide range of applications which are used in aircraft structural elements manufacturing. Study comprises laboratory testing of bars for the simultaneous influence of corrosive environment, static and dynamic load. The problems are pinpointed regarding the use of strain gauges for continuous monitoring of the condition in real time. In addition, this paper deals with a modern non-destructive testing and evaluation system (NDT&E), whose operation is based on thermal image processing. Thermographic method has been used to detect a hidden corrosion in the aircraft structure in real life. The study results have shown the possibility of NDT application in simple and quick detection of areas affected by corrosion that are visually invisible.

Seven species of the genus Pipiza, collected throughout the southern and western Balkans, were used for the analysis of habitat preferences and potential geographical distribution on the Balkan Peninsula. The analyzed species show a wide and uneven distribution across the delineated geographical-biogeographical regions. The highest number of species noted is from two regions - the Dinaric mountain chain and the Pannonian and subpannonian regions (seven and six). Land cover patch analysis revealed that forests dominate the landscape surroundings of the analyzed species. “Presenceonly models” developed by Maxent support the understanding of the distribution and ecology of each analyzed species. The low probability values of current potential distribution correspond to large non-forested and fragmented forest areas, where, on the other hand, relatively high probabilities overlap with areas of deciduous forests across the peninsula. Results confirm species preference to forest landscapes and emphasize the need for local scale analysis. The studies are of importance in developing regional monitoring schemes and conservation strategies.

Determination of 25-hydroxyvitamin D [25(OH)D] represents a unique challenge, considering its lipophilic nature. Considering the widespread prevalence of vitamin D deficiency, which leads to increasing number of requests for 25(OH)D determination, immunoassay measurements adjusted to automated analyzers are being developed. Because of the variability among assays, it is often difficult to monitor vitamin D status and supplementation. The aim of this study was to compare the results of two immunoassays with high performance liquid chromatography with ultraviolet detection (HPLC-UV). Also, the aim was to estimate vitamin D status, since up to date the prevalence of vitamin D deficiency in Serbia was not examined. We have evaluated analytical characteristics of two automated immunoassays for 25(OH)D determination, from Roche (Cobas® e601) and Abbott (Architect). For comparison studies we used HPLC analysis of 25-(OH)-Vitamin D3/D2 from Chromsystems (Waters isocratic system). In order to estimate vitamin D status in general population, we have searched the database of the laboratory information system and analyzed the data from 533 patients whose 25(OH)D was determined together with intact parathyroid hormone (iPTH). For imprecision assessment, four serum pools were prepared with following 25(OH)D concentrations: 35 nmol/L, ?50 nmol/L, ?75 nmol/L and ?125 nmol/L. Obtai ned CVs for Roche method were 1.5-2.8% for within-run and 4.0-6.7% for between-run imprecision. For Abbott method, CVs were 0.7-4.4% for withinrun and 3.8-7.2% for between-run imprecision. Inaccuracy was analyzed with commercial control sera. Obtained deviations from target value were 2.1% for Roche assay and 1.3-1.5% for Abbott method, and were not statistically significant (P>0.05). Comparison of Roche and HPLC-UV methods using Passing-Bablok regression analysis gave the following equation for the regression line y=0.937x+9.518 (r=0.739; n=97) and the regression line equation from the comparison of Abbott and HPLC-UV methods was y=0.745x+10.343 (r=0.793; n=97). Mean difference and SD for Bland-Altman plot were -4.5 nmol/L and 21.75 nmo/L, respectively for Roche method and 6.4 nmol/L and 18.8 nmol/L, respectively for Abbott. Statistical analysis (Chi-square test) of frequency distribution among different vitamin D status categories (75 nmol/L sufficiency) showed that the frequency distribution obtained with Abbott method was significantly different from the distribution of the HPLC results, in contrast to Roche results frequency distribution which did not differ significantly. Also, statistical analysis of the agreement between the three methods for each vitamin D status category showed that results of both Roche and Abbott methods were significantly higher than HPLC in the two deficiency categories (P=0.005 for Roche, P=0.0407 for Abbott), and in the sufficiency category Abbott method significantly underestimated concentration of 25(OH)D compared to HPLC results (P75 nmol/L).

Vitamin D is not technically a vitamin, since it is not an essential dietary factor. It is rather a prohormone produced photochemically in the skin from 7-dehydrocholesterol. Vitamin D and its metabolites may be categorized as either cholecalciferols or ergocalciferols. Cholecalciferol (vitamin D3) is the parent compound of the naturally occurring family and is produced in the skin from 7-dehydrocholesterol on exposure to the ultraviolet B portion of sunlight. Vitamin D2 (ergocalciferol), the parent compound of the other family, is manufactured by irradiation of ergosterol produced by yeasts and its potency is less than one-third of vitamin D3's potency. The steps in the vitamin D endocrine system include the following: 1) the photoconversion of 7-dehydrocholesterol to vitamin D3 in the skin or dietary intake of vitamin D3; 2) metabolism of vitamin D3 by the liver to 25-hydroxyvitamin-D3 [25(OH)D3], the major form of vitamin D circulating in the blood compartment; 3) conversion of 25(OH)D3 by the kidney (functioning as an endocrine gland) to the hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3 ]; 4) systemic transport of the dihydroxylated metabolite 1,25(OH)2D3 to distal target organs; and 5) binding of 1,25(OH)2D3 to a nuclear receptor (VDR) at target organs, followed by generation of appropriate biological responses. The activation of vitamin D to its hormonal form is mediated by cytochrome P450 enzymes. Six cytochrome P450 (CYP) isoforms have been shown to hydroxylate vitamin D. Four of these, CYP27A1, CYP2R1, CYP3A4 and CYP2J3, are candidates for the enzyme vitamin D 25-hydroxylase that is involved in the first step of activation. The highly regulated, renal enzyme 25-hydroxyvitamin D-1a-hydro xylase contains the component CYP27B1, which completes the activation pathway to the hormonal form 1,25(OH)2D3. A five-step inactivation pathway from 1,25(OH)2D3 to calcitroic acid is attributed to a single multifunctional CYP, CYP24A1, which is transcriptionally induced in vitamin D target cells by the action of 1,25(OH)2D3. An additional key component in the operation of the vitamin D endocrine system is the plasma vitamin D binding protein (DBP), which carries vitamin D3 and its metabolites to their metabolism and target organs. DBP is a specific, high-affinity transport protein. It is synthesized by the liver and circulates in great excess, with fewer than 5% of the binding sites normally occupied. 1,25(OH)2D3, acts as a ligand for a nuclear transcription factor, vitamin D receptor - VDR, which like all other nuclear receptors, regulates gene transcription and cell function. The widespread presence of VDR, and the key activating (1a-hydroxylase, CYP27B1) and inactivating (24-hydroxylase, CYP24A1) enzymes in most mammalian cells means that the cells in these tissues have the potential to produce biological responses, depending on the availability of appropriate amounts of vitamin D3. Thanks to this widespread presence of elements of vitamin D endocrine system, its biological features are being recognized outside bone tissue, i.e. calcium and phosphate metabolism.

The Third Report of the expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III, ATP III) constitutes the National Cholesterol Education Program's (NCEP's) updated clinical guidelines for cholesterol testing and clinical management of patients with high blood cholesterol. While ATP III maintains attention to intensive treatment of patients with coronary heart disease (CHD), its major new feature is a focus on primary prevention in persons with multiple risk factors. ATP III continues to identify elevated LDL cholesterol as the primary target of cholesterol lowering therapy. A basic principle of prevention is that the intensity of risk reduction therapy should be adjusted to a person's absolute risk. Risk assessment requires measurement of LDL cholesterol as part of lipoprotein analysis and identification of accompanying risk determinants (presence or absence of CHD, other clinical forms of atherosclerotic disease, diabetes, cigarette smoking, hypertension, low HDL cholesterol, family history of premature CHD, age). The category of highest risk consists of CHD and CHD risk equivalents - persons with absolute 10-year risk for major coronary events (death and myocardial infarction) >20%. The second category consists of persons with multiple (2+) risk factors in whom 10-year risk for CHD is >-20%. Absolute risk is estimated from Framingham risk scores. The third category consists of persons having 0-1 risk factor. The LDL cholesterol goal for each category is defined and it can be achieved with dietary changes and/or drug therapy. European guidelines on cardiovascular disease (CVD) prevention in clinical practice recommend using the SCORE (Systematic COronary Risk Evaluation) Risk Charts in order to assess the risk for development of CVD, which is defined in terms of the absolute 10 year probability of developing a fatal cardiovascular event. The aim of this paper is to introduce parts of the NCEP's ATP III and European guidelines important for their implementation in laboratory practice.

Numerous studies have shown that the major risk factors for coronary heart disease (cigarette smoking, hypertension, elevated serum total cholesterol and low-density lipoprotein cholesterol - LDL, low serum high-density lipoprotein cholesterol - HDL, diabetes mellitus and advancing age), are additive in predictive power. Accordingly, the total risk of a person can be estimated by summing up the risk imparted by each of the major risk factors. Using data obtained from population studies, various risk assessment algorithms have been developed. The aim of this study was to compare the two most common risk scores. Risk assessment for determining 10-year risk in 185 healthy, asymptomatic individuals of both sexes, 30-85 years old, was carried out according to both Framingham (FRS) and SCORE risk scoring. The risk factors included in the calculation of 10-year risk are gender, age, total cholesterol, HDL-cholesterol, systolic blood pressure, treatment for hypertension and cigarette smoking. The determinations of total cholesterol and HDL-cholesterol were made in sera collected after a 12h fasting period using an Olympus AU2700 automated analyzer. The Framingham risk score was determined using an electronic calculator - ATP III Risk Estimator, and the risk status according to SCORE was obtained using charts for the 10-year risk in populations at high risk. Among 185 participants, in 152 (82%) 10-year risk for Coronary Heart Disease (CHD) death was 20%) according to FRS. According to SCORE, 110 (60%) participants had 5% of 10-year risk for cardiovascular death. Different categories of risk were assigned to ∼30% of individuals according to different risk assessment models. Differences in risk classification when using two different risk assessment algorithms can be explained with several important issues including different endpoints, consideration of interactions and incorporation of antihypertensive use. It is important to note that neither FRS nor SCORE have been appropriately adjusted for our population, according to the national cardiovascular mortality rate.

Patients suffering from cholelithiasis have an increased risk of developing cardiovascular complications, particularly ischemic myocardial disease. Ursodeoxycholic acid (UDCA), already used in clinical practice for the treatment of cholelithiasis and related conditions, has proven antioxidative, anti-inflammatory, and cytoprotective effects. Therefore, the aim of this study was to investigate the cardioprotective effect of UDCA pre-treatment on isoprenaline-induced myocardial injury in rats. Male Wistar albino rats were randomized into four groups. Animals were pre-treated for 10 days with propylene glycol + saline on days 9 and 10 (control), 10 days with propylene glycol + isoprenaline on days 9 and 10 (I group), 10 days with UDCA + saline on days 9 and 10 (UDCA group), and 10 days with UDCA + isoprenaline on days 9 and 10 (UDCA + I group). UDCA pre-treatment significantly reduced values of high-sensitivity troponin I (hsTnI) and aspartate aminotransferase (AST) cardiac markers ( p < 0.001 and p < 0.01, respectively). The value of thiobarbituric acid reactive substances (TBARS) was also decreased in the UDCA + I group compared to the I group ( p < 0.001). UDCA also significantly increased glutathione (GSH) levels, while showing a tendency to increase levels of superoxide dismutase (SOD) and catalase (CAT). The level of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression, a key regulatory gene of inflammation, was diminished when UDCA was administered. A reduction of cardiac damage was also observed in the UDCA pre-treated group. In conclusion, UDCA pre-treatment showed a cardioprotective effect on isoprenaline-induced myocardial injury in rats, primarily by reducing oxidative stress and inflammation.

The ultimate goal of value-based laboratory medicine is maximizing the effectiveness of laboratory tests in improving patient outcomes, optimizing resources and minimizing unnecessary costs. This approach abandons the oversimplified notion of test volume and cost, in favor of emphasizing the clinical utility and quality of diagnostic tests in the clinical decision-making. Several key elements characterize value-based laboratory medicine, which can be summarized in some basic concepts, such as organization of in vitro diagnostics (including appropriateness, integrated diagnostics, networking, remote patient monitoring, disruptive innovations), translation of laboratory data into clinical information and measurable outcomes, sustainability, reimbursement, ethics (e.g., patient empowerment and safety, data protection, analysis of big data, scientific publishing). Education and training are also crucial, along with considerations for the future of the profession, which will be largely influenced by advances in automation, information technology, artificial intelligence, and regulations concerning in vitro diagnostics. This collective opinion paper, composed of summaries from presentations given at the two-day European Federation of Laboratory Medicine (EFLM) Strategic Conference "A vision to the future: value-based laboratory medicine" (Padova, Italy; September 23-24, 2024), aims to provide a comprehensive overview of value-based laboratory medicine, projecting the profession into a more clinically effective and sustainable future., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

New Findings: What is the central question of this study? What are the biggest challenges in performing in vitro studies on isolated human umbilical arteries? What is the main finding and its importance? The protocols presented in this study indicate some potential outcomes important for interpretation of the vascular responsivities of human umbilical arteries and could be useful for planning future in vitro studies with human umbilical arteries., Abstract: Human umbilical artery (HUA) preparations are of particular importance for in vitro studies on isolated blood vessels because their sampling is not risky for the patient, and they can provide the closest possible impression of changes related to the uteroplacental circulation during pre-eclampsia. Using organ bath techniques, useful experimental protocols are provided for measuring some pathophysiological phenomena in the vascular responses of HUAs. Several vasoconstrictors (serotonin, prostaglandin F and phenylephrine) and vasodilators (acetylcholine and minoxidil) were seleted for determination of their vasoactivity in HUAs. The role of L-type voltage-operated calcium channels and different types of potassium channels (K ATP , BK Ca and K V ) were assessed, as was the impact of homocysteine. Serotonin was confirmed to be the most potent vasoconstrictor, while acetylcholine and phenylephrine caused variability in the relaxation and contraction response of HUA, respectively. The observed increase in serotonin-induced contraction and a decrease in minoxidil-induced relaxation in the presence of homocysteine suggested its procontractile effect on HUA preparations. Using selective blockers, it was determined that K ATP and K V channels participate in the minoxidil-induced relaxation, while L-type voltage-dependent Ca 2+  channels play an important role in the serotonin-induced contraction. The presented protocols reveal some of the methodological challenges related to HUA preparations and indicate potential outcomes in interpreting the vascular effects of the investigated substances, both in physiological conditions and in the homocysteine-induced pre-eclampsia model., (© 2023 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Takotsubo syndrome (TTS) is an acute heart failure syndrome characterised by catecholamine-induced oxidative tissue damage. Punica granatum , a fruit-bearing tree, is known to have high polyphenolic content and has been proven to be a potent antioxidant. This study aimed to investigate the effects of pomegranate peel extract (PoPEx) pre-treatment on isoprenaline-induced takotsubo-like myocardial injury in rats. Male Wistar rats were randomised into four groups. Animals in the PoPEx(P) and PoPEx + isoprenaline group (P + I) were pre-treated for 7 days with 100 mg/kg/day of PoPEx. On the sixth and the seventh day, TTS-like syndrome was induced in rats from the isoprenaline(I) and P + I groups by administering 85 mg/kg/day of isoprenaline. PoPEx pre-treatment led to the elevation of superoxide dismutase and catalase ( p < 0.05), reduced glutathione ( p < 0.001) levels, decreased the thiobarbituric acid reactive substances ( p < 0.001), H 2 O 2 , O 2 - ( p < 0.05), and NO 2 - ( p < 0.001), in the P + I group, when compared to the I group. In addition, a significant reduction in the levels of cardiac damage markers, as well as a reduction in the extent of cardiac damage, was found. In conclusion, PoPEx pre-treatment significantly attenuated the isoprenaline-induced myocardial damage, primarily via the preservation of endogenous antioxidant capacity in the rat model of takotsubo-like cardiomyopathy.

Over time, the metrological concept of uncertainty in measurement has been very successfully integrated into laboratory sciences. For proper implementation, an understanding of specific metrology terminology and additional concepts such as metrology traceability and commutability is necessary. Although the original thinking about measurement uncertainty in laboratory medicine suggests the complexity of the concept, it basically refers to the result as the end product of the entire laboratory process. Although the data on measurement uncertainty can be expressed quantitatively, the basis of this concept is the continuous evaluation of all phases of the laboratory process. This means that laboratory experts should keep in mind that the extra-analytical phases (on which the uncertainty of the measurement results may depend the most) must be continuously monitored. The analytical phase can be "held in check" by established internal and external quality control processes. It is the internal/external quality control data that is used to calculate the numerical value of the measurement uncertainty of the measurement results. Although over time the awareness of laboratory experts regarding the concept of measurement uncertainty has increased, there are still many challenges that need to be followed, and the last one is how to achieve a balance between understanding, evaluation process and application of measurement uncertainty data of measurement results for complete and ultimate practical use., (Copyright © 2023. Published by Elsevier Inc.)

Measurement uncertainty (MU) of results is one of the basic recommended and accepted statistical methods in laboratory medicine, with which analytical and clinical evaluation of laboratory test quality is assessed. Literature data indicate that the calculation of MU is not a simple process, but that its assessment in daily laboratory practice should be reduced to routine and simple presentation, understandable to both laboratory professionals and physicians. In order to achieve this, it is necessary to understand the purpose of the test for which MU is to be determined. Various suggestions have been given for presentation of MU as a quantitative indicator of the quality of the final measurement result in the medical laboratory. Although MU refers to the final measurement result, this metrological concept reflects the entire laboratory measurement process. The data on estimated MU is used to interpret the measured numerical result, and represents quantitatively the quality of the measurement itself, i.e. how different are the results of multiple measurements of the analyte of interest in the same sample, as well as whether the method of determination itself is subjected to significant random and systematic deviation. Initially, in the metrological concept, the MU is viewed in relation to the true value of the analyte of interest. However, the true value of the analyte measured in the biological fluid matrix of the study population cannot be known. It is therefore considered the closest value obtained by the perfect method, for which the bias and inaccuracy, as measures of systematic and random error, are equal to zero, which is practically impossible to achieve in routine laboratory practice. Although current standards require accredited medical laboratories to estimate MU, none of these guidelines provide clear guidance on how this can be achieved in daily laboratory work. This review examines literary data and documents dealing with MU issues, but also highlights what additional terms and data should be considered when interpreting MU. This paper ultimately draws attention, and once again points out, that a simpler solution is needed for this universal concept to be formally and universally applicable in routine laboratory medicine practice.

Objectives: There are many mobile health applications (apps) now available and some that use in some way laboratory medicine data. Among them, patient-oriented are of the lowest content quality. The aim of this study was to compare the opinions of non-laboratory medicine professionals (NLMP) with those of laboratory medicine specialists (LMS) and define the benchmarks for quality assessment of laboratory medicine apps., Methods: Twenty-five volunteers from six European countries evaluated 16 selected patient-oriented apps. Participants were 20-60 years old, 44% were females, with different educational degrees, and no professional involvement in laboratory medicine. Each participant completed a questionnaire based on the Mobile Application Rating Scale (MARS) and the System Usability Scale, as previously used for rating the app quality by LMS. The responses from the two groups were compared using the Mann-Whitney U test and Spearman correlation., Results: The median total score of NLMP app evaluation was 2.73 out of 5 (IQR 0.95) compared to 3.78 (IQR 1.05) by the LMS. All scores were statistically significantly lower in the NLMP group (p<0.05), except for the item Information quality (p=0.1631). The suggested benchmarks for a useful appear: increasing awareness of the importance and delivering an understanding of persons' own laboratory test results; understandable terminology; easy to use; appropriate graphic design, and trustworthy information., Conclusions: NLMP' evaluation confirmed the low utility of currently available laboratory medicine apps. A reliable app should contain trustworthy and understandable information. The appearance of an app should be fit for purpose and easy to use., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Jungian active imagination is a well known and valuable method in analytical psychology and psychotherapy. The present study assessed, for the first time, psychological and psycho-acoustical (voice and speech quality) effects of active imagination experiment in outdoor, forest, ambient. In order to analyse the voice and speech quality, participants' verbal expressions were recorded before and after the experiment. Psychological observations were based on the thirteen features and were rated according to the bipolar Comparison Mean Opinion Score scale. The results showed a noticeable positive participants' experiences after the experiment, connected with themselves, others, their behaviour, other verbal and non-verbal expressions and relations towards nature. Voice and speech quality analysis, based on the speech signal processing approach, was done based on the fourteen acoustic features. The results showed a statistically significantly better voice and speech quality of the participants at the end of the experiment (p < 0.05). Applying the averaging model from the Information Integration Theory, we obtained integral evaluative ratings in active imagination for psychological observations E AI and voice and speech quality observations E VQ , for each participant. The value of Pearson's correlation coefficient R = 0.6385 (p < 0.05) has shown a significant correlation between these two ratings. Overall results highlight starting hypothesis that exist some strong voice and speech correlates of psychological observations in Jungian active imagination experiment.

Background Many of the mobile applications (apps) used for delivering health interventions involve laboratory medicine data. This survey was conducted to search the online market for health apps that manage laboratory medicine data. The aim was to review them and perform a quality evaluation. Methods Apps search criteria were "Lab results blood work", "Lab results", and "Health apps". After the stepwise exclusion process, 52 selected apps were downloaded and analyzed. For review and content analysis of the apps, a multidimensional tool for classifying and rating the quality of mobile health apps - Mobile App Rating Scale (MARS), was used. Results Selected apps were classified into five categories according to their intended use by patients or physicians, and the type of data engaged. Spearman's correlation analysis found significant correlations between MARS individual scoring items, as with the subjective quality and number of technical aspects. Kruskal-Wallis analysis showed a significant difference in the number of technical aspects employed, MARS engagement and informational quality score items, total score, and subjective quality. The lowest values for all of these items were in the category of apps designed for patients, and the post hoc test showed that the difference was statistically significant between this and the values in all other categories. Conclusions Apps designed for patients, are of the poorest quality, considering the total quality of the content and information they provide, estimated using the MARS tool. This estimation needs to be validated for laboratory medicine apps, and eventually modified after consideration of specific quality benchmarks.

The diversity of bee (Hymenoptera: Apoidea) and hoverfly (Diptera: Syrphidae) pollinators from ten localities in Vojvodina, Serbia was surveyed. Among different types of Pannonian habitat (grasslands, heathland and scrub, woodland and forest habitats) all localities were categorised as forest and steppe. They were in protected areas, mostly undisturbed by human activity. Censuses of pollinators took place from 30 March to 10 October, 2014. We recorded 218 pollinator species; 135 bee species (42 Halictidae; 32 Apidae; 29 Andrenidae; 24 Megachilidae; 7 Colletidae; 1 Melittidae) and 83 species of hoverflies. We describe a new species of hoverfly, Eumerus pannonicus sp. nov., and compare it to other similar species. Based on our study, the Special Nature Reserve of Pašnjaci Velike Droplje is critical for the conservation of this new Eumerus-being only found at this locality-and other species such as Chrysotoxum lineare (Zetterstedt), which is rare in Europe and protected under Serbian legislation. The highest numbers of bee species were recorded in the Deliblato and Subotica sand areas (40 and 32, respectively), while Fruška Gora Mountain and the Vršac Mountains harboured the highest number of hoverfly species.

Objectives: Defining adequate reference limits (RLs) for thyroid hormones is an important task for support monitoring and the treatment of subclinical thyroid disease. We determined whether there are age-related RLs for thyroid parameters in male and female outpatients free of overt thyroid disease., Design: We analyzed 22,860 results (11,440 male and 11,420 female outpatients above the age of 18) for thyrotropin (TSH), free thyroxine (fT4) and total triiodothyronine (T3) that were stored in our laboratory information system between 2008 and 2011. We calculated the 2.5th and 97.5th centiles for the analyzed thyroid parameters., Results: Our results indicate higher TSH levels with ageing, with a significant difference (p < 0.05) between the 97.5th centiles for males and females older than 70 (5.07 mIU/L and 4.10 mIU/L), but also a significant difference between male and female fT4 from 31 to 40 and from 41 to 50 years old (18.4 vs 14.9 pmol/L and 19.0 vs 15.9 pmol/L, p < 0.05), respectively. Overall indirect estimates of the 97.5th centiles for TSH for males and females were not significantly different and were below the generally recommended upper limit (4.01 mIU/L and 4.20 mIU/L, respectively). In addition, we found no statistically significant change in mean T3 values in the analyzed population., Conclusions: This cross-sectional study indicates change in TSH and fT4 levels with ageing and gender-related upper limits. This suggests that by using indirect estimation a laboratory could provide clinicians with more accurate gender- and age-specific RLs for thyroid parameters.