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Precision medicine is a developing trend in oncology, and it includes the prognosis and treatment of advanced-stage ccRCC. New predictive factors and therapeutic targets for this disease are steadily needed. The aim of this study was to explore the tumor expression of inversin as a potential prognostic factor and/or therapeutic target in ccRCC. We compared the expression of inversin between primary ccRCC and normal renal tissues by using immunohistochemistry and rtPCR in our cohort, and we also analyzed publicly available data from the TCGA-KIRC cohort. We found that the expression of inversin was significantly lower in primary tumor tissue, in comparison to solid normal tissue. Data from the KIRC study confirmed that a lower INVS expression level in ccRCC was significantly related with the overall and disease-specific survival, as well as with a shorter progression-free interval (p < 0.05). Four out of ten inversin interactome partners were significantly related with the overall and disease-specific survival in ccRCC. A lower expression of ANKS6 was a negative survival predictor, while a higher expression of NPHP3, DVL1, or DVL3 was related with a lower survival. The expression of INVS and its interactome partners in ccRCC was correlated with the differentiation of the tumor and metastasis. The expression of INVS and its partners was also correlated with tumor leukocyte infiltration and the expression of immune checkpoint genes. The results of this study point to inversin and a distinguished group of its interactome partners as potential prognostic factors in ccRCC, with their predominant involvement in the modulation of the inflammatory infiltration of the tumor microenvironment and a strong relationship with the metastatic potential of the tumor.

Amila Kovčić, Šefika Umihanić, Hasan Osmić, Almedina Muhić, Enida Trumić, Eldar Hamzić, E. Bećirović, Semir Hadžić et al.

AIM To investigate the predictors of biochemical relapse (BCR) among patients with non-metastatic prostate cancer treated with radiotherapy as the first-line therapy. METHODS The study included 91 patients diagnosed with prostate cancer at the University Clinical Centre in Tuzla, Bosnia and Herzegovina. After the radiation treatment as the first line of treatment, the patients were monitored for the next 36 months. If patients were classified in medium and high-risk groups, hormone therapy was administered. The occurrence of BCR was determined based on prostate-specific antigen (PSA) values. Potential prognostic parameters, including Gleason score (GS), PSA, tumour size (TNM), and standardised risk classification (RC), were monitored. RESULTS A total of 46 (50.5%) patients were aged 66-75, with a median PSA of 14.50 ng/mL. A Gleason score <6 was found in 72 (79.1%) of patients, and 31 (34.1%) had T2c tumours. The BCR occurred in 32 (35.2%) patients, with a median relapse time of 18 months. Significant predictors of BCR were Gleason score ≥6 (OR:4.46; p=0.006) and tumour stage >T2b (OR:3.59; p=0.021). The RC showed an Area Under Curve (AUC) of 0.634 (p=0.050), indicating its potential diagnostic accuracy. CONCLUSION Gleason score ≥6 and TNM>T2b are significant predictors of biochemical relapse in prostate cancer patients treated with radiotherapy. These results emphasize the need for additional monitoring and timely treatment of clinical disease progression in patients with Gleason score ≥6 and tumour stage >T2b.

AIM Care for the inflammatory bowel disease (IBD) patients presents unique challenges as decisions regarding therapy must consider numerous distinct characteristics of each patient. The aim of the study was to recognize patients' characteristics as predictors of success in vedolizumab treatment. METHODS In a retrospective observational study, data regarding age, gender, body mass index (BMI), length of disease, previous exposure to anti-tumour necrosis factor (TNF), drugs, and smoking status were extracted from the routine clinical practice. Patients were assessed for clinical remission and steroid-free remission after the 26-week treatment with vedolizumab. RESULTS The study included 76 patients with UC and 63 with CD. A total of 63 (out of 76; 82.9%) (Cl: 72.5-90.6% ) of UC and 54 (out of 63; 85.7%) (Cl: 74.6-93.3%) CD patients achieved clinical remission in the 26-week vedolizumab treatment. Over five years, illness was noticed in 32 (53.1%) CD patients. Clinical remission was not achieved in six (out of 13; 46.1%) UC patients aged 40-49 years and six (out of nine; 66.6%) CD patients aged 30-49 years. Among CD patients, remission was achieved in 22 (85.7%) females and 23 (63.6%) males. Remission rates were generally higher in patients with a BMI of 18.6-25 and 25.1-30. Previous exposure to anti TNF drugs and smoking status did not influence treatment outcomes. CONCLUSION The efficacy of vedolizumab is a viable treatment option for both ulcerative colitis and Crohn's disease. The exploration of individual patient characteristics holds promise in predicting a treatment outcome.

AIM Acute kidney injury (AKI) presents a high mortality complication in patients with acute myocardial infarction (AMI). Yet, its correlation with non-ST elevation myocardial infarction (NSTEMI) remains neglected in the literature. This study aims to investigate the prevalence, risk factors, clinical features, and short-term outcomes associated with AKI development in patients with acute NSTEMI. METHODS A one-year prospective observational cohort study involved 170 consecutive patients hospitalized in the Intensive Care Department of the Internal Medicine Clinic at the University Clinical Centre Tuzla diagnosed with acute NSTEMI. Patients were subsequently categorized into AKI and non-AKI groups based on AKI development within 48 hours. Demographic characteristics, laboratory findings, and short-term clinical outcomes were compared between the groups. RESULTS Of 170 patients, 31 (18.2%) developed AKI within 48 hours of acute NSTEMI. Significant age differences, blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), blood glucose level (BGL), C-reactive protein (CRP), and high sensitivity (hs) troponin were observed, making patients with lower baseline kidney function, more extensive myocardial infarction, and a heavier systemic inflammatory response following acute NSTEMI more susceptible to AKI development. In the follow-up period, mortality rates were significantly higher in the AKI group, amounting to 35.5% compared to 10.1% in the non-AKI group. Additionally, mortality increased with the severity of AKI, reaching 100% in AKI stage 2. CONCLUSION This study highlights demographic, clinical and laboratory findings in patients with acute NSTEMI, which contribute to AKI development. Early detection and tailored interventions are crucial in mitigating AKI-associated morbidity and mortality.

Besides the quality of colour reproduction itself, there are other secondary print quality attributes. Secondary print quality evaluation is very important and is influenced primarily by the print method and type of substrate. For textile printers, there is an additional challenge related to macro non-uniformities due to the nature of the substrate. One of these secondary quality attributes is print mottle, which is influenced by macro non-uniformities that remain at the top layer of the print after the ink is fixed on the substrate. Print mottle values primarily consist of an analysis of macro non-uniformities and can be analysed using the Gray Level Co-occurrence Matrix (GLCM) method, among others. In this study, the GLCM method was used as well as the macro non-uniformity index or NU value verification method performed by ImageJ software. Four different textile printing methods and one cotton fabric substrate are used. The objective is to examine print mottle and the impact of printing method on macro non-uniformities. The printing methods include DTF, DTG, screen printing, and screen transfer printing. The aim is to compare the results of different printing methods and to determine their relation to perceived non-uniformity as assessed visually.

N. Hadžimusić, D. HADŽIJUNUZOVIĆ-ALAGIĆ

Background: Age-related changes in physiological parameters are crucial in understanding the health and performance of working dogs, particularly those in demanding roles such as military and law enforcement. However, limited research exists on how aging affects the hematological and biochemical health of these dogs. Aim: This study aims to characterize age-related variations in hematological and biochemical parameters in working Belgian Shepherd dogs to provide insights that could inform health management strategies for these animals. Methods: Blood samples were collected from 26 male Belgian Malinois working dogs, categorized into three age groups: adults (2–6 years), seniors (7–10 years), and geriatrics (11+ years). Comprehensive hematological and biochemical analyses were conducted. Analysis of complete blood count was performed for a total of 16 parameters: red blood cell, white blood cell, packed cell volume, hemoglobin, platelet, neutrophil, basophil, leukocyte, monocyte, lymphocyte, and eosinophil counts. Mean cell volume, mean cell hemoglobin, mean corpuscular hemoglobin concentration, red cell distribution width, and mean platelet volume were subsequently determined. The biochemistry parameters included glucose, creatinine, urea, blood urea nitrogen:creatinive ratio, phosphorus, calcium, sodium, potassium, Na:K ratio, chloride, total protein, albumin, globulin, albumin:globulin ratio, as well as alanine aminotransferase, alkaline phosphatase, gamma glutamyl transeferase, total cholesterol, amylase, and lipase. Results: Significant age-related changes were observed in various parameters. Older dogs exhibited decreased creatinine and increased phosphorus and potassium levels, indicating potential changes in muscle mass, renal function, and electrolyte balance. Additionally, the albumin-to-globulin ratio decreased with age, reflecting shifts in protein synthesis and immune function. Conclusion: The study highlights important age-related variations in hematological and biochemical parameters in working Belgian Shepherd dogs. These findings emphasize the need for age-specific health management strategies to maintain the health, performance, and longevity of these dogs, thereby enhancing their effectiveness in critical service roles.

A. Rotter, Despoina Varamogianni-Mamatsi, A. Z. Pobirk, M. Matjaž, Mercedes Cueto, A. Díaz-Marrero, Rósa Jónsdóttir, K. Sveinsdóttir et al.

Nevena Antić, M. Kašanin-Grubin, László Bertalan, Violeta Gajić, Lazar Kaluđerović, N. Mijatović, B. Jovančićević

Amar Aganovic, G. Buonanno, Guangyu Cao, Christian Delmaar, J. Kurnitski, A. Mikszewski, Lidia Morawska, L. Vermeulen et al.

Milena Mlakić, Maja Sviben, A. Ratković, Anamarija Raspudić, Danijela Barić, Ivana Šagud, Z. Lasić, I. Odak et al.

In previous research, 1,2,3-triazolium salts showed significant biological activity as potential inhibitors of cholinesterase enzymes (ChEs), which are crucial for neurotransmission. In this research, pairs of uncharged thienobenzo-triazoles and their charged salts were prepared in order to further examine the role of the positive charge on the nitrogen of the triazole ring in interactions within the active site of the enzymes, and to compare the selectivity of 1,2,3-triazolium salts in relation to their uncharged analogs obtained by photochemical cyclization. Neutral thienobenzo-triazoles showed very good selective activity toward butyrylcholinesterase (BChE), while their salts showed excellent non-selective inhibition toward both BChE (the most active 23: IC50 0.47 μM) and acetylcholinesterase (AChE) enzymes (the most active 23: IC50 4.4 μM). These new structures with incorporated 1,2,3-triazolium salts present the new scaffold for drug development as it is known that the current therapy in Alzheimer’s disease (AD) comprises selective AChE inhibitors, while in Parkinson’s and all stages of AD, non-selective inhibitors of ChEs are preferred. Molecular docking of the selected compounds and their corresponding salts into the active sites of ChEs was conducted to identify the interactions responsible for the stability of the non-covalent cholinesterase–ligand complexes. As genotoxicity studies are crucial when developing new active substances and finished drug forms, in silico studies for all the synthesized compounds have shown that compound 18 is the most promising candidate for genotoxic safety.

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