Retraction: Five papers from Open Access Maced J Med Sci. Vol. 7 No. 18 (2019): Sep 30 (Global Dermatology).

Editor-in-Chief has retracted the following articles from the special issue Vol. 7 No. 18 (2019): Sep 30 (Global Dermatology): (1) DNA Waves and Their Applications in Biology - Massimo Fioranelli et al. - Open Access Macedonian Journal of Medical Sciences (2019) - DOI: 10.3889/oamjms.2019.767; (2) Recovery of Brain in Chick Embryos by Growing Second Heart and Brain - Massimo Fioranelli et al. - Open Access Macedonian Journal of Medical Sciences (2019) - DOI: 10.3889/oamjms.2019.777; (3) A Mathematical Model for the Signal of Death and Emergence of Mind Out of Brain in Izhikevich Neuron Model - Massimo Fioranelli et al. - Open Access Macedonian Journal of Medical Sciences (2019) - DOI: 10.3889/oamjms.2019.774; (4) A Black Hole at the Center of Earth Plays the Role of the Biggest System of Telecommunication for Connecting DNAs, Dark DNAs and Molecules of Water on 4+N- Dimensional Manifold - Massimo Fioranelli et al. - Open Access Macedonian Journal of Medical Sciences (2019) - DOI: 10.3889/oamjms.2019.776 (5) New System Delivering Microwaves Energy for Inducing Subcutaneous Fat Reduction: In - Vivo Histological and Ultrastructural Evidence - Nicola Zerbinati et al., Open Access Macedonian Journal of Medical Sciences (2019) - DOI: 10.3889/oamjms.2019.778. An internal investigation has raised sufficient evidence that they are not directly connected with the special issue Global Dermatology and contain inconsistent results. As such, we retract these articles from the literature and by guidelines and best editorial practices from the Committee on Publication Ethics. We apologize to our audience about this unfortunate situation.

Retraction: Singhal R, Rai B. sTNF-R Levels: Apical Periodontitis Linked to Coronary Heart Disease. Open Access Maced J Med Sci. 2017; 5(1):68-1.

[This retracts the article on p. 68 in vol. 5, PMID: 28293320.].

Vascular Genetic Variants and Ischemic Stroke Susceptibility in Albanians from the Republic of Macedonia.

BACKGROUND: Acute first-ever ischemic stroke (FIS) is a heterogeneous, polygenic disorder. The contribution of vascular genetic variants as inherited causes of ischemic stroke has remained controversial. AIM: To examine the association of genetic variants in vascular factors with the occurrence of FIS. MATERIAL AND METHODS: The current research was performed in a group of 39 patients with FIS (study group) and 102 healthy volunteers (control group). We analyzed the prevalence of vascular genetic variants in following genes: factor V, prothrombin, methylenetetrahydrofolate reductase (MTHFR), factor XIII, plasminogen activator 1, endothelial protein C receptor (EPCR), apolipoprotein B, apolipoprotein E, ß-fibrinogen, human platelet antigen 1, angiotensin-converting enzyme (ACE), endothelial nitric oxide synthase (eNOS) and lymphotoxin alpha. RESULTS: It was found that heterozygous LTA 804C>A and FXIII V34L Leu/Leu were significantly more frequent in patients with FIS than in control group (p = 0.036 and p = 0.017, respectively). The frequency of FXIII V34L Val/Val was significantly lower in patients with FIS than in control group (p = 0.020). Other frequencies of vascular gene variants in patients with FIS and in control group were not significantly different. CONCLUSIONS: This is the first comprehensive study to present data indicating that polymorphism of vascular genes in the prevalence of acute FIS exists in the Albanian population from the Republic of Macedonia. Variations in these genes have been detected in patients with acute FIS, suggesting that their combination might act in a susceptible or protective manner in this Albanian population.

How to Recognize and Avoid Potential, Possible, or Probable Predatory Open-Access Publishers, Standalone, and Hijacked Journals.

INTRODUCTION AND AIM: The Internet has enabled an easy method to search through the vast majority of publications and has improved the impact of scholarly journals. However, it can also pose threats to the quality of published articles. New publishers and journals have emerged so-called open-access potential, possible, or probable predatory publishers and journals, and so-called hijacked journals. It was our aim to increase the awareness and warn scholars, especially young researchers, how to recognize these journals and how to avoid submission of their papers to these journals. METHODS: Review and critical analysis of the relevant published literature, Internet sources and personal experience, thoughts, and observations of the authors. RESULTS: The web blog of Jeffrey Beall, University of Colorado, was greatly consulted. Jeffrey Beall is a Denver academic librarian who regularly maintains two lists: the first one, of potential, possible, or probable predatory publishers and the second one, of potential, possible, or probable predatory standalone journals. Aspects related to this topic presented by other authors have been discussed as well. CONCLUSION: Academics should bear in mind how to differentiate between trustworthy and reliable journals and predatory ones, considering: publication ethics, peer-review process, international academic standards, indexing and abstracting, preservation in digital repositories, metrics, sustainability, etc.

How to Verify Plagiarism of the Paper Written in Macedonian and Translated in Foreign Language?

AIM: The aim of this study was to show how to verify plagiarism of the paper written in Macedonian and translated in foreign language. MATERIAL AND METHODS: Original article "Ethics in Medical Research Involving Human Subjects", written in Macedonian, was submitted as an assay-2 for the subject Ethics and published by Ilina Stefanovska, PhD candidate from the Iustinianus Primus Faculty of Law, Ss Cyril and Methodius University of Skopje (UKIM), Skopje, Republic of Macedonia in Fabruary, 2013. Suspected article for plagiarism was published by Prof. Dr. Gordana Panova from the Faculty of Medical Sciences, University Goce Delchev, Shtip, Republic of Macedonia in English with the identical title and identical content in International scientific on-line journal "SCIENCE & TECHNOLOGIES", Publisher "Union of Scientists - Stara Zagora". RESULTS: Original document (written in Macedonian) was translated with Google Translator; suspected article (published in English pdf file) was converted into Word document, and compared both documents with several programs for plagiarism detection. It was found that both documents are identical in 71%, 78% and 82%, respectively, depending on the computer program used for plagiarism detection. It was obvious that original paper was entirely plagiarised by Prof. Dr. Gordana Panova, including six references from the original paper. CONCLUSION: Plagiarism of the original papers written in Macedonian and translated in other languages can be verified after computerised translation in other languages. Later on, original and translated documents can be compared with available software for plagiarism detection.

Genomic Imprinting.

BACKGROUND: Genomic imprinting is the inheritance out of Mendelian borders. Many of inherited diseases and human development violates Mendelian law of inheritance, this way of inheriting is studied by epigenetics. AIM: The aim of this review is to analyze current opinions and options regarding to this way of inheriting. RESULTS: Epigenetics shows that gene expression undergoes changes more complex than modifications in the DNA sequence; it includes the environmental influence on the gametes before conception. Humans inherit two alleles from mother and father, both are functional for the majority of the genes, but sometimes one is turned off or "stamped" and doesn't show in offspring, that gene is imprinted. Imprinting means that that gene is silenced, and gene from other parent is expressed. The mechanisms for imprinting are still incompletely defined, but they involve epigenetic modifications that are erased and then reset during the creation of eggs and sperm. Genomic imprinting is a process of silencing genes through DNA methylation. The repressed allele is methylated, while the active allele is unmethylated. The most well-known conditions include Prader-Willi syndrome, and Angelman syndrome. Both of these syndromes can be caused by imprinting or other errors involving genes on the long arm of chromosome 15. CONCLUSIONS: Genomic imprinting and other epigenetic mechanisms such as environment is shown that plays role in offspring neurodevelopment and autism spectrum disorder.

Relative Citation Ratio of Top Twenty Macedonian Biomedical Scientists in PubMed: A New Metric that Uses Citation Rates to Measure Influence at the Article Level.

AIM: The aim of this study was to analyze relative citation ratio (RCR) of top twenty Macedonian biomedical scientists with a new metric that uses citation rates to measure influence at the article level. MATERIAL AND METHODS: Top twenty Macedonian biomedical scientists were identified by GoPubMed on the base of the number of deposited abstracts in PubMed, corrected with the data from previously published paper, and completed with the Macedonian biomedical scientists working in countries outside the Republic of Macedonia, but born or previously worked in the country. iCite was used as a tool to access a dashboard of bibliometrics for papers associated with a portfolio. RESULTS: The biggest number of top twenty Macedonian biomedical scientists has RCR lower than one. Only four Macedonian biomedical scientists have bigger RCR in comparison with those in PubMed. The most prominent RCR of 2.29 has Rosoklija G. RCR of the most influenced individual papers deposited in PubMed has shown the biggest value for the paper of Efremov D (35.19). This paper has the biggest number of authors (860). CONCLUSION: It is necessary to accept top twenty Macedonian biomedical scientists as an example of new metric that uses citation rates to measure influence at the article level, rather than qualification of the best Macedonian biomedical scientists.

Current Scientific Impact of Ss Cyril and Methodius University of Skopje, Republic of Macedonia in the Scopus Database (1960-2014).

AIM: The aim of this study was to analyze current scientific impact of Ss Cyril and Methodius University of Skopje, Republic of Macedonia in the Scopus Database (1960-2014). MATERIAL AND METHODS: Affiliation search of the Scopus database was performed on November 23, 2014 in order to identify published papers from the Ss Cyril and Methodius University of Skopje (UC&M), Republic of Macedonia. A total number of 3960 articles (3055 articles from UC&M, 861 articles from Faculty of Medicine, UC&M, and 144 articles from Faculty of Pharmacy, UC&M) were selected for analysis (1960-2014). SCImago Journal Rank (SJR), Source Normalized Impact per Paper (SNIP) and h-index were calculated from the Scopus database. RESULTS: The number of published papers was sharply increased with maximum of 379 papers in 2012 year. The largest number of papers has been published in Macedonian Journal of Medical Sciences, Journal of Molecular Structure, Lecture Notes in Computer Science, Acta Pharmecutica, and Macedonian Journal of Chemistry and Chemical Engineering. The biggest SJR and SNIP has journal Nephrology Dialysis Transplantation. First three places of the top ten authors belong to Dimirovski GM, Gavrilovska L, and Gusev M. Top three places based on Scopus h-index (total number of published papers) belong to Kocarev L, Stafilov T, and Polenakovic M. The majority of papers originate from UC&M, but significant numbers of papers are affiliated to Faculty of Medicine, Faculty of Pharmacy, and Institute of Chemistry as members of UC&M, as well as Macedonian Academy of Sciences and Arts. Articles are the most dominant type of documents followed by conference papers, and review articles. Medicine is the most represented subject. CONCLUSION: Officials of the Ss Cyril and Methodius University of Skopje should undertake more effective and proactive policies for journal publishers and their Editorial Boards in order to include more journals from UC&M in the Scopus database.

Total IgE Distribution in Food Allergy Suspected Patients in Republic of Macedonia (2001-2011).

BACKGROUND: IgE may be considered the hallmark of allergic disorders. It is easily detected in serum and can be measured as total IgE and as allergen-specific IgE. In fact, the serum IgE assay is used to diagnose an allergy. AIM: The aim of this study is to evaluate, investigate and present the distribution of total serum IgE levels, determined with UniCap system, in food-allergy suspected patients in a Republic of Macedonia. MATERIAL AND METHODS: In this study we analyzed retrospectively 8898 consecutive patients that were admitted for allergy testing at the Institute of Immunobiology and Human Genetics during the ten year period between 01.01.2001 and 01.01.2011. Total IgE levels in patient sera were detected with the in vitro system UniCAP100 (Pharmacia, Uppsala, Sweden). RESULTS: When we analyzed the number of patients according to the total IgE groups, we noted that most of the patients have normal levels of total IgE in serum. However, we also discovered a group of patients with elevated levels of total IgE that are greater than 200 kU/L. The average concentration of total serum IgE is higher in women in the age group 6 (6-7 years), followed by a steep decrease in the age group 9 (9-10 years), and after that the average concentrations of total IgE were mostly constant with the exception of a partial increase in the age group 21 (65-69 years). For men, the average serum concentrations of total IgE were highest in the age group of 6 (6-7 years), which was significantly higher than the average concentrations of total IgE in all other age groups. CONCLUSION: The large number of enrolled patients, a particular strength of this study, revealed that average concentrations of total IgE in men are higher than in women and that total IgE did not decrease with age. On the contrary, increased total IgE levels were found in patients aged 65 and 69 of both genders. We continue our work with analyses of the specific IgE antibodies values toward food and the correlation with total IgE values.

The Effect of Combined Therapy ICS/LABA and ICS/LABA plus Montelukast in Patients with Uncontrolled Severe Persistent Asthma Based on the Serum IL-13 and FEV1.

BACKGROUND: IL-13 is one of many cytokines responsible for the chronic inflammation of asthma. AIM: The aim of this study was to determine the effect of combined therapy ICS/LABA and ICS/LABA plus Montelukast in patients with uncontrolled severe persistent asthma by analyzing of serum IL-13 and FEV1 before the treatment and after 6 months of therapy. MATERIAL AND METHODS: In study we included two groups. First group with 27 patients were treated with ICS/LABA. Second group with 29 patients were treated with ICS/LABA plus Montelukast. In each of them were measured serum IL-13 levels by the ELISA method and FEV1 before and after 6 months of treatment. Results were statistically analyzed according to the Wilcoxon Pairs Test and T-test. RESULTS: The obtained results in both groups showed that the serum IL-13 before the start of therapy were much higher and after 6 months of treatment significantly reduces their value, which in the second group were more expressed. The difference in the average value of FEV1 in both groups before and after therapy was statistically significant. CONCLUSION: Treatment with ICS/LABA plus Montelukast proved superior compared to therapy of ICS/LABA in patients with uncontrolled severe persistent asthma and allows achievement of well controlled of asthma with subjective clinical improvement.

Current biomedical scientific impact (2013) of institutions, academic journals and researchers in the Republic of Macedonia.

AIM: To analyse current ranking (2013) of institutions, journals and researchers in the Republic of Macedonia. MATERIAL AND METHODS: the country rankings of R. Macedonia were analyzed with SCImago Country & Journal Rank (SJR) for subject area Medicine in the years 1996-2013, and ordered by H-index. SCImago Institutions Rankings for 2013 was used for the scientific impact of biomedical institutions in the Republic of Macedonia. Journal metrics from Elsevier for the Macedonian scholarly journals for the period 2009-2013 were performed. Source Normalized Impact per Paper (SNIP), the Impact per Publication (IPP), and SCImago Journal Rank (SJR) were analysed. Macedonian scholarly biomedical journals included in Google Scholar metrics (2013, 2012) were analysed with h5-index and h5-median (June 2014). A semantic analysis of the PubMed database was performed with GoPubMed on November 2, 2014 in order to identify published papers from the field of biomedical sciences affiliated with the country of Macedonia. Harzing's Publish or Perish software was used for author impact analysis and the calculation of the Hirsh-index based on Google Scholar query. RESULTS: The rank of subject area Medicine of R. Macedonia according to the SCImago Journal & Country Rank (SJR) is 110th in the world and 17th in Eastern Europe. Of 20 universities in Macedonia, only Ss Cyril and Methodius University, Skopje, and the University St Clement of Ohrid, Bitola, are listed in the SCImago Institutions Rankings (SIR) for 2013. A very small number of Macedonian scholarly journals is included in Web of Sciences (2), PubMed (1), PubMed Central (1), SCOPUS (6), SCImago (6), and Google Scholar metrics (6). The rank of Hirsh index (h-index) was different from the rank of number of abstracts indexed in PubMed for the top 20 authors from R. Macedonia. CONCLUSION: The current biomedical scientific impact (2013) of institutions, academic journals and researchers in R. Macedonia is very low. There is an urgent need for organized measures to improve the quality and output of institutions, scholarly journals, and researchers in R. Macedonia in order to achieve higher international standards.

Killer cell immunoglobulin-like receptor genes in four human West Nile virus infections reported 2011 in the Republic of Macedonia.

West Nile virus (WNV) is a neurotropic, arthropod-borne flavivirus that is maintained in an enzootic cycle between mosquitoes and birds, but can also infect and cause disease in horses and humans. The aim of this study was to examine KIR gene polymorphisms by determining the frequencies of 16 KIR genes and pseudogenes and KIR genotypes in Macedonian patients with West Nile virus infection, and to compare with healthy Macedonians. The studied sample consists Republic of Macedonia, hospitalized at the University Clinic of Infective Diseases between September 2011 and October 2011, and reported through WHO. For KIR genotyping, commercially available PEL-FREEZ KIR genotyping SSP kit (Dynal Biotech, Brown Deer, WI) was used. The population genetics analysis package, Arlequin, was used for analysis of the data. We found that all 16 KIR genes were observed in the studied individuals and framework genes (KIR3DL3, KIR3DP1, KIR2DL4, and KIR3DL2) were present in all individuals. Comparison of KIR frequencies between Macedonian patients with West Nile virus infection and healthy Macedonian population reveals several significant differences in the inhibitory group (KIR2DL2), and in the non inhibitory group (KIR2DS1, KIR2DS2, KIR2DS5, and KIR3DS1). The single most frequent genotypes in the Bx group were genotypes ID71 and ID89 with statistically significant difference compared to healthy Macedonians. Our results suggest that specific KIR genotypes could be connected with West Nile virus infection.

Distribution of 22 cytokine gene polymorphisms in Roma from the Republic of Macedonia.

The aim of this study was to analyze 22 cytokine polymorphisms in the Roma population from the Republic of Macedonia. The Roma population consists of 77 healthy unrelated individuals, residents of different geographical regions of the Republic of Macedonia (Skopje, Gostivar, and Kochani). Blood samples were collected after obtaining written consent. DNA was isolated from peripheral blood and 22 polymorphisms were typed: IL1A -889, IL1B -511, IL1B +3962, IL1R pst1 1970, IL1RN mspa11100, IL4RA +1902, IL12 -1188, IFNG utr5644, TGF-ß1 cdn10, TGF-ß1 cdn25, TNF-α -308, TNF-α -238, IL-2 -330, IL-2 +166, IL-4 -1098, IL-4 -590, IL-4 -33, IL-6 -174, IL-6 565, IL-10 -1082, IL-10 -819, and IL-10 -592. Cytokine genotyping was performed by PCR-SSP. The population genetics analysis package, PyPop, was used for analysis of the cytokine data. Fnd was negative and significantly different from 0 for IL-4 -590 (p of F=0.006), IL-10 -1082 (p of F=0.010), IFN utr5644 (p of F=0.024), IL-4 -1098 (p of F=0.026) and TGF-1 cdn25 (p of F=0.001) alleles, as well as for IL-2 haplotypes (p=0.025). Several SNPs (IL-12B -1188, IL-2 -330, IL-4 -1098, IL-4 -590, and IL-10 -1082) were not in HWP (p<0.05). A few SNPs (IL-12B -1188, IL-2 -330, IL-4 -1098, IL-4 -590, and IL-10 -1082) and several observed frequencies of cytokine diplotypes (IL-2/GG:TG, IL-2/TG:TG, IL-4/GCC:GCC, IL-4/TTC:TTC, IL-4/TTT:TTC, IL-10/GCC:GCC, IL-10/ATA:GCC, IL-10/ACC:GCC, and IL-10/ACC:ATA) were not in HWP and were significantly different from the expectations. Hardy Weinberg proportion could not be calculated for TNF genotypes and diplotypes because nearly all genotypes and diplotypes belong to GG genotype or GG:GG diplotype. The results of cytokine polymorphisms in Roma population can be used for characterization of the current genetic profile of the Gypsies, anthropological comparisons, as well as for the association studies with different diseases.

IL10 -1082, IL10 -819 and IL10 -592 polymorphisms are associated with chronic periodontitis in a Macedonian population.

Genetic polymorphisms in the interleukin 10 (IL10) gene have been reported to influence the host response to microbial challenge by altering levels of cytokine expression. We analyzed nucleotide polymorphisms in the promoter region of the IL10 gene and its relation with periodontal disease in a Macedonian population. The study population consisted of 111 unrelated subjects with chronic periodontitis and 299 healthy controls. DNA was isolated and IL10 genotyping performed by PCR-SSP (Heidelberg kit) for the alleles and genotypes of IL10 -1082, IL10 -819 and IL10 -592. Frequencies of IL10 haplotypes and the haplotype zygotes were also examined. Comparisons between groups were tested using the Pearson's p-value. After Bonferroni adjustment, significant associations were detected between subjects with chronic periodontitis and IL10 genotypes (IL10 -1082/A:G was negative or protective and IL10 -1082/G:G was positive or susceptible). Cytokine polymorphism on the IL10 gene appears to be associated with susceptibility to chronic periodontitis in Macedonians.

Gene polymorphisms of 22 cytokines in Macedonian children with atopic dermatitis.

Atopic dermatitis (AD) is a common chronically relapsing skin disease associated with abnormal cytokine production, and activation of T-helper 2 cells. The aim if this study was to determine whether cytokine gene polymorphisms might influence the development of AD. Single nucleotide polymorphisms in the genes for I-L1alpha, IL-1beta, IL-1R, IL-2, IL-4, IL-6, IL-10, IL-12, TGF beta, TNF and IFNgamma were investigated by PCR and sequence specific primers in Macedonian patients with AD (67 children, age of 6 months to 5 years) and 301 normal unrelated individuals. Susceptible cytokine polymorphisms for AD for eleven genotypes (IL-4 -33/T:T IL-4 -1098/G:G, TGFbeta cdn25C:G, IL-4 -1098/T:T, IL-1alpha -889/C:T, IL-2 +166/T:T, IL-1beta -511/C:T, IL-12 -1188/C:T, IL-10 -1082/A:G, IL-1beta +3962/C:T, IFNgamma +874/A:T), five diplotypes, six haplotypes, and for alleles were found. Protective cytokine polymorphisms for AD for seven cytokine genotypes (IL-4 -1098/G:T, TGFbeta cdn25/G:G, IL-4 -33/C:C, IL-1alpha -889/C:C, IFNgamma +874/A:A, IL-10 -1082/A:A, IL-1beta -511/C:C), one cytokine diplotypes, two cytokine haplotypes, and four cytokine alleles were also found. We concluded that several cytokine polymorphisms are protective, or susceptible associated with AD in population of Macedonians.

IL4 gene polymorphisms and their relation to periodontal disease in a Macedonian population.

Genetic polymorphisms in the interleukin-4 (IL4) gene have been reported to influence the host response to microbial challenge by altering levels of cytokine expression. We analyzed nucleotide polymorphisms in the promoter region of the IL4 gene and its relation with periodontal disease in a Macedonian population. The study population consisted of 92 unrelated subjects with chronic periodontitis and 286 healthy controls. DNA was isolated and IL4 genotyping performed by polymerase chain reaction-single-strand polymorphism (Heidelberg kit) for the alleles and genotypes of IL4 -1098, IL4 -590, and IL4 -33. Frequencies of IL4 haplotypes and the haplotype zygotes were also examined. Comparisons between groups were tested using the Pearson's p value. After Bonferroni adjustment, significant associations were detected between subjects with periodontitis and the following: (1) cytokine alleles IL4 -1098 and IL4 -33; (2) cytokine genotypes IL4 -1098/G:T; IL4 -1098/T:T, and IL4 -33/T:T, (3) cytokine haplotypes IL4/GCC, IL4/TCC, and IL4/TTC; and (4) cytokine haplotype zygotes IL4/TTC: TCC, IL4/TCT:TTT, and IL4/GCC:TTC. Cytokine polymorphism on the IL4 gene appears to be associated with susceptibility to chronic periodontitis in Macedonians.

Distribution of killer cell immunoglobulinlike receptors in the Macedonian population.

The aim of this study was to analyze killer immunoglobulinlike receptor (KIR) gene polymorphism in the Macedonian population. The study sample consists of 214 healthy unrelated individuals, aged 20-35 years. All individuals are of Macedonian origin and nationality, and residents of different geographic regions. The population genetics analysis package, Arlequin, was used for analysis of the data. We found that all 16 KIR genes were observed in the Macedonian population and framework genes KIR3DL3, KIR2DL4, and KIR3DL2 were present in all individuals. A total of 56 different KIR genotypes were found in the Macedonian population, based on the presence of 16 KIR genes. Neighbor-joining phylogenetic tree, constructed on the basis of standard genetic distances of KIR genes, shows that Macedonian population is in the same cluster with England West Midlands Indian Asian, Brazil SouthEast Caucasian, Romania Caucasians, Spain Basque, England West Midlands Caucasian, France Reunion, and Spain Granada populations. The frequency of KIR loci in Macedonian population shares several general features with other Caucasoid populations studied before.

Family analysis of immunoglobulin classes and subclasses in children with autistic disorder.

Autistic disorder is a severe neurodevelopment disorder characterized by a triad of impairments in reciprocal social interaction, verbal and nonverbal communication, and a pattern of repetitive stereotyped activities, behaviours and interests. There are strong lines of evidence to suggest that the immune system plays an important role in the pathogenesis of autistic disorder. The aim of this study was to analyze quantitative plasma concentration of immunoglobulin classes, and subclasses in autistic patients and their families. The investigation was performed retrospectively in 50 persons with autistic disorder in the Republic of Macedonia. Infantile autistic disorder was diagnosed by DSM-IV and ICD-10 criteria. Plasma immunoglobulin classes (IgM, IgA, and IgG) and subclasses (IgG1, IgG2, IgG3, and IgG4) were determined using Nephelometer Analyzer BN-100. Multiple comparisons for the IgA variable have shown statistically significant differences between three pairs: male autistic from the fathers (p = 0,001), female autistic from the mothers (p = 0,008), as well as healthy sisters from the fathers (p = 0,011). Statistically significant differences found between three groups regarding autistic disorder (person with autistic disorder, father/mother of a person with autistic disorder, and brother/sister) independent of sex belongs to IgA, IgG2, and IgG3 variables. Multiple comparisons for the IgA variable have shown statistically significant differences between children with autistic disorder from the fathers and mothers (p < 0,001), and healthy brothers and sisters from the fathers and mothers (p < 0,001). Comparison between healthy children and children with autistic disorder from the same family should be tested for immunoglobulin classes and subclasses in order to avoid differences between generations.

Investigation of SERPINE1 genetic polymorphism in Macedonian patients with occlusive artery disease and deep vein thrombosis.

BACKGROUND: Raised SERPINE1 plasma levels are related to a 1-bp guanine deletion/insertion (4G5G) polymorphism in the promoter of the SERPINE1 (plasminogen activator inhibitor 1 - PAI1) gene. Evidence suggested that the plasma levels of SERPINE1 modulate the risk of coronary artery disease; furthermore, that the 4G5G polymorphism affects the expression of the SERPINE1 gene. AIM: To analyse association of SERPINE1 polymorphism with occlusive artery disease (OAD) and deep venous thrombosis (DVT) in Macedonians in order to investigate its role as a part of candidate genes in different vascular diseases in Macedonians. METHODS: Investigated groups consisted of 82 healthy patients, 75 with OAD, and 66 with DVT. Blood samples were collected after written informed consent was obtained, and DNA was isolated from peripheral blood leukocytes. Identification of SERPINE1 polymorphism was done with CVD StripAssay (ViennaLab, Labordiagnostica GmbH, Austria). The population genetics analysis package, PyPop, was used for analysis of the SERPINE1 data. Pearson's P-values, crude odds ratio and Wald's 95% CI were calculated with Bonferroni corrected p value. RESULTS: The frequency of 4G allele for SERPINE1 was 0.538 for DVT, 0.555 for healthy participants, and 0.607 for OAD. The frequency of 5G allele for SERPINE1 was the smallest in patients with OAD (0.393) and was higher in healthy participants (0.445), and patients with DVT (0.462). Test of neutrality (Fnd) showed negative value, but was significantly different from 0 for SERPINE1 in healthy participants (p of F = 0.041) and in patients with DVT (p of F = 0.030). SERPINE1 genotypes in healthy participants and patients with OAD were not in Hardy Weinberg proportions (p = 0.019 and 0.001, respectively). No association between SERPINE1 polymorphisms and OAD or DVT was found. CONCLUSION: There is no significant relationship between SERPINE1 polymorphisms and occlusive artery disease or deep venous thrombosis in Macedonian population.