AIM To determine whether demographic data, clinical features, and laboratory variables at disease onset can predict the response to methotrexate in juvenile idiopathic arthritis (JIA) patients. METHODS A cohort of 143 newly diagnosed JIA patients initially treated with methotrexate was enrolled in this study. Demographic, clinical, and laboratory parameters were analysed using univariate and multivariate logistic regression to identify predictors of response to methotrexate. The variables included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelets, IgA, IgG, the number of active joints and age at disease onset. Treatment response was assessed at six months, with patients classified as responders (those who achieved clinically inactive disease according to the American College of Rheumatology - ACR criteria) or non-responders. RESULTS Poor response to methotrexate was associated with the number of active joints (p=0.0001; OR=2.7), baseline levels of CRP (p=0.044; OR=1.138), IgA (p=0.004; OR=2.159), and platelet count (p=0.01; OR=1.05). IgG level (P=0.236) did not correlate with the treatment response. CONCLUSION We identified widely available and clinically acceptable biomarkers that can be utilized as predictive indicators of response to methotrexate in JIA patients.

AIM To determine the prevalence of aerobic vaginitis (AV) caused by Enterococcus faecalis (E. faecalis) in human papilloma virus (HPV)-positive women with pathological Pap test and to determine the most prevalent HPV type associated with E. faecalis infection. METHODS This prospective study was conducted at the Gynaecology Centre "Dr. Mahira Jahić" Tuzla and Primary Health Care Centre Tešanj (Bosnia and Herzegovina) in the period between February 2023 and March 2024. The research included 200 women aged 25 to 50 years. The examined group consisted of 100 women with a pathological (examined group) and 100 with a normal (control group) Pap test result. RESULTS Pathological Pap smears were found in 60 (out of 100; 60 %) women in the examined group: cervical intraepithelial neoplasia (CIN) 1 and CIN 2 in two women, respectively, CIN 3 in seven, atypical squamous cells of undetermined significance (ASCUS) in 29 and atypical squamous cells-high-grade cannot be excluded (ASC-H) in two women. Overall (both groups) prevalence of E. faecalis was 25.5% (51women); in 45 (22.5%) women E. faecalis was the only bacterial isolate, of which 42 (21%) in the examined group and three (1.5%) in the control group. High-risk HPV types were found in 62 (out of 100; 62%) women with the pathological Pap smear test. The association of E. faecalis and high-risk HPV positive women was found in 35 (35%) cases (moderately positive correlation; r=0.198). CONCLUSION E. faecalis is very common in HPV 16 and 18 positive women and may represent a risk factor in the development of cervical intraepithelial lesions.

The development of point-of-care wearable devices capable of measuring insulin concentration has the potential to significantly improve diabetes management and life quality of diabetic patients. However, the lack of a suitable point-of-care device for personal use makes regular insulin level measurements challenging, in stark contrast to glucose monitoring. Herein, we report an electrochemical transdermal biosensor that utilizes a high-density polymeric microneedle array (MNA) to detect insulin in interstitial fluid (ISF). The biosensor consists of gold-coated polymeric MNA modified with an insulin-selective aptamer, which was used for extraction and electrochemical quantification of the insulin in ISF. In vitro testing of biosensor, performed in artificial ISF (aISF), showed high selectivity for insulin with a linear response between 0.01 nM and 4 nM (sensitivity of ∼65 Ω nM-1), a range that covers both the physiological and the pathological concentration range. Furthermore, ex vivo extraction and quantification of insulin from mouse skin showed no impact on the biosensor's linear response. As a proof of concept, an MNA-based biosensing platform was utilized for the extraction and quantification of insulin on live mouse skin. In vivo application showed the ability of MNs to reach ISF, extract insulin from ISF, and perform electrochemical measurements sufficient for determining insulin levels in blood and ISF. We believe that our MNA-based biosensing platform based on extraction and quantification of the biomarkers will help move insulin assays from traditional laboratory approaches to personalized point-of-care settings.

Background/Objectives: The importance of fixed-dose combinations (FDCs) for the treatment of hypertension is well established. However, from a stability perspective, FDCs present a challenge since the degradation of one active pharmaceutical ingredient (API) can be affected by the presence of another API. The aim of this study was to compare the degradation behaviors and evaluate the degradation kinetics of three antihypertensive drugs, perindopril tert-butylamine (PER), amlodipine besylate (AML), and indapamide (IND). Methods: The degradation processes were studied using the previously developed reverse phase high-performance liquid chromatographic (RP-HPLC) method after exposing each drug individually, as well as the combinations of two/three drugs, to different stress factors, such as light, oxidation, acidic, basic, or neutral pH values at different temperatures. Results: The results show that PER is most unstable under basic conditions and that AML displays a negative, while IND displays a positive effect, on PER stability when combined. AML is most affected by basic conditions and oxidation, and its stability is affected by both drugs positively; IND undergoes extreme photolysis, which is positively affected by AML but negatively by PER. Conclusions: Great care must be taken when formulating FDCs with these three drugs, as well as solutions or oral suspensions adjusted for geriatric or pediatric populations, since the stability of all three drugs is greatly affected by pH conditions, as well as light or oxidation factors and their interactions.

The role of γ- aminobutyric acid (GABA) and GABAA receptors is not only essential for neurotransmission in the central nervous system (CNS), but they are also involved in communication in various peripheral tissues such as the pancreas, liver, kidney, gastrointestinal tract, trachea, immune cells and blood vessels. GABAA receptors located outside the CNS ("peripheral GABAA receptors") enable both neuronal and non-neuronal GABA-ergic signaling in various physiological processes and are generally thought to have similar properties to the extrasynaptic receptors in the CNS. By activating these peripheral receptors, GABA and various GABAA receptor modulators, including drugs such as benzodiazepines and general anesthetics, may contribute to or otherwise affect the maintenance of general body homeostasis. However, the existing data in the literature on the role of non-neuronal GABA-ergic signaling in insulin secretion, glucose metabolism, renal function, intestinal motility, airway tone, immune response and blood pressure regulation are far from complete. In fact, they mainly focus on the identification of components for the local synthesis and utilization of GABA and on the expression repertoire of GABAA receptor subunits rather than on subunit composition, activation effects and (sub)cellular localization. A deeper understanding of how modulation of peripheral GABAA receptors can have significant therapeutic effects on a range of pathological conditions such as multiple sclerosis, diabetes, irritable bowel syndrome, asthma or hypertension could contribute to the development of more specific pharmacological strategies that would provide an alternative or complement to existing therapies. Selective GABAA receptor modulators with improved peripheral efficacy and reduced central side effects would therefore be highly desirable first-in-class drug candidates. This review updates recent advances unraveling the molecular components and cellular determinants of the GABA signaling machinery in peripheral organs, tissues and cells of both, humans and experimental animals.

The goal of this abstract is to present available artificial intelligence (AI) software and tools for the development, assessment, and implementation of artificial intelligence/machine learning in cardio - vascular research and clinical care, ensuring they are safe, reliable

Background: There is no specified diagnostic procedure that can help in determining the cause of death and the diagnosis of drowning because the pathohistological signs are almost identical and non-specified. Aim: Our study aims to recognize and prove diatom appearance in organs from a forensic aspect in Bosnia and Herzegovina, and to examine which is the more specific method in the diagnosis of drowning, the diatom test or the pathohistological finding. Methods: Rats of the recommended body weight were divided into four groups: G1 (n = 8; mechanism of death—asphyxia; cause of death—suffocation, submerged 1 hour after death); G2 (n = 8: mechanism of death-asphyxia; cause of death-suffocation, immersed 72 hours after death); G3 (n = 8: mechanism of death-asphyxia; cause of death-drowning, autopsy immediately after death), and G4 (n = 8: mechanism of death-asphyxia; cause of death-drowning, post mortem 24 hours after death). Results: During the diatom analysis, four species of diatoms, Diatoma vulgaris, Melosira varians, Epithemia adnata, and Cymbella sp, were successfully recovered from the stomach. Microscopic analysis did not detect diatoms in the kidneys and brains of rats, while the pathohistological changes were relatively uniform. Conclusion: Our results propose that the diatom test is a sustainable tool for supporting the diagnosis of drowning in the forensic pathology analysis of the cause of death. This experimental study is a starting point toward the optimization of tests and sampling in cases of unexplained etiology.

: It is known that in recent years there have been major changes in all branches of industry, especially in the automotive and electro-electronic industry, because new business methods are on the scene, and production processes are being transformed so that they are flexible. In the automotive and electro-electronic industry, the leading technology is robotic technology, the application of which increases the return on investment. Advanced robotics as the basic technology of Industry 4.0 in the new era of production in the automotive and electro-electronic industry plays a very important role because it enables: mobility, readiness, reliability, adaptability, transformation of production, integration with machines, increase of flexibility, improvement of quality, storage and production systems integrated as Cyber-Physical Systems, workers are freed from routine and repetitive tasks. The paper provides an overview of applied and issued patents in robotic technology, the application of robots in the World and China as the leader in the implementation of robotic technology in the world. An analysis of the implementation of industrial robots, as well as advanced robots in the automotive and electro-electronic industries of China, is given, as well as the forecast of the application in the coming years.