Prognostic significance of bone morphogenetic protein 6 (BMP6) expression, clinical and pathological factors in clinically node-negative oral squamous cell carcinoma (OSCC).

Bone morphogenetic protein 6 (BMP6) has unique properties regarding structure and function in supporting bone formation during development and adult life. Despite its known role in various malignant tumors, the prognostic significance of BMP6 expression in oral squamous cell carcinoma (OSCC) remains unknown. The aim of the study was to investigate immunohistochemical expression of BMP6 in OSCC in correlation with clinical and pathological parameters, disease recurrence and survival. In addition, we investigated other parameters in order to identify prognosticators of neck metastases and final outcome. The study included 120 patients with clinically T1-3N0 OSCC who were primarily surgically treated between 2003 and 2008. There were 99 (82.5%) male and 21 (17.5%) female patients. The five-year disease-specific survival for the whole cohort was 79.7%. Tumors smaller than 2 cm in diameter showed higher incidence of strong BMP6 expression. No statistical correlation was observed between other clinico-pathological factors and BMP6 expression. Expression of BMP6 was not associated with disease recurrence and survival. BMP6 may not serve as prognosticator of final outcome or recurrence in clinically node-negative OSCC subjects. In multivariate analysis predictors of poorer survival were positive surgical margin, moderate tumor cell differentiation and pathological involvement of levels IV and/or V.

Positron emission tomography-computed tomography and 4-hydroxynonenal-histidine immunohistochemistry reveal differential onset of lipid peroxidation in primary lung cancer and in pulmonary metastasis of remote malignancies.

The Aim of the study was to reveal if PET-CT analysis of primary and of secondary lung cancer could be related to the onset of lipid peroxidation in cancer and in surrounding non-malignant lung tissue. METHODS: Nineteen patients with primary lung cancer and seventeen patients with pulmonary metastasis were involved in the study. Their lungs were analyzed by PET-CT scanning before radical surgical removal of the cancer. Specific immunohistochemistry for the major bioactive marker of lipid peroxidation, 4-hydroxynonenal (HNE), was done for the malignant and surrounding non-malignant lung tissue using genuine monoclonal antibody specific for the HNE-histidine adducts. RESULTS: Both the intensity of the PET-CT analysis and the HNE-immunohistochemistry were in correlation with the size of the tumors analyzed, while primary lung carcinomas were larger than the metastatic tumors. The intensity of the HNE-immunohistochemistry in the surrounding lung tissue was more pronounced in the metastatic than in the primary tumors, but it was negatively correlated with the cancer volume determined by PET-CT. The appearance of HNE was more pronounced in non-malignant surrounding tissue than in cancer or stromal cells, both in case of primary and metastatic tumors. CONCLUSIONS: Both PET-CT and HNE-immunohistochemistry reflect the size of the malignant tissue. However, lipid peroxidation of non-malignant lung tissue in the vicinity of cancer is more pronounced in metastatic than in primary malignancies and might represent the mechanism of defense against cancer, as was recently revealed also in case of human liver cancer.

Research Misconduct in the Croatian Scientific Community: A Survey Assessing the Forms and Characteristics of Research Misconduct.

The prevalence and characteristics of research misconduct have mainly been studied in highly developed countries. In moderately or poorly developed countries such as Croatia, data on research misconduct are scarce. The primary aim of this study was to determine the rates at which scientists report committing or observing the most serious forms of research misconduct, such as falsification , fabrication, plagiarism, and violation of authorship rules in the Croatian scientific community. Additionally, we sought to determine the degree of development and the extent of implementation of the system for defining and regulating research misconduct in a typical scientific community in Croatia. An anonymous questionnaire was distributed among 1232 Croatian scientists at the University of Rijeka in 2012/2013 and 237 (19.2 %) returned the survey. Based on the respondents who admitted having committed research misconduct, 9 (3.8 %) admitted to plagiarism, 22 (9.3 %) to data falsification, 9 (3.8 %) to data fabrication, and 60 (25.3 %) respondents admitted to violation of authorship rules. Based on the respondents who admitted having observed research misconduct of fellow scientists, 72 (30.4 %) observed plagiarism, 69 (29.1 %) observed data falsification, 46 (19.4 %) observed data fabrication, and 132 (55.7 %) respondents admitted having observed violation of authorship rules. The results of our study indicate that the efficacy of the system for managing research misconduct in Croatia is poor. At the University of Rijeka there is no document dedicated exclusively to research integrity, describing the values that should be fostered by a scientist and clarifying the forms of research misconduct and what constitutes a questionable research practice. Scientists do not trust ethical bodies and the system for defining and regulating research misconduct; therefore the observed cases of research misconduct are rarely reported. Finally, Croatian scientists are not formally educated about responsible conduct of research at any level of their formal education. All mentioned indicate possible reasons for higher rates of research misconduct among Croatian scientists in comparison with scientists in highly developed countries.

Zagreb Amblyopia Preschool Screening Study: near and distance visual acuity testing increase the diagnostic accuracy of screening for amblyopia.

AIM: To present and evaluate a new screening protocol for amblyopia in preschool children. METHODS: Zagreb Amblyopia Preschool Screening (ZAPS) study protocol performed screening for amblyopia by near and distance visual acuity (VA) testing of 15 648 children aged 48-54 months attending kindergartens in the City of Zagreb County between September 2011 and June 2014 using Lea Symbols in lines test. If VA in either eye was >0.1 logMAR, the child was re-tested, if failed at re-test, the child was referred to comprehensive eye examination at the Eye Clinic. RESULTS: 78.04% of children passed the screening test. Estimated prevalence of amblyopia was 8.08%. Testability, sensitivity, and specificity of the ZAPS study protocol were 99.19%, 100.00%, and 96.68% respectively. CONCLUSION: The ZAPS study used the most discriminative VA test with optotypes in line as they do not underestimate amblyopia. The estimated prevalence of amblyopia was considerably higher than reported elsewhere. To the best of our knowledge, the ZAPS study protocol reached the highest sensitivity and specificity when evaluating diagnostic accuracy of VA tests for screening. The pass level defined at ≤0.1 logMAR for 4-year-old children, using Lea Symbols in lines missed no amblyopia cases, advocating that both near and distance VA testing should be performed when screening for amblyopia.

Venous thromboembolism in Croatia - Croatian Cooperative Group for Hematologic Diseases (CROHEM) study.

AIM: To analyze the incidence and characteristics of venous thromboembolism (VTE) in Croatia. METHODS: The Croatian Cooperative Group for Hematologic Diseases conducted an observational non-interventional study in 2011. Medical records of patients with newly diagnosed VTE hospitalized in general hospitals in 4 Croatian counties (Sibenik-Knin, Koprivnica-Krizevci, Brod-Posavina, and Varazdin County) were reviewed. According to 2011 Census, the population of these counties comprises 13.1% of the Croatian population. RESULTS: There were 663 patients with VTE; 408 (61.54%) had deep vein thrombosis, 219 (33.03%) had pulmonary embolism, and 36 (5.43%) had both conditions. Median age was 71 years, 290 (43.7%) were men and 373 (56.3%) women. Secondary VTE was found in 57.3% of participants, idiopathic VTE in 42.7%, and recurrent VTE in 11.9%. There were no differences between patients with secondary VTE and patients with idiopathic VTE in disease recurrence and sex. The most frequent causes of secondary VTE were cancer (40.8%), and trauma, surgery, and immobilization (38.2%), while 42.9% patients with secondary VTE had ≥2 causes. There were 8.9% patients ≤45 years; 3.3% with idiopathic or recurrent VTE. Seventy patients (10.6%) died, more of whom had secondary (81.4%) than idiopathic (18.6%) VTE (P<0.001), and in 50.0% VTE was the main cause of death. Estimated incidence of VTE in Croatia was 1.185 per 1000 people. CONCLUSION: Characteristics of VTE in Croatia are similar to those reported in large international studies. Improved thromboprophylaxis during the presence of risk factors for secondary VTE might substantially lower the VTE burden.

Medical informatics in croatia - a historical survey.

A historical survey of medical informatics (MI) in Croatia is presented from the beginnings in the late sixties of the 20th century to the present time. Described are MI projects, applications in clinical medicine and public health, start and development of MI research and education, beginnings of international cooperation, establishment of the Croatian Society for MI and its membership to EFMI and IMIA. The current status of computerization of the Croatian healthcare system is sketched as well as the present graduate and postgraduate study MI curricula. The information contained in the paper shows that MI in Croatia developed and still develops along with its advancement elsewhere.

Occupational exposures in healthcare workers in University Hospital Dubrava--10 year follow-up study.

Occupational hazardous exposure in healthcare workers is any contact with a material that carries the risk of acquiring an infection during their working activities. Among the most frequent viral occupational infections are those transmitted by blood such as hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Therefore, they represent a significant public health problem related to the majority of documented cases of professionally acquired infections. Reporting of occupational exposures in University Hospital Dubrava has been implemented in connection with the activity of the Committee for Hospital Infections since January 2002. During the period of occupational exposures' monitoring (from January 2002 to December 2011) 451 cases were reported. The majority of occupational exposures were reported by nurses and medical technicians (55.4%). The most common type of exposure was the needlestick injury (77.6%). 27.9% of the accidents occurred during the blood sampling and 23.5% during the surgical procedure. In 59.4% of the exposed workers aHBs-titer status was assessed as satisfactory. Positive serology with respect to HBV was confirmed in 1.6% of patients, HCV in 2.2% of patients and none for HIV. Cases of professionally acquired infections were not recorded in the registry. Consequences of the occupational exposure could include the development of professional infection, ban or inability to work further in health care services and last but not least a threat to healthcare workers life. It is therefore deemed necessary to prevent occupational exposure to blood-borne infections. The most important preventive action in respect to HBV, HCV and HIV infections is nonspecific pre-exposure prophylaxis.

Etiology and epidemiology of obstructive jaundice in Continental Croatia.

The etiology and epidemiology of obstructive jaundice in Continental Croatia has been studied in 174 patients. The objective of this research was also to explore the importance and efficiency of endoscopic retrograde cholangiopancreatography (ERCP) as a non-surgical method of treatment of obstructive jaundice in the population of Continental Croatia. Obstructive jaundice is the illness of elderly population which is also confirmed by the information on the average age of our patients. The frequency of illness is higher among female population, and the most frequent cause of obstructive jaundice are gallstones (54.1% of patients). In 29.8% of patients the primary or secondary malignant disease was the cause of blockage in gall flow and subsequent jaundice, and the most frequent malignant cause of obstructive jaundice is pancreas cancer in 11.5% of patients. The mean value of serum concentrations of total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and gamma glutamiltransferase 24 hours before the biliary decompression by ERCP has been significantly above the upper referential value, and 24 hours after the ERCP it has dropped to normal with their statistically significant difference (p < 0.0001). The normal values of markers for synthetic liver function (total proteins and prothrombin time) have been noticed as well as elevated values of inflammatory markers in obstructive jaundice independently of etiology. Out of the total number of patients, 37.7% required the surgical treatment while 60.3% of patients were treated by ERCP, i.e. either the stone extraction or the implantation of endobiliary stent was performed.

Correlation of endothelin-1 concentration and angiotensin-converting enzyme activity with the staging of liver fibrosis.

Increased serum angiotensin-converting enzyme (SACE) activity and serum concentration of endothelin-1 (ET-1) were found in liver cirrhosis. We investigated a correlation between the different stages of liver fibrosis and SACE activity and serum ET-1 concentration. Seventy patients with pathohistologically established chronic liver disease were divided in three groups according to Ishak criteria for liver fibrosis: minimal fibrosis (Ishak score 0-1, n =20), medium fibrosis (Ishak score 2-5, n=20) and cirrhosis (Ishak score 6, n=30). SACE activity and ET-1 concentration were determined using commercial ELISA kits. SACE activity and ET-1 concentrations were proportional to the severity of disease, the highest being in patients with liver cirrhosis. Maximal increase in SACE activity was found between minimal and medium fibrosis while maximal increase in ET-1 concentration was revealed between medium fibrosis and cirrhosis. The analysis of the Receiver Operating Characteristic (ROC) curve for SACE activity suggested a cut-off value to separate minimal from medium fibrosis at 59.00 U/L (sensitivity 100%, specificity 64.7%). The cut-off value for serum ET-1 concentration to separate medium fibrosis from cirrhosis was 12.4 pg/mL (sensitivity 96.8%, specificity 94.4%). A positive correlation between SACE activity and ET-1 concentration was registered (Spearman's ñ = 0.438, p = 0.004). Both SACE activity and ET-1 concentration were increased in all stages of liver fibrosis. Cut-off points for SACE activity and ET-1 concentration could be a biochemical marker for the progression of fibrosis. Positive correlation between SACE activity and ET-1 concentration might indicate their interaction in the development of liver cirrhosis.

Analysis of censored data.

Analyzing events over time is often complicated by incomplete, or censored, observations. Special non-parametric statistical methods were developed to overcome difficulties in summarizing and comparing censored data. Life-table (actuarial) method and Kaplan-Meier method are described with an explanation of survival curves. For the didactic purpose authors prepared a workbook based on most widely used Kaplan-Meier method. It should help the reader understand how Kaplan-Meier method is conceptualized and how it can be used to obtain statistics and survival curves needed to completely describe a sample of patients. Log-rank test and hazard ratio are also discussed.

Prevalence of plagiarism in recent submissions to the Croatian Medical Journal.

To assess the prevalence of plagiarism in manuscripts submitted for publication in the Croatian Medical Journal (CMJ). All manuscripts submitted in 2009-2010 were analyzed using plagiarism detection software: eTBLAST, CrossCheck, and WCopyfind. Plagiarism was suspected in manuscripts with more than 10% of the text derived from other sources. These manuscripts were checked against the Déjà vu database and manually verified by investigators. Of 754 submitted manuscripts, 105 (14%) were identified by the software as suspicious of plagiarism. Manual verification confirmed that 85 (11%) manuscripts were plagiarized: 63 (8%) were true plagiarism and 22 (3%) were self-plagiarism. Plagiarized manuscripts were mostly submitted from China (21%), Croatia (14%), and Turkey (19%). There was no significant difference in the text similarity rate between plagiarized and self-plagiarized manuscripts (25% [95% CI 22-27%] vs. 28% [95% CI 20-33%]; U = 645.50; P = 0.634). Differences in text similarity rate were found between various sections of self-plagiarized manuscripts (H = 12.65, P = 0.013). The plagiarism rate in the Materials and Methods (61% (95% CI 41-68%) was higher than in the Results (23% [95% CI 17-36%], U = 33.50; P = 0.009) or Discussion (25.5 [95% CI 15-35%]; U = 57.50; P < 0.001) sections. Three authors were identified in the Déjà vu database. Plagiarism detection software combined with manual verification may be used to detect plagiarized manuscripts and prevent their publication. The prevalence of plagiarized manuscripts submitted to the CMJ, a journal dedicated to promoting research integrity, was 11% in the 2-year period 2009-2010.

Summarizing and presenting numerical data.

Scientific hypothesis and type of the study define variables that have to be measured. Measurements are determined by four distinct scales of measurement; nominal, ordinal, interval and ratio, producing two distinct types of data: categorical and numerical. Numerical data are usually summarized and presented by distribution, measures of central tendency and dispersion. For normally distributed data, arithmetic mean and standard deviation are used. For data not normally distributed, median with data range (minimum to maximum, interquartile range or percentile range) and mode are used. Commonly used graph types in descriptive statistics for numerical data presentation are error bar and box-and-whisker plots. Outliers are values that are numerically distant from the rest of the data and must be recognized.

Clinical laboratory as an economic model for business performance analysis.

AIM: To perform SWOT (strengths, weaknesses, opportunities, and threats) analysis of a clinical laboratory as an economic model that may be used to improve business performance of laboratories by removing weaknesses, minimizing threats, and using external opportunities and internal strengths. METHODS: Impact of possible threats to and weaknesses of the Clinical Laboratory at Nasice General County Hospital business performance and use of strengths and opportunities to improve operating profit were simulated using models created on the basis of SWOT analysis results. The operating profit as a measure of profitability of the clinical laboratory was defined as total revenue minus total expenses and presented using a profit and loss account. Changes in the input parameters in the profit and loss account for 2008 were determined using opportunities and potential threats, and economic sensitivity analysis was made by using changes in the key parameters. The profit and loss account and economic sensitivity analysis were tools for quantifying the impact of changes in the revenues and expenses on the business operations of clinical laboratory. RESULTS: Results of simulation models showed that operational profit of €470 723 in 2008 could be reduced to only €21 542 if all possible threats became a reality and current weaknesses remained the same. Also, operational gain could be increased to €535 804 if laboratory strengths and opportunities were utilized. If both the opportunities and threats became a reality, the operational profit would decrease by €384 465. CONCLUSION: The operational profit of the clinical laboratory could be significantly reduced if all threats became a reality and the current weaknesses remained the same. The operational profit could be increased by utilizing strengths and opportunities as much as possible. This type of modeling may be used to monitor business operations of any clinical laboratory and improve its financial situation by implementing changes in the next fiscal period.

The chronology of third molar eruption in the Croatian population.

Dental age estimation is common in orthodontics, paedodontics, paleodontology and forensic dentistry. The aim of this study was to assess chronological course of eruptive developmental phases of third molar and to establish parameters for the Croatian population. Sample of this study consisted of 1249 orthopantomograms of 530 (42.4%) male and 719 (57.6%) female subjects, aged 10 to 25 years. Eruptive phases were classified in 4 stages. No significant sex difference was found. Established chronology of the third molar eruption can be used as a standard for the assessment of dental age in clinical and forensic research on samples of Croatian population.

Anti-cyclic citrullinated peptide and rheumatoid factor in HIV positive patients.

The aim of this study was to determine the difference of anti-CCP and RF between HIV positive patients and a healthy control group. The rheumatological complications in HIV positive patients are rather common and are recognized as a serious problem that requires more attention. Anti-CCP and RF are the only laboratory tools for rheumatoid disorder diagnostics and predictors of the course of the disease. We determined anti-CCP and RF in sera of 35 healthy volunteers and 45 HIV positive patients. Data were compared using chi-square test, Mann-Whitney test and ROC curve statistics. Both parameters were significantly higher in HIV positive patients, and significant differences between areas under the anti-CCP and RF curves were observed. Median value for anti-CCP in HIV positive patients was higher than the reference interval, and RF values were, in the reference interval, suggested by the manufacturer. Both anti-CCP and RF are significantly higher in HIV positive patients. ROC analysis showed that anti-CCP distinguishes the two groups better than RF. Because of that, it would be of a great interest to investigate the HIV positive patients after the detailed rheumatological examination.

Construction and validation of attitudes toward plagiarism questionnaire.

AIM: To develop and test the psychometric characteristics of a questionnaire measuring attitudes toward plagiarism. METHODS: Participants were 227 undergraduates and graduate students (128 women and 99 men) from three Croatian universities, with a median age of 21 years (range 18 to 48). Research was conducted from March to June 2009. For the purpose of construction of the first version of the questionnaire, 67 statements (items) were developed. The statements were based on the relevant literature and were developed following rules and recommendations for questionnaire writing, and 36 items were chosen for final validation. Factor analysis was used to find out the factor structure of the questionnaire and to measure construct validity. RESULTS: The final version of the questionnaire consisted of 29 items divided into a three-factor structure: factor I - positive attitude toward plagiarism (12 items); factor II - negative attitude toward plagiarism (7 items); and factor III - subjective norms toward plagiarism (10 items). Cronbach alpha was calculated to confirm the reliability of the scale: factor I - alpha=0.83; factor II - alpha=0.79; and factor III - alpha=0.85. Correlations between factors were: -0.37 between I and II, -0.41 between I and III, and +0.31 between II and III. CONCLUSION: Attitudes Toward Plagiarism questionnaire was developed, with good psychometric characteristics. It will be used in future research as a standardized tool for measuring attitudes toward plagiarism.

Undergraduate grade point average is a poor predictor of scientific productivity later in career.

The aim of this study was to investigate the usefulness of the undergraduate grade point average in prediction of scientific production of research trainees during their fellowship and later in career. The study was performed in 1320 research trainees whose fellowships from the Croatian Ministry of Science, Education and Sports were terminated between 1999 and 2005. The data were analyzed using logistic regression. The results indicated that undergraduate grade point average was negatively associated with scientific productivity both during and after the fellowship termination. Other indicators, such as undergraduate scientific productivity exhibited much stronger positive association with scientific productivity later in career and should be given more weight in candidate selection process in science and research.

Lipoprotein(a) predicts progression of carotid artery intima-media thickening in patients with type 2 diabetes: A four-year follow-up.

BACKGROUND: The aim of the study was to establish whether increased levels of serum lipoprotein(a) significantly contribute to an increase in intima-media thickness and the number of carotid artery plaques, and consequently to cardiovascular risk in patients with type 2 diabetes mellitus. METHODS: Lipoprotein(a) levels, intima-media thickness and the number of carotid artery plaques were determined at the beginning of the study in 146 patients with type 2 diabetes. Patients were divided into two groups according to serum lipoprotein(a) levels (> or 30 mg/dl had more cardiovascular events, the difference was not statistically significant. CONCLUSIONS: These results indicate that lipoprotein(a) is an independent, genetically determined risk factor closely associated with progression of intima-media thickness in type 2 diabetes.