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This scoping review examines the use of CRISPR/Cas9 gene editing in glioblastoma (GBM), a predominant and aggressive brain tumor. Categorizing gene targets into distinct groups, this review explores their roles in cell cycle regulation, microenvironmental dynamics, interphase processes, and therapy resistance reduction. The complexity of CRISPR-Cas9 applications in GBM research is highlighted, providing unique insights into apoptosis, cell proliferation, and immune responses within the tumor microenvironment. The studies challenge conventional perspectives on specific genes, emphasizing the potential therapeutic implications of manipulating key molecular players in cell cycle dynamics. Exploring CRISPR/Cas9 gene therapy in GBMs yields significant insights into the regulation of cellular processes, spanning cell interphase, renewal, and migration. Researchers, by precisely targeting specific genes, uncover the molecular orchestration governing cell proliferation, growth, and differentiation during critical phases of the cell cycle. The findings underscore the potential of CRISPR/Cas9 technology in unraveling the complex dynamics of the GBM microenvironment, offering promising avenues for targeted therapies to curb GBM growth. This review also outlines studies addressing therapy resistance in GBM, employing CRISPR/Cas9 to target genes associated with chemotherapy resistance, showcasing its transformative potential in effective GBM treatments.

E. Selimović, H. Bečulić, Emir Begagić, Ivan Galić

Introduction: Fear of intervention in the oral cavity is declared as dental fear and is defined as a specific form of anxiety. The reaction to oral-surgical intervention will also depend on the feeling the patient acquires about the operator, but the positive experience also plays an important role.Aim: The aim is to evaluate differences between the sexes and the influence of experience from a previous oral surgical intervention on a similar subsequent intervention.Material and methods: In the research, anxiety was assessed using Corah's Dental Anxiety Scale (DASR) and Spielberger's State-Trait Anxiety Inventory (X1 and X2). The study included adult patients of both sexes with an indication for surgical extraction of impacted third permanent molars. Preoperative and postoperative anxiety was assessed: 1st measurement (day of examination) - DASR, and STAI (X1 and X2); 2nd measurement (immediately before the intervention) – STAI (X1 and X2); 3rd measurement (day after the intervention) – STAI (X1 and X2).Results: Preoperatively determined high levels of general, immediate, and dental anxiety decreased before the surgical procedure itself and were significantly reduced in the postoperative period. The downward trend continued in line with the positive experience. Women had higher anxiety scores than men for all monitored parameters. The use of the STAI scales to assess anxiety by dental practitioners is on par with other well-known anxiety assessment instruments, such as the DASR. Conclusion: In order to increase patient satisfaction and to prevent possible complications in such oral-surgical procedures, it would be useful to consider adequate therapy for high anxiety.

E. Selimović, Emir Begagić, H. Bečulić, Muharem Adilović

This review paper explores the use of miswak, a teeth-cleaning twig made from the Salvadora persica plant, in maintaining oral hygiene and preventing oral diseases. Various aspects of miswak are analyzed, including its historical significance, chemical composition, pharmacological characteristics, and beneficial effects on oral health. The paper also investigates the Islamic perspective on oral hygiene and the use of miswak, as well as the socio-medical aspect of oral disease prevention. While there are studies that point out potential drawbacks of miswak usage, proper application and combination with conventional oral hygiene methods can result in good oral health. Considering its cost-effectiveness and the need for affordable oral hygiene methods, further research on the use of miswak is valuable and necessary. This paper provides an overview of modern and relevant scientific literature on miswak and its significance in maintaining oral health, highlighting its journey from tradition to paradigm. Keywords: miswak, oral health, social medicine.

Fatima Juković-Bihorac, H. Bečulić, Emir Begagić, Rasim Skomorac

Introduction: Basal cell carcinoma is the most common non melanoma skin cancer. It accounts for approximately 80% of all skin cancers. Case report: We presented a 62-year-old patient with a giant, deeply infiltrative, destructive lesion of the head which lasted for 15 years. Microbiological analysis showed contamination, computed tomography (CT) scan showed deep infiltration and bone destruction. The risks of operative treatment were numerous. The treatment was more complicated by infection, infiltrative spreading and the patient's comorbidity. Regardless, we decided on a wide surgical resection with pathohistological evaluation of the resection margins. The patient denied oncological treatment. After 10 years, there were no recurrent tumours. Conclusion: Aggressive surgical treatment is the treatment of choice for giant basal cell carcinoma. In the case of giant locally aggressive and advanced neoplasms, when surgery is not appropriate or not possible, medical treatment becomes oncological.

Emir Begagić, Ragib Pugonja, H. Bečulić, Amila Čeliković, Lejla Tandir Lihić, Samra Kadić Vukas, Lejla Čejvan, Rasim Skomorac et al.

This systematic review assesses current molecular targeted therapies for glioblastoma multiforme (GBM), a challenging condition with limited treatment options. Using PRISMA methodology, 166 eligible studies, involving 2526 patients (61.49% male, 38.51% female, with a male-to-female ratio of 1.59/1), were analyzed. In laboratory studies, 52.52% primarily used human glioblastoma cell cultures (HCC), and 43.17% employed animal samples (mainly mice). Clinical participants ranged from 18 to 100 years, with 60.2% using combined therapies and 39.8% monotherapies. Mechanistic categories included Protein Kinase Phosphorylation (41.6%), Cell Cycle-Related Mechanisms (18.1%), Microenvironmental Targets (19.9%), Immunological Targets (4.2%), and Other Mechanisms (16.3%). Key molecular targets included Epidermal Growth Factor Receptor (EGFR) (10.8%), Mammalian Target of Rapamycin (mTOR) (7.2%), Vascular Endothelial Growth Factor (VEGF) (6.6%), and Mitogen-Activated Protein Kinase (MEK) (5.4%). This review provides a comprehensive assessment of molecular therapies for GBM, highlighting their varied efficacy in clinical and laboratory settings, ultimately impacting overall and progression-free survival in GBM management.

Lejla Čano Dedić, Arzija Pašalić, Emsel Papić, Emir Begagić, Sabina Šečić – Selimović, Mario Gazibarić, Sabina Šegalo

Introduction: Insulin resistance (IR) is a complex pathophysiological condition multifactorial etiology characterized by diminished responsiveness of insulin target tissues. Today, various diagnostic approaches involving different laboratory parameters are available, but simple and non-invasive indices based on mathematical models are increasingly used in practice. This study aims to assess the effectiveness of various clinical surrogate indices in predicting IR across a population with varying body weights. Methods: The matched case-control study was conducted between January 2021 and December 2022. Secondary data extracted from the medical records of 129 subjects was analyzed, including demographic characteristics (age and gender), anthropometric measures (height and weight), and biochemical laboratory test results. y further divided into two subgroups based on body mass index (BMI): overweight (BMI between 25 and 29.9 kg/m2) and obese (BMI of 30 kg/m2 or higher). Using laboratory data values for six widely used clinical surrogate markers were calculated: Homeostatic model assessment for IR (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Mcauley index (MCAi), metabolic score for IR (METS-IR), Triglyceride to Glucose Index (TyG), and TyG to BMI (TyG-BMI). Results: Significant differences in HOMA-IR levels were observed between the groups (p < 0.001). A similar pattern was found for the TyG-BMI, with notable differences (p < 0.001). The obese participants had the highest mean levels for METS-IR and the TyG index while the control group had the highest mean values for the QUICKI and MCAi indices (p < 0.001). According to the analysis, three indices showed statistical significance in predicting IR independent of BMI (p < 0.05). Sensitivity and specificity were higher in the obese group (0.704 and 0.891) than in the overweight group (0.631 and 0.721). Conclusion: Given that IR is a multifactorial disease, using derived indices based on a combination of biochemical parameters and anthropometric indicators can significantly aid in predicting and mitigating numerous complications.

H. Bečulić, Denis Spahić, Emir Begagić, Ragib Pugonja, Rasim Skomorac, Aldin Jusic, E. Selimović, Anes Masovic et al.

Background and Objectives: Cranial defects pose significant challenges in low and middle-income countries (LIMCs), necessitating innovative and cost-effective craniofacial reconstruction strategies. The purpose of this study was to present the Bosnia and Herzegovina model, showcasing the potential of a multidisciplinary team and 3D-based technologies, particularly PMMA implants, to address cranial defects in a resource-limited setting. Materials and Methods: An observational, non-experimental prospective investigation involved three cases of cranioplasty at the Department of Neurosurgery, Cantonal Hospital Zenica, Bosnia and Herzegovina, between 2019 and 2023. The technical process included 3D imaging and modeling with MIMICS software (version 10.01), 3D printing of the prototype, mold construction and intraoperative modification for precise implant fitting. Results: The Bosnia and Herzegovina model demonstrated successful outcomes in cranioplasty, with PMMA implants proving cost-effective and efficient in addressing cranial defects. Intraoperative modification contributed to reduced costs and potential complications, while the multidisciplinary approach and 3D-based technologies facilitated accurate reconstruction. Conclusions: The Bosnia and Herzegovina model showcases a cost-effective and efficient approach for craniofacial reconstruction in LIMICs. Collaborative efforts, 3D-based technologies, and PMMA implants contribute to successful outcomes. Further research is needed to validate sustained benefits and enhance craniofacial reconstruction strategies in resource-constrained settings.

Emir Begagić, H. Bečulić, Rasim Skomorac, Mirza Pojskić

Advancements in neurosurgical visualization have been made possible by the introduction of the operating microscope (OM) and the emergence of exoscopic technology (EX). Both OMs and EXs provide enhanced magnification and illumination, but they come with their own set of advantages and disadvantages. OMs provide high-quality magnification and illumination and have been used successfully in a variety of surgical procedures. They can be customized to fit the specific needs of the surgeon and are a well-established technology. However, they can be bulky, expensive, and cause discomfort during extended procedures. EXs provide high-definition magnification and illumination, improved depth perception and ergonomics, and can be cost-effective. They can be customized to fit the specific needs of the surgeon and can be made using locally available materials, reducing the need for expensive imports. However, they may require adjustment and have a learning curve for surgeons who are used to operating with OMs. Additionally, they may have limited availability in some healthcare settings. The choice between OMs and EXs will depend on the specific needs of the surgeon and the healthcare setting. The integration of 3D EX systems has revolutionized neurosurgery, offering improved depth perception and ergonomics. EX's cost-effectiveness addresses accessibility concerns, making it an attractive alternative, particularly for low and middle-income healthcare settings. The exoscope seems to be a safe alternative compared to an operative microscope for the most common brain and spinal procedures. The exoscope may help expand access to neurosurgical care and training worldwide. In conclusion, both technologies have their own set of advantages and disadvantages, and the choice between them will depend on the specific needs of the surgeon and the healthcare setting.

H. Bečulić, Emir Begagić, Rasim Skomorac, Aldin Jusic, E. Selimović, Lejla Čejvan, Mirza Pojskić

Intraorbital and transorbital injuries are included in the group of head injuries with low frequency. In particular, such injuries rarely result in infectious processes in the brain parenchyma. This case presents a case where a 57-year-old man reported to the neurosurgery department that he had sustained an injury to the conjunctiva of the upper eyelid a month earlier. The patient was injured by a tree branch, which he removed on his own initiative. After persistent eye abduction palsy, an MRI was performed, which showed a compressive mass in the frontal lobe of the brain. A surgical procedure was indicated, which found a piece of twig 3 mm long inside the abscess. Surgical intervention and antibiotic therapy led to the complete recovery of the patient.

Belma Jaganjac, Amina Džidić-Krivić, H. Bečulić, A. Šljivo, Emir Begagić, Adis Šišić

Aim To investigate morphometric determinants of lumbar canal in patients treated in Cantonal Hospital Zenica, and their variation according to gender. Methods Morphometry of lumbar spinal canal was assessed in 52 patients treated at the Department of Neurosurgery of Cantonal Hospital Zenica in the period between September 2022 and November 2022. Data were collected retrospectively: anteroposterior and transverse diameter of lumbar vertebrae and intervertebral discs, as well as anteroposterior diameter of the spinal canal. Results Gender appeared to be an important morphometric determinant, since it significantly differed when it comes to lumbar vertebral anteroposterior and transverse diameter, being mostly larger in males. Conclusion This study increases anatomical knowledge of the vertebras and spinal canal of the lumbar region. Therefore, the measured dimensions of the lumbar vertebrae and spinal canal could be used as a baseline point for evaluation of patients presenting with low back pain and potential spinal canal stenosis.

H. Bečulić, Emir Begagić, Rasim Skomorac, Aldin Jusic, A. Efendic, E. Selimović, Anes Masovic, Lejla Bečulić

Aim To examine a correlation of demographic characteristics of patients, preoperative modality of conservative therapy and timing on the postoperative outcome of patients six months after the operation. Methods A retrospective, non-randomized, clinical study involved 48 patients of different age and gender with a verified diagnosis of cauda equina syndrome (CES). The inclusion criteria were patients with CES caused by discus hernia. Observed research variables were age, gender, affected vertebral level, conservative modalities of perioperative therapy (nonsteroidal anti-inflammatory drugs - NSAIDs and physiotherapy), duration of symptoms, and outcome parameters (motor and sensory function, sphincter function of the urinary bladder and bowel). Results A statistically significant negative correlation was found between age and postoperative outcome (p<0.05). The affected vertebral level was positively correlated with the motor and sensory outcome (p<0.05). A positive correlation between the use of NSAIDs and the outcome was found (R=0.570; p<0.001), as well as a negative correlation with perioperative physiotherapy (R=-0.201; p= 0.001). Postponement of surgery was negatively correlated with outcome variables (p<0.001). Conclusion The results of the study bring new conclusions that were not previously observed. Possible new characteristics associated with the outcome of cauda equina syndrome were determined.

A. Efendic, H. Bečulić, Rasim Skomorac, Aldin Jusic, E. Selimović, Emir Begagić, Fatima Juković-Bihorac

Aim: To present a very rare case of empyema cavuma septi pellucidi. Case report: A 5-year-old male child was admitted to the Department of Infectious Diseases Cantonal Hospital Zenica because of fever (38.30C), headache and vomiting. The patient developed intracranial hypertension as a result of a compressive purulent collection formed due to meningitis between the lamine of the septum pelucidum with consequent intracranial hypertension. Conclusion: The decision regarding the modality of treatment was not easy. We considered that empyema evacuation using the transcallosalinterhemispheric approach allows the complete removal of purulent collection and the placement of drainage, which allows additional emptying of the empyema cavity and prevents empyema recurrence. Empyema evacuation with drainage and antibiotic therapy have shown beneficial results.

Emir Begagić, N. Duzic, Zlatan Memic, N. Arandelovic, Anida Celebic, H. Bečulić

Abstract Objective To provide relevant insight into the current degree of usage of the research potential of students of biomedical sciences in Bosnia and Herzegovina. Method The chosen data collection method was online surveying via Google search engine. The target group were students of biomedical sciences in Bosnia and Herzegovina. The surveying was conducted in July 2019, and responses were subjected to descriptive statistics. Results Although the majority of participants claimed that they were familiar with the seminar and scientific papers writing methodology and that the related course is available in their faculty’s curriculum, the quality of such courses may be questioned as the majority of study participants self-reported that they do not possess or did not posses necessary knowledge for writing and publishing a scientific paper. Also, the majority of respondents reported that they have never participated in any scientific research, which questions the involvement of students in scientific research in our country as well. More than half of respondents were actively reading scientific papers, but a third of them did not have that habit. Two-thirds of students reported that they have never attended any scientific event where they could learn more about the scientific research methods. Inadequate awareness of the importance of research, lack of students’ interest in making a research, and lack of knowledge were characterized as main obstacles in conducting scientific research according to survey responses. Conclusion Information obtained through research indicate that the student potential in scientific research in Bosnia and Herzegovina has not been used in its maximal capacity, requiring several steps to be taken towards its improvement.

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