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Synthesis of new Pyridazinone derivatives and their dual inhibitory activity on aldose reductase and ?-glucosidase
No full textDiabetes mellitus is a chronic metabolic disorder associated with microvascular complications such as neuropathy, nephropathy, and retinopathy. Two complementary therapeutic strategies are targeting the polyol pathway via aldose reductase (ALR2) inhibition and controlling postprandial hyperglycemia through alpha-glucosidase (alpha-Glu) inhibition. In this study, we designed and synthesized a novel series of eight pyridazinone derivatives incorporating thiosemicarbazide, S-triazole, and 1,3,4-thiadiazole 2-amine scaffolds. These compounds were evaluated for their dual inhibitory potential against ALR2 and alpha-Glu enzymes using in vitro kinetic assays. Among the tested molecules, compound 4, bearing a fluorinated thiadiazole moiety, exhibited the most potent activity with Ki values of 0.094 mu M (ALR2) and 0.171 mu M (alpha-Glu), surpassing standard inhibitors epalrestat and acarbose, respectively. Structure-activity relationship analysis indicated that fluorine substitution and a 1,3,4-thiadiazole core significantly enhance dual inhibitory potency. Docking studies further confirmed strong binding interactions within the active site of ALR2, supported by it-it stacking, hydrogen bonding, and hydrophobic interactions. These findings suggest that halogenated pyridazinone derivatives, especially fluorinated thiadiazole analogs, represent promising dual inhibitors for managing hyperglycemia and preventing diabetic complications. The dual-targeting approach demonstrated in this work offers a rational design framework for future antidiabetic drug development.TUBITAK [1919B012201490, 1919B012206852]This project was funded by TUBITAK under grant numbers 1919B012201490 and 1919B012206852
Evaluation of ARTN and PSPN Gene Polymorphisms in Breast Cancer Risk: Insights from a Case-Control Study in Turkish Population
No full text22.GENEL.023RET, çeşitli dokuların normal gelişimi ve olgunlaşması için gerekli olan reseptör tirozin kinaz ailesinin bir üyesidir. RET sinyalizasyonu, çevredeki stromayı ve hücre kompozisyonunu değiştiren tümör mikroçevresindeki değişiklikleri teşvik eder. RET ve ligandları artemin (ARTN) ve persefin (PSPN) gen polimorfizmleri, kanser patogenezi, riski, invazyonu ve metastazında bir araştırma odağıdır. RET polimorfizmleri birçok etnik köken ve popülasyonda çeşitli kanserlerde araştırılmış olsa da, literatürde ARTN ve PSPN polimorfizmlerinin meme kanseri riski üzerindeki etkisine ilişkin sınırlı sayıda çalışma bulunmaktadır. Çalışmaya 102 meme kanseri hastası ve 102 sağlıklı kontrol dahil edildi. rs3762422 ve rs2304198 polimorfizmleri polimeraz zincir reaksiyonu ve dizileme yöntemleri ile tespit edildi ve genotip dağılımları belirlendi. Çalışma grupları her iki varyantta da genotip dağılımları açısından benzer bir profil gösterdi ve istatistiksel olarak anlamlı bir fark bulunmadı (sırasıyla p>0,05, p>0,05). Bulgularımız, ARTN rs3762422 ve PSPN rs2304198 polimorfizmlerinin kohortumuzda meme kanseri riskiyle ilişkili olmadığını göstermektedir. Bu çalışmada ARTN geni rs3762422 ve PSPN geni rs2304198 varyantları ile meme kanseri arasındaki olası riski araştırmayı ve değerlendirmeyi amaçladık. Bilgilerimize göre bu çalışma meme kanserindeki bu varyantları araştıran ilk çalışmadır ve gelecekteki araştırmalara katkıda bulunabilir.RET is a member of the receptor tyrosine kinase family, which is essential for the normal development and maturation of various tissues. RET signaling promotes changes in the tumor microenvironment that alter the surrounding stroma and cellular composition. Gene polymorphisms of RET and its ligands artemin (ARTN) and persephin (PSPN) are a research focus in cancer pathogenesis, risk, invasion, and metastasis. Although RET polymorphisms have been investigated in various cancers in many ethnicities and populations, there are limited studies in the literature on the effect of ARTN and PSPN polymorphisms on breast cancer risk. The study included 102 breast cancer patients and 102 healthy controls. rs3762422 and rs2304198 polymorphisms were detected by polymerase chain reaction and sequencing methods and genotype distributions were determined. The study groups showed a similar profile in terms of genotype distributions in both variants and no statistically significant difference was found (p>0.05, p>0.05, respectively). Our findings suggest that ARTN rs3762422 and PSPN rs2304198 polymorphisms are not associated with breast cancer risk in our cohort. In this study, we aimed to investigate and evaluate the possible risk between ARTN gene rs3762422 and PSPN gene rs2304198 variants and breast cancer. To our knowledge, this is the first study investigating these variants in breast cancer, and it may contribute to future research.This study was supported by Afyonkarahisar Health Sciences University Scientific Research Projects Coordination Unit project number 22.GENEL.023
Macular and optic disc vascular densities measured by optical coherence tomography angiography in pediatric patients with different amblyopia types
No full textPurpose The present study aimed to compare macular and peripapillary vascular density values measured by optical coherence tomography angiography (OCTA) in different types of amblyopia (ametropic amblyopia, anisometropic amblyopia, strabismic amblyopia, deprivation amblyopia) with age- and gender-matched healthy controls. Materials and methods In this prospective, cross-sectional study, between the ages of 8-18 years, 32 eyes of 32 patients with hypermetropic ametropic amblyopia and 21 amblyopic eyes of 21 patients with hypermetropic anisometropic amblyopia, 15 amblyopic eyes of 15 patients with strabismic amblyopia due to esotropia, 12 amblyopic eyes of 12 patients with deprivation amblyopia, and 30 eyes of 30 emmetropic individuals aged 8-18 years without any ocular pathology who were admitted to the same clinic were included in the control group. Refractive errors and best-corrected visual acuity (BCVA) with the Snellen chart were recorded as LogMAR. In all cases, superficial vascular plexus and deep vascular plexus whole image vessel density, foveal vessel density, parafoveal vessel density, perifoveal vessel density, and foveal avascular zone area (FAZ) values were measured and recorded for macular vascular density determination with OCTA. The whole image, intrapapillary, and peripapillary vessel density measurements were performed for peripapillary vessel density determination. The Kruskal-Wallis test was used for statistical analysis and the post hoc test was used for inter-group comparisons. Results The mean BCVA (LogMAR) was found to be significantly lower in the anisometropic amblyopia, strabismic amblyopia, and deprivation amblyopia groups (unilateral amblyopia) compared to the ametropic amblyopia (bilateral amblyopia) and healthy group (p < 0.001). The whole image vessel density, foveal vessel density, and parafoveal vessel density of superficial and deep vascular plexus were found to be significantly lower in anisometropic amblyopia, strabismic amblyopia, and deprivation amblyopia compared to ametropic amblyopia and healthy volunteers (p < 0.001). In the correlation analysis, a negative correlation was found between the mean visual acuity in LogMAR and superficial vascular plexus foveal vessel density (p < 0.001, r = - 0.622), superficial vascular plexus parafoveal vessel density (p < 0. 001, r= -0.556), deep vascular plexus foveal vessel density (p < 0.001, r= -0.636), and deep vascular plexus parafoveal vessel density (p < 0.001 r=-0.596). Conclusion Superficial and deep vascular plexus vessel densities in the macular region are affected in anisometropic amblyopia, strabismic amblyopia, and deprivation amblyopia, and OCTA may be useful in detecting these changes
Investigation of the Anticancer Effects of Combined Therapy with Liraglutide and Metformin on Lung Cancer A549 Cells
No full text[Abstract Not Available]Afyonkarahisar Health Sciences University Scientific Research Projects Coordination Unit [22.KARIdot;YER.018]This study was supported by the Afyonkarahisar Health Sciences University Scientific Research Projects Coordination Unit (Project No: 22.KAR & Idot;YER.018)
Evaluation of Pediatric Cases With Cholelithiasis: 5-Year Single-Center Experience
No full textGallstones are sometimes detected as a cause of a clinical finding in children and sometimes incidentally. This study aimed to investigate the demographic and clinical characteristics of pediatric patients with gallstones. Pediatric cases diagnosed with gallstones between 2017 and 2023 in a tertiary hospital were retrospectively examined. A total of 65 patients were included in the study. The mean age of the cases was 10.8 +/- 5.3 years, and 44 (67.7%) were adolescents. The most common complaint of the cases was abdominal pain (60%), and 33.8% were diagnosed incidentally. Obesity was the most frequently identified cause (26.2%) and was significantly higher in adolescents. Forty-five (69.2%) cases were symptomatic, and 10 (15.3%) were complicated. This study found that the frequency of gallstones in children increases with age, and that the underlying cause is likely to be obesity as age increases. Clinicians should avoid medications that may cause gallstones in obese adolescents
Investigation of factors predicting quality of life of drivers working on long-haul transport: pain, fatigue, stress and work role functions
No full textThis cross-sectional study aimed to investigate the factors that affect the quality of life of drivers. Data were collected from 62 drivers working on long-haul transport who completed the short form-12 (SF-12), perceived stress scale (PSS), Nordic musculoskeletal questionnaire (NMQ), work role function questionnaire-27 (WRFQ-27) and visual analog scale (VAS). According to the regression analysis, the physical health-related quality of life of drivers was predicted by age, marital status, unemployment, having an extra job, pain and stress (R2 = 0,663). Due to intense working conditions, employers need to take various precautions against drivers' stress, fatigue, pain and job requirements. In addition, it is important for these people to be directed to occupational therapy services in order to increase their occupational balance and quality of life
Medical device-related pressure injuries: The mediating role of attitude in the relationship between ICU nurses' knowledge levels and self-efficacy
No full textAim: This study examines the mediating role of attitude towards preventing pressure injuries (PIs) in the effect of knowledge about Medical Device-Related Pressure Injuries (MDRPI) on self-efficacy in PI management among Turkish intensive care unit (ICU) nurses. Materials and methods: A descriptive, cross-sectional study was conducted with 302 ICU nurses in Turkey from October 15, 2023, to April 30, 2024. Data were collected using the Nurse Information Form, Medical Device Related Pressure Injury Knowledge Assessment Test (MDRPI-KAT), Attitude towards Pressure Ulcer Prevention Instrument (APuP), and the Pressure Ulcer Management Self-Efficiency Scale (PUMSES). Results: ICU nurses had a knowledge score of 9.20 +/- 2.32, with a correct response rate of 57.5 %. Their attitude score was 42.41 +/- 5.46, with 76.5 % showing a satisfactory attitude (>= 75 %). The self-efficacy score for PI management was 60.59 +/- 21.03. Knowledge level positively and significantly affected attitude (B = 0.963, 95 % CI [0.720-1.206]), and attitude positively and significantly affected self-efficacy (B = 0.837, 95 % CI [0.370-1.304]). The direct effect of knowledge on PI management self-efficacy was non-significant without a mediator (B = 0.339; p = 0.542; 95 % CI [-0.756-1.435]), but the indirect effect through attitude was significant (B = 0.806; 95 % CI [0.289-1.399]). Conclusion: The study found that Turkish ICU nurses' knowledge of MDRPIs was below desired levels, though their self-efficacy was slightly above average and their attitudes were satisfactory. Attitude fully mediated the relationship between knowledge and self-efficacy, suggesting that enhancing nurses' knowledge and attitudes can improve their self-efficacy in managing PIs
Evaluation of nutrition knowledge and attitudes among adults engaged in regular exercise
No full textObjective The aim of this study is to determine the knowledge levels and nutritional attitudes of individuals who exercise regularly regarding sports nutrition and to examine the relationship between these two variables. Methods This study was conducted on a total of 200 adults, 100 female and 100 males, aged 18-48, who do regularly exercise. In this study, data were collected using the International Physical Activity Questionnaire-Short Form (IPAQ-SF), the Sports Nutrition Knowledge Questionnaire, and the Attitude Scale Toward Healthy Nutrition (ASHN). The questionnaire was administered online via Google Forms. Data were analyzed with IBM SPSS v25; Following descriptive statistics, analyzes were carried out with parametric test methods (Independent Samples T-Test, One-Way ANOVA, Pearson Correlation) in line with the research purposes, and the significance level was accepted as p < 0.05. Results The mean body mass index (BMI) was calculated as 20.5 +/- 2.1 kg/m(2) for female participants and 24.9 +/- 2.4 kg/m(2) for male participants. Participants showed high physical activity levels (IPAQ-SF: females 1675.4 +/- 1085.6; males 2000.8 +/- 1845.7 MET-min/week), yet their sports nutrition knowledge remained insufficient. A significant negative correlation was found between sports nutrition knowledge and BMI (r = -0.228; p < 0.01). Those who received nutrition education had higher knowledge scores (58.2 +/- 19.8) and lower malnutrition tendencies (p < 0.05), highlighting the importance of educational interventions. Conclusion The study revealed that regular exercisers may have limited sports nutrition knowledge, which negatively impacts their dietary attitudes. Future research should focus on targeted nutrition education interventions to enhance knowledge and support healthier eating behaviors
Eco-friendly nanoscale recognition: a MIP-based electrochemical sensor for selective determination of abacavir in pharmaceutical and serum samples
No full textAn advantageous electrochemical sensor was designed and fabricated for the sensitive and selective analysis of abacavir, an antiviral agent, by integrating the molecularly imprinted polymer (MIP) strategy and nanomaterial-based performance enhancement. The molecular imprinting was achieved on the glassy carbon electrode (GCE) surface through photopolymerization, using acrylamide (ACR) as the functional monomer and abacavir (ABC) as the template drug, and the system was computationally designed. Amine-functionalized multi-walled carbon nanotubes (MWCNT-NH2) were incorporated into the polymeric network as a supporter to improve binding efficiency, active surface area, and porosity. The successfully formed MIP and specific recognition capability were verified through electrochemical and microscopic characterizations using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR) methods. A systematic optimization procedure was followed to design an efficient MIP sensor. As a result, the ACR-ABC/MWCNT-NH2@MIP/GCE sensor exhibited a linear response in the range of 0.2 and 1 pM for standard solution and serum sample (corresponding correlation coefficient value of 0.999), with the corresponding limit of detection (LOD) values of 26.5 fM and 8.04 fM. In both solutions, good RSD% values (1.23% and 1.48%) were obtained, confirming the sensor's repeatability performance. Detailed selectivity tests validated the sensor's high affinity to ABC in the presence of structurally and pharmaceutically related drugs (lamivudine, zidovudine, tenofovir, etc.). The relative imprinting factor (IF') values were found to be higher than 2 for each compound. The ACR-ABC/MWCNT-NH2@MIP/GCE sensor's sensitive and selective determination performance was further validated in serum and tablet samples, providing reliable recovery results (98.99-102.01%). Additionally, the Analytical GREEnness Metric Approach (AGREE), the Analytical Greenness Metric for Sample Preparation (AGREEprep), the Blue Applicability Grade Index (BAGI), and the Analytical Greenness Assessment Tool for Molecularly Imprinted Polymer Synthesis (AGREEMIP) tools were utilized to assess sensor's green profile. The ACR-ABC/MWCNT-NH2@MIP/GCE sensor demonstrated its potential to provide a selective, reliable, low-cost, and efficient analytical tool for ABC analysis.Scientific and Technological Research Council of Turkiye (TUBITAK) [BIDEB/2211-A]Seyda Nur Samanci thanks the financial support from the Scientific and Technological Research Council of Turkiye (TUBITAK) under the BIDEB/2211-A Ph.D. Scholarship Program
Topology design and structural optimization of Co-Cr frameworks for implant-supported prostheses
No full textStatement of problem: Cobalt chromium (Co-Cr) frameworks for complete arch implant-supported fixed dental prostheses may be excessively heavy in patients with increased occlusal vertical dimension. This limitation necessitates consideration of lower density materials, which may substantially increase treatment costs. Purpose: The purpose of this study was to investigate the effects of topology optimization on the biomechanical behavior and weight reduction of Co-Cr frameworks used in complete arch implant-supported fixed dental prostheses. Material and methods: Different occlusogingival heights (10 mm and 14 mm) of complete arch implant-supported fixed dental prosthesis frameworks were virtually modeled using a dental computer-aided design (CAD) software program. For each height, 4 lattice types (Schwarz, Gyroid, Diamond, and Neovius) and 2 different maximum lattice thicknesses (2 and 3 mm) were designed. Subsequently, topology optimization was applied to each framework configuration. A total of 16 framework designs were generated, while 2 solid, nonoptimized frameworks without lattice structures were used as controls. In all optimized designs, vertical occlusal loads of 200 N were applied to the canine, premolar, and molar (cantilever) regions. Finite element analysis (FEA) was conducted for all designs to assess von Mises stress (MPa), maximum displacement (?m), reaction force (N), and weight reduction (%). Statistical analyses were performed with 1-way ANOVA and the t test (?=.05). Results: Topology-optimized lattice frameworks achieved up to 51.2% weight reduction without exceeding the material's yield strength. The occlusogingival height of the framework significantly affected von Mises stress, displacement, and reaction force values (P<.05). The Gyroid lattice demonstrated optimal performance in terms of weight reduction (P<.001). All stress and displacement values remained within the physiological tolerance limits of the supporting structures. Conclusions: Co-Cr frameworks can be significantly reduced in weight through topology optimization without compromising their mechanical integrity. The lattice geometry and the occlusogingival height of the framework are critical factors contributing to successful optimization. © 2025 Editorial Council for The Journal of Prosthetic DentistrySağlık Bilimleri Üniversitesi, SBU; Afyon Kocatepe Üniversites