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BACKGROUND: The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) initiated the CArdiac MARker Guidelines Uptake in Europe (CAMARGUE) Study to survey if current biomarker testing for heart failure (HF) in Europe is in accordance with up-dated guidelines. METHODS: A web-based questionnaire was distributed to clinical laboratories via European biochemical societies in 2019. Questions covered the type of natriuretic peptide (NP) assays performed, decision limits for HF, and opinion concerning requirement of different thresholds in patients with renal failure or obesity. RESULTS: There were 347 participating laboratories mostly from European countries with 266 offering NP testing. NP testing was increased from 67% to 77% between 2013 and 2019. NT-proBNP remained the preferred biomarker. Recommended decision limits were implemented for BNP (85%) and better focused for NT-proBNP (40%) than in the previous survey. The survey revealed that laboratorians are willing to support the translation of adjusted cut-off values for age, gender and for patients with conditions like renal insufficiency. CONCLUSION: Guidelines stimulate clinical laboratories to offer NP testing with high value for the diagnosis and management of HF, and to present adjusted medical decision limits. Future guidelines should encourage the use of personalized cut-offs for some confounding factors.

BACKGROUND: The CArdiac MARker Guidelines Uptake in Europe Study (CAMARGUE) initiated by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) aims to survey the current use of evidence-based guidelines for dyslipidemia testing in Europe. METHODS: In 2019 a web-based questionnaire was distributed via EFLM National Societies to clinical laboratories in Europe. Questions covered pre-analytics, analytical methods, measurement units, flagging of decision thresholds, and use of decision-enhancing comments. RESULTS: Returns were obtained from 452 laboratories from 28 countries. Most laboratories always use nonfasting blood samples for lipid assays (66%). Lipid profiles are reported in mmol/L by 59% of the laboratories, mainly from 14 countries promoting the use of SI units. Important differences in flagging of decision thresholds were observed, with less than half of the laboratories applying the guideline-recommended LDL cholesterol threshold. Only 17% of the laboratories add an alert comment when familial hypercholesterolemia is suspected and 23% when risk of pancreatitis from hypertriglyceridemia is high. CONCLUSIONS: There are marked differences among laboratories in Europe in terms of pre-analytical, analytical, and post-analytical lipid management that could have an important clinical impact. This relates to different availability of assays or different laboratory practices on reporting and flagging of lipid profiles.

The joint consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), LDL cholesterol (LDLC), and calculated non-HDLC (=total - HDLC) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDLC is the primary target of lipid-lowering therapies. For on-treatment follow-up, LDLC shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a) [Lp(a)]-cholesterol is part of measured or calculated LDLC and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDLC declines poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDLC or apolipoprotein B (apoB), especially in patients with mild-to-moderate hypertriglyceridemia (2-10 mmol/L). Non-HDLC includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apoB measurement can detect elevated LDL particle (LDLP) numbers often unidentified on the basis of LDLC alone. Reference intervals of lipids, lipoproteins, and apolipoproteins are reported for European men and women aged 20-100 years. However, laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds.

DIU Libertas International University is committed to developing the intellectual capacity, creativity and professionalism of our students, immersing them in the rich diversity of human experience and aspirations, thereby preparing them to shape the future of our world while adding to the knowledge base of humankind. The university includes professors, students and graduates from almost 100 countries and a clinical training program involving more than 10 hospitals from seven countries. How to cite this article Kurjak A, Stavljenic Rukavina A, Zaputovic S, Stanojevic M, Raic N, Zuzul M. Higher Education Internationalization: DIU Libertas Response? Donald School J Ultrasound Obstet Gynecol 2013;7(3):231-238.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Epidemiological and molecular genetic studies have shown the existence of several genes associated with increased risk of AD, the major genetic susceptibility locus coding for apolipoprotein E (apoE). A polymorphism in the myeloperoxidase gene (MPO) has previously been associated with AD susceptibility. However, results in the literature are controversial and seem to be dependent on several factors such as gender, apoE polymorphism or the genetic structure of the population. We investigated MPO G-463A and apoE polymorphism in 265 cases and 246 controls from the ApoEurope Study. In females, we found a significant association between MPO genotype and AD ( P =0.034), GG genotype frequency being lower in cases (52.4%) as compared to controls (64.2%). In men, there was no significant effect of MPO polymorphism. No interaction was found between MPO polymorphism and apoE e4 allele. In conclusion, the G-463A polymorphism of MPO was statistically associated with AD in a gender-specific manner. However, given the low significance of P value we suggest no causal effect of the MPO gene in AD, as also evidenced in a recent meta-analysis. Our results support the hypothesis of a possible linkage disequilibrium between the MPO G-463A gene polymorphism and another functional variant involved in AD.

As part of the ApoEurope Project, apolipoprotein E (apo E) common polymorphism and serum concentration were determined in 489 Alzheimer's disease patients and 429 controls. Patients and controls were recruited through nine centres in eight European countries. Age, sex ratios and education levels of both case and control populations were similar, although discrete differences appeared between centres. The prevalence of the ε4 allele was higher in Alzheimer's disease than in controls (increased by 140%), while serum apo E concentration was lower by 11.2% (p

1. Five groups of laying hens were treated with different gizzerosine doses (0, 2 5; 5 0; 7 5; 10 0 mg/kg/body weight of gizzerosine) daily over a 21-day period to determine the serum concentrations of 1 25-dihydroxycholecalciferol (1,25(OH) 2 D), total calcium, inorganic phosphorus and magnesium. Blood samples were taken on days 7, 14, and 21 of the experiment. 2. The concentration of 1,25(OH) 2 D remained unchanged after day 7 in the gizzerosine-treated birds compared to the control group. 3. After 14 days, it was significantly lower in the birds receiving. gizzerosine, compared with the control group. 4. On day 21, 1,25(OH 2 )D concentrations were also significantly decreased in all 4 gizzerosine-treated groups compared with the control hens. 5. The serum total calcium, inorganic phosphorus and total magnesium concentrations varied significantly, but irregularly , during the period of the study.

The original Cardiac MarkerGuideline Uptake in Europe (CARMAGUE) study (1 ) surveyed laboratory practice against the then current clinical practice recommendations.Responses were obtained from 303 laboratories in 28 countries.The responders were from a full range of laboratories: 34% universityhospital laboratories, 36% districthospitals, 25% central hospitals, and 5% primary care acilities.Ninety-five percent of the laboratories used troponin as the preferred marker for routine diagnosis of suspected acute coronary syndromes.Fifty percent of the laboratories use troponin T, and 45% used troponin I.Thirty-one percent of the laboratories used troponin as the sole marker, but 69% combined troponin measurement with another marker and offered other marker tests in suspected cases of acute coronary syndrom.The wide range of choice of decision limits may in part represent laboratory conservatism, physician resistance, or a feeling that assay performance is inadequate for using a 99th percentile value. There is a need for independent validation of both assay performance and 99th percentile values to provide decision limits for MI independent of manufacturers’.

The aim of the overview is to show the distribution of common apolipoprotein E (APOE) genotypes in the Croatian population, and to test whether it could serve as a new molecular biomarker in some clinical entities. The study included the following groups: patients with angiographically confirmed coronary artery disease, myocardial infarction, Alzheimer's dementia, vascular dementia, hyperlipidemias, diabetes mellitus, pancreatitis, and healthy subjects. Group comparisons of different clinical entities and control group were performed using Pearson's Chi2-test. There was no difference in APOE genotype frequencies between coronary artery disease neither myocardial infarction and control group. The ApoE genotype frequencies in patients with Alzheimer's disease were significantly different from those in the control group. APOE-4 allele tends to be a risk factor for the development of Alzheimer's disease. The frequencies were only marginally different in vascular dementia. Patients with hypercholesterolemia, those with inherited familial hypercholesterolemia, children with diabetes mellitus, and patients with pancreatitis of different etiology showed distributions of APOE genotypes that differed from the control group. It is concluded that the frequencies of APOE genotypes yielded no statistically significant result to confirm the association between APOE genotypes and any specific disease with the exception of Alzheimer's disease; APO-epsilon4 allell has become one of the important biomarkers in diagnosis of Alzheimer's dementia.

Periodontal diseases result from interactions between periodontal microflora and the multifaceted response of the host. Markers of this interrelationship can be found in gingival crevicular fluid and saliva samples indicating early periodontal disease activity. Studies of host defense mediators in saliva of patients with periodontal diseases are very scarce. AIM: The goal of this study was therefore to investigate interrelationships between mediators of local immunity in host saliva and clinical parameters of periodontal destruction in persons with chronic and aggressive periodontitis. METHODS AND SUBJECTS: Host defense indicators were measured using enzyme-immunochemistry tests in unstimulated saliva samples of persons with periodontitis. The degree of periodontal destruction was determined by measuring attachment loss. Subjects were divided into two groups: persons with mild signs of chronic periodontitis and persons with severe signs of aggressive periodontitis. Hypotheses about the structure of those samples and their interrelationship were tested using non-parametric methods. RESULTS: Results indicated that C-reactive protein, C3 component of the complement, alfa 2-macroglobulin and interleukin-6 levels differ significantly between patients with chronic and aggressive periodontitis. Interleukin-6, influencing cells with osteoblastic phenotype, is present at a high level in patients with aggressive periodontitis. Calcium was much lower than in healthy persons. Trypsin levels were lower in patients with periodontitis than in healthy persons. We found a significant interrelationship between host response mediators as measured in saliva and periodontal destruction measured by clinical attachment loss. CONCLUSION: The levels of host defense mediators in saliva are different for chronic and aggressive periodontitis. This findings might help in estimating the course and progression of periodontal destruction, thus providing clinical benefits in treatment planning.

Cytochrome P450 enzyme debrisoquine 4-hydroxylase, responsible for the metabolism of different classes of drugs and other chemical substances, exhibits genetic polymorphism with great interindividual and interethnic differences in metabolic capacity. The activity of enzyme ranges from very expressed, rapid, to total absence of activity. Up to 7% of Caucasians may demonstrate ultrarapid metabolism--UEM of debrisoquine and other drugs, substrates of debrisoquin hydroxylase, due to inheritance of multiplicate functional CYP2D6 gene, causing an increased amount of enzyme to be expressed. Identification of subjects with ultrarapid metabolism is of potential clinical value for optimization of therapy and avoidance of therapeutic failure due to inadequate dosage. In our study we wanted to determine the prevalence of UEM genotype in Croatian population applying long-PCR method. We found a 4% prevalence of ultrarapid metabolizers with multiplicated CYP2D6 gene.

The aim of our investigation was to evaluate possible connection between burning mouth syndrome and hematinic deficiencies, a hypothesis previously reported in the literature with contradictory results. Serum levels of iron, vitamin B12, folic acid, calcium and magnesium were determined in 41 (aged 31-87 years, mean 68,7 yrs) patients with burning mouth syndrome and 35 matched controls (35-83, mean 63 yrs). Serum iron levels were determined according to Fairbanks and Klee. Levels of vitamin B12 and folic acid were determined on commercially available kits (Imx12 and Imx folate assay, Abbot Park lab, IL, USA) on Imx analyser. Calcium and magnesium levels were determined using atomic absorption spectrophotometry. No statistically significant differences in serum levels of iron, folic acid, calcium and magnesium were found between patients with burning mouth syndrome and controls. Statistically significant lowered vitamin B12 levels were found in patients with burning mouth syndrome. Our results suggest that serum deficiencies of iron, folic acid, calcium and magnesium are not etiological factor in patients with burning mouth syndrome.

case report

Childhood onset proximal spinal muscular atrophy presents with considerable clinical variability. This study included 14 Croatian children aged 11 days to 8 years with spinal muscular atrophy types I-III verified clinically and electromyoneurographically. DNA of affected children was screened for deletions of exons 7 and 8 of the survival motor neuron gene and for deletion of exon 5 of the neuronal apoptosis inhibitor protein gene. Motor nerve conduction velocity and compound muscle action potential amplitude were decreased in children with spinal muscular atrophy type I and II. Deletions of exons 7 and 8 of the survival motor neuron gene and of exon 5 of the neuronal apoptosis inhibitor protein gene in children with spinal muscular atrophy type I-II suggested existence of more genetic abnormalities as compared to type III. A decrease in compound muscle action potential amplitude and motor nerve conduction velocity in children with spinal muscular atrophy correlated with the disease severity, probably as a result of axonal degeneration. Phenotypic severity in children onset spinal muscular atrophy is directly correlated with the extent of survival motor neuron and neuronal apoptosis inhibitor protein exon deletions.