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.
Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory autoimmune disease in childhood, significantly contributing to both short- and long-term disability. While certain human leukocyte antigen (HLA) class II alleles are known to be associated with specific subgroups of JIA, emerging evidence suggests a strong correlation between these alleles and treatment response. This study involved 143 JIA patients diagnosed according to International League of Associations for Rheumatology criteria. Each patient underwent HLA class II typing, including HLA-B27, as well as tests for rheumatoid factor (RF) and antinuclear antibodies (ANA). Comprehensive rheumatological assessments were conducted at diagnosis, with follow-ups at three and six months post-onset. After six months of methotrexate (MTX) treatment, patients were categorized as responders or non-responders. Responders achieved clinically inactive disease based on the American College of Rheumatology Provisional Criteria for Defining Clinical Inactive Disease and Clinical Remission. Non-responders, who did not reach clinically inactive disease after six months of treatment, required the addition of another non-biological disease-modifying antirheumatic drug (DMARD) or a biological DMARD. Our analysis revealed that the HLA-DRB1*01 allele is a significant prognostic marker for therapeutic response, predicting therapeutic resistance (P ═ 0.01). The most prevalent HLA-DRB1 alleles in the treatment-resistant group were HLA-DRB1*08:11 (11.3%), HLA-DRB1*01:01 (8.5%), HLA-DRB1*01:13, HLA-DRB1*04:11 (7%), HLA-DRB1*08:13, and HLA-DRB1*08:15 (4.2%). These findings highlight the critical role of HLA class II alleles in pediatric rheumatology, particularly in relation to treatment response and disease prognosis. In the era of personalized medicine, understanding the genetic contributions to treatment response and outcomes in JIA patients is essential. A key limitation of this study was the lack of comparison of treatment responses across different JIA subtypes. Future studies should prioritize evaluating MTX efficacy within specific JIA subgroups to enable a more tailored understanding of its effectiveness.
Diffuse large B cell lymphoma (DLBCL) is classified into Germinal Center B‐cell (GCB) and activated B‐cell (ABC) subgroups originating from different stages of lymphoid differentiation. Cell of origin dictates the behavior and therapeutic response of DLBCL. This study aimed to evaluate single and combinatorial effects of metformin and thymoquinone (TQ) in two DLBCL cell lines belonging to GCB and ABC subtypes. Metformin and TQ caused dose‐dependent responses in both ABC and GCB DLBCL subtypes. Metformin had a greater impact on the ABC subtype while TQ demonstrated more pronounced effects on the GCB subtype. Synergistic effects were observed in the DHL4 (GCB subtype) but not in the HBL1 (ABC subtype) cell line. This is the first study to compare the effects of metformin and TQ in ABC versus GCB subtype of DLBCL. It brings valuable results that could be utilized in further research aimed at reshaping treatments for subtype‐specific lymphomas.
Hepatic steatosis, a key factor in chronic liver diseases, is difficult to diagnose early. This study introduces a classifier for hepatic steatosis using microwave technology, validated through clinical trials. Our method uses microwave signals and deep learning to improve detection to reliable results. It includes a pipeline with simulation data, a new deep-learning model called HepNet, and transfer learning. The simulation data, created with 3D electromagnetic tools, is used for training and evaluating the model. HepNet uses skip connections in convolutional layers and two fully connected layers for better feature extraction and generalization. Calibration and uncertainty assessments ensure the model's robustness. Our simulation achieved an F1-score of 0.91 and a confidence level of 0.97 for classifications with entropy ≤0.1, outperforming traditional models like LeNet (0.81) and ResNet (0.87). We also use transfer learning to adapt HepNet to clinical data with limited patient samples. Using 1H-MRS as the standard for two microwave liver scanners, HepNet achieved high F1-scores of 0.95 and 0.88 for 94 and 158 patient samples, respectively, showing its clinical potential.
Hrast kitnjak (Quercus petraea (Matt.) Lieblein) jedna je od ekonomski i ekološki vrlo važnih vrsta šumskog drveća i javlja se u oko 15% svih šuma u Bosni i Hercegovini. Prirodne populacije hrasta kitnjaka u Bosni i Hercegovini predstavljaju specifične zajednice koje se razlikuju od jedinki iz svog optimuma u zapadnoj, južnoj i istočnoj Europi, te predstavljaju genetičke specifikume bitne za očuvanje biološke raznolikosti hrasta kitnjaka u Europi. Istraživanjem morfoloških svojstava listova željelo se utvrdi stupanj unutarpopulacijske i međupopulacijske varijabilnosti hrasta kitnjaka na području Bosne i Hercegovine, te veze između variranja populacija u fenotipskim svojstvima i geoklimatskih čimbenika. Rezultati istraživanja bit će iskorišteni prilikom odabira mjera za očuvanje ove vrste šumskog drveća. Analizirano je 13 svojstava listova hrasta kitnjaka, sakupljenih sa 237 stabala iz 24 prirodne populacije. Rezultati su pokazali da su koeficijenti varijacije za sva mjerena svojstava u rasponu od 13.3% za duljinu plojke, do 26.5% za duljinu peteljke. Analiza varijance (ANOVA) otkrila je postojanje fenotipskih varijacija unutar i među populacijama. Varijacija unutar populacija bila je prosječno 28.44% i veća nego između populacija (prosječno 16.2%). Klaster analiza pokazala je razdvajanje populacija u dva glavna klastera, gdje su jednom klasteru pripale populacije Jajce Komotin i Fojnica, a drugom klasteru sve ostale populacije. Većina analiziranih svojstava lista (osim duljine peteljke, omjera širine i duljine lista i broja režnjeva) bila je u korelaciji sa geografskom širinom, srednjom temperaturom kvartala s najviše padalina i količinom padalina u najtoplijem kvartalu. Ovi rezultati mogu biti korišteni za očuvanje raznolikosti i upravljanje resursima hrasta kitnjaka u budućnosti.
INTRODUCTION AND AIM Weight-adjusted waist index (WWI) represents a novel anthropometric measure for assessing obesity. Bearing in mind that there is insufficient data in the literature regarding gender differences in WWI values, the aim of the current study was to examine gender differences in WWI values among older adults.
The highest representative of the judicial authority and one of the most im- portant levers in the administrative apparatus of the Ottoman Empire in one province (eyalet) was the molla. He was granted extensive powers and the ability to control other officials of the Ottoman authority. Considering the role and importance of those high-ranking Ottoman officials, the paper aims to present the individuals who were appointed to the Eyalet of Bosna as well as the dynamics of changes in these positions in the second half of the 17th century. In cases where it was possible, insight was given into their education and experience, as well as some interesting facts from their lives. In order to achieve this, the contents of various individual and collective documents were analyzed. The presented data contribute to a better understanding of Ottoman judicial practice and the specific activities of judges in Bosnia in the 17th century.
Osteoarthritis (OA) is the most common form of synovial joint arthritis that causes chronic pain and disability to a large number of people worldwide. Most often, osteoarthritis affects the joints of the knees, hips, spine and hands. The Global Burden of Disease (GBD, 2021) estimates that osteoarthritis will be the fourth leading cause of disability by 2030, with enormous healthcare costs for treatment, as well as significant indirect costs due to loss of productivity and premature retirement. The aim of our research is to determine in what way prevalent metabolic syndrome is among participants with osteoarthritis of one of the synovial joints (knees, hips, hands), and whether metabolic disorders are a risk factor for the development and worsening of osteoarthritis. A prospective clinical study was conducted at the Public Health Institution Health Center Živinice, from July 2022 to May 2024, on a random sample of 200 participants with a confirmed clinical diagnosis of osteoarthritis (OA), who were divided into a group with metabolic syndrome and a group without metabolic syndrome based on the NCEP ATP III panel criteria for metabolic syndrome. The prevalence of knee osteoarthritis is significantly higher compared to the prevalence of hip and hand osteoarthritis, and it is greater among participants with a higher BMI (in participants with the highest BMI, knee osteoarthritis occurs with a 100% probability) and with the presence of metabolic syndrome, especially in more severe forms, specifically radiologically confirmed osteoarthritis, regardless of age and gender. Unlike OA knees the prevalence of OA hips and hands shows no correlation with BMI and metabolic syndrome. Multiple comparative analysis of differences in the average severity of osteoarthritis of the knee of subjects with normal glycemia / prediabetes / diabetes type 2 it showed a statistically significant difference in the average severity of knee osteoarthritis in subjects with regular blood sugar compared to subjects with prediabetes/diabetes mellitus type 2 regardless of age and gender. This means that with an increase in blood sugar levels, the degree of severity of osteoarthritis of the knee increases, since each subsequent Group has a higher average value of this indicator (p<0.05; CI 95%).
Improper nutrition leads to changes in the body that are not only an aesthetic problem, but also lead to chronic diseases. The goals of the research are to analyze knowledge, habits and attitudes about nutrition and knowledge about obesity, to determine the body mass index (BMI) of all respondents, to analyze the connection between nutrition, excess body weight and the frequency of chronic non-communicable diseases. The study was cross-sectional epidemiological, descriptive-analytical, was conducted on a sample of 200 respondents of patients Family medicine, Public Health Center of the Sarajevo Canton. The survey was conducted by interviewing respondents using a modified questionnaire, made up of 27 questions. Analyzing the results, it was determined that the respondents' knowledge of nutrition is satisfactory, but that the majority of respondents (121) have a BMI over 25. For men in the age group of 46-55 years, the average BMI is 29.3, and for women in the same age group, it is 27. 5, which shows that they do not apply their own knowledge about nutrition. The majority of respondents (32%) whose BMI is over 25 have one or more chronic non-communicable diseases. Most respondents stated that they get information about proper nutrition through the media, although many of them suffer from some chronic diseases, they do not get information at the health center. In the family doctor's clinic, it is very important to recognize excess body weight, bad eating habits of patients in time, plan a prevention strategy, and prevent the further development of chronic diseases with professional counseling.
Glioblastoma presents a formidable clinical challenge because of its complex microenvironment. Here, we characterized tumor-associated foam cells (TAFs), a type of lipid droplet-loaded macrophage, in human glioblastoma. Through extensive analyses of patient tumors, together with in vitro and in vivo investigations, we found that TAFs exhibit distinct protumorigenic characteristics related to hypoxia, mesenchymal transition, angiogenesis, and impaired phagocytosis, and their presence correlates with worse outcomes for patients with glioma. We further demonstrated that TAF formation is facilitated by lipid scavenging from extracellular vesicles released by glioblastoma cells. We found that targeting key enzymes involved in lipid droplet formation, such as diacylglycerol O-acyltransferase or long-chain acyl-CoA synthetase, effectively disrupted TAF functionality. Together, these data highlight TAFs as a prominent immune cell population in glioblastoma and provide insights into their contribution to the tumor microenvironment. Disrupting lipid droplet formation to target TAFs may represent an avenue for future therapeutic development for glioblastoma.
Background: High hypericin-loaded polyvinylpyrrolidone (HHL-PVP) constitutes a novel approach to utilize the promising characteristics of hypericin for photodynamic diagnosis (PDD) and therapy (PDT) of brain tumors in an orally bioavailable formulation. The aim of this study was to investigate the ability of a Complementary Metal-Oxide-Semiconductor (CMOS) camera-based fluorescence imaging system to selectively visualize HHL-PVP in glioblastoma tissue even in the presence of 5-Aminolvevulinic acid (5-ALA) induced fluorescence, which is widely utilized in brain tumor surgery. Methods: We applied a previously established system with a non-hypericin specific filter for 5-ALA fluorescence visualization and a newly introduced hypericin-specific filter at 575–615 nm that transmits the spectrum of hypericin, but not 5-ALA fluorescence. Glioblastoma specimens obtained from 12 patients (11 with preoperative 5-ALA intake) were ex vivo incubated with HHL-PVP. Subsequently, fluorescence intensity and lifetime changes using both the non-hypericin specific filter and hypericin-specific filter were measured before and after HHL-PVP incubation and after subsequent rinsing. Results: While no significant differences in fluorescence signal were observed using the non-hypericin specific filter, statistically significant increases in fluorescence intensity (p = 0.001) and lifetime (p = 0.028) after HHL-PVP incubation were demonstrated using the hypericin-specific filter. In consequence, specimens treated with HHL-PVP could be identified according to the fluorescence signal with high diagnostic sensitivity (87.5%) and specificity (100%). Conclusions: Our CMOS camera-based system with a hypericin-specific filter is capable of selectively visualizing hypericin fluorescence in glioblastoma tissue after ex vivo HHL-PVP incubation. In the future, this technique could facilitate clinical investigations of HHL-PVP for PDD and PDT while maintaining the current standard of care with 5-ALA guidance.
The aim of the study is the isolation and identification of fungi using passive air sedimentation. This study analyzed 540 mycological samples from three primary schools in Zenica, collected in September, December, February, and May. Each season, 135 samples were taken from five rooms (two classrooms, a gym, a locker room, and a library) in each school. Samples were collected three times daily at three different heights with 15-minute exposure times. Samples were refrigerated and transported in sterile bags, incubated for 24 hours, and inoculated on specific agars with and without additives. Plates were incubated at 37°C and 25°C for up to 7 days, followed by examinations. Petri dishes were used for passive air sampling, and colonies were counted after incubation. The average number of microorganisms (CFU/m³) was calculated using Omeliansky’s method. Statistical methods included the Chi-squared test and p-value. Colony appearance was assessed visually and microscopically using a light microscope. Growth rate, size, structure, and color changes were monitored. In September, the highest mold concentrations were at H. Kikić Primary School (796 CFU/m³, not significant), M. Dizdar Primary School (1260 CFU/m³, not significant), and A. Šantić Primary School (3980 CFU/m³, significant). Penicillium spp. and Alternaria spp. were most prevalent, with Alternaria spp. significant at H. Kikić Primary School. In December, the highest mold/yeast concentrations were at H. Kikić Primary School (4578 CFU/m³, not significant), M. Dizdar Primary School (1924 CFU/m³, significant), and A. Šantić Primary School (2587 CFU/m³, not significant). Penicillium spp. was most prevalent. In February, the highest mold concentrations were at H. Kikić Primary School (4578 CFU/m³, not significant), M. Dizdar Primary School (2786 CFU/m³, not significant), and A. Šantić Primary School (5838 CFU/m³, significant). Aspergillus spp. and Penicillium spp. were equally prevalent. In May, the highest mold/yeast concentrations were at H. Kikić Primary School (6568 CFU/m³, significant), M. Dizdar Primary School (3516 CFU/m³, significant), and A. Šantić Primary School (7431 CFU/m³, significant). Aspergillus spp. was most prevalent. These findings highlight the importance of regular monitoring and implementing appropriate ventilation measures to manage air quality and health concerns in schools.
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