Background: The main feature of osteoarthritis (OA) is the deterioration of articular cartilage, but numerous studies have demonstrated the role of synovial inflammation in the early stages of the disease, leading to further progression of OA. The WNT signaling pathway is involved in numerous activities in joint tissue, but there is a lack of evidence considering the role of WNT in OA synovitis. Our research aims to investigate the expression of WNT Family Member 5A/B (WNT5A/B), β-catenin, acetyl-α-tubulin, Dishevelled-1 (DVL-1), and Inversin (INV) in the synovial membrane of osteoarthritis (OA) hips. Methods: The immunohistochemical expressions of the aforementioned proteins in the synovial membrane were analyzed and compared with samples of control group participants with fractured femoral necks. Results: The immunoexpression of acetyl-α-tubulin was significantly increased in the intima (p < 0.0001) and subintima (p < 0.0001) of the group with OA compared with the intima and subintima of the control group. At the same time, acetyl-α-tubulin was also more highly expressed in the intima of the OA group than in the subintima of the OA group (p < 0.05); we found the same expression pattern in the control group (p < 0.0001). The differential analysis of the GEO dataset did not show significant differences between the osteoarthritis (OA) and control groups in the expression of TUBA1A. β-catenin was significantly increased in the subintima (p < 0.01) of the group with OA compared to the subintima of the control group. WNT expression has significantly higher positivity in the subintima than in the intima, especially in the control group (p < 0.01). WNT5A and WNT5B were significantly down-regulated in OA compared to the control in the differential analysis of the GEO dataset. The expression of INV and DVL-1 in our study and the differential analysis of the GEO dataset did not differ significantly between the osteoarthritis (OA) and control groups. Conclusions: Based on our results, we suggest that acetyl-α-tubulin and β-catenin might be involved in synovial membrane inflammation in OA and serve as potential therapeutic targets.

Background: Different dietary components can affect hematological and biochemical profiles, potentially causing pathohistological changes in liver and kidney tissue. Aim: The animals in the experiment consumed various bakery and meat products, and ultimately, the potential effects on hematological, biochemical, and pathological parameters were evaluated. Methods: The study involved 24 clinically healthy adult rats, randomized into three groups of eight rats each, as follows: rats that consumed meat products (group M), rats that consumed bakery products (group H), and a control group that consumed conventional rodent food (group K) for 7 weeks. After 7 weeks, hematological and biochemical blood analyses were conducted along with pathohistological examinations of the liver and kidneys. Results: Significant differences (p < 0.05) were observed among groups for several hematological and biochemical parameters, including creatinine (CREA), urea, blood urea nitrogen /CREA, calcium, alanine transaminase, alkaline phosphatase, and lipase. Consuming meat products had a less favorable impact on the occurrence of kidney function disorders. Group H exhibited significant differences in leukocyte and platelet counts compared with groups M and K. Extreme echinocytosis was recorded in group M, whereas sideropenic anemia was prominent in group H. Analysis of the livers of rats in groups K and H did not show significant differences in the observed parameters (gamma-glutamyl transferase and total bilirubin), whereas group M had a significantly higher degree of hepatocyte degeneration and steatosis, and the observed infiltrate was also more pronounced, but not significantly. The kidneys of group M showed discrete alterations of the microstructure, i.e., slightly increased cellularity of renal corpuscles and hypertrophy of proximal nephrocyte, whereas the kidney tissue of group K had a regular appearance. Conclusion: Consuming meat products was associated with adverse liver and kidney changes, whereas bakery products led to sideropenic anemia and altered hematological values.

In this article, we analyze the stability properties of stochastic linear systems in closed loop with an optimal policy that minimizes a discounted quadratic cost in expectation. In particular, the linear system is perturbed by both additive and multiplicative stochastic disturbances. We provide conditions under which mean-square boundedness, mean-square stability, and recurrence properties hold for the closed-loop system. We distinguish two cases, when these properties are verified for any value of the discount factor sufficiently close to 1, or when they hold for a fixed value of the discount factor in which case tighter conditions are derived, as illustrated in an example. The analysis exploits properties of the optimal value function, as well as a detectability property of the system with respect to the stage cost, to construct a Lyapunov function for the stochastic linear quadratic regulator problem.

Background: All currently used therapeutic protocols and drugs for Clostridioides difficile infection (CDI) treatment do not have a satisfying success and usually cost a lot. Objectives: To compare the efficacy of vancomycin monotherapy vs modified dual therapy with vancomycin + nifuroxazide as a therapeutic protocol for a medium–severe form of CDI. In addition, the effects of a modified therapeutic protocol with standard monotherapy on the number of stools and stool consistency in a medium–severe CDI will be compared. Materials and Methods: A prospective, randomized, controlled clinical trial that included 60 patients divided into two groups was conducted. One group of patients was treated with vancomycin monotherapy. The other group was treated with the modified therapeutic protocol (vancomycin + nifuroxazide). Results: The modified therapy with vancomycin + nifuroxazide demonstrated enhanced pharmacological efficacy in the management of CDI compared to the standard vancomycin monotherapy. Patients treated with dual therapy reported a significantly lower number of stools in first, second and third control; first control (4.47 ± 2.20 compared to 5.70 ± 1.91 in vancomycin group (p = 0.024)), second control (2.37 ± 0.85 compared to 3.13 ± 0.90 in vancomycin group (p = 0.001)), and third control (1.53 ± 0.51 compared to 1.80 ± 0.61 in vancomycin group (p = 0.035)). Also, the first and third controls noted significant improvements in stool consistency, measured as a decrease in the number of completely watery stools (p = 0.011 and p < 0.001, respectively). Conclusions: Nifuroxazide and vancomycin have demonstrated accelerated improvement in patient status and hold promise as a novel dual therapeutic regimen for managing patients diagnosed with a medium–severe form of CDI.

Background/Objectives: Composite hemangioendothelioma (CHE) is a rare vascular endothelial tumor with borderline malignancy. This study presents a case of CHE and an updated systematic review of previously reported cases, providing insights into recurrence patterns and survival outcomes. Methods: A comprehensive electronic search was conducted across PubMed, Scopus, the Cochrane Library, and Web of Science up to 31 December 2024, to identify eligible case reports. Kaplan–Meier curves were used to estimate event-free survival. Results: We report a 61-year-old man with a splenic lesion associated with weight loss and abdominal pain persisting for 1 year. Intraoperative findings revealed an enlarged spleen and multiple hepatic deposits. Splenectomy and liver biopsy revealed a well-demarcated, nodular tumor measuring 160 × 145 × 100 mm, with histological and immunohistochemical findings consistent with CHE, complicated by hepatic metastasis. Of 405 potentially eligible studies, 59 were included in the review, covering cases from 2000 to 2024, with a peak in 2020 and 2023. The median age of patients was 42 years, with the most common tumor sites being the lower extremities (30.48%), followed by the face, head, and neck (20.95%), and upper extremities (18.1%). Surgical intervention was the most common treatment (60.95%). Recurrence-free survival was observed in 42.86% of cases, while 15.24% experienced recurrence with or without metastasis. Two patients (1.90%) died from the disease. The median recurrence-free survival was 48 months (95% CI: 7.3–88.7). Conclusions: CHE exhibits significant morphological variation and can mimic other vascular tumors. Accurate diagnosis is crucial for proper prognosis and avoiding overtreatment due to misdiagnosis as more aggressive neoplasms. Patients with high-risk CHE should undergo closer surveillance to ensure timely detection of progression.

Introduction Faculty of Medicine is often recognized as one of the most laborious. Student workload, constant exposure to stressful situations, fear of failure, pressure from parents, exposure to death and human suffering are some of the many factors associated with increasing levels of anxiety and depression among medical students. Objectives The aim of this study was to estimate the severity of anxiety and depression disorders among medical students. Methods In this cross-sectional study, self-report anonymous online survey was distributed to the students of all six years of the Faculty of Medicine, University of Sarajevo. In this survey, which consisted of 33 questions, we gathered general information and the Beck’s Anxiety and Depression Inventory were used to assess the severity of anxiety and depression, whereby respondents received points by answering each question, and after scoring, they were categorized in different groups based on the severity of anxiety and depression. Results 129 students completed the survey. Considering the Beck’s Anxiety Inventory, 56% scored for the “Low anxiety” group, 33% scored for the “Moderate Anxiety” group, 11% scored for the “Potentially concerning levels of anxiety”. Considering the Beck’s Depression Inventory, 43% of the students scored for the group “These ups and downs are considered normal”, 21% scored for “Mild mood disturbances”, 9% for the “Borderline clinical depression”, 19% for “Moderate depression”, 6% for “Severe depression”, 2% for “Extreme depression”. Conclusions Psychiatric morbidity found needs to be identified and treated at the earliest, because it can lead to suicidal ideation. Medical students should be encouraged to seek help and adequate facilities should be available to all of them. Disclosure of Interest None Declared

U ovom radu predstavljeni su podaci o spahijama na području današnje općine Hadžići kroz popise koji obuhvaćaju period od 1828. do 1831. godine, a čuvaju se u Arhivu Orijentalnog instituta u Sarajevu u okviru zbirke sidžila pod brojem S 68. Rad se sastoji od tri cjeline. U prvoj uvodnoj cjelini predstavljeni su podaci o sadržaju sveska S 68, dok je druga cjelina rada poslužila za osvrt na izvore i literaturu vezane za hadžićki kraj u prvoj polovini 19. stoljeća kao perioda u kojem su nastali tretirani popisi. Treća i najopširnija cjelina rada tematizira podatke vezane za spahije hadžićkog kraja u svesku S 68 uz poseban osvrt na karaktere popisa te na određene nedoumice vezane za administrativno teritorijalnu pripadnost ovog kraja u prvoj polovini 19. stoljeća.

Introduction Autistic spectrum disorders belong to the group of neurodevelopmental disorders, where the manifestations of the disorder differ depending on the severity of the autistic condition. These disorders are often associated with intellectual impairments and structural language disorders. In his patients, Asperger described cases with above-average intelligence as well as cases with low language and intellectual abilities. What they had in common was that they had significant disorders in social and affective communication. The diagnosis of autism spectrum disorders is usually made in childhood, but there are also cases where the diagnosis is made at an older age due to the later manifestation of symptoms. Objectives To present a case report of 18 years old girl who was diagnosed with moderate intellectual disability in childhood, while later established with symptoms of Asperger’s syndrome and mild intellectual disability. Methods Psychiatric interview, medical history, psychological testing Results An 18-year-old girl, accompanied by her mother, presented herself to psychiatrist for the first time due to affective disorders that manifested in the form of increased nervousness and outbursts of anger. Early psychomotor development was slow, she started walking at the age of 1.5 years and spoke at the age of two. From early childhood, stereotypies in movements and hypervigilant attention were observed, along with very poor social interactions. Due to difficulties at school, she was categorized at the age of 12 as having moderate intellectual insufficiency and IQ of 35. She underwent long-term speech therapy treatment and finished elementary and high school with the help of teaching assistant. Somewhere in high school, the patient’s pronounced talent for drawing was noticed. Observation during the psychiatric examination reveals emotional immaturity, stereotypes and rigidity in social interactions. The patient is referred again for psychological testing, results show IQ of 88 with a lag in emotional development and development of basic social skills. The patient is referred to another psychiatrist for an additional opinion, who agrees with diagnose of Asperger’s syndrome. Low dose of lamotrigine was included in therapy, after which affective state stabilized. The patient is referred again for categorization. Conclusions This case report that a diagnosis established in childhood period does not have to be definitive and that revision of diagnosis is necessary over time and as necessary, initially due to increase of patient’s IQ, as well as due to the later presentation of symptoms characteristic of certain disorder. Disclosure of Interest None Declared

Background: The incorporation of polymers into drug delivery vehicles has been shown to be an effective strategy to prolong the residence time of active ingredients in the precorneal tear film and to increase ocular bioavailability. Objectives: The aim of this study was to develop novel, viscous eye drops containing olopatadine (OCH) as the active ingredient, polysaccharides hydroxypropyl guar gum (HPG), and sodium hyaluronate (SH), individually, and in combination as functional polymers. Methods: Viscous eye drops containing 0.1% OCH in combination with HPG (0.25%) and SH (0.4%), were prepared and evaluated for their physicochemical properties, rheological behavior, mucoadhesion, and preliminary stability. A novel rheological method was used to evaluate the resistance of the eye drops under simulated blinking conditions. In vivo efficacy was evaluated using an ocular itch test in mice to compare the formulations with a commercial product. Results: The formulations remained stable and transparent, with physicochemical parameters within acceptable ranges. Rheological studies confirmed pseudoplastic flow, with the HPG-SH combination exhibiting enhanced viscosity and shear-thinning properties for prolonged retention in the eye. Mucoadhesion was highest in SH-HPG formulations. During simulated blinking cycles, eye drops containing a combination of SH and HPG polymers fully regained their initial viscosity during the resting periods. Preliminary stability studies indicate that the formulated eye drops exhibit satisfactory physicochemical stability under various storage conditions. In vivo, OCH-SH and OCH-HPG-SH drops provided prolonged antipruritic and analgesic effects compared to the reference product. Conclusions: Polysaccharide-based innovative formulations improve OCH retention, enhancing therapeutic efficacy and patient compliance in the treatment of allergic conjunctivitis.

Six novel green extraction techniques were evaluated and optimized to extract pyrethrin from dried Dalmatian pyrethrum (Tanacetum cinerariifolium (Trevir./Sch.Bip.). This approach offers a promising natural alternative to conventional chemotherapeutics. Four methods are presented for the first time in this study: microwave-assisted extraction (MAE), high-voltage electric discharge (HVED) extraction, subcritical water extraction (SWE), and deep eutectic solvent (DES) extraction, together with supercritical CO2 extraction (SC-CO2) and ultrasound-assisted extraction (UAE), for pyrethrin extraction from Dalmatian pyrethrum. The study revealed that supercritical CO2 extraction was the most effective method for extracting all six pyrethrins, yielding the highest total amount of 124.37 ng/mg. This approach offers a “natural” insecticide produced with a clean, environmentally friendly technology that can contribute to the development of sustainable and effective insecticide strategies that are in line with environmental safety and organic production standards. In addition, this research highlights the potential application of pyrethrins as antiparasitic agents, emphasizing their role in environmentally friendly and ecological practices.

This study explores pyrometallurgical and hydrometallurgical methods for decarbonizing and recovering valuable metals from bauxite residue, with direct hydrogen reduction in a rotary kiln without smelting and dissolution of solid residues under high pressure in an autoclave. The goal is to offer decarbonizing techniques for the removal of iron from bauxite residue, a by-product of the Bayer process, which cannot be disposed of in an environmentally sustainable manner. In contrast to traditional carbon-based reductive melting, which generated significant CO₂ emissions, hydrogen is now being investigated as a cleaner alternative. Through hydrogen reduction in rotary kiln, approximately 99.9% of iron is recovered as iron, which can be separated using magnetic separation from the solid residue containing other valuable metals. We concluded that hydrogen can reduce iron oxide from bauxite residues to metallic iron in contrast to very stable oxides such as titanium oxide, silica and aluminum oxide. Leaching of titanium, iron and aluminum with sulfuric acid has high efficiency under high pressure in an autoclave.