Defining screening panel of functional variants of CYP1A1, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 genes in Serbian population.

Plethora of drugs and toxic substances is metabolized by cytochrome P450 enzymes (CYP450). These enzymes are coded by highly variable genes abundant with single nucleotide variants (SNVs) and small insertions/deletions (indels) that affect the functionality of the enzymes, increasing or decreasing their activity. CYP genes genotyping, followed by haplotype inference, provides substrate specific metabolic phenotype prediction. This is crucial in pharmacogenetics and applicable in molecular autopsy. However, high number of alleles in CYP450 superfamily and interethnic variability in frequency distribution require precise gene panel customization. To estimate informativeness of SNVs and alleles in CYP gene families 1, 2, and 3, associated with metabolic alterations, 500 unrelated individuals from 5 regions of Serbia were genotyped using TaqMan assays to determine frequencies of CYP2C9 *2 and *3, CYP2C19 *2 and *17 alleles, four variants in CYP2D6 (rs3892097, rs1065852, rs28371725, rs28371706) gene, and CYP3A4*1B allele. In addition, CYP1A1 rs4646903 and rs1048943 (m1 and m2) variants were genotyped by RFLP. Our results showed that frequencies of tested variants in Serbian population corresponded to general European population and somewhat differed from neighboring populations. SNV rs1065852, the main contributor to non-functional CYP2D6 *4, significantly departed from Hardy-Weinberg equilibrium. With the exception of rs28371706 in CYP2D6 and rs2740574 in CYP3A4, which were very rare in our sample, all other tested variants in CYP2 family are informative and appropriate for pharmacogenetic testing, molecular autopsy, and medico-legal genetic analyses.

Complete mitogenome data for the Serbian population: the contribution to high-quality forensic databases.

Mitochondrial genome (mtDNA) is a valuable resource in resolving various human forensic casework. The usage of variability of complete mtDNA genomes increases their discriminatory power to the maximum and enables ultimate resolution of distinct maternal lineages. However, their wider employment in forensic casework is nowadays limited by the lack of appropriate reference database. In order to fill in the gap in the reference data, which, considering Slavic-speaking populations, currently comprises only mitogenomes of East and West Slavs, we present mitogenome data for 226 Serbians, representatives of South Slavs from the Balkan Peninsula. We found 143 (sub)haplogroups among which West Eurasian ones were dominant. The percentage of unique haplotypes was 85%, and the random match probability was as low as 0.53%. We support previous findings on both high levels of genetic diversity in the Serbian population and patterns of genetic differentiation among this and ten studied European populations. However, our high-resolution data supported more pronounced genetic differentiation among Serbians and two Slavic populations (Russians and Poles) as well as expansion of the Serbian population after the Last Glacial Maximum and during the Migration period (fourth to ninth century A.D.), as inferred from the Bayesian skyline analysis. Phylogenetic analysis of haplotypes found in Serbians contributed towards the improvement of the worldwide mtDNA phylogeny, which is essential for the interpretation of the mtDNA casework.

Stature and education among Roma women: taller stature is associated with better educational and economic outcomes.

The association between body height and educational outcome, as measured by years of completed schooling, was investigated among Roma women in Serbia in 2014-2018. Height, demographic data, level of schooling and reproductive histories were collected from 691 Roma women aged between 16 and 80 years living in rural settlements in central and western Serbia. Multinomial logistic regression analysis showed that short stature was associated with an increased risk of low education, possibly as a result of poor growth and developmental disadvantage in early life. Roma cultural practices were also shown to influence the school achievement of these Roma girls: in addition to height, education was positively associated with a higher bride price and better socioeconomic status, as acquired through marriage. For Roma women, height might influence not only their level of education but also their lifetime prospects.

Perceived Skill and Willingness to Address Child Sexual Abuse: Assessing Serbian and Montenegrin Pediatricians.

Most research on pediatricians' reporting of child sexual abuse (CSA) is based in western countries. Only recently have studies focused on low-income countries. We are the first to survey pediatricians in Serbia and Montenegro on their encounters, competence and beliefs regarding CSA. Pediatricians in Serbia (n = 358) were recruited during a professional conference; pediatricians in Montenegro (n = 121) were sent an online survey. Demographic information was not obtained. Frequencies and percentages were calculated. A quarter of pediatricians in both countries felt competent detecting medical evidence of CSA. Twenty-seven percent in Serbia and 7% in Montenegro felt adequately trained to assess and diagnose CSA. Forty percent believed that CSA occurs predominately in poor, unstable or disorganized families. Twenty-nine percent in Montenegro and 15% in Serbia believed that complete strangers perpetrate CSA. Both Serbian (23%) and Montenegrin (30%) pediatricians were uncomfortable asking questions about possible abuse. One third of pediatricians in both countries were interested in further training. CSA is underreported at a concerning rate in Serbia and Montenegro, yet only a third of pediatricians in both countries were interested in further training. Future studies should focus on barriers to reporting in these regions, to increase awareness and competencies related to CSA.

John Henryism, Gender and Self-reported Health Among Roma/Gypsies in Serbia.

We describe how self-reported health (SRH) varies with gender and John Henryism (a strong behavioral predisposition to engage in high-effort coping to overcome adversity) in a low income sample of Serbian Roma. Data were collected in 2016 in several Roma settlements around Belgrade, Serbia. The sample consisted of 90 men and 112 women. In addition to John Henryism (JH), measured by a Serbian version of the John Henryism Scale, demographic data and data on SRH and family relationships dynamics were collected. SRH was positively correlated with age and JH, and negatively correlated with a history of chronic disease. Roma males and females differed significantly on JH and a number of other variables. For Roma women, multiple regression analyses revealed that a history of chronic disease, unemployment, age and daily stress level were negatively associated with SRH, while JH, SES and harmonious relationships with one's family/children were positively associated with SRH. For Roma men, there was no association between JH and SRH, but older age, being on welfare, a diagnosis of hypertension and extended family disputes were associated with poorer SRH. Hence, despite economic disadvantage and social exclusion from mainstream society, some Roma report good health and the ability to cope actively with economic disadvantage and social exclusion. This study adds to the literature on the cross-cultural relevance of JH theory for understanding health variations within socially and economically marginalized populations.

[Psychiatric and Psychotherapeutic Care of Refugees by Reference of a Large Psychiatric Care Hospital in Western Germany]. / Psychiatrisch-psychotherapeutische Versorgung von Geflüchteten am Beispiel eines großen psychiatrischen Versorgungskrankenhauses im Rheinland.

Medical and psychological care of refugees is among the most important current challenges in German health politics. Work with patients from this heterogeneous group who have often faced severe stress before, during and after their migration is currently based on a thin data foundation. Based on introductory information on current knowledge concerning psychiatric morbidity of refugees this article presents the psychiatric care of refugees at LVR Clinics Cologne - a psychiatric specialty hospital situated in North Rhine-Westphalia, Germany. A sample of 239 cases of refugee patients who were referred to in- and outpatient departments of the LVR Clinics Cologne between April 2015 and March 2016 are evaluated in respect of diagnoses, admission modalities and socio-demographic variables. The majority of principal diagnoses (40.2%) belong to the group of stress-related and somatoform disorders (F4 in ICD-10). Mood disorders (F3 in ICD-10) represented 31.0%, followed by mental and behavioral disorders due to psychoactive substance use (F1 in ICD-10) with 15.1%. Posttraumatic Stress Disorder (PTSD) was the most prevalent diagnose (13.0%). Among the 29 countries of the patients' origin Afghanistan (10,0%), Serbia (9.6%) and Kosovo (8.8%) were the most abundant. The diagnoses and the high rate of acute psychiatric events reflect the massive psychological pressure of the patients. The important role of interpreters and mediators specialized in language and integration in the treatment process is emphasized.

Cross-cultural Measurement Equivalence of the KINDL Questionnaire for Quality of Life Assessment in Children and Adolescents.

This cross-cultural study aimed to assess whether Iranian and Serbian children, and also their parents, perceived the meaning of the items in the KINDL quality of life questionnaire consistently. The sample included 1086 Iranian and 756 Serbian children and adolescents, alongside 1061 and 618 of their parents, respectively. The ordinal logistic regression was used to assess differential item functioning (DIF) of the self and proxy-reports of the two versions of the KINDL, including Kid-KINDL and Kiddo-KINDL, across Iranian and Serbian samples. Statistically significant DIF was flagged for 14 out of 24 (58%) and 20 out of 24 (83%) items in the self-report of the Kid-KINDL and Kiddo-KINDL, respectively. Moreover, 20 out of 24 (83%) in the proxy reports of the both Kid-KINDL and Kiddo-KINDL, showed DIF across two samples. Accordingly, considerable caution is warranted when using the KINDL for cross-cultural comparisons.

A cross-cultural study to assess measurement invariance of the KIDSCREEN-27 questionnaire across Serbian and Iranian children and adolescents.

PURPOSE: The KIDSCREEN questionnaire for health-related quality of life (HRQOL) assessments in children and adolescents was simultaneously developed across 13 European countries, and it was subsequently translated and culturally adapted to over 30 different languages across the world. The aim of this study was to evaluate the measurement equivalence of the KIDSCREEN-27 across Serbian and Iranian children and adolescents. METHODS: The items in the KIDSCREEN-27 were analyzed for differential item functioning (DIF) across Iranian and Serbian populations using ordinal logistic regression with three different criteria. The sample included 330 Iranian and 329 Serbian children and adolescents and 330 and 314 of their parents, respectively. RESULTS: Across the two samples, DIF was detected in 16 (59 %) of 27 items in the child self-reports and in 20 (74 %) of 27 items in the parent/proxy report. However, using alternative criteria based on magnitude detected for DIF, only three items in the parent/proxy report showed significant DIF. CONCLUSION: Our study provided more evidence that the KIDSCREEN-27 possesses DIF items across different cultures, but their impact is probably small, and the questionnaire could be used for cross-cultural HRQOL comparisons.

Knowledge of, beliefs about, and perceived barriers to organ and tissue donation in Serbian, Macedonian, and Greek Orthodox communities in Australia.

CONTEXT: Despite the lifesaving benefits of organ and tissue donation, a worldwide shortage of suitable and registered donors exists. Although the reasons for this shortage are multifactorial, it has been recognized that distinct barriers to registration, family discussion, and consent that require targeted intervention and action are present among minority cultural, religious, and immigrant communities. OBJECTIVE: To explore the knowledge, attitudes, and beliefs of 3 orthodox religious communities in Australia (Macedonian, Greek, and Serbian Orthodox) and determine the implications for engaging with these communities to improve knowledge, attitudes, family discussion, and the ability to make an informed decision about donation. DESIGN: Qualitative approach using focus groups moderated by researchers and bicultural health workers with the assistance of accredited interpreters. PARTICIPANTS: 98 adult members of the Greek, Macedonian, and Serbian Orthodox communities in the Illawarra region of New South Wales, Australia. RESULTS: Clear barriers to discussing and making an informed decision about organ and tissue donation were identified. Knowledge of processes and procedures was low and discussion about death (and organ and tissue donation) with family members and loved ones was considered taboo. Despite these barriers, all 3 communities expressed a desire for more information and engagement. Of particular interest were the perspectives of 3 types of "experts": medical, religious, and other community members (who had experience with the organ and tissue donation system). Future programs designed for orthodox religious communities should consider the need for active strategies that facilitate information sharing and engagement between community members and these 3 types of experts.

Challenges in sexual and reproductive health of Roma people who live in settlements in Serbia.

OBJECTIVE: To investigate the differences in sexual and reproductive health (SRH) between Roma women of reproductive age who live in settlements and the general population of women of the same age in Serbia who do not live in settlements. METHODS: The Multiple Indicator Cluster Survey 4 (MICS4) was administered to Roma and Serbian women and the results were compared between the two groups. In order to get a qualitative perspective, a specifically designed, short open-ended questionnaire about Roma women was given to Roma Health Mediators (RHMs). RESULTS: Roma women have a higher total fertility rate and adolescent birth rate, and early marriage is much more common among them. Differences are less clear regarding antenatal care and assistance during delivery from skilled personnel. Roma women more frequently rely on traditional contraception, and are less likely to use modern contraceptives than the general female population. Problems in the socio-economic sphere, poor school enrolment and maintenance of traditional patterns in Roma people living in settlements contribute to the disparities observed. CONCLUSION: Although data on the SRH of the general population of women in Serbia are far from being satisfactory, those for women who live in Roma settlements are much worse. Political actions aimed at the empowerment of Roma women in the spheres of education, employment and health promotion have been implemented with the hope that they might improve the SRH of this vulnerable population group.

Parental knowledge, attitudes, and behaviors towards children with epilepsy in Belgrade (Serbia).

OBJECTIVE: The aim of our study was to assess knowledge, attitudes, and behaviors of parents whose children were diagnosed with epilepsy. METHODS: This cross-sectional study included 213 consecutive parents who accompanied their children, diagnosed with epilepsy, at regular checkups in the outpatient department of the Child and Adolescent Neurology and Psychiatry Clinic in Belgrade. Data were obtained through a questionnaire before completion of the child's neurological checkup, while clinical parameters of children with epilepsy were taken from medical records. RESULTS: Almost all respondents knew that epilepsy is not an infectious disease (99.5%), while the least proportion of parents (31.9%) knew that epilepsy is not, for the most part, hereditary. Parents felt that their family and friends should know that their child is suffering from epilepsy (average score: 4.3 out of 5). Also, parents felt the most confident in taking care of their child during seizures (4.7 out of 5), while they felt the least confident in letting their child go on school trips for several days (3.4 out of 5). Parental longer schooling (i.e., higher education level) was an independent predictor of higher epilepsy knowledge. Taking less number of medications was an independent predictor of more supportive parental behavior towards children with epilepsy. CONCLUSION: Some epilepsy-related issues still require improvement in parental knowledge. Ensuring education and support at community and school levels for both parents and children with epilepsy should be the principal goal of health-care service.

Can 'we' share the contested territory with 'them'? Shared territorial ownership perceptions and reconciliation intentions in Kosovo.

Territorial ownership claims are central to many interethnic conflicts and can constitute an obstacle to conflict resolution and reconciliation. However, people in conflict areas might also have a perception that the territory simultaneously belongs to one's ingroup and the rival outgroup. We expected such perceptions of shared ownership to be related to higher reconciliation intentions. We examined this expectation in relation to the territory of Kosovo among random national samples of Albanians and Serbs from Kosovo, and Serbs from Serbia (Study 1, total N = 995). In general, participants perceived low levels of shared ownership, however, shared ownership perceptions were positively related to reconciliation intentions in Kosovo. In Study 2 (total N = 375), we experimentally manipulated shared ownership (vs. ingroup ownership) and found that shared ownership elicited stronger reconciliation intentions. It is concluded that fostering a sense of shared ownership can be important for improving intergroup relations in post-conflict settings.

Possible genetic heterogeneity of spinocerebellar ataxia linked to chromosome 15.

Autosomal dominant spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative disorders. We investigated an SCA family from Serbia of Roma ethnic origin; four affected and nine unaffected family members underwent a detailed neurological examination. The presenting symptom in all patients was gait unsteadiness in early adulthood. Additional features included pyramidal signs, depression, and cognitive impairment. The condition follows an autosomal dominant pattern of inheritance. After excluding repeat expansions in nine known SCA genes, a genome-wide linkage analysis with 412 microsatellite markers localized the putative disease gene to a 40.7 cM (42.5 Mb) region on chromosome 15q between markers D15S1006 and D15S116. The maximum model-based multipoint LOD score was 1.75. This region is only 4.3 Mb away from the SCA11 (TTBK2) gene. Accordingly, mutations in TTBK2 were not found, suggesting a second SCA gene on chromosome 15q as cause of this novel form of SCA. In addition, we excluded alterations in two candidate genes in the linked region, namely expansion of a polyglutamine-coding CAG repeat in ARID3B and mutations in SEMA6D.

In vivo evaluation of CYP2A6 and xanthine oxidase enzyme activities in the Serbian population.

PURPOSE: The main aim of the study was to investigate the distribution of cytochrome P450 2A6 (CYP2A6) and xanthine oxidase (XO) enzyme activities in the Serbian population. Secondly, we tested the influence of genetics (CYP2A6 polymorphism), sex, and cigarette smoking on both enzymes. METHODS: One hundred forty healthy Serbian volunteers were genotyped for common CYP2A6 alleles. In 100 of them, CYP2A6 and XO activities were determined by the urinary 17U/17X and 1U/(1U + 1X) ratios, respectively, after oral administration of 100 mg caffeine as a probe. RESULTS: A 21-fold variation in the 17U/17X ratio was observed (range: 0.49-10.28, mean = 1.65, 95% CI: 1.49-1.83). The urinary 1U/(1U + 1X) ratios displayed four-fold variation, ranging from 0.17 to 0.71 (mean = 0.43, 95% CI: 0.41-0.45). CYP2A6 alleles *1A, *1B1, *9, *4 and *1B1x2 were found with frequencies of 0.579, 0.307, 0.082, 0.029, and 0.004 respectively. CYP2A6*5 was not detected. CYP2A6 genotype influenced interindividual variability in CYP2A6 enzyme activity (P = 0.04). Cigarette smoking inhibited CYP2A6 enzyme activity (P = 0.02), but had no effect on activity of XO (P = 0.16).There was no significant difference between men and women in terms of CYP2A6 or XO activity. CONCLUSIONS: Serbs displayed interindividual variations in CYP2A6 activity. CYP2A6 genotype and cigarette smoking, but not sex, influenced CYP2A6 enzyme activity. Unimodal distribution of XO enzyme activity in Serbs implies the absence of subjects with low enzyme activity in this population. XO activity is not influenced by sex or cigarette smoking.

Polymorphisms of the prion protein gene (PRNP) in a Serbian population.

Prion diseases are a group of etiologically heterogeneous neurodegenerative disorders. We have analyzed the coding region of PRNP gene in 121 healthy citizens of Serbia to determine whether the frequencies of M129V, E219K, and octapeptide repeat number polymorphism. For Serbian population, polymorphism of PRNP gene at codon 129 does not differ from healthy European populations. Also codon 219 is monomorphic for the Glu allele both in Serbian population and other European populations. On the contrary, in Serbian population we did not detect any deletions or insertions in octapeptide repeat region, whereas deletions were detected in other European populations.

Schizophrenia and apolipoprotein E gene polymorphism in Serbian population.

Apolipoprotein E (APOE) gene variants are associated with alterations in brain function and increased risk of Alzheimer's disease (AD) and conflicting results have been reported in schizophrenia. Our results showed no significant differences in APOE allele or genotype frequencies between the Serbian schizophrenic patients and control individuals. However, we observed a possible association between particular subtypes of schizophrenia and APOE epsilon3/epsilon3 genotype (p = .01221) and epsilon4 allele showed a tendency toward positive association with responding to typical neuroleptics. APOE genotypes have no major influence on risk of schizophrenia, treatment and response to conventional antipsychotics, and age of onset in schizophrenia.

Elevated risk of myocardial infarction in very young immigrants from former Yugoslavia.

We performed a hospital based case-control study to assess if the risk of myocardial infarction at a very young age (< or =40 years) was elevated in immigrants from the region of former Yugoslavia. Patients were classified as "exposed" if they or both their parents were born in former Yugoslavia. Consecutive myocardial infarction patients were recruited in the immediate post-infarction period from two Viennese hospitals over a 3.5-year period. Control patients free of myocardial infarction were frequency matched on age, gender, centre, and time in an approximate 1:2 ratio. Logistic regression was used for the assessment of an association between Yugoslavian descent and myocardial infarction. Overall, we recruited 102 myocardial infarction patients and 200 controls. The median age of infarction patients was 37.3 years. Yugoslavian descent was strongly associated with myocardial infarction (crude OR 7.3, 95% CI 3-18). This association was attenuated after multivariate adjustment (OR 3.9, 95% CI 1.2-13) but remained statistically significant. Using Miettinen's formula for population attributable risk, we calculated that between 15.3% (adjusted) and 17.8% (unadjusted) of myocardial infarction cases in very young patients could be attributable to immigrants from the studied region. In conclusion, we found that the risk of developing myocardial infarction at a young age is elevated in immigrants from the region of former Yugoslavia and their offspring. Even though residual confounding cannot be ruled out definitively, this risk seems to be independent of established cardiovascular risk factors.

Migrants' perceptions of using interpreters in health care.

BACKGROUND: The number of foreign-born people who do not share a common language has increased due to extensive international migration, which will increase in the future. There is limited knowledge about the users' perceptions of interpreters in health care. AIM: To describe how individuals from former Yugoslavia, living in Sweden, perceived the use of interpreters in Swedish healthcare services. METHOD: A phenomenographic approach was employed. Data were collected by semi-structured interviews during 2006-2007 with 17 people, aged 29-75 years, from former Yugoslavia, living in Sweden. FINDINGS: Three descriptive categories were identified: (1) prerequisites for good interpretation situations; (2) the interpretation situation - aspects of satisfaction or dissatisfaction; and (3) measures to facilitate and improve the interpreter situation. The interpreter's competence, attitude, appearance and an appropriate environment are important prerequisites for interpretation. The interpreter was perceived as being a communication aid and a guide in the healthcare system in terms of information and practical issues, but also as a hindrance. A desirable professional interpreter was perceived as highly skilled in medical terminology and language, working in face-to-face interaction. CONCLUSION: Using an interpreter was perceived as a hindrance, though also needed in communication with healthcare staff and as a guide in the healthcare system. Face-to-face interaction was preferred, with the interpreter as an aid to communication. As part of individual care planning it is important to use interpreters according to the patients' desires. Healthcare organizations and guidelines for interpreters need to be developed in order for patients to have easy access to highly skilled professional interpreters.

The sequencing and interpretation of the genome obtained from a Serbian individual.

Recent genetic studies and whole-genome sequencing projects have greatly improved our understanding of human variation and clinically actionable genetic information. Smaller ethnic populations, however, remain underrepresented in both individual and large-scale sequencing efforts and hence present an opportunity to discover new variants of biomedical and demographic significance. This report describes the sequencing and analysis of a genome obtained from an individual of Serbian origin, introducing tens of thousands of previously unknown variants to the currently available pool. Ancestry analysis places this individual in close proximity to Central and Eastern European populations; i.e., closest to Croatian, Bulgarian and Hungarian individuals and, in terms of other Europeans, furthest from Ashkenazi Jewish, Spanish, Sicilian and Baltic individuals. Our analysis confirmed gene flow between Neanderthal and ancestral pan-European populations, with similar contributions to the Serbian genome as those observed in other European groups. Finally, to assess the burden of potentially disease-causing/clinically relevant variation in the sequenced genome, we utilized manually curated genotype-phenotype association databases and variant-effect predictors. We identified several variants that have previously been associated with severe early-onset disease that is not evident in the proband, as well as putatively impactful variants that could yet prove to be clinically relevant to the proband over the next decades. The presence of numerous private and low-frequency variants, along with the observed and predicted disease-causing mutations in this genome, exemplify some of the global challenges of genome interpretation, especially in the context of under-studied ethnic groups.