Publications by authors named "Marko Pavlovic"

45 Publications

Association of polygenic risk scores, traumatic life events and coping strategies with war-related PTSD diagnosis and symptom severity in the South Eastern Europe (SEE)-PTSD cohort.

J Neural Transm (Vienna) 2021 Nov 27. Epub 2021 Nov 27.

Department of Psychiatry, University Clinical Center, Sarajevo, Bosnia and Herzegovina.

Objectives: Posttraumatic stress disorder (PTSD) is triggered by extremely stressful environmental events and characterized by high emotional distress, re-experiencing of trauma, avoidance and hypervigilance. The present study uses polygenic risk scores (PRS) derived from the UK Biobank (UKBB) mega-cohort analysis as part of the PGC PTSD GWAS effort to determine the heritable basis of PTSD in the South Eastern Europe (SEE)-PTSD cohort. We further analyzed the relation between PRS and additional disease-related variables, such as number and intensity of life events, coping, sex and age at war on PTSD and CAPS as outcome variables.

Methods: Association of PRS, number and intensity of life events, coping, sex and age on PTSD were calculated using logistic regression in a total of 321 subjects with current and remitted PTSD and 337 controls previously subjected to traumatic events but not having PTSD. In addition, PRS and other disease-related variables were tested for association with PTSD symptom severity, measured by the Clinician Administrated PTSD Scale (CAPS) by liner regression. To assess the relationship between the main outcomes PTSD diagnosis and symptom severity, each of the examined variables was adjusted for all other PTSD related variables.

Results: The categorical analysis showed significant polygenic risk in patients with remitted PTSD and the total sample, whereas no effects were found on symptom severity. Intensity of life events as well as the individual coping style were significantly associated with PTSD diagnosis in both current and remitted cases. The dimensional analyses showed as association of war-related frequency of trauma with symptom severity, whereas the intensity of trauma yielded significant results independently of trauma timing in current PTSD.

Conclusions: The present PRS application in the SEE-PTSD cohort confirms modest but significant polygenic risk for PTSD diagnosis. Environmental factors, mainly the intensity of traumatic life events and negative coping strategies, yielded associations with PTSD both categorically and dimensionally with more significant p-values. This suggests that, at least in the present cohort of war-related trauma, the association of environmental factors and current individual coping strategies with PTSD psychopathology was stronger than the polygenic risk.
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http://dx.doi.org/10.1007/s00702-021-02446-5DOI Listing
November 2021

Stimuli-Responsive Aggregation of High Molar Mass Poly(N,N-Diethylacrylamide)-b-Poly(4-Acryloylmorpholine) in Tetrahydrofuran.

Macromol Rapid Commun 2021 Nov 15:e2100656. Epub 2021 Nov 15.

School of Chemistry, University of Glasgow, Glasgow, G12 8QQ, UK.

The self-assembly of block copolymers constitutes a timely research area in polymer science with implications for applications like sensing or drug-delivery. Here, the unprecedented aggregation behavior of high molar mass block copolymer poly(N,N-diethylacrylamide)-b-poly(4-acryloylmorpholine) (PDEA-b-PAM) (M >400 kg mol ) in organic solvent tetrahydrofuran (THF) is investigated. To elucidate the aggregation, dynamic light scattering, cryo-transmission electron microscopy, and turbidimetry are employed. The aggregate formation is assigned to the unprecedented upper critical solution temperature behavior of PAM in THF at elevated concentrations (> 6 wt.%) and high molar masses. Various future directions for this new thermo-responsive block copolymer are envisioned, for example, in the areas of photonics or templating of inorganic structures.
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http://dx.doi.org/10.1002/marc.202100656DOI Listing
November 2021

Facile Monitoring of Water Hardness Levels Using Responsive Complex Emulsions.

Anal Chem 2021 07 2;93(27):9390-9396. Epub 2021 Jul 2.

Department of Colloid Chemistry, Max Planck Institute of Colloids & Interfaces, Am Muehlenberg 1, Potsdam 14476, Germany.

The cationic content of water represents a major quality control parameter that needs to be followed by a rapid, on-site, and low-cost method. Herein, we report a novel method for a facile monitoring of the mineral content of drinking water by making use of responsive complex emulsions. The morphology of biphasic oil-in-water droplets solely depends on the balance of interfacial tensions, and we demonstrate that changes in the surfactant effectiveness, caused by variations in the mineral content inside the continuous phase, can be visualized by monitoring internal droplet shapes. An addition of metal cations can significantly influence the surfactant critical micelle concentrations and the surface excess values and therefore induce changes in the effectiveness of ionic surfactants, such as sodium dodecyl sulfate. The morphological response of Janus emulsions droplets was tracked via a simple microscopic setup. We observed that the extent of the droplet response was dependent on the salt concentration and valency, with divalent cations (responsive for water hardness), resulting in a more pronounced response. In this way, Ca and Mg levels could be quantitatively measured, which we showcased by determination of the mineral content of commercial water samples. The herein demonstrated device concept may provide a new alternative rapid monitoring of water hardness levels in a simple and cost-effective setup.
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http://dx.doi.org/10.1021/acs.analchem.1c00868DOI Listing
July 2021

The true colours of the Formidable Pygmy Grasshopper ( Günther, 1974) from the Sava region (Madagascar).

Zookeys 2021 7;1042:41-50. Epub 2021 Jun 7.

University of Zagreb, Faculty of Science, Department of Biology, Division of Zoology, Evolution Lab, Rooseveltov trg 6, HR-10000 Zagreb, Croatia University of Zagreb Zagreb Croatia.

The Formidable Pygmy Grasshopper, Günther, 1974 (Tetrigidae: 'Malagasy Metrodorinae'), is certainly a stunning, extraordinary insect. Despite the fact that the species was described almost 50 years ago, its beauty had remained completely hidden until recently. The bright yellow colouration of the minute warts on its dorsal hump and even brighter purple-yellowish colouration of its abdomen have been, tragically, completely lost in museum specimens. Luckily, photographs of three live females taken in 2007, 2009 and 2015 were recently uploaded to the iNaturalist platform by the first author of this paper, where they were identified as by the middle and last authors. Along with a male and a female discovered in the MNHN collections (Paris) and the holotype female, these are the only records of the species. All six records are presented and depicted in the present study, and the variation of the species is discussed for the first time. This rare species seems to be endemic to NE Madagascar, a region of truly wonderful diversity.
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http://dx.doi.org/10.3897/zookeys.1042.66381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203595PMC
June 2021

Nanocomposite-based dual enzyme system for broad-spectrum scavenging of reactive oxygen species.

Sci Rep 2021 02 22;11(1):4321. Epub 2021 Feb 22.

MTA-SZTE Lendület Biocolloids Research Group, Interdisciplinary Excellence Centre, Department of Physical Chemistry and Materials Science, University of Szeged, 6720, Szeged, Hungary.

A broad-spectrum reactive oxygen species (ROS)-scavenging hybrid material (CASCADE) was developed by sequential adsorption of heparin (HEP) and poly(L-lysine) (PLL) polyelectrolytes together with superoxide dismutase (SOD) and horseradish peroxidase (HRP) antioxidant enzymes on layered double hydroxide (LDH) nanoclay support. The synthetic conditions were optimized so that CASCADE possessed remarkable structural (no enzyme leakage) and colloidal (excellent resistance against salt-induced aggregation) stability. The obtained composite was active in decomposition of both superoxide radical anions and hydrogen peroxide in biochemical assays revealing that the strong electrostatic interaction with the functionalized support led to high enzyme loadings, nevertheless, it did not interfere with the native enzyme conformation. In vitro tests demonstrated that ROS generated in human cervical adenocarcinoma cells were successfully consumed by the hybrid material. The cellular uptake was not accompanied with any toxicity effects, which makes the developed CASCADE a promising candidate for treatment of oxidative stress-related diseases.
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http://dx.doi.org/10.1038/s41598-021-83819-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900168PMC
February 2021

Cascade communication in disordered networks of enzyme-loaded microdroplets.

Chem Commun (Camb) 2021 Feb 18;57(13):1631-1634. Epub 2021 Jan 18.

Department of Colloid Chemistry, Max Planck Institute of Colloids and Interfaces, Am Muehlenberg 1, 14476 Potsdam, Germany.

A network of aqueous emulsion droplets that exhibits programmed and directional chemical inter-droplet communication is described. A non-reciprocal transfer of substrates between enzyme-containing aqueous emulsion droplets is realized by (biochemically) induced osmolarity gradients and concomitant concentration gradients are used to direct a multistep enzymatic cascade reaction across multiple droplets.
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http://dx.doi.org/10.1039/d0cc08310kDOI Listing
February 2021

Cockscomb-shaped twighopper, Cladonotus bhaskari sp. n., a new and rare pygmy grasshopper species from Sri Lanka (Orthoptera: Tetrigidae: Cladonotinae).

Zootaxa 2020 Jul 31;4821(2):zootaxa.4821.2.5. Epub 2020 Jul 31.

Auf der Hees 1, D-41849 Wassenberg, Germany.

The paper describes a new species of a Sri Lankan twighopper, genus Cladonotus Saussure, 1862 (Orthoptera: Tetrigidae: Cladonotini), C. bhaskari sp. n., based on a single female specimen collected and photographed by T. Kirschey in 2016 in Sinharaja rainforest (SW Sri Lanka). The new species is clearly distinguished from other species of the genus by its long and spine-like frontomedial projection and cockscomb-shaped promedial projection. Species of this genus resemble tiny twigs, hence the name 'twighopper'. Our new specimen is the first known female of the genus, and we also present the first photograph of the member of this genus in the natural habitat. An annotated identification key for the Cladonotus species is provided. Furthermore, we synonymize genus Hypsaeus Bolívar, 1887 syn. nov. with Hymenotes Westwood, 1837, based on the pronotal variability of the leaf-like pygmy grasshoppers in the Philippines and introduce one new combination-Hymenotes westwoodi (Bolívar, 1887) comb. nov..
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http://dx.doi.org/10.11646/zootaxa.4821.2.5DOI Listing
July 2020

Mental Health and Self-Esteem of Active Athletes.

Psychiatr Danub 2020 Sep;32(Suppl 2):236-243

Faculty of Health Studies, University of Mostar, 88000 Mostar, Bosnia and Herzegovina.

Introduction: Systematic and continuous physical exercise of certain intensity and volume is irreplaceable in the stages of growth and development and in preventing impairments of the biological, functional and health state of the human organism.Many studies show that physical exercise contributes to development and reinforcement of mental health and increases self-esteem. Examine mental health and self-esteem of active athletes.

Subjects And Methods: The subjects of the study are active athletes from Herzegovina and students of the Faculty of Health Studies in Mostar. Mental health and self-esteem were measured by a sociodemographic questionnaire, The Symptom Checklist-90 and the Satisfaction With Life Scale.

Results: There is a statistically significant difference in the frequency of exercise, active athletes have the highest percentage (100%) and state that they exercise often (almost every day) while university students have a significantly lower percentage (20%).Students scored significantly higher on the subscales for somatization, obsessive - compulsive symptoms, interpersonal vulnerability, depression, anxiety, aggression, phobia, and paranoia than active athletes. Active athletes have statistically higher scores for almost all the claims of the subjective assessment of life satisfaction.

Conclusion: Active athletes showed significantly less psychological symptoms and better mental health, greater life satisfaction and higher self-esteem than students of the Faculty of Health Studies in Mostar.
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September 2020

The story of the Malagasy devils (Orthoptera, Tetrigidae): in the north and sp. nov. in the south?

Zookeys 2020 10;957:1-15. Epub 2020 Aug 10.

University of Zagreb, Faculty of Science, Department of Biology, Division of Zoology, Evolution Lab, Rooseveltov trg 6, HR-10000, Zagreb, Croatia University of Zagreb Zagreb Croatia.

Madagascar is home to some of the largest and most colorful pygmy grasshoppers (Tetrigidae) in the world, known as 'Malagasy Metrodorinae'. Among them, Devil's pygmy grasshoppers (genus Bolívar, 1887) are unique in having two long spines on the back, which are modified internal lateral pronotal carinae. The genus was composed of two species - (Serville, 1838) and Rehn, 1929 , but here it is evidenced that the latter represents a junior synonym of the former. Simultaneously, is described as a species new to science. is a northern species of paler coloration and longer spines (distributed from Marojejy and Maroantsetra in the north to Zahamena in the south), whereas . represents the southern and darker species (distributed from Vohimana and Andasibe-Mantadia in the south to the Antongil Bay in the north). There are potential overlaps in the distribution of the two species, but without more georeferenced localities, it is impossible to discriminate whether they occur only sympatrically or also syntopically.
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http://dx.doi.org/10.3897/zookeys.957.52565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431442PMC
August 2020

Temperature sensitive water-in-water emulsions.

Chem Commun (Camb) 2020 Jun 20;56(50):6814-6817. Epub 2020 May 20.

Max Planck Institute of Colloids and Interfaces, Department of Colloid Chemistry, Am Mühlenberg 1, 14476 Potsdam, Germany.

A novel approach for a temperature-sensitive stabilization of water-in-water (W/W) emulsions is described. Specifically, we leveraged the thermal induced conformation change of tailored thermoresponsive block copolymers to reversibly stabilize and destabilize water-water interfaces. In addition, we investigated our approach to reversibly tune the reaction kinetics of enzymes compartmentalized within aqueous two-phase systems.
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http://dx.doi.org/10.1039/d0cc02171gDOI Listing
June 2020

Responsive Janus and Cerberus emulsions via temperature-induced phase separation in aqueous polymer mixtures.

J Colloid Interface Sci 2020 Sep 22;575:88-95. Epub 2020 Apr 22.

Department of Colloid Chemistry, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany. Electronic address:

Complex aqueous emulsions represent a promising material platform for the encapsulation of cells, pharmaceuticals, or nutrients, for the fabrication of structured particles, as well as for mimicking the barrier-free compartmentalization of biomolecules found in living cells. Herein, we report a novel, simple, and scalable method of creating multicomponent aqueous droplets with highly uniform internal droplet morphologies that can be controllably altered after emulsification by making use of a thermal phase separation approach. Specifically, temperature-induced phase separation inside as-formed emulsion droplets comprising aqueous mixtures of two or more hydrophilic polymers allows for the generation of Janus and Cerberus emulsion droplets with adjustable internal morphologies that are solely controlled by a balance of interfacial tensions. We demonstrate our approach by applying both, microfluidic and scalable batch production, and present a detailed model study with predictive capabilities that enables fine-tuning and dynamically altering the droplet morphology as a function of types, molecular weights, and hydrophilicities of the polymers as well as the surfactant hydrophilic-lipophilic balance. The ability to rationally design complex aqueous emulsion droplets with previously unattainable dynamic control over their morphologies after emulsification entails the potential to design new responsive soft materials with implications for a variety of applications beyond encapsulation, including the design of complex adaptive and self-regulating materials, e.g. for chemical and biological sensing applications.
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http://dx.doi.org/10.1016/j.jcis.2020.04.067DOI Listing
September 2020

Biomimetic Synthesis of Sub-20 nm Covalent Organic Frameworks in Water.

J Am Chem Soc 2020 02 6;142(7):3540-3547. Epub 2020 Feb 6.

Department of Chemistry and Applied Biosciences, Institute for Chemical and Bioengineering , ETH Zurich , Vladimir Prelog Weg 1 , 8093 Zurich , Switzerland.

Covalent organic frameworks (COFs) are commonly synthesized under harsh conditions yielding unprocessable powders. Control in their crystallization process and growth has been limited to studies conducted in hazardous organic solvents. Herein, we report a one-pot synthetic method that yields stable aqueous colloidal solutions of sub-20 nm crystalline imine-based COF particles at room temperature and ambient pressure. Additionally, through the combination of experimental and computational studies, we investigated the mechanisms and forces underlying the formation of such imine-based COF colloids in water. Further, we show that our method can be used to process the colloidal solution into 2D and 3D COF shapes as well as to generate a COF ink that can be directly printed onto surfaces. These findings should open new vistas in COF chemistry, enabling new application areas.
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http://dx.doi.org/10.1021/jacs.9b12389DOI Listing
February 2020

Cascade Kinetics in an Enzyme-Loaded Aqueous Two-Phase System.

Langmuir 2020 02 6;36(6):1401-1408. Epub 2020 Feb 6.

Department of Colloid Chemistry , Max Planck Institute of Colloids and Interfaces , Am Mühlenberg 1 , 14476 Potsdam , Germany.

Macromolecular crowding plays a critical role in the kinetics of enzymatic reactions. Dynamic compartmentalization of biological components in living cells due to liquid-liquid phase separation represents an important cell regulatory mechanism that can increase enzyme concentration locally and influence the diffusion of substrates. In the present study, we probed partitioning of two enzymes (horseradish-peroxidase and urate-oxidase) in a poly(ethylene glycol)-dextran aqueous two-phase system (ATPS) as a function of salt concentration and ion position in the Hofmeister series. Moreover, we investigated enzymatic cascade reactions and their kinetics within the ATPS, which revealed a strong influence of the ion hydration stemming from the background electrolyte on the partitioning coefficients of proteins following the Hofmeister series. As a result, we were able to realize cross-partitioning of two enzymes because of different protein net charges at a chosen pH. Our study reveals a strong dependency of the enzyme activity on the substrate type and crowding agent interaction on the final kinetics of enzymatic reactions in the ATPS and therefore provides substantial implications en route toward dynamic regulation of reactivity in synthetic protocells.
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http://dx.doi.org/10.1021/acs.langmuir.0c00186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307955PMC
February 2020

Association of colorectal carcinoma and metabolic syndrome.

Med Glas (Zenica) 2020 Feb;17(1):151-157

School of Medicine, University Mostar, Mostar, Bosnia and Herzegovina.

Aim Colorectal carcinoma is one of the most common neoplasms, especially in Western countries and those with westernisation. On the other hand, high rate of metabolic syndrome (MetSy) has also been noticed, as well as in Western countries. It seems like these two conditions are somehow connected. In this study, we wish to explore some characteristics of colorectal carcinoma and its correlation with MetSy. Methods In this retrospective study the data were taken from medical records of 67 patients with colorectal carcinoma, and for 30 healthy controls. Input parameters of patients were compared mutually, as well as with parameters of healthy, control examinees that had negative screening colonoscopy for neoplasm. Results Average age of patients was 68 years. The most frequent localisation of neoplasm was on rectum (53.7%) and most frequent level was Dukes C (38.8%). The patients had MetSy more frequently when compared with controls (p=0.048), and also they had more MetSy components (p=0.006). The link between MetSy and localisation of neoplasm was not found, neither with its pathohystological characteristics. Conclusion Patients with MetSy should be warned about the increased risk of colorectal carcinoma, and, in this way, motivated for earlier and more frequent screening colonoscopies, as well as of a change of unhealthy lifestyle.
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http://dx.doi.org/10.17392/1079-20DOI Listing
February 2020

A Candidate Gene Association Study of FKBP5 and CRHR1 Polymorphisms in Relation to War-Related Posttraumatic Stress Disorder.

Psychiatr Danub 2019 Jun;31(2):269-275

Department of Psychiatry, University Hospital Centre Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia,

Background: Posttraumatic stress disorder (PTSD) is a highly frequent and disabling psychiatric condition among war-affected populations. The FK506-binding protein 5 (FKBP5) gene and the corticotropin-releasing hormone receptor 1 (CRHR1) gene have previously been implicated in an elevated risk of peritraumatic dissociation and PTSD development. Our aim was to investigate the association between FKBP5 and CRHR1 genotypes and PTSD diagnosis and severity among individuals who were affected by the Balkan wars during the 1990s.

Subjects And Methods: This study included participants with current PTSD, remitted PTSD and healthy volunteers (N=719, 487 males), who were recruited between 2013 and 2015 within the framework of the South Eastern Europe (SEE) - PTSD Study. Psychometric methods comprised the Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administrated PTSD Scale (CAPS), and the Brief Symptom Inventory (BSI). FKBP5 rs1360780 and CRHR1 rs17689918 genotypes were determined using a KASP genotyping assay.

Results: Tests for deviation from Hardy Weinberg equilibrium showed no significant results. Logistic and linear regression was used to examine the associations between the FKBP5 SNP rs1360780 and the CRHR1 SNP rs17689918 with PTSD diagnosis and severity, as well as general psychiatric symptom severity, separately for current and remitted PTSD patients. There were nominally significant associations under a dominant model between the rs1360780 C allele and PTSD diagnosis as well as symptom severity, which however, were not significant anymore after Bonferroni adjustment (α=0.002). For CRHR1 rs17689918 no significant associations were detected.

Conclusion: We found nominally, but not Bonferroni corrected significant associations between the FKBP5 polymorphism rs1360780 and PTSD susceptibility among individuals affected by the Balkan wars. For elucidating this gene's real resilience/vulnerability potential, environmental influences should be taken into account.
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http://dx.doi.org/10.24869/psyd.2019.269DOI Listing
June 2019

The Role of TaqI DRD2 (rs1800497) and DRD4 VNTR Polymorphisms in Posttraumatic Stress Disorder (PTSD).

Psychiatr Danub 2019 Jun;31(2):263-268

Department of Psychiatry, University Clinical Centre of Kosovo, Prishtina, Kosovo,

Background: Posttraumatic stress disorder (PTSD) is a complex stress related disorder, that follows a severe traumatic experience, characterized with an intense sense of terror, fear, and helplessness. The aim of this study is to identify associations of genetic variations within candidate genes DRD2 and DRD4 with various PTSD related phenotypes. PTSD lifetime and PTSD current subjects were analyzed separately, each of them were analyzed in a Case/Control design, as well as regarding BSI and CAPS within cases only.

Subjects And Methods: 719 (487 male, 232 female) participants who had experienced war-related trauma between 1991 and 1999 in Bosnia and Hercegovina, Kosovo and Croatia were included in the study. Sociodemographic questionnaire, Clinician Administered PTSD Scale (CAPS) and the Brief Symptom Inventory (BSI) were used to collect clinical data.

Results: The DRD2 rs1800497 variant and a variable number tandem repeat (VNTR) located in exon three of DRD4 were investigated for association with PTSD. In case control analyses we did not identify any significant associations. Within the PTSD current patients, we identified an association of DRD2 rs1800497 with BSI in the genotypic and the recessive model with the T allele as the risk allele.

Conclusion: Our findings suggest that rs1800497 of DRD2 gene is involved in pathogenesis of PTSD.
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http://dx.doi.org/10.24869/psyd.2019.263DOI Listing
June 2019

Role of the Allelic Variation in the 5-Hydroxytryptamine Receptor 1A (HTR1A) and the Tryptophan Hydroxylase 2 (TPH2) Genes in the Development of PTSD.

Psychiatr Danub 2019 Jun;31(2):256-262

Department of Psychiatry, University Clinical Centre of Kosovo, Str, Hile Mosi, nr 11, 10000 Prishtina, Kosovo,

Background: Post-traumatic stress disorder (PTSD) is a stress related disorder which can occur in an individual after exposure to a traumatic event. It most commonly co-occurs with depression. The two disorders share not only overlapping symptoms, but also genetic diathesis. The aim of this study was to investigate the potential role of single nucleotide polymorphisms (SNPs) of the two serotonergic candidate genes 5-hydroxytryptamine receptor 1A (HTR1A) and tryptophan hydroxylase 2 (TPH2) in the pathogenesis of PTSD and comorbid psychopathology.

Subjects And Methods: 719 (487 males, 232 females) participants who had experienced war-related trauma between 1991 and 1999 in Bosnia and Herzegovina, Kosovo and Croatia were included in the study. The Sociodemographic questionnaire, Mini International Neuropsychiatric Interview (M.I.N.I.), Clinician Administered PTSD Scale (CAPS) and Brief Symptom Inventory (BSI) were used to collect clinical data. The SNPs rs6295 (HTR1A), rs11178997 and rs1386494 (TPH2) were investigated for their association with PTSD and comorbid psychopathology.

Results: A nominal significant association was found between the BSI total score in Lifetime PTSD with the SNP rs6295 of the HTR1A gene. The best result was seen in the dominant model (P=0.018), with the minor allele (C) being the risk allele. Several BSI subscores were also associated with the minor (C) allele in Lifetime PTSD. No association was found for the TPH2 SNPs rs11178997 and rs1386494 in relation to PTSD or comorbid psychopathology.

Conclusions: Our findings suggest that rs6295 in the HTR1A gene may contribute to the psychopathology of PTSD.
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http://dx.doi.org/10.24869/psyd.2019.256DOI Listing
June 2019

Association of Neuropeptide S Receptor 1 and Glutamate Decarboxylase 1 Gene Polymorphisms with Posttraumatic Stress Disorder.

Psychiatr Danub 2019 Jun;31(2):249-255

Institute of Kosovo Forensic Psychiatry, University Clinical Centre of Kosovo, Prishtina, Kosovo.

Background: Posttraumatic stress disorder (PTSD) is an anxiety disorder caused by highly traumatic experiences. The aim of this study was to investigate the influence of single nucleotide polymorphisms (SNPs) in the neuropeptide S receptor 1 (NPSR1) and the glutamate decarboxylase 1(GAD1) gene on PTSD and its psychopathological aspects among individuals affected by the Balkan wars during the 90s.

Subjects And Methods: This study was conducted as part of the South Eastern Europe (SEE) study on molecular mechanisms of PTSD. It comprised 719 participants (539 males), including those with current PTSD, remitted PTSD and healthy volunteers. Psychometric evaluation was performed using the Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administrated PTSD Scale (CAPS) andthe Brief Symptom Inventory (BSI). We examined NPSR1 single nucleotide polymorphism (SNP) rs324981 and GAD1 variant rs3749034 genotypes. Case-control analyses were carried out using logistical regression to determine genotype differences between all patients that had either current or remitted PTSD and control individuals. To analyse the influence of the analysed SNPs on PTSD severity, we performed linear regression analyses with CAPS and BSI within each of the two patient groups separately. All of the calculations were performed for additive allelic, recessive, dominant and genotypic models.

Results: We observed a nominally significant association for the major allele (G) of GAD1 rs3749034 with an increased risk to develop PTSD in a case control analysis in the recessive model (P=0.0315, odds ratio=0.47, SE=0.35). In contrast, a nominally significant association of the minor allele (A) with higher CAPS scores was identified within the patient group with lifetime PTSD in the dominant model (P=0.0372, β=6.29, SE=2.99). None of these results did withstand correction for multiple tests. No nominal significant results of GAD1 rs3749034 were found with regard to the intensity of psychological BSI symptoms. Case-control analyses of NPSR1 rs324981 revealed a nominally significant higher risk for homozygous T allele carriers to develop PTSD (P=0.0452) in the recessive model. On the other hand, the T allele showed a nominally significant association with higher BSI scores in patients suffering from lifetime PTSD in the recessive model (P=0.0434). Again, these results were not significant anymore after correction for multiple tests. No associations of NPSR1 rs324981 and CAPS score was identified.

Conclusion: The findings of this study provide some evidence that the NPSR1 and GAD1 polymorphisms might play a role in the development of war-related PTSD and its related psychological expressions. Further research is needed to elucidate the interactions of specific gene variants and environmental factors in the development of PTSD.
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http://dx.doi.org/10.24869/psyd.2019.249DOI Listing
June 2019

The Association of Catechol-O-Methyl-Transferase and Interleukin 6 Gene Polymorphisms with Posttraumatic Stress Disorder.

Psychiatr Danub 2019 Jun;31(2):241-248

Department of Clinical Biochemistry, University Clinical Centre of Kosovo, Prishtina, Kosovo.

Background: Posttraumatic stress disorder (PTSD) is a disorder that occurs in some people who have experienced a severe traumatic event. Several genetic studies suggest that gene encoding proteins of catechol-O-methyl-transferase (COMT) may be relevant for the pathogenesis of PTSD. Some researchers suggested that the elevation of interleukin-6 (IL6) correlates with major depression and PTSD. The aim of this study was to investigate whether the single nucleotide polymorphisms COMT rs4680 (Val158Met) and IL6 rs1800795 are associated with PTSD and contribute to the severity of PTSD symptoms.

Subjects And Methods: This study comprised 747 participants that experienced war between 1991 and 1999 in the South Eastern Europe conflicts. COMT rs4680 (Val158Met) and IL6 rs1800795 genotypes were determined in 719 participants (369 with and 350 without PTSD). The Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administrated PTSD Scale (CAPS) questionnaire and the Brief Symptom Inventory (BSI) were used for data collection.

Results: Regarding the COMT gene polymorphism, the results of the regression analyses for BSI total score were significant in the lifetime PTSD group in the dominant (P=0.031) and the additive allelic model (P=0.047). Regarding the IL6 gene, a significant difference was found for the recessive model predicting CAPS total score in the lifetime PTSD group (P=0.048), and indicated an association between the C allele and higher CAPS scores. n the allelic, genotypic and rezessive model, the results for BSI total score were significant in the lifetime PTSD group (P=0.033, P=0.028 and P=0.009), suggesting a correlation of the C allele with higher BSI scores.

Conclusion: Although our nominally significant results did not withstand correction for multiple tests they may support a relevance of the COMT (Val158Met) and IL6 rs1800795 polymorphism for aspects of PTSD in war traumatized individuals.
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http://dx.doi.org/10.24869/psyd.2019.241DOI Listing
June 2019

Associations between Polymorphisms in the Solute Carrier Family 6 Member 3 and the Myelin Basic Protein Gene and Posttraumatic Stress Disorder.

Psychiatr Danub 2019 Jun;31(2):235-240

Community Health Center Zivinice, Alije Izetbegovica 17, 75270 Zivinice, Bosnia & Herzegovina,

Background: Previous research showed inconsistent results concerning a possible association between solute carrier family 6 member 3 (SLC6A3) gene polymorphisms and dopamine symptoms of posttraumatic stress disorder (PTSD). Several studies also indicate that the myelin basic protein (MBP) gene is of importance in the etiology of several psychiatric disorders. The aim of this study was to investigate the relation of distinct SLC6A3 and MBP gene polymorphisms with PTSD and whether SLC6A3 and MBP genotypes contribute to PTSD symptom severity.

Subjects And Methods: The study included 719 individuals who had experienced war trauma in the South Eastern Europe (SEE). Genotypes of variable number tandem repeat (VNTR) polymorphism within the SLC6A3 gene were assessed in 696 participants, and the single nucleotide polymorphism (SNP) rs12458282 located within the MBP gene region was genotyped in a total of 703 subjects. The Mini International Neuropsychiatric Interview, the Clinical Administrated PTSD Scale (CAPS) and Brief Symptom Inventory (BSI), were used for data collection.

Results: No significant differences concerning the investigated SLC6A3 and MBP polymorphisms was identifiable between PTSD and non PTSD participants. Also we could not detect significant influence of these distinct SLC6A3 and MBP alleles on the severity of PTSD symptoms (CAPS) or BSI scores. However, the results of MBP rs12458282 within the patients with lifetime PTSD may point to a possible correlation of the major allele (T) with elevated CAPS scores.

Conclusions: Our results do not support an association of the analysed SLC6A3 and MBP gene polymorphisms with PTSD in war traumatized individuals. We found that there is a possibility for a correlation of the T allele rs12458282 within the MBP gene with higher CAPS scores in lifetime PTSD patients which would need to be tested in a sample providing more statistical power.
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http://dx.doi.org/10.24869/psyd.2019.235DOI Listing
June 2019

Associations of Gene Variations in Neuropeptide Y and Brain Derived Neurotrophic Factor Genes with Posttraumatic Stress Disorder.

Psychiatr Danub 2019 Jun;31(2):227-234

International Burch University, Department of Genetics and Bioengineering, Francuske revolucije bb, 71000 Sarajevo, Bosnia and Herzegovina,

Background: Individuals who are exposed to traumatic events are at an increased risk of developing posttraumatic stress disorder (PTSD), a condition during which an individual's ability to function is impaired by emotional responses to memories of those events. The gene coding for neuropeptide Y (NPY) and the gene coding for brain-derived neurotrophic factor (BDNF) are among the number of candidate gene variants that have been identified as potential contributors to PTSD. The aim of this study was to investigate the association between NPY and BDNF and PTSD in individuals who experienced war-related trauma in the South Eastern Europe (SEE) conflicts (1991-1999).

Subjects And Methods: This study included participants with current and remitted PTSD and healthy volunteers (N=719, 232 females, 487 males), who were recruited between 2013 and 2015 within the framework of the South Eastern Europe (SEE) - PTSD Study. Psychometric methods comprised the Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administered PTSD Scale (CAPS), and the Brief Symptom Inventory (BSI). DNA was isolated from whole blood and genotyped for NPY rs5574 via PCR - RFLP and NPY rs16147 and BDNF rs6265 using the KASP assay.

Results: Tests for deviation from Hardy-Weinberg equilibrium showed no significant results. Analyses at the categorical level yielded no associations between the affected individuals and all three SNPs when compared to controls. Within lifetime PTSD patients, the major alleles of both NPY variants showed a nominally significant association with higher CAPS scores (p=0.007 and p=0.02, respectively). Also, the major allele of rs5574C>T was associated with higher BSI scores with a nominal significance among current PTSD patients (p=0.047). The results did not withstand a Bonferroni adjustment (α=0.002).

Conclusion: Nominally significant associations between NPY polymorphisms and PTSD susceptibility were found that did not withstand Bonferroni correction.
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http://dx.doi.org/10.24869/psyd.2019.227DOI Listing
June 2019

Genetic Susceptibility to Posttraumatic Stress Disorder: Analyses of the Oxytocin Receptor, Retinoic Acid Receptor-Related Orphan Receptor A and Cannabinoid Receptor 1 Genes.

Psychiatr Danub 2019 Jun;31(2):219-226

Department of Psychiatry, Clinical Center University Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina,

Background: Exposure to life-threatening events is common and everyone will most likely experience this type of trauma during their lifetime. Reactions to these events are highly heterogeneous and seems to be influenced by genes as well. Some individuals will develop posttraumatic stress disorder (PTSD), while others will not. In this study, our aim was to analyze the correlation between single nucleotide polymorphisms (SNPs) within the oxytocin receptor (OXTR) gene (rs53576 and rs2254298), the RAR-related orphan receptor A (RORA) gene (rs8042149) and the cannabinoid receptor 1 (CNR1) gene (rs1049353) and PTSD. All candidate genes have been previously associated with stress related disorders and the reaction to traumatic events.

Subjects And Methods: Participants (N=719) have been exposed to war-related trauma during the war in South-Eastern Europe (Bosnia and Herzegovina, Croatia and Kosovo). We correlated the presence and absence of current and lifetime PTSD as well as PTSD severity (Clinician Administered PTSD scale (CAPS)) and current psychopathology (Brief Symptom Inventory (BSI) score) with the mentioned SNPs. DNA was isolated from whole blood and genotyped for OXTR rs2254298 and rs53576 following previously published protocols, for RORA rs8042149 via PCR-RFLP and CNR1 rs1049353 via KASP.

Results: Nominally significant results were found for OXTR rs53576 in connection with the CAPS and BSI scores within lifetime PTSD patients. The additive allelic model indicated that G allele carriers achieved lower CAPS (p=0.0090) and BSI (p=0.0408) scores than participants carrying one or two copies of the A allele. These results did not withstand correction for multiple tests. No significant results were observed for OXTR rs2254298, RORA rs8042149 and CNR1 rs1049353 although the results for RORA showed a slight tendency that rs8042149 may influence the level of BSI scores in current PTSD patients.

Conclusions: This study points to a role of the OXTR gene in PTSD and the related psychopathology following war related trauma.
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http://dx.doi.org/10.24869/psyd.2019.219DOI Listing
June 2019

Association Analysis of Maoa and Slc6a4 Gene Variation in South East European War Related Posttraumatic Stress Disorder.

Psychiatr Danub 2019 Jun;31(2):211-218

Department of Psychiatry, University Clinical Centre Tuzla, Rate Dugonjića bb, 75000 Tuzla, Bosnia and Herzegovina,

Background: The aim of this study is to investigate the association of gene variations of the monoamine oxidase A (MAOA) and the serotonin transporter solute carrier family 6 member 4 (SLC6A4) gene with posttraumatic stress disorder (PTSD) severity and coping strategies in patients with war related PTSD.

Subjects And Methods: The study included 747 individuals who had experienced war trauma in the South Eastern Europe conflicts between 1991 and 1999. Genotyping of the MAOA VNTR and SLC6A4 tandem repeat polymorphism in combination with rs25531 was done in 719 participants: 232 females and 487 males. Among them, 369 have had current or lifetime PTSD and 350 have had no PTSD symptoms. For psychometric approach we used the Clinician Administrated PTSD Scale (CAPS), the Brief Symptom Inventory (BSI), the adapted Hoffman-Lazarus Coping scale and a basic socio-demographic data questionnaire.

Results: There were no significant intergroup (PTSD versus non PTSD) differences in the genotype distribution of MAOA and SLC6A4 gene polymorphisms. The primary finding of our study was that the MAOA short allele (MAOA-S) was nominally significantly associated with the severity of PTSD symptoms in the total subgroup of participants with lifetime PTSD; males for symptoms of hyperarrousal and females with symptoms of re-experience and hyperarousal. In our research the male subsample with current PTSD and MAOA-S genotype had nominally significantly higher scores for some positive coping strategies compared to those carrying the long allele genotype (MAOA-L). There was no significant association between the severity of PTSD symptoms, BSI phenotype, coping scores and the SLC6A4 genotype.

Conclusion: The present results support the notion that MAOA VNTR gene variation modulates development and recovery of posttraumatic stress disorder in a war traumatised population, but did not support a connection between SLC6A4 gene variations and war related PTSD.
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http://dx.doi.org/10.24869/psyd.2019.211DOI Listing
June 2019

Cavitation Wear of Basalt-Based Glass Ceramic.

Materials (Basel) 2019 May 12;12(9). Epub 2019 May 12.

High Business Technical School, 31000 Uzice, Serbia.

This paper examines the possibility of using basalt-based glass ceramics for construction of structural parts of equipment in metallurgy and mining. An ultrasonic vibration method with a stationary sample pursuant to the ASTM G32 standard was used to evaluate the possibility of the glass ceramic samples application in such operating conditions. As the starting material for synthesis of samples, olivine-pyroxene basalt from the locality Vrelo-Kopaonik Mountain (Serbia) was used. In order to obtain pre-determined structure and properties of basalt-based glass ceramics, raw material preparation methods through the sample crushing, grinding, and mechanical activation processes have been examined together with sample synthesis by means of melting, casting, and thermal treatment applied for the samples concerned. The mass loss of samples in function of the cavitation time was monitored. Sample surface degradation level was quantified using the image analysis. During the test, changes in sample morphology were monitored by means of the scanning electronic microscopy method. The results showed that basalt-based glass ceramics are highly resistant to cavitation wear and can be used in similar exploitation conditions as a substitute for other metal materials.
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http://dx.doi.org/10.3390/ma12091552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539832PMC
May 2019

Highly stable enzyme-mimicking nanocomposite of antioxidant activity.

J Colloid Interface Sci 2019 May 16;543:174-182. Epub 2019 Feb 16.

MTA-SZTE Lendület Biocolloids Research Group, University of Szeged, H-6720 Szeged, Hungary; Interdisciplinary Excellence Center, Department of Physical Chemistry and Materials Science, University of Szeged, H-6720 Szeged, Hungary. Electronic address:

A highly stable nanocomposite of antioxidant activity was developed by immobilization of a superoxide dismutase-mimicking metal complex on copolymer-functionalized nanoclay. The layered double hydroxide (LDH) nanoclays were synthesized and surface modification was performed by adsorbing poly(vinylpyridine-b-methacrylic acid) (PVPMAA). The effect of the adsorption on the charging and aggregation properties was investigated and the copolymer dose was optimized to obtain stable LDH dispersions. The LDH-PVPMAA hybrid particles showed high resistance against salt-induced destabilization in aqueous dispersions. Copper(II)-histamine (Cu(Hsm)) complexes were immobilized via the formation of dative bonds between the metal ions and the nitrogen atoms of the functional groups of the copolymer adsorbed on the particles. Changes in the coordination geometry of the complex upon immobilization led to higher superoxide radical anion scavenging activity than the one determined for the non-immobilized complex. Comparison of superoxide dismutase (SOD)-like activity of the obtained hybrid LDH-PVPMAA-Cu(Hsm) with the nanoclay-immobilized SOD enzyme revealed that the developed composite maintained its activity over several days and was able to function at elevated temperature, while the immobilized native enzyme lost its activity under these experimental conditions. The developed nanocomposite is a promising antioxidant candidate in applications, where high electrolyte concentration and elevated temperature are applied.
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http://dx.doi.org/10.1016/j.jcis.2019.02.050DOI Listing
May 2019

Effect of Polyelectrolyte Mono- and Bilayer Formation on the Colloidal Stability of Layered Double Hydroxide Nanoparticles.

Nanomaterials (Basel) 2018 Nov 28;8(12). Epub 2018 Nov 28.

MTA-SZTE Lendület Biocolloids Research Group, Department of Physical Chemistry and Materials Science, University of Szeged, H-6720 Szeged, Hungary.

Sequential adsorption of polyelectrolytes on nanoparticles is a popular method to obtain thin films after deposition. However, the effect of polyelectrolyte multilayer formation on the colloidal stability of the nanoparticles has not been studied in detail. In the present work, layered double hydroxides (LDH) were synthesized and interaction with oppositely and like-charged polyelectrolytes was investigated. Electrophoretic and light scattering measurements revealed that colloidal stability of LDH can be tuned by adsorption of poly(styrene sulfonate) (PSS) on the oppositely charged LDH surface in appropriate doses and thus, unstable or stable dispersions can be designed. Negatively charged LDH of adsorbed PSS monolayer was obtained and a poly(diallyldimethyl ammonium chloride) (PDADMAC) second layer was systematically built on the particles. The obtained polyelectrolyte bilayer provided high colloidal stability for the LDH-PSS-PDADMAC dispersions due to the presence of repulsive interparticle forces of electrostatic and steric origin. The results provide crucial quantitative information on designing highly stable particle-polyelectrolyte systems for the preparation of thin films or immobilization of guest substances between the layers for delivery processes.
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http://dx.doi.org/10.3390/nano8120986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316193PMC
November 2018

Addictions without Drugs: Contemporary Addictions or Way of Life?

Psychiatr Danub 2018 Sep;30(Suppl 6):371-379

Department of Psychiatry, University Clinical Hospital Mostar, Bijeli Brijeg bb, 88000 Mostar, Bosnia and Herzegovina,

In the five thousand years of recorded history there is written evidence of various types of addiction. In recent decades scientists focus their attention on addictions without the immediate introduction of psychoactive substances into the organism or the so-called "addictions without drugs". Studies have revealed a number of similarities between drug addictions and addictions without drugs that also carry biological, psychological and social consequences in the form of addictive activity carvings, adrenaline alarm, dopamine and serotonin secretion, tolerance and abstinence syndrome same as classical forms of addiction. Although the physiological effect of addiction without drugs on the brain and nervous system is not yet sufficiently explored, scientists have found equivalent effects on addicts suffering from one or the other type of addiction. These addicts are almost generally dysfunctional persons who become prisoners of their own passions, and the consequences are numerous technological advantages offered by modern times and in some respects a punishment due to the civilization for forgetting the man himself. Considering that most people, so and many psychiatrist, often accept these addictions as a lifestyle and without any delay and awareness of the potential dangers they may pose, we can with certainty say that the so-called "addictions without drugs" are the scourge of the 21 century. With pathological gambling, which is as old as human civilization, in recent decades we meet the growing problems of internet addiction, gambling games, which are classified for the first time at DSM V in addictive disorder, uncontrolled shopping, food cravings, addiction to sex, weight loss, sports, work and many more, which are mostly true addictions, and not only the way of life. The aim of this paper is to point to the growing problem of addiction without drugs, which is becoming an increasing problem within our community.
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September 2018

Horseradish peroxidase-nanoclay hybrid particles of high functional and colloidal stability.

J Colloid Interface Sci 2018 Aug 3;524:114-121. Epub 2018 Apr 3.

MTA-SZTE Lendület Biocolloids Research Group, University of Szeged, H-6720 Szeged, Hungary; Department of Physical Chemistry and Materials Science, University of Szeged, H-6720 Szeged, Hungary. Electronic address:

Highly stable dispersions of enzyme-clay nanohybrids of excellent horseradish peroxidase activity were developed. Layered double hydroxide nanoclay was synthesized and functionalized with heparin polyelectrolyte to immobilize the horseradish peroxidase enzyme. The formation of a saturated heparin layer on the platelets led to charge inversion of the positively charged bare nanoclay and to highly stable aqueous dispersions. Great affinity of the enzyme to the surface modified platelets resulted in strong horseradish peroxidase adsorption through electrostatic and hydrophobic interactions as well as hydrogen bonding network and prevented enzyme leakage from the obtained material. The enzyme kept its functional integrity upon immobilization and showed excellent activity in decomposition of hydrogen peroxide and oxidation of an aromatic compound in the test reactions. In addition, remarkable long term functional stability of the enzyme-nanoclay hybrid was observed making the developed colloidal system a promising antioxidant candidate in biomedical treatments and industrial processes.
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http://dx.doi.org/10.1016/j.jcis.2018.04.007DOI Listing
August 2018

Anthropometric characteristics and traffic accident circumstances of patients with isolated whiplash injury in University Clinical Hospital Mostar.

Med Glas (Zenica) 2018 Feb;15(1):59-65

Department of Orthopaedic Surgery and Traumatology, University Clinical Hospital Mostar; Department of Anatomy, School of Medicine, University of Mostar, Mostar, Bosnia and Herzegovina.

Aim To investigate anthropometric characteristics and traffic accident circumstances of subjects with isolated whiplash injury. Methods This cross sectional study involved 75 subjects from traffic accidents with isolated whiplash injury classified by Quebec Task Force (QTF). Anthropometric data were collected as well as claims about circumstances of traffic accidents. Results Distribution of 1st (28; 37.3%), 2nd (25; 33.3%) and 3rd (22; 29.3%) grade of whiplash injury was almost equal. Females had smaller anthropometric measurements than males; neck circumference was the most significant difference between males and females in the context of whiplash injury. The most frequent collision mechanism was impact to front (26; 34.7%) or to rear end (26; 34.7%) of a small passenger's car. Assertions of participants were that their car damage was significant (37; 49.2%) or total (24; 32%). A total of 38 (50.7%) participants claimed that they were not wearing safety belt and 52 (69.3%) did not find themselves responsible for accident. Conclusion Driving habits of our participants facilitate incidence of whiplash injuries, especially in vulnerable groups such as women and elderly.
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http://dx.doi.org/10.17392/918-18DOI Listing
February 2018
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