Institutional projects

Associates:

Prof. Igor Filipčić

Doc. dr. sc. Ivona Šimunović Filipčić

Dr. sc. Tomislav Gajšak

Dr. sc. Željko Milovac

Summary:

Background: Heart rate variability (HRV) reflects autonomic regulation relevant to impulse control. Deep repetitive transcranial magnetic stimulation (rTMS) with the H7 coil targets inhibitory control networks; HRV may serve as a physiological predictor of treatment response in Gambling Disorder (GD). This stand-alone, single-arm prognostic pilot (n = 20) focuses on the feasibility of HRV acquisition and the predictive value of HRV for 6-week H7 outcomes, with no overlap of equipment funding from other sources.

Objective: Primarily, to test whether baseline HRV and/or early change in HRV (A during week 1) predict response (2 30 % GSAS reduction at week 6). Secondarily, to assess feasibility (adherence and completeness of HRV recordings), safety/tolerability, and associations between HRV and craving/behavioural outcomes.

Design and Methods: Prospective, single-ann cohort in a dayhospital setting (n = 20); standardised 6-week H7 protocol. HRV acquisition: (a) 5-min resting baseline, (b) 20-min intra-session, (c) 5-min post-session; standardised conditions (posture, caffeine/nicotine, breathing). Metrics: time-domain (SDNN, RMSSD, pNN50), frequency-domain (LF, HF, LF/HF), and nonlinear indices (SDI/SD2, sample entropy, DFA al).

Analysis: Descriptive statistics with 95 % Cls (bootstrap). Penalised logistic regression (Firth/ridge) with a priori at most 1—2 predictors (e.g., baseline RMSSD, early AHF); AUC with optimism correction via bootstrap and calibration (slope/intercept). Longitudinally, mixed-effects models for craving (VAS/GUS) with HRV as a time-varying covariate. Reporting will be TRIPOD/STROBE-compliant.

Expected impact: Achieving AUC 2 0.70 for at least one prespecified HRV predictor will justify further validation and inform personalised rTMS pathways. The project is low-cost, ethically acceptable, and will deliver a TRIPOD-compliant prognostic report by 30 Sept 2026.

Associates:

izv. prof. dr. sc. Barbara Ebling
dr. sc. Renata Sikora, dr. med. Dcnt
dr. sc. Tea Omanović Kolarić, dr. med
Suzana Blažanović, mag. biol. Exp
Lidija Tomas, mag.med.techn.

Summary:

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. Despite advances in surgery, chemotherapy, and immunotherapy, the high recun•ence rate and therapeutic resistance highlight the urgent need for novel treatment strategies. Semaglutide, a glucagon-like peptide-l receptor (GLPIR) agonist, is primarily approved for the treatment of type 2 diabetes and obesity. However, emerging evidence suggests that GLP-IR signaling extends beyond metabolic regulation and łnay influence cell proliferation, apoptosis, and tumor progression. While epidemiological data hint at potential anticancer effects of GLP-I analogues, the direct impact of semaglutide on colorectal cancer cells remains poorly understood. This project aims to establish in vitro CRC cell models (e.g., HCTI 16, SW480) to investigate semaglutide's direct effects on cell proliferation, apoptosis, oxidative stress, and expression of key cancer-related signaling proteins. Particular emphasis will be placed on the P13WAKT/mTOR and Wnt/ß-catenin pathways, which are central to CRC progression and survival. The study will include viability assays, protein expression analysis (ELISA, Western blot), fluorescence microscopy for apoptosis detection, and oxidative stress profiling. Outcomes may reveal whether semaglutide possesses direct anticancer activity beyond its metabolic role. Positive findings could open new perspectives for repositioning semaglutide as an adjunct therapeutic strategy in CRC management and lay the foundation for further in vivo and clinical research.

Associates:

prof. prim. dr. sc. Marija Glasnović, dr. med.
dr. sc. Lucija Kuna Roguljić, mag.biol.
Marija Hefer, mag. chem.
Vice Tomičić, univ.mag.ing.proc
Elizabeta Knezović, mag. biol. Exp
Ivana Mihin Huskić, dr. med.

Summary:

Hepatic steatosis refers to the excessive accumulation of lipids within hepatocytes, which impairs their function and may lead to further damage. This process is often associated with dysregulations in lipid metabolism and resulting oxidative stress, contributing to inflammatory changes and disease progression. Although numerous studies have focused on various bioactive compounds of plant origin, there is a limited number of investigations that specifically address the protective effects of natural colored compounds, i.e. plant pigments, in cellular models of hepatic steatosis.
Betalains, pigments from beetroot that include betacyanins and betaxanthins, have demonstrated a range of biological activities in animal models, including antioxidant, hypolipidemic, and antiinflammatory effects. Results suggest that these compounds may influence lipid homeostasis in the liver and reduce hepatocyte injury. However, systematic in vitro studies on human cell lines are limited, and most existing evidence refers more to general antioxidant effects than to specific mechanisms of steatosis.
In vivo studies have shown that betalains reduce triglyceride and cholesterol accumulation in the liver, increase the activity of antioxidant enzymes such as catalase and superoxide dismutase (SOD), and decrease levels of proinflammatory cytokines such as TNF-a. These changes are typically associated with reduced oxidative damage to membranes and improved insulin sensitivity. Furthermore, betalains may modulate the activity of PPARa, which is crucial for fatty acid oxidation, and reduce the expression of the lipogenic factor SREBP-1c, thereby potentially inhibiting the synthesis of new triglycerides. Since elevated lipid levels in hepatocytes are the main indicators of steatosis, the mentioned effects indicate the potentially important protective role of betalains.
Apocarotenoids from saffron (crocin and crocetin) have also been less frequently investigated in both in vitro and in vivo studies. Some studies have demonstrated that they can modulate hepatocyte energy metabolism, activate signaling pathways related to fatty acid oxidation, and inhibit lipogenesis. Additionally, these compounds exhibit pronounced antioxidant properties and can improve mitochondrial function, which is particularly important in the context of energy metabolism dysregulations that accompany steatosis. However, most of these findings originate from in vivo experiments, while the number of studies using cell culture models remains limited.
Further animal studies indicate that crocin may reduce SREBP- 1 c expression and increase PPARa and PPARY activity, thereby promoting fatty acid oxidation and decreasing lipogenesis. Crocetin has also been shown to reduce lipid peroxidation and increase glutathione (GSH) levels, further emphasizing the antioxidant potential of apocarotenoids.
Therefore, by applying cell culture models, particularly the HepG2 line, it will be possible to perform a detailed analysis of the mechanisms of action of plant pigments. Steatotic changes within hepatocytes will be reproduced using oleic or palmitic acid, thereby providing a suitable model for investigating pathophysiological processes associated with hepatic fat accumulation.
As part of the project, lipid accumulation in cells, levels of oxidative stress, and changes in key proteins involved in lipid metabolism and inflammatory response, including PPARa, PPARY, SREBP-1c, and TNF-a, will be monitored. The impact of plant pigments on the cellular antioxidant status and their potential to mitigate the cytotoxic effects of free fatty acids will also be examined. In this way, the protective potential of plant pigments in a fatty liver model will be assessed, with the aim of exploring their possible application in the prevention and alleviation of liver metabolic disorders.

Associates:

Izv. prof. dr. sc. Damir Erceg, dr. med.
Dr. sc. Vjera Mihaljević, dr. med.
Zeljka Berbić, dr. med.
Ana Petrović, dr. med.
Doc. dr. sc. Majda Grah, dr. med.
Doc. dr. sc. Davor Bodor, dr. med.
Doc. dr. sc. Sandra Kocijan, dr. med.
Dr. sc. Vanja Lovretić, dr. med.
Dr. sc. Lada Grošić, dr. med.

Summary:

Around 300 million people suffer from depression all over the world, according to the data from the World Health Organization (WHO). One form of this disease that represents a major clinical problem is treatment-resistant depression (TRD). This form of depressive disorder occurs in about one third of patients and is a form of depression in which the affected person does not adequately respond to at least two different pharmacotherapies with antidepressants, with the obligatory use of each of the therapies in the appropriate dose and for a sufficiently long period of time. The definition of therapeutically resistant depression is still not universal and unified, treatment recommendations vary, and due to the ineffectiveness of pharmacotherapy, alternative approaches to the treatment of this disease are widely researched. By now, it is already known that patients with depression in most cases have mild to significantly increased serum values of proinflammatory cytokines such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-u) and interferon gamma (INF-y). Such a chronic inflammatory condition in the body gradually leads to the development of neuroinflammation, which additionally contributes to an increase of pro-inflammatory cytokines in serum and cerebrospinal fluid, and worsens the symptoms of depression through changes in neuroplasticity, disruption of the neurotransmitter system and disruption of the function of the hypothalamic-pituitary-adrenal axis (HPA axis). Transcranial magnetic stimulation has proven to be one of the most effective non-invasive, non-pharmacological methods of treating depression. This method induces a weak electric current in the regions of the brain that are responsible for the development of depression. Treatments are carried out over several weeks, and because TMS has proven to be a good alternative to pharmacotherapy in the treatment of depression, it is assumed that TMS therapy will reduce the amount of proinflammatory cytokines in the plasma and serum of the subjects. Thus, the selected cytokines would serve as a biomarker of depression. The main objectives of the research within the project will be to examine changes in the levels of selected pro-inflammatory cytokines in the plasma and serum of patients suffering from therapeutically resistant depression before and after TMS therapy. Subjects will undergo the second edition of the Beck Depression Questionnaire (BDI-II) to quantify depressive symptoms in subjects before and after TMS therapy. Cytokines will be measured before and after TMS therapy with the ProcartaPlexTM 5-PLEX test, and the obtained results will be analyzed by appropriate statistical methods. It is expected that the research within the project will contribute to improving the understanding of the role of proinflammatory cytokines in therapeutically resistant depression and provide insight into the therapeutic impact of TMS on changes in the levels of selected pro-inflammatory cytokines.

Associates:

doc.dr. sc. Nikolina Farčić, mag.med.techn.

doc. dr. sc. Stana Pačarić

doc. dr. sc. Zvjezdana Gvozdanović

dr.sc. Jasenka Vujanić, mag.med.techn.

dr. sc. Maja Čebohin

Marija Barišić, mag.med.techn. asistentica – doktorandica poslijediplomskog studija Biomedicine i zdravstva, Medicinskog fakulteta Osijek

Željko Mudri, mag. med. techn., doktorand poslijediplomskog doktorskog studija Sociologija: vrijednosti, identitet i društvene promjene u hrvatskome društvu

Željka Dujmić, asistentica – doktorandica poslijediplomskog studija Biomedicine i zdravstva, Medicinskog fakulteta Osijek

Summary:

Contemporary higher education in nursing is based on a competency-oriented approach aimed at acquiring the necessary competencies for assessing, planning, implementing, and evaluating nursing care. The educational context includes the achievement of various learning outcomes across the cognitive, psychomotor, and affective domains, realised through constructive alignment of educational content with teaching formats, instructional methods, and assessment procedures. The development of student competencies is not understood as a spontaneous or passive process but is systematically planned, implemented, and evaluated through structured processes of assessment and self-assessment. Such an approach allows for clearer monitoring of student progress, identification of developmental needs, and the assurance of achieving professional standards required for the quality provision of nursing care. In this context, simulation-based learning, particularly in the preclinical educational setting, represents a transitional space between structured, predictable, and controlled learning conditions and the unpredictable situations encountered in clinical practice. By using simulation methods, students are enabled to gradually integrate theoretical knowledge with practical application in a safe environment where professional attitudes can be developed, practical skills acquired, and competencies strengthened in accordance with professional requirements. The possibility of practicing various clinical situations in a simulated setting significantly contributes to the transition from theoretical to practical aspects of education. This facilitates the gradual assumption of the professional role while simultaneously encouraging the development of autonomy and responsibility among students. It is particularly important to highlight that simulation allows for adaptation to situations that are, by nature, unpredictable and dynamic, requiring continuous flexibility, rapid assessment, and decision-making, as well as constant alignment with patient needs and the dynamics of the clinical environment. From the perspective of scientific contribution, simulation can be considered a potential moderator in the educational process, that is, a factor that influences the relationship between the initial and final levels of self-assessed competencies of nursing students in a preclinical context. In this sense, simulation-based learning may play a significant role in shaping students’ perception of their own readiness to work in complex and unpredictable conditions of real clinical practice. Systematic reviews of the literature indicate that simulation-based learning (SBL) often results in significant improvements in nursing students’ knowledge and clinical skills, particularly in comparison to traditional teaching methods. However, despite its recognised value and proven effectiveness, the application of simulation in the field of gerontological care still appears to be insufficient. Simulation elements in education focused on caring for older adults are rarely systematically integrated into curricula, even though this area requires specific competencies that go beyond the basic technical execution of care. Moreover, most of the quasi-experimental studies conducted to date have focused on examining the impact of simulation on one or two dimensions of competence, while comprehensive evaluations including all three domains (cognitive, affective, and psychomotor) are underrepresented. The aspect of retention is also insufficiently explored, i.e., how long the acquired competencies are maintained after the simulation intervention. In light of all the above, the current scientific and educational literature identifies a research gap, indicating the need for further studies aimed at examining the contribution of simulation-based learning to the development of nursing student competencies in the field of gerontological care. Such research could provide an important theoretical and practical contribution to the design of more effective and content-rich curricula in healthcare education.

Associates:

Izv. prof. dr. sc. Ivica Kelam

Izv. prof. dr. sc. Dario Galić

Doc. dr. sc. Dubravka Holik

Dr. sc. Sanja Pešić

Dr. sc. Tamara Alebić

Emanuela Ham, ma . aed. ct ma . educ. hil.

Summary:

This topic explores the complex relationship between the legal and ethical obligations of dentists in daily clinical practice. Criminal responsibility includes criminal acts and criminal sanctions. Procedures in which the doctor of dental medicine causes damage to the patient through his negligent or inappropriate actions are included. In this context, a clear distinction is made between criminal acts: spreading and transmitting infectious diseases, negligent treatment, illegal taking and transplanting of human body parts, and failure to provide medical assistance in emergency situations. For the aforementioned criminal acts, prison terms of one to fifteen years are provided. Misdemeanor liability refers to minor violations of regulations, and the sanctions are fines. Bioethical responsibility includes the professional and moral treatment of dental medicine doctors towards patients. Norms regulating bioethical responsibility are incorporated into Croatian legislation and mainly by the Statute of the Croatian Chamber of Dental Medicine and the Code of Dental Ethics and Deontology. The development and validation of the knowledge and attitudes questionnaire is purposefully aimed at assessing the information, knowledge and attitudes of doctors of dental medicine about their legal and bioethical obligations. Such a questionnaire enables the identification of deficiencies in education and raising awareness of the importance of responsible and legal action in clinical practice. The validation of such a questionnaire confirms its authority and reliability for use in research and education. This contributes to the improvement of patient safety, the quality of dental care and the reduction of legal risks for doctors of dental medicine.

Associates:

izv. prof. dr. sc Jasminka Talapko, mag.med.lab.
izv. prof. dr. sc. Dragan  Schwarz, dr. med.
izv. prof. dr. sc Rajko Fureš, dr. med.  
doc. dr. sc. Šapina Matej, dr. med. 
doc. dr. sc. Makarović Vedrana, dr. med.

Summary:

Hypoxia-inducible transcription factor 1 (HIF-1) is a key transcription factor that enables cells to adapt to conditions of reduced oxygen concentration (hypoxia). HIF-1 regulates numerous genes that enable cells to survive in hypoxic environments, and its functionality consists of two subunits: HIF-1α and HIF-1β. HIF-1β is stable and present in the cell regardless of oxygen concentration, while HIF-1α is subject to accelerated degradation under normoxia and stabilizes under hypoxic conditions. This mechanism allows HIF-1α to accumulate and migrate to the nucleus, where it induces the transcription of specific genes involved in the process of cell adaptation to hypoxia. Although the response to hypoxia is primarily protective, excessive or dysfunctional activation of HIF-1 is associated with numerous pathological conditions, including neoplasms, cardiovascular diseases, neurological disorders, as well as inflammatory and metabolic diseases. During  hypoxia, HIF-1α stabilizes, accumulates in the cytoplasm, and enters the nucleus, where it binds to HIF-1β and forms a functional transcriptional complex. The complex activates the expression of genes involved in processes such as angiogenesis, glucose metabolism, cell survival and adaptation to oxidative stress. HIF-1 plays a central role in the adaptation of tumor cells to hypoxic conditions, enabling their growth and survival. HIF-1 induces the expression of vascular endothelial growth factor (VEGF), which promotes angiogenesis and allows the tumor to be supplied with oxygen and nutrients. HIF-1 also, activates genes that support anaerobic metabolism, enabling cell survival in hypoxic conditions. Excessive activation of HIF-1 can increase the ability to metastasize by inducing changes in the cell that enable migration and invasion into surrounding tissues. In ischemia (heart attack or stroke), HIF-1 plays a key role in cell survival and modification of vascular function. Hypoxia in tissues activates HIF-1, leading to increased angiogenesis. Chronic hypoxia stimulates the development of fibrosis and remodeling of cardiac or cerebral tissue, which contributes to the progression of the disease. In neurological diseases, including neurodegenerative disorders such as Alzheimer's and Parkinson's, HIF-1 has a dual role. On the one hand, HIF-1 activation can be neuroprotective because it increases neuronal survival in hypoxia and oxidative stress. However, excessive activation may contribute to neurodegeneration, as HIF-1 induces processes that lead to increased oxidative stress and apoptosis. HIF-1 also plays a role in glucose metabolism in the brain, which may be crucial for maintaining energy balance in nerve cells. HIF-1 plays a significant role in the immune response. In inflammatory conditions, hypoxia activates HIF-1, which leads to the production of cytokines, which help fight pathogens. However, chronic activation of HIF-1 in inflammatory processes can contribute to the development of autoimmune diseases and other pathological conditions, including rheumatoid arthritis, Crohn's disease, and systemic lupus erythematosus. HIF-1 regulates glucose and lipid metabolism, and plays a key role in maintaining cellular energy balance. Activation of HIF-1 under hypoxia promotes the transition to anaerobic glucose metabolism, allowing cells to survive in conditions of low oxygen supply. However, excessive activation of HIF-1 in metabolic disorders can contribute to the development of diseases such as type 2 diabetes, as impaired regulation of metabolism leads to insulin resistance and hyperglycemia. HIF-1 is a key regulator of cells in hypoxic conditions, and its role in the pathophysiology of disease is complex and multifaceted. Although HIF-1 plays a protective role in cell survival under hypoxia, its excessive or dysfunctional activation can be associated with numerous diseases. Understanding the mechanisms by which HIF-1 regulates these processes may open new therapeutic approaches in the treatment of diseases associated with its dysfunction. Therefore, HIF-1 represents a key target in the development of new therapeutically directed interventions, with the aim of modifying its activity in pathological conditions.

Associates:

Prof. dr. sc. Aleksandar Včev, redoviti profesor, dekan, Zavod za integrativnu medicinu

Doc. dr. sc. Tanja Kovač Lukić, docent, Katedra za anatomiju, histologiju, embriologiju, patološku anatomiju i patološku histologiju

Dr. sc. Jelena Jakab, viši asistent, Katedra za patofiziologiju, fiziologiju i imunologiju

Dr. sc. Nikola Volarić, viši asistent, Katedra za patofiziologiju, fiziologiju i imunologiju

Dr. sc. Robert Mujkić, viši asistent, Katedra za anatomiju, histologiju, embriologiju,

patološku anatomiju i patološku histologiju

Dunja Igrec, asistent, Katedra za patofiziologiju, fiziologiju i imunologiju

Nikolina Lazić, asistent, Zavod za teleradiologiju i umjetnu inteligenciju

Karla Rožac, asistent, Katedra za anatomiju, histologiju, embriologiju, patološku anatomiju i patološku histologiju

Summary:

Balance, stability, and efficient gait are fundamental elements of functional ability and sports performance. They enable the effective execution of daily activities, participation in sports, and a reduced risk of injuries. Balance refers to the ability to maintain control over the body's center of mass in relation to the base of support, while stability involves dynamic adaptation to changes in external and internal forces. Gait is one of the most complex motor patterns, requiring synchronization of neuromuscular, biomechanical, and cognitive components. Although dysfunctions of these functions are more often associated with the older population, it is important to study them at a younger age, since it is precisely during this period that movement patterns are formed which can significantly affect long-term quality of life. During adolescence and early adulthood, processes of neuromuscular control and postural stability are still maturing, and the early development of improper patterns may lead to cumulative biomechanical overload and predispose young individuals to injuries later in life. The young population is exposed to specific risk factors. On the one hand, intensive sports activities and repetitive loads increase the risk of acute and chronic injuries of the lower extremities, particularly the ankle and knee. On the other hand, the increasing prevalence of a sedentary lifestyle and insufficient physical activity is associated with poorer motor development, reduced proprioception, and impaired postural stability. Scientific research has shown that physical inactivity during youth can negatively affect the biomechanical and cognitive mechanisms of gait control, while regular physical activity improves coordination, strength, and efficiency of the locomotor system.

Timely recognition of deviations in balance and gait among young individuals is of great importance for injury prevention and the preservation of long-term functionality. Systematic measurements make it possible to identify risky movement patterns and to develop personalized preventive programs. In this way, not only is the risk of injuries reduced in both the sporting and recreational population, but also the foundations for healthy functional ability in later stages of life are strengthened.

Beyond aspects of prevention and health preservation, research into balance and gait in young populations is also important for understanding the processes of neurological and motor control. Youth is a period during which the central nervous system continues to refine coordination and sensorimotor integration, which directly influences postural control and the efficiency of locomotor patterns. Analyzing balance and gait in this age group can provide valuable insights into how key motor mechanisms develop and stabilize.

Furthermore, biomechanical research in young populations may contribute to a better understanding of the relationship between cognitive functions and motor control. Increasing evidence suggests that gait and balance are not merely mechanical functions but also require the integration of attention, perception, and executive functions. In young individuals, who are in a phase of intensive learning and adaptation, monitoring these interactions can yield significant scientific and clinical value. In this project, the application of the Euleria Lab system is proposed. This certified medical device combines inertial sensors, a stabilometric board, and software for the objective assessment of movement.

The device enables precise measurement of static and dynamic balance, gait parameters, identification of irregularities not observable to the clinical eye. Its advantage lies in standardized and repeatable measurements, which reduce subjectivity in assessment and allow for a detailed analysis of the biomechanical aspects of movement.

The scientific relevance of this research lies in the fact that most existing studies have focused on older populations and fall prevention, while younger individuals have often been overlooked. By introducing objective and quantitative measurements into this age group, it becomes possible to expand current knowledge and to establish a database for comparisons in future research.

Associates:

prof.dr.sc. Stjepan Špalj, dr.med.dent.
doc.dr.sc. Matej Tomas, dr. med. dent.
dr.sc. Martina Juzbašić, dr.med.dent.
prof.prim.dr.sc. Daniela Kovačević Pavičić, dr.med.dent. 
prof.dr.sc. Vlatka debeljak, dr.med.dent.
doc.dr.sc. Damir Šnjarić, dr.med.dent.

Summary:

The success of oncological and supportive treatment in children and adolescents with malignant diseases has resulted in a growing population of survivors (Childhood Cancer Survivors, CCS). However, CCS often develop late complications that can affect various organ systems. Oncological treatment (chemotherapy, radiotherapy and/or stem cell transplantation) can lead to qualitative and quantitative changes in the body’s physiological bacterial flora, including the oral microbiota, which may have significant consequences for the oral health. A particular concern is potentially increasing salivary levels of cariogenic bacteria such as Streptococcus mutans and Lactobacillus spp., which are factors in the development of caries. Previous studies have shown a higher prevalence of caries among CCS, which emphasizes the need for regular monitoring and the implementation of preventive measures in these patients. Various methods are used for the detection of oral microorganisms, such as conventional cultures, enzymatic and immunoenzymatic assays, and conventional polymerase chain reaction (PCR). However, these methods do not allow precise quantification of bacteria, while on the other hand quantitative real-time PCR method (qRT-PCR) is a highly specific and sensitive method.  
The aim of the research is to evaluate the impact of oncological therapy on the salivary levels of cariogenic bacteria in CCS compared to a control group of healthy individuals using the qRT-PCR method. Additional objectives include the analysis of the relationship between the salivary levels of cariogenic bacteria, the KEP index and the type of oncological therapy. The visual detection of non-cavitated caries is difficult and can vary between examiners. The use of the DIAGNOcam was found to be an effective method for detecting early-stage, non-cavitated caries. Analysis of salivary levels of cariogenic bacteria in CCS can provide the basis for the developing targeted preventive measures and guidelines for monitoring and treatment of dental complications arising from intensive oncological therapy. 

Associates:

izv.prof.dr.sc. Željka Perić Kačarević, mag. biol.

doc.prim.dr.sc. Miroslav Sikora, dr. med. dent.

doc.dr.sc. Marinka Baranović Baričević, dr.med.dent.

dr.sc. Martina Čalušić Šarac, dr.med.dent.

Dora Dragičević, dr. med. dent., asistent

Summary:

Introduction: The success of implant-prosthetic therapy primarily depends on the adequate volume of alveolar bone and soft tissue. This essential requirement presents a particular challenge in patients with a history of periodontitis or in cases of bone and soft tissue loss following tooth extraction. Over the past decades, numerous augmentation techniques have been developed, with Guided Bone Regeneration (GBR) holding a central place in clinical practice. GBR is based on the application of either resorbable or non-resorbable membranes. Conventional resorbable membranes, such as collagen, have reduced mechanical stability, making them more prone to collapse into the defect, while their degradation is often unpredictable. On the other hand, non-resorbable membranes, such as polytetrafluoroethylene membranes, require an additional surgical intervention for removal. A newly developed resorbable metallic membrane made entirely of magnesium provides the necessary stability during osteogenesis, while being completely resorbed in vivo, thereby eliminating the need for a second surgical procedure. Beyond the challenge of bone regeneration, bone loss is almost invariably accompanied by a parallel loss of soft tissue. Acellular collagen matrices (ACM) have been developed as an alternative to autologous soft tissue grafts, reducing morbidity and enabling optimal aesthetic and functional soft tissue healing. A review of the current literature revealed a lack of clinical studies investigating the simultaneous use of a magnesium membrane and an acellular collagen matrix within a single surgical procedure.

Objectives: The aim of this project is to evaluate, through clinical and histological follow-up, the effectiveness of simultaneous bone and soft tissue regeneration using a magnesium membrane in combination with an acellular collagen matrix. Special emphasis will be placed on patients with a periodontal history, in whom the loss of alveolar bone and soft tissue is typically more pronounced. The project will analyze histological and histomorphometric parameters of regeneration, clinical outcomes of soft tissue healing, and radiological changes in ridge volume during healing.

Methodology: The study will include patients with a periodontal background who require extraction of one or more teeth and are scheduled for implant rehabilitation. Following atraumatic extraction, the socket will be augmented with a mixture of xenograft and autogenous bone and covered with a magnesium membrane, while an acellular collagen matrix will be used for soft tissue augmentation. Clinical healing parameters will be recorded during follow-up visits, and volumetric analysis of bone regeneration will be performed using CBCT. Prior to implant placement, bone samples will be collected using a trephine bur for histological and histomorphometric analysis, including quantification of newly formed bone, residual biomaterial, and connective tissue. It is expected that the simultaneous application of a magnesium membrane and a collagen matrix will enable successful bone regeneration while simultaneously improving soft tissue quality, thereby ensuring the long-term stability of implant-prosthetic therapy.

Associates:

izv. prof. dr. sc. Snježana Džijan
doc. dr. sc. Cecilija Rotim
dr. sc. Đorđe Pojatić
Kristina Bosak, mag. med. tech.
doc. dr. sc. Natko Gereš
izv. prof. prim. dr. sc. Darko Katalinić

Summary:

Hashimoto's thyroiditis (HT) is a prevalent autoimmune disorder characterized by chronic lymphocytic infiltration of the thyroid gland, often leading to hypothyroidism. While its etiology is multifactorial, emerging evidence suggests that circadian rhythm disruption may play a contributory role in autoimmune pathogenesis. Melatonin, a key regulator of circadian rhythms, exerts immunomodulatory effects through its interaction with the MTNR1B receptor expressed on immune cells. Alterations in melatonin signaling, particularly via genetic polymorphisms in the MTNR1B gene, may influence susceptibility to autoimmune conditions such as HT. The hypothalamic-pituitary-thyroid axis is under the control of the circadian clock via the suprachiasmatic nucleus, and it has been observed that the diurnal profile of TSH secretion is disturbed in some patients with impaired thyroid function (hypothyroidism) and increased thyroid function (hyperthyroidism). However, it is not clear whether there is a difference in melatonin concentration and the profile of the circadian melatonin rhythm in circadian phenotypes. Numerous studies have shown that there is a link between melatonin, thyroid function, and circadian phenotypes. Melatonin can suppress the mitosis of thyroid follicular cells in vivo and suppress thyroid hormone secretion. Melatonin and melatonin receptors are present in the thyroid gland, suggesting that melatonin may influence thyroid-specific gene expression and the synthesis and regulation of thyroid hormones. 
This study should explore the relationship between MTNR1B gene polymorphisms and circadian phenotypes—specifically chronotype and daytime sleepiness—in patients diagnosed with Hashimoto's thyroiditis. Given that melatonin deficiency has been linked to immune dysregulation, and that MTNR1B receptor function is critical for melatonin-mediated signaling, genetic variations in MTNR1B may represent a mechanistic link between circadian misalignment and autoimmune thyroid dysfunction. Melatonin not only regulates sleep but also modulates cellmediated and antibody-mediated immunity via membrane-bound MTNR1B receptors expressed by immune cells. Alterations in the melatonin-MTNR1B receptor signaling pathway may contribute to the development of different clinical phenotypes of autoimmune diseases and circadian phenotypes. This dual role of melatonin in regulating both the immune system and sleep behavior is critical to understanding its link to autoimmune diseases and circadian phenotypes. In addition, abnormal thyroid function can disrupt sleep architecture, further complicating the relationship between these disorders. Preliminary findings suggest that specific MTNR1B polymorphisms are associated with a preference for evening chronotypes and increased daytime sleepiness among HT patients, indicating a potential disruption in circadian homeostasis. These phenotypic traits may reflect underlying alterations in melatonin receptor sensitivity or expression, which in turn could exacerbate immune system dysregulation and contribute to disease progression. 
Understanding the genetic basis of circadian disturbances in HT not only provides insight into disease mechanisms but also opens avenues for chronobiological interventions. Targeting melatonin pathways or tailoring lifestyle modifications to align with individual circadian profiles may offer novel therapeutic strategies for managing autoimmune thyroid disorders. This research underscores the importance of integrating circadian biology into the broader framework of endocrine and immune system interactions, with MTNR1B polymorphisms serving as a promising biomarker for personalized approaches in HT care.

Associates:

Hrvoje Brkić, FDMZ

Ivana Krpan, FDMZ

Nevija Brstilo, FDMZ

Svjetlana Marić, FDMZ

Berislav Marković, FDMZ

Lucija Faj, Kifos

Matko Škarica, Odjel za fizikalnu medicinu, rehabilitaciju i reumatologiju, OBŽ  Vukovar

Dragan Mirkov,  Fakultet sporta i tjelesnog odgoja

Sveučilišta u Beogradu, Srbija, gostujući profesor FDMZ

Summary:

Biomechanics is a scientific discipline that connects the principles of mechanics with the biology of the human body, especially the musculoskeletal system. It provides an understanding of how forces and loads act on tissues during movement and how the body reacts and adapts during repetitive movements. This project will experimentally investigate the biomechanical responses of muscle and tendon subjects under controlled laboratory conditions and propose biomechanical models that describe these responses. The main goal of the research is to analyze changes in the kinematics of movement, the distribution of forces and the mechanical properties of tissues during the performance of standardized series of movements of different parts of the body under different loads. For this purpose, modern measurement methods will be used: 3D motion analysis, motion sensors, dynamometers, radiological and laboratory diagnostics. Measurements will be taken before and after the experimental protocol to assess acute changes in movement coordination, tissue stiffness, and muscle function during athlete diagnostics or during rehabilitation.

The results are expected to show an association between the type and intensity of load and biomechanical adjustments of the musculoskeletal system. The obtained findings will have applications in sports (optimization of training and injury prevention), ergonomics (adaptation of working conditions) and rehabilitation (planning exercises in accordance with the mechanical capacities of tissues). Undergraduate and graduate students of physiotherapy will be involved in the project. They will actively participate in the planning, collection and analysis of data, thus gaining practical knowledge of biomechanical measurement systems and developing research skills. The results and experiences gathered in the project will be integrated into the teaching process through practical exercises and seminars and will improve the implementation of teaching at the study.

Summary:

Breast cancer (BC) is the most common malignant tumor in women and represents a highly heterogeneous disease. Molecular subtypes such as luminal A, luminal B, HER2-positive, and triple-negative breast cancer (TNBC) significantly influence treatment strategies and patient prognosis. While standard subtyping is based on immunohistochemical analysis of biomarkers (ER, PR, HER2, Ki-67), increasing attention is being directed toward the development of non-invasive methods for predicting molecular status, especially using radiological features and artificial intelligence (AI).

Breast magnetic resonance imaging (MRI) demonstrates high sensitivity for BC detection and is already used in studies linking radiological features to molecular subtypes. Radiomics based on multiparametric MRI (particularly DCE-MRI) suggests that certain quantitative imaging features may correlate with tumor biology. At the same time, an increasing body of evidence supports the efficacy of AI in the detection, quantification, and classification of mammographic findings, opening the door for the development of so-called "virtual biopsy"—a non-invasive approach to predict tumor behavior based on advanced radiological analysis, without the need for invasive procedures.

In recent years, the use of contrast-enhanced mammography (CEM) has grown—this dual-energy technique provides both morphological and functional information about tumor vascularity, similar to MRI. CEM offers advantages such as broader availability, simpler implementation in clinical practice, shorter exam duration, and lower cost, making it suitable for evaluating patients with unclear findings on standard mammography or contraindications for MRI.

Our project hypothesis is that specific quantitative and qualitative CEM features—including lesion conspicuity, shape, margins, contrast enhancement pattern, breast density, and background parenchymal enhancement intensity and symmetry—combined with malignancy scores derived from AI analysis, may serve as non-invasive radiological biomarkers for the prediction of breast cancer molecular subtypes.

The aim of the project is to develop and validate an integrated radiologic-pathologic predictive model that combines CEM features, AI-based malignancy scores, and immunohistochemical data. We expect that such a model will enable earlier and more accurate identification of aggressive tumor subtypes (e.g., HER2+ and TNBC), improve initial diagnostic accuracy, reduce unnecessary biopsies, accelerate treatment decisions, and decrease psychological burden for patients.

The project aligns with the priorities of modern healthcare in the field of precision oncology, early cancer detection, and personalized treatment. The proposed model has strong potential for rapid integration into clinical practice and widespread application in the radiological assessment of breast cancer patients.