Augmented Reality Integration in Skull Base Neurosurgery: A Systematic Review.

Background and Objectives: To investigate the role of augmented reality (AR) in skull base (SB) neurosurgery. Materials and Methods: Utilizing PRISMA methodology, PubMed and Scopus databases were explored to extract data related to AR integration in SB surgery. Results: The majority of 19 included studies (42.1%) were conducted in the United States, with a focus on the last five years (77.8%). Categorization included phantom skull models (31.2%, n = 6), human cadavers (15.8%, n = 3), or human patients (52.6%, n = 10). Microscopic surgery was the predominant modality in 10 studies (52.6%). Of the 19 studies, surgical modality was specified in 18, with microscopic surgery being predominant (52.6%). Most studies used only CT as the data source (n = 9; 47.4%), and optical tracking was the prevalent tracking modality (n = 9; 47.3%). The Target Registration Error (TRE) spanned from 0.55 to 10.62 mm. Conclusion: Despite variations in Target Registration Error (TRE) values, the studies highlighted successful outcomes and minimal complications. Challenges, such as device practicality and data security, were acknowledged, but the application of low-cost AR devices suggests broader feasibility.

Histopathological spectrum of lumbar disc changes in obesity: analysis of intervertebral discs in lumbar hernia patients in Zenica-Doboj Canton, Bosnia and Herzegovina.

Aim To investigate the correlation of body mass index (BMI) with severity of intervertebral disc degeneration. Methods The study enrolled patients who had undergone surgical intervention for a herniated disc at the Department of Neurosurgery of the Cantonal Hospital Zenica. Patients underwent thorough preoperative evaluation, including medical history, neurological and physical assessments, and radiological analysis. The surgical intervention consisted of a posterior lumbar discectomy, and the excised disc material was preserved and subjected to histopathological analysis based on Histopathologic Degeneration Score (HDS). Patients were divided in two groups according to Body Mass Index (BMI): study group with BMI≥25 and control group with BMI<25. Results Among 69 patients with herniated IVD, 26 (37.7%) were with BMI≥25 (study group), and 43 (62.3%) were with BMI<25 (controls). The study group displayed substantial increase in height, 1.80±0.06 m compared to controls, 1.74±0.06 m (p=0.001). Weight and BMI were significantly higher in the study group of patients (weight: 91.60±10.22 vs. 67.37±9.20 kg, BMI: 28±2 vs. 22±2; p<0.001). Differences were confirmed in HDS values in the study group comparing to the control group (p<0.001). The study group exhibited significant differences in chondrocyte proliferation, tears and clefts, granular changes, and mucous degeneration (p<0.05), and positive correlations were found between BMI and these alterations found in the herniated discs (p<0.05). Therefore, HDS showed positive correlations with BMI (R=0.599; p<0.001) and weight (R=0.696; p<0.001). Conclusion The study's findings confirmed that BMI has a significant impact on intervertebral disc degeneration, emphasizing the importance of weight management in preventing disc degeneration.

CRISPR/Cas9-Mediated Gene Therapy for Glioblastoma: A Scoping Review.

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.

Unveiling drug induced nephrotoxicity using novel biomarkers and cutting-edge preventive strategies.

Drug-induced nephrotoxicity is still a significant obstacle in pharmacotherapy of various diseases and it accounts for around 25 % of serious side-effects reported after drug administration. Furthermore, some groups of drugs such as nonsteroidal anti-inflammatory drugs, antibiotics, antiviral drugs, antifungal drugs, immunosuppressants, and chemotherapeutic drugs have the "preference" for damaging the kidney and are often referred to as the kidney's "silent killer". Clinically, the onset of acute kidney injury associated with drug administration is registered in approximately 20 % of patients and many of them develop chronic kidney disease vulnerability. However, current knowledge about the mechanisms underlying this dangerous phenomenon is still insufficient with many unknowns. Hence, the valuable use of these drugs in clinical practice is significantly limited. The main aim of this study is to draw attention to commonly prescribed nephrotoxic drugs by clinicians or drugs bought over the counter. In addition, the complex relationship between immunological, vascular and inflammatory events that promote kidney damage is discussed. The practical use of this knowledge could be implemented in the engineering of novel biomarkers for early detection of drug-associated kidney damage such as Kidney Injury Molecule (KIM-1), lipocalin associated with neutrophil gelatinase (NGAL) and various microRNAs. In addition, the utilization of artificial intelligence (AI) for the development of computer algorithms that could detect kidney damage at an early stage should be further explored. Therefore, this comprehensive review provides a new outlook on drug nephrotoxicity that opens the door for further clinical research of novel potential drugs or natural products for the prevention of drug-induced nephrotoxicity and accessible education.

Novel therapeutical approaches based on neurobiological and genetic strategies for diabetic polyneuropathy - A review.

BACKGROUND: Neuropathy is among the most often reported consequences of diabetes and the biggest cause of morbidity and mortality in people suffering from this life-long disease. Although different therapeutic methods are available for diabetic neuropathy, it is still the leading cause of limb amputations, and it significantly decreases patients' quality of life. AIM: This study investigates potential novel therapeutic options that could ameliorate symptoms of DN. METHODOLOGY: Research and review papers from the last 10 years were taken into consideration. RESULTS: There are various traditional drugs and non-pharmacological methods used to treat this health condition. However, the research in the area of pathogenic-oriented drugs in the treatment of DN showed no recent breakthroughs, mostly due to the limited evidence about their effectiveness and safety obtained through clinical trials. Consequently, there is an urgent demand for the development of novel therapeutic options for diabetic neuropathy. CONCLUSION: Some of the latest novel diagnostic methods for diagnosing diabetic neuropathy are discussed as well as the new therapeutic approaches, such as the fusion of neuronal cells with stem cells, targeting gene delivery and novel drugs.

HEART Score and Its Implementation in Emergency Medicine Departments in the West Balkan Region-A Pilot Study.

BACKGROUND: Chest pain represents a prevalent complaint in emergency departments (EDs), where the precise differentiation between acute coronary syndrome and alternative conditions assumes paramount significance. This pilot study aimed to assess the HEART score's implementation in West Balkan EDs. METHODS: A retrospective analysis was performed on a prospective cohort comprising patients presenting with chest pain admitted to EDs in Sarajevo, Zenica, and Belgrade between July and December 2022. RESULTS: A total of 303 patients were included, with 128 classified as low-risk based on the HEART score and 175 classified as moderate-to-high-risk. The low-risk patients exhibited younger age and a lower prevalence of cardiovascular risk factors. Laboratory and anamnestic findings revealed higher levels of C-reactive protein, ALT, and creatinine, higher rates of moderately to highly suspicious chest pain history, a greater number of cardiovascular risk factors, and elevated troponin levels in moderate-to-high-risk patients. Comparatively, among patients with a low HEART score, 2.3% experienced MACE, whereas those with a moderate-to high-risk HEART score had a MACE rate of 10.2%. A moderate-to-high-risk HEART score demonstrated a sensitivity of 91.2% (95%CI 90.2-93.4%) and specificity of 46.5% (95%CI 39.9-48.3%) for predicting MACE. CONCLUSION: This pilot study offers preliminary insights into the integration of the HEART score within the emergency departments of the West Balkan region.

Effects of Zofenopril on Arterial Stiffness in Hypertension Patients.

Angiotensin-converting enzyme inhibitors (ACEIs) reduce arterial stiffness beyond their antihypertensive effect. Studies showed that sulfhydryl ACEIs have the antioxidative potential to improve endothelial function, which might have a clinical effect on arterial distensibility. However, there are no studies that directly compare the effects of sulfhydryl (zofenopril) and non-sulfhydryl ACEIs (enalapril) on arterial stiffness. Therefore, this prospective study aims to compare the effects of enalapril and zofenopril on arterial stiffness and oxidative stress in both short- and long-term treatment of arterial hypertension (AH). Baseline and post-treatment peripheral and central arterial pressure indices, augmentation index (Aix), aortic pulse wave velocity (ao-PWV), serum levels of oxidized low-density cholesterol lipoprotein, LDL and uric acid (UA) were measured. The results showed that acute treatment with zofenopril, in contrast to enalapril, significantly decreased peripheral and central Aix (p < 0.001). Chronic treatment with zofenopril showed a superior effect over enalapril on the reduction of the peripheral systolic arterial pressure with reduction of ao-PWV (p = 0.004), as well as a reduction in peripheral Aix (p = 0.021) and central Aix (p = 0.021). Therefore, this study indicates that zofenopril has beneficial effects on the reduction of arterial stiffness compared to enalapril. It has potent clinical efficacy in AH treatment and further studies should compare its safety and long-term efficacy to other AH drugs that would aid clinicians in treating AH and other various cardiovascular diseases that have arterial stiffness as a common denominator.

Magnetic resonance morphometry of the lumbar spinal canal in Zenica - Doboj Canton in Bosnia and Herzegovina.

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.

Cellular therapeutic potential of genetically engineered stem cells in cancer treatment.

Traditional therapeutic approaches in the treatment of cancer have many side effects and are often ineffective and non-specific, leading to the development of therapy-resistant tumour cells. Recently, numerous discoveries about stem cells have given a new outlook on their application in oncology. Stem cells are unique because of their biological attributes, including self-renewal, differentiation in different types of specialized cells and synthesis of molecules that interplay with tumour niche. They are already used as an effective therapeutic option for haematological malignancies, such as multiple myeloma and leukaemia. The main goal of this study is to investigate the possible applications of different types of stem cells in cancer treatment and to summarize novel advances, as well as the limitations of their application in cancer treatment. Research and clinical trials that are underway revealed and confirmed the enormous potential of regenerative medicine in the treatment of cancer, especially when combined with different nanomaterials. Nanoengineering of stem cells has been the focus of novel studies in the area of regenerative medicine, such as the production of nanoshells and nanocarriers that enhance the transport and uptake of stem cells in their targeted tumour niche and enable the effective monitoring of stem cell effects on tumour cells. Although nanotechnology has a lot of limitations, it provides new opportunities for the development of effective and innovative stem cell therapies.

Functional biotransformation of phytoestrogens by gut microbiota with impact on cancer treatment.

The human gut is a host for trillions of microorganisms, divided into more than 3,000 heterogeneous species that is called the gut microbiota. The gut microbiota composition can be altered by many different endogenous and exogenous factors, especially diet and nutrition. A diet rich in phytoestrogens, a variable group of chemical compounds similar to 17-ß-estradiol (E2), the essential female steroid sex hormone is potent to change the composition of gut microbiota. However, the metabolism of phytoestrogens also highly depends on the action of enzymes produced by gut microbiota. Novel studies have shown that phytoestrogens could play an important role in the treatment of different types of cancers, such as breast cancer in women, due to their potential to decrease estrogen levels. This review aims to summarize recent findings about the lively dialogue between phytoestrogens and gut microbiota and to address their possible future application, especially in treating patients with diagnosed breast cancer. A potential therapeutic approach for the prevention and improving outcomes in breast cancer patients could be based on targeted probiotic supplementation with the use of soy phytoestrogens. A positive effect of probiotics on the outcome and survival of patients with breast cancer has been established. However, more in vivo scientific studies are needed to pave the way for the use of probiotics and phytoestrogens in the clinical practice of breast cancer treatment.

Effects of intestinal flora on pharmacokinetics and pharmacodynamics of drugs.

Gut microbiota is known as unique collection of microorganisms (including bacteria, archaea, eukaryotes and viruses) that exist in a complex environment of the gut. Recently, this has become one of the most popular areas of research in medicine because this plays not only an important role in disease development, but gut microbiota also influences drug pharmacokinetics. These alterations in drug pharmacokinetic pathways and drug concentration in plasma and blood often lead to an increase in the incidence of toxicological events in patients. This review aims to present current knowledge of the most commonly used drugs in clinical practice and their dynamic interplay with the host's gut microbiota as well as the mechanisms underlying these metabolic processes and the consequent effect on their therapeutic efficacy and safety. These new findings set a foundation for the development of personalized treatments specific to each metabolism, maximizing drugs' therapeutic effects and minimizing the side effects because they are one of the major limiting factors in treating patients.

Covid-19 a triggering factor of autoimmune and multi-inflammatory diseases.

SARS-CoV-2 virus has attracted a lot of attention globally due to the autoimmune and inflammatory processes that were observed during the development of Covid-19 disease. Excessive activation of immune response and triggering of autoantibodies synthesis as well as an excessive synthesis of inflammatory cytokines and the onset of cytokine storm has a vital role in the disease outcome and the occurring autoimmune complications. This scenario is reminiscent of infiltration of lymphocytes and monocytes in specific organs and the increased production of autoantibodies and chemoattractants noted in other inflammatory and autoimmune diseases. The main goal of this study is to investigate the complex inflammatory processes that occur in Covid-19 disease and to find similarities with other inflammatory diseases such as multiple sclerosis (MS), acute respiratory distress syndrome (ARDS), rheumatoid arthritis (RA) and Kawasaki syndrome to advance existing diagnostic and therapeutic protocols. The therapy with Interferon-gamma (IFN-γ) and the use of S1P receptor modulators showed promising results. However, there are many unknowns about these mechanisms and possible novel therapies. Therefore, the inflammation and autoimmunity triggered by Covid-19 should be further investigated to improve existing diagnostic procedures and therapeutic protocols for Covid-19.