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ArticleAçık Erişim2026/r/ebyu/10615
β-caryophyllene attenuates lead acetate-induced hepatotoxicity through regulation of oxidative stress, inflammation, and PI3K/AKT/mTOR signaling
Manavoğlu Kirman, Esra; Bolat, İsmail; Karaarslan, Tuba; Tekin, Samet; Atasever, Aslıhan
Lead acetate (PbAc) is an environmental toxicant known to induce liver injury through oxidative stress, inflammation, and apoptosis. This study aimed to investigate the potential hepatoprotective effects of β-caryophyllene (BCP), a natural sesquiterpene with antioxidant and anti-inflammatory properties, against PbAc-induced hepatotoxicity and to explore the underlying molecular mechanisms. Sixty male Sprague–Dawley rats were randomly assigned to five groups: control, BCP200, PbAc, PbAc + BCP100, and PbAc + BCP200. PbAc was used to induce hepatotoxicity, while BCP was administered at doses of 100 and 200 mg/kg. Serum liver enzymes (ALT, AST, ALP, and GGT), oxidative stress parameters (MDA, SOD, and GSH), and inflammatory cytokines (TNF-α, IL-1β, and IL-6) were evaluated. Immunohistochemical and immunofluorescence analyses were performed to assess Nrf2, HO-1, Sirt1, Keap1, and 8-OHdG expression. In addition, the mRNA expression of PI3K, AKT, mTOR, Bax, Bcl-2, and Caspase-3 was determined by qRT-PCR, and histopathological examinations of liver tissue were conducted. PbAc exposure significantly increased serum liver enzyme levels, lipid peroxidation, and pro-inflammatory cytokines while reducing antioxidant defense markers. It also suppressed Nrf2/HO-1 signaling and PI3K/AKT/mTOR gene expression, accompanied by increased Bax and Caspase-3 and decreased Bcl-2 expression, indicating enhanced apoptosis. Histopathological analysis confirmed severe hepatic degeneration and necrosis. BCP treatment significantly attenuated these alterations by reducing oxidative stress and inflammatory responses, restoring Nrf2/HO-1 signaling, improving PI3K/AKT/mTOR pathway activity, and regulating apoptosis-related gene expression. These findings suggest that β-caryophyllene may exert protective effects against PbAc-induced hepatotoxicity through modulation of oxidative stress, inflammation, cell survival signaling, and apoptosis pathways, highlighting its potential as a supportive therapeutic candidate for heavy metal-induced liver injury.
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ArticleAçık Erişim2026/r/ebyu/10606
Explainable AI for accurate diagnosis of papillary thyroid carcinoma via fine-needle aspiration cytopathology
Kilicarslan, Ahmet; Tastimur, Canan; Gundogdu, Gokhan; Akin, Erhan
Papillary thyroid carcinoma (PTC) represents most thyroid cancer cases worldwide, making early and accurate diagnosis crucial for successful treatment. This study introduces an explainable AI framework for the automated analysis of fine-needle aspiration (FNA) cytopathology images. By integrating handcrafted features with deep learning-derived abstract features, the proposed model achieves high classification performance (~ 92% accuracy and ~ 96% AUC). The proposed architecture, incorporating multi-scale dilated and deformable convolutions, effectively captures irregularities in cell morphology. Visualizations demonstrate alignment with pathologists’ diagnostic criteria, enhancing the model’s clinical applicability and reliability. The code, dataset, and comprehensive documentation are publicly available via Zenodo (https://zenodo.org/records/18428647), ensuring full reproducibility of the experiments and results presented.
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ArticleAçık Erişim2026/r/ebyu/10605
Cetirizine and Dexamethasone in Sepsis: Insights into Maresin-1 Signaling and Cytokine Regulation
Aydin, Yalcin; Borku, Mehmet Kazim; Ugur, Kader; Eroksuz, Yesari; Emre, Elif; Incili, Canan Akdeniz; Sahin, İbrahim; Acarturk, İlknur Zeynep; Aydin, Suleyman; Lee, Do-Youn
Background/Objectives: Sepsis remains one of the leading causes of mortality, yet its etiopathogenesis is still not fully understood. This study aimed to investigate the effects of cetirizine and dexamethasone (alone and in combination) on serum levels of Maresin-1 (MaR-1), TNF-α, IFN-γ, IL-1, IL-2, IL-6, IL-8, and IL-10 in a rat model of sepsis induced by the cecal ligation and puncture (CLP) method. Methods: Male Sprague Dawley rats aged 8–10 weeks were used and randomly divided into 7 groups, each containing 7 rats: Group 1 (Control), Group 2 (Sham), Group 3 (Sepsis), Group 4 (Sepsis + Saline), Group 5 (Sepsis + Cetirizine), Group 6 (Sepsis + Dexamethasone), and Group 7 (Sepsis + Cetirizine + Dexamethasone). Sepsis was induced via CLP in all groups except Control and Sham. Results: In the sepsis groups (G3–G7), neutrophil and white blood cell counts increased while lymphocyte counts decreased (p < 0.05). In groups treated with cetirizine and/or dexamethasone (G5–G7), a significant decrease in neutrophils and an increase in lymphocytes were observed. MaR-1 levels significantly decreased (p < 0.05) in all sepsis-induced groups compared to controls, while interleukin levels significantly increased. Cetirizine and dexamethasone supplementation significantly increased MaR-1 levels and decreased interleukin levels (p < 0.05). The combined treatment was more effective. Conclusions: This study is the first to highlight the potential of MaR-1 as a critical biomarker in sepsis diagnosis and monitoring, and cetirizine and dexamethasone, especially in combination, may represent a promising therapeutic option in sepsis management.
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ArticleYalnız künye2026/r/ebyu/10602
Antioxidant and enzyme inhibitory potential of Tilia platyphyllos: An LC-MS/MS-guided phytochemical insight
Dikici, Emrah; Altin, Sevgi; Isik, Mesut; Aggul, Ahmet Gokhan; Koksal, Ekrem; Rudrapal, Mithun
This study focused on assessing the phenolic composition and biological activities of the ethanol extract of Tilia platyphyllos, including its anticholinesterase, antidiabetic, and antioxidant potential. LC-MS/MS analysis identified 14 phenolic compounds, with catechin as the major component. The total phenolic/flavonoid contents were determined as 48.07 µg GAE/mg and 88.46 µg QE/mg, respectively. The extract exhibited significant antioxidant capacity in DPPH, ABTS, FRAP, and CUPRAC assays, with radical scavenging activities of 20.61 ± 1.52% for DPPH and 28.13 ± 1.61% for ABTS at 0.2 μg/mL. It also inhibited linoleic acid peroxidation by approximately 51%, exhibiting greater efficacy than the standart antioxidants Trolox and α-tocopherol. In terms of cholinesterase inhibition, the extract showed potent activity against AChE and BChE, with IC₅₀ values of 1.08 ± 0.02 µg/mL and 1.18 ± 0.08 µg/mL, respectively—markedly more effective than tacrine, which had IC50 values of 3.19 ± 0.11 µg/mL for AChE and 2.51 ± 0.03 µg/mL for BChE. For antidiabetic evaluation, α-glucosidase inhibition was observed with an IC50 of 0.44 ± 0.01 µg/mL, outperforming acarbose (3.24 ± 0.09 µg/mL). These findings suggest that the phenolic-rich extract of Tilia platyphyllos may possess notable antioxidant, neuroprotective, and antidiabetic activities, highlighting its potential as a functional food or natural therapeutic agent.
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ArticleAçık Erişim2026/r/ebyu/10600
Pharmacologic Activation of TRPA1 Induces Multi-Target Anticancer Responses via Apoptotic and Mitochondrial Pathways
Çakır, Murat; Aydın, Ali; Türkmenoğlu, Burçin; Seçme, Mücahit
Objectives: Transient Receptor Potential Ankyrin 1 (TRPA1) has emerged as a stress-responsive ion channel involved in calcium homeostasis, redox signaling, migration, and cancer cell survival; however, the therapeutic relevance of TRPA1 activation versus inhibition remains poorly understood. In this study, we comparatively investigated the anticancer potential of the TRPA1 agonist ASP7663 and the TRPA1 antagonist HC030031 across a broad panel of human cancer cell lines. Methods: Antiproliferative and cytotoxic effects were evaluated using MTT and LDH assays, while apoptotic signaling, DNA fragmentation, mitochondrial membrane potential, migration inhibition, DNA/BSA interactions, topoisomerase I inhibition, and molecular docking analyses were comprehensively assessed. Results: ASP7663 exhibited markedly lower GI50 values than HC030031 in most cancer models and demonstrated favorable tumor selectivity relative to normal cells. Mechanistically, ASP7663 induced robust apoptotic activation characterized by significant upregulation of Caspase-3, Caspase-8, and Caspase-9, together with enhanced DNA fragmentation and pronounced nuclear condensation. Rhodamine-123 staining further revealed substantial mitochondrial membrane depolarization, indicating activation of intrinsic apoptotic pathways. In addition, ASP7663 produced selective membrane damage in malignant cells, stronger inhibition of migration in osteosarcoma and chondrosarcoma models, enhanced CT-DNA/BSA binding affinity, partial topoisomerase I inhibition, and superior docking interactions with apoptosis-related targets, including Caspase-3, Caspase-8, Caspase-9, Bax, and Bcl-2. Conclusions: Collectively, these findings suggest that ASP7663 is a promising multi-target candidate for anticancer therapy and support further investigation of TRPA1-associated pathways as potential therapeutic targets in cancer.
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ArticleAçık Erişim2026/r/ebyu/10599
The Mediating Role of Climate Change Anxiety in the Effect of Nurses’ Environmental Behaviors on Their Carbon Footprint Awareness
Özdemir, Hicran; Tarsuslu, Sinan; Agaoglu, Ferhat Onur
Background: Climate change and related environmental issues are among the major global threats affecting health systems. While nurses’ eco-friendly behaviors are critical for reducing the environmental impact of health care services, the psychological mechanisms through which these behaviors influence carbon footprint awareness have not been sufficiently explained. Objective: The aim of this study is to examine the effect of nurses’ eco-friendly behaviors on carbon footprint awareness and to assess the mediating role of climate change anxiety in this relationship. Methods: The study was conducted using a cross-sectional and analytical design. The sample consisted of 386 nurses selected through convenience sampling based on voluntary participation from among nurses working in secondary and tertiary healthcare facilities in Turkey. Results: It was determined that environmentally friendly behavior significantly and positively predicted carbon footprint awareness (B = 0.542, p < 0.001) and climate change anxiety (B = 0.602, p < 0.001). In addition, climate change anxiety was found to have a significant positive effect on carbon footprint awareness (B = 0.458, p < 0.001). Bootstrap analysis showed that climate change anxiety played a significant partial mediating role in the effect of eco-friendly behavior on carbon footprint awareness (indirect effect = 0.176, 95% CI = 0.165–0.369). Conclusions: Nurses’ eco-friendly behaviors increase carbon footprint awareness both directly and through climate change anxiety. The findings highlight the importance of practices that support eco-friendly behaviors and educational programs that strengthen climate change awareness in the development of sustainable health services.
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ArticleYalnız künye2026/r/ebyu/10598
Insights into the protective role of trigonelline in 5-fluorouracil–induced lung injury: targeting oxidative stress, inflammation, and apoptosis
Uslu, Hamit; Atila Uslu, Gözde; Çoban, Taha Abdulkadir; Şahin, Mahmut; Güngör, Ali; Aygörmez, Serpil
5-Fluorouracil (5-FU) is an effective chemotherapeutic agent; however, its clinical use is frequently limited by toxicity in normal tissues, including the lungs. This study investigated the prophylactic protective effect of trigonelline (TRIG), a naturally occurring alkaloid, against 5-FU-induced pulmonary injury, with particular emphasis on oxidative stress, inflammation, and apoptosis. Twenty-eight male Sprague-Dawley rats were randomly assigned to four groups (n = 7): Control, TRIG, 5-FU, and TRIG + 5-FU. TRIG (50 mg/kg) was administered orally for seven consecutive days before a single intraperitoneal injection of 5-FU (100 mg/kg). Pulmonary injury was evaluated using biochemical, histopathological, and immunohistochemical analyses. Administration of 5-FU reduced body weight gain, increased relative lung weight, disrupted oxidant–antioxidant homeostasis, and induced histopathological alterations in lung tissue. These changes were accompanied by increased TNF-α, NFκB-p65, MAPK, and Bax expression together with decreased Bcl-2 expression, indicating activation of inflammatory and apoptotic pathways. Prophylactic TRIG administration restored oxidant–antioxidant balance, suppressed TNF-α, NFκB-p65, MAPK, and Bax expression, increased Bcl-2 expression, and markedly improved histopathological findings, demonstrating attenuation of oxidative stress, inflammation, and apoptosis. TRIG protects against 5-FU-induced pulmonary injury through coordinated antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. These findings provide experimental evidence supporting the prophylactic use of TRIG as a potential adjunctive strategy for reducing chemotherapy-associated pulmonary toxicity. Further experimental and preclinical studies are warranted to validate its efficacy, elucidate its molecular targets, and evaluate its translational potential.
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ArticleYalnız künye2026/r/ebyu/10596
The effect of tub bathing on stress, comfort, and physiological parameters in newborns
Kasımoğlu, Necla; Beşiktaş, Sultan; Gürol, Ayşe
Purpose This study aimed to investigate the effects of tub bathing on stress levels, comfort, and physiological parameters in newborns undergoing phototherapy. Methods A randomized controlled trial was conducted with 62 newborns receiving phototherapy in a university hospital neonatal intensive care unit (June 2024–June 2025). Infants were randomized to an experimental (tub bathing) or a control group. Physiological parameters, stress (Neonatal Stress Scale), and comfort (Neonatal Comfort Behavior Scale) were assessed at three time points: before, 15 min after initiation, and 15 min before completion of phototherapy. Data were analyzed using SPSS version 30.0. Results There were significant differences between the groups in terms of sex ( p = .005, φ = 0.35) and gestational week ( p = .045, φ = 0.36). Respiratory rate, heart rate, and oxygen saturation values in the experimental group were statistically higher compared with the control group ( p < .001, Cohen's d = 1.37–1.85). Mean scores of the Neonatal Stress Scale and Neonatal Comfort Behavior Scale revealed a significant decrease in stress and a significant increase in comfort in the experimental group (p < .001, Cohen's d > 1.40). The post-hoc power analysis indicated a test power of 1.00. Conclusion Tub bathing reduces stress levels, enhances comfort, and positively affects physiological parameters in newborns undergoing phototherapy. Therefore, it is recommended that nurses incorporate tub bathing as a safe and feasible nursing practice in neonatal care. Implications to practice Tub bathing is recommended as a standardized intervention to enhance physiological comfort in infants undergoing phototherapy. Additionally, involving parents in this process strengthens family-centered care and emotional bonding in the neonatal setting.
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ArticleYayıncıda açık erişim2026/r/ebyu/10595
Determinate the effects of Arabic gum and Lactobacillus acidophilus on the gut microbiota ALPK1/NFKB/NLRP6 and NLRP2 signaling pathway and virulence gene profile in rats with Campylobacter jejuni exosome application
Ucar, Mahmut; Celebi, Ozgur; Celebi, Demet; Baser, Sumeyye; Guler, Mustafa Can; Tanyeli, Ayhan; Kiliclioglu, Metin; Dabanlioglu, Bulent; Shahbazova, Masma; Yilmaz, Ahmet
Campylobacter jejuni (CJ), a major cause of bacterial gastroenteritis, employs exosomes to disseminate virulence factors and disrupt host immune homeostasis. This study investigated the therapeutic potential of Arabic Gum (AZ) and Lactobacillus acidophilus (LA), individually and in combination, against CJ exosome-induced intestinal injury in rats, with emphasis on inflammasome-related signaling and microbiota modulation. Rats received AZ, LA, or both following CJ exosome exposure. Molecular analyses, histopathology, and microbiome sequencing were performed to elucidate mechanistic responses. CJ exosomes activated key virulence pathways and triggered pronounced inflammatory signaling characterized by alpha kinase 1 (ALPK1), Nuclear Factor Kappa B (NF-κB), and NOD-like Receptor Pyrin (NLRP) upregulation, accompanied by epithelial injury and dysbiosis. Treatment with AZ or LA alone attenuated inflammasome activation and partially restored immune and microbial balance. Notably, the combined treatment produced a synergistic effect, effectively suppressing ALPK1/NF-κB/NLRP signaling and reestablishing a more physiologic microbial community structure. These improvements were associated with reductions in pro-inflammatory cytokines and markers of tissue damage, as well as substantial recovery in intestinal, hepatic, and splenic architecture. Overall, AZ and LA significantly mitigated CJ exosome-mediated pathology, with the combined therapy demonstrating superior efficacy. The findings suggest that co-administration of AZ and LA may offer a promising dual-modal strategy to counteract CJ-induced inflammatory and microbial disturbances, potentially supporting future therapeutic approaches targeting exosome-mediated pathogenesis.
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ArticleYalnız künye2026/r/ebyu/10588
Comprehensive Organ-Specific Phenolic Characterization of Endemic Hedysarum candidissimum by Liquid Chromatography–Tandem Mass Spectrometry: Antioxidant, Enzyme-Inhibitory, and Antiproliferative Activities Supported by Chemometric Analysis
Şimşek, Samed; Varol, Tuğçe; Altın, Sevgi; Yılmaz, Mustafa Abdullah; Aydın, Ali; Elveren, Müjgan; Alp, Cemalettin; Köksal, Ekrem; Osma, Etem
Hedysarum candidissimum (HC), a species endemic to Türkiye, represents a potential source of bioactive phytochemicals with pharmacological applications. This study provides the first comprehensive investigation of the species, integrating organ-specific phytochemical profiling with biological activity evaluations. Methanolic extracts from leaf, stem, and root were analyzed for their phytochemical composition and biological activities. Liquid Chromatography–Tandem Mass Spectrometry analysis quantified 53 phenolic compounds and revealed organ-dependent differences in metabolite distribution. Quinic acid was the major phenolic acid, with the highest content in the stem (91.81 mg/g extract), while flavonoid glycosides such as isoquercitrin (90.72 mg/g extract) and astragalin (43.61 mg/g extract) were higher in leaves. Antioxidant activity was determined by DPPH, FRAP, TPC, and TFC assays. The leaf extract showed the strongest activity, with the lowest DPPH IC50 (5.43 ± 0.18 µg/mL), highest reducing power (192.47 ± 0.91 mg TE/g extract), and highest phenolic and flavonoid contents (220.84 ± 1.07 mg GAE/g extract and 107.26 ± 0.77 mg QE/g extract). Enzyme inhibition assays demonstrated strong activity against acetylcholinesterase, butyrylcholinesterase, and α-glucosidase (2.44 ± 0.11, 3.35 ± 0.37, and 3.40 ± 0.20 µg/mL). Antiproliferative activity showed moderate growth inhibition in lung (A549, Calu1, H1650) and breast (MCF-7, MDA-MB-231) cancer cell lines (GI50: 2.40–19.15 µg/mL), with higher sensitivity in breast cells. The stem extract exhibited the highest tumor selectivity index (1.83), while LDH assays indicated low toxicity. Multivariate analyses confirmed organ-specific metabolite patterns and relationships between phenolic composition and biological activities. These findings indicate that the species, particularly the leaf extract, represents a source of phenolic metabolites for further phytochemical and biological investigation.
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ArticleAçık Erişim2026/r/ebyu/10585
Evaluation of the Potential Effects of Intra-Articular Rifamycin SV Injection into the Knee Joint on Articular Cartilage and Synovial Membrane
Bilgin, Yücel; Özkök, Elif; Cin, Merve; Birişik, Fevzi; Doğan, Ibrahim; Kalyenci, Ahmet Sinan
Introduction: Rifamycin is widely used as a broad-spectrum antimicrobial agent; recent studies have demonstrated the anti-inflammatory properties of rifamycin SV. Our study aimed to determine the adverse effects of intra-articular injection of rifamycin SV on the articular cartilage and synovial membrane of the knee joint. Methods: Thirty-two Wistar albino male rats were assigned to experimental and control groups (n=8 per group). On the first day, a single dose of 5mg/kg rifamycin SV (Rif; Koçak Farma, Türkiye) was injected into the right knee of the rats in the experimental groups (E1/E2), and a single dose of 0.9% isotonic sodium solution was injected into the right knee of the rats in the control groups (C1/C2). E1 and C1 rats were euthanized on the 7th day, and E2 and C2 rats were euthanized on the 28th day. Macroscopic and histopathological evaluations of the articular cartilage structures and synovial inflammation were performed. The histopathological grading and staging system of the Osteoarthritis Research Society International was used to evaluate the cartilage structures, with p<0.05 considered statistically significant. Results: There were no statistically significant differences between the E1 and C1 groups or between the E2 and C2 groups in cartilage damage degree, stage, or score on the 7th day (p=0.117, p=0.197, p=0.197) and on the 28th day (p=0.077, p=0.061, p=0.062). When the E1 and C1 groups were examined to determine degrees of synovial inflammation, inflammation was significantly more common in the rifamycin SV (E1) group (p<0.001 on day 7). In contrast, degrees of synovial inflammation did not differ significantly between the E2 and C2 groups (p=0.256, day 28). Conclusion: The intra-articular administration of rifamycin SV did not have a negative effect on articular cartilage but increased synovial inflammation on the 7th day.
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Review ArticleAçık Erişim2026/r/ebyu/10584
Chronic Pain and Stiffness After Total Knee Arthroplasty: A Comprehensive, Phenotype-Based Review of Mechanisms, Diagnosis and Management
Yapıcı, Furkan
Background/Objectives: Total knee arthroplasty (TKA) relieves pain and restores function for most patients with end-stage knee disease; yet, a clinically important minority are left with persistent pain, stiffness or both despite well-fixed, well-aligned implants. These “hidden failures” are poorly captured by implant survivorship but drive disability, dissatisfaction and disproportionate cost—stiff knees incur roughly 1.5–7.5 times the two-year treatment costs of non-stiff knees. This review integrates three usually separate studies within one phenotype-based framework. Methods: A structured comprehensive narrative review and thematic synthesis was undertaken; PubMed/MEDLINE, Web of Science and Google Scholar were searched between 30 October 2025 and 1 May 2026, identifying 467 records, of which 239 met the eligibility criteria and informed the synthesis. Results: Clinically meaningful chronic pain affects roughly 10–30% of recipients and stiffness approximately 1–7%, with high-impact chronic pain persisting in about one-in-five and neuropathic features in a third to a half of those affected. Contemporary dissatisfaction estimates appear closer to 7–14% than the historical “one-in-five” paradigm, with persistent pain and stiffness the dominant drivers of residual dissatisfaction. Symptoms arise from interacting mechanical, fibrotic, infective, neuropathic, central and psychosocial mechanisms. Six practical phenotypes are proposed—pain-dominant with preserved motion, stiffness-dominant, combined stiff-and-painful, neuropathic-dominant, centrally sensitized, and arthrofibrosis with true mechanical block—and diagnosis, prevention and management are organized around them, spanning risk stratification, surgical technique, manipulation under anesthesia (mean gains ~30–47°, ~6% failure), arthrolysis, revision and multidisciplinary pain care. Conclusions: Chronic pain and stiffness are the quiet arithmetic of arthroplasty success—rare on the survivorship curve, common in the clinic. Matching treatment to phenotype and reserving the operating theater for a knee with a mechanical fault to fix rather than a nervous system to calm, offers the clearest path from a technically successful operation to a genuinely successful recovery.
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Review ArticleAçık Erişim2026/r/ebyu/10583
Beyond the Surgical Bill: Pharmacoeconomics and Real-World Utilization Across the Knee Osteoarthritis Care Pathway—A Critical Narrative Review
Yapıcı, Furkan
Background: Knee osteoarthritis (KOA) is often framed as degenerative knee pain, yet behaves as a decades-long care pathway in which medication, injections, comorbidity, productivity loss, and surgery accumulate into a major economic footprint. This critical narrative review synthesizes pharmacoeconomic and pharmacoepidemiologic evidence across that pathway. Methods: Structured source identification was conducted in PubMed, Web of Science, Scopus, and Google Scholar for publications from 2000 to 2026, with citation tracking. Sources were appraised against predefined critical-interpretation domains and mapped narratively rather than pooled; no meta-analysis was performed. Results: Global Burden of Disease 2019 estimates approximately 364.6 million prevalent KOA cases worldwide. Reported evidence indicates that KOA spending is highly concentrated: in a large U.S. claims analysis, knee arthroplasty was performed in approximately 8.8% of patients yet accounted for 61.5% of KOA-related costs, whereas hyaluronic acid represented 3.0% of overall costs; the remaining pathway burden was distributed across years of outpatient care, analgesics, injections, and other nonsurgical utilization. Medication and injection findings were stage- and phenotype-dependent, and observational studies associated opioid exposure with higher fall risk, healthcare utilization, and cost. Intra-articular hyaluronic acid was repeatedly associated with longer time to arthroplasty, interpreted here as an association limited by confounding and immortal-time bias, not a causal effect; platelet-rich plasma value remained price- and durability-sensitive. Conclusions: KOA economics resembles an iceberg—arthroplasty is the visible peak, while the submerged mass is years of pathway-level care. Value-based policy should measure the full pathway, not the surgical episode, using linked claims, registries, patient-reported outcomes, and productivity data.
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ArticleAçık Erişim2026/r/ebyu/10580
Physical education and sports teachers’ health and well-being: workload, psychological resilience and social support perspective
Seçer, Emrah
Introductıon and aim: The purpose of this study is to examine the relationship between physical education and sports teachers' perceptions of workload and their psychological well-being, and to evaluate the roles of psychological resilience and perceived social support in this relationship. Method: The study employed a correlational survey design, and 276 physical education and sports teachers from public schools in Turkey participated. Data collection tools included the Teacher Workload Scale (TWP), the Connor-Davidson Resilience Scale (CD-RISC), the Psychological Well-being Scale (PWB), and the Perceived Social Support Scale (PSS). The validity of the measurement models was tested using confirmatory factor analysis, and the hypotheses were evaluated using Hayes' Process Macro (Models 1, 4, and 7) and SPSS 25. Results: Under the first hypothesis, the indirect effect of workload on psychological well-being via psychological resilience was significant (b = −0.234, 95% CI [−0.327, −0.142]), explaining approximately 57% of the total variance. In the second hypothesis, perceived social support was found to moderate the relationship between workload and psychological resilience. At high levels of social support, the negative effect of workload on psychological resilience weakened (b = −0.079, 95% CI [−0.184, 0.025]). Within the scope of the third hypothesis, moderates mediation analysis showed that social support significantly mediated the indirect effect of workload on psychological well-being through psychological resilience (b = 0.004, 95% CI [0.001, 0.008]). While negative effects were evident at low levels of social support, they decreased significantly at high levels. Conclusion: The study reveals that the negative effect of teacher workload on psychological well-being operates through psychological resilience, and that perceived social support can mitigate these effects by moderating this process. The findings show that teachers' psychological resilience and social support resources play a critical role in mitigating the negative effects of workload. Educational policies and practices can be designed within the framework of workload management, strengthening social support mechanisms, and resilience-building programs.
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ArticleYalnız künye2026/r/ebyu/10575
Design and synthesis of piperazine-based 3,5-disubstituted-1,2,4-oxadiazole derivatives as dual AChE and BChE inhibitors: In vitro and in silico studies
Faydali, Nagihan; Erol, Meryem; Arpaci, Özlem Temiz; Küçükoğlu, Kaan; Dilek, Esra; Muhammed, Muhammed Tilahun
In this study, ten original 3,5-disubstituted-1,2,4-oxadiazole derivatives were successfully synthesized and characterized by mass spectrometry and ¹H and ¹³C NMR spectroscopy. The potential of these compounds to inhibit butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) was assessed, and the results were reported as IC50 and Kᵢ values. The compounds' Ki values ranged from 21.82 ± 7.87 to 83.67 ± 22.16 nM against BChE and from 9.52 ± 2.10 to 34.99 ± 11.33 nM against AChE. Consequently, it was found that all compounds, except 4f, demonstrated more effective inhibitory action against BChE than donepezil, and that 4g, 4e, and 4i demonstrated more effective inhibitory activity against AChE than donepezil. All compounds were subjected to molecular docking against AChE and BChE, and hydrogen bonding and π-interactions between the compounds and the enzymes were observed. Stabilities of enzyme-compound complexes generated from the docking were investigated by molecular dynamics (MD) simulation. The generated complexes were determined to be stable during the simulation period. To further deepen our understanding, computational DFT analysis revealed key insights into the structures, electronic properties, and reactivity of these materials. To broaden our research, absorption, distribution, metabolism, excretion, and toxicity (ADMET) calculations of the compounds were also carried out.
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ArticleAçık Erişim2026/r/ebyu/10568
Protective Effects of Ranolazine in a Rat Model of Ovarian Ischemia/Reperfusion Injury
Admis, Mesut; Sezgin, Esra Tuba; Suleyman, Zeynep; Admis, Ozlem; Ozkaraca, Mustafa; Gungor, Ali; Aliyev, Aydin; Suleyman, Halis
Ovarian ischemia/reperfusion (I/R) injury is a major cause of tissue damage following the surgical detorsion of ovarian torsion and is characterized by excessive oxidative stress, inflammation, and progressive cellular injury. Although ranolazine has been reported to exert antioxidant and anti-inflammatory effects in various experimental models, its potential protective effects against ovarian I/R injury have not yet been investigated. This study aimed to evaluate whether pretreatment with ranolazine protects ovarian tissue against experimental I/R injury in rats. Twenty-four female Wistar albino rats were randomly assigned to four groups: a healthy group (HG), sham-operated group (SOG), ovarian ischemia/reperfusion (OIR) group, and ranolazine-treated ovarian ischemia/reperfusion (ROIR) group. Ovarian ischemia was induced by 1 h of torsion followed by 6 h of reperfusion. Ranolazine (50 mg/kg) was administered 1 h before the induction of ischemia as a preventive pretreatment. Oxidative stress markers (MDA, tGSH, SOD, and CAT), pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), histopathological alterations, and the expression of COX-1, COX-2, IL-1β, and IL-6 were evaluated by double immunofluorescence staining. Ovarian I/R significantly increased MDA and pro-inflammatory cytokine levels while markedly decreasing tGSH levels and SOD and CAT activities (p < 0.001). These biochemical alterations were accompanied by severe follicular degeneration, mononuclear cell infiltration, interstitial edema, decreased COX-1 immunoreactivity, and increased expression of COX-2, IL-1β, and IL-6. Ranolazine treatment significantly attenuated oxidative stress and inflammatory responses, preserved the antioxidant defense system, ameliorated histopathological damage, restored COX-1 immunoreactivity, and inhibited the expression of COX-2, IL-1β, and IL-6. This is the first experimental study evaluating ranolazine in ovarian I/R injury. These findings suggest that preventive pretreatment with ranolazine attenuates experimental ovarian I/R injury through antioxidant and anti-inflammatory mechanisms. Future studies are needed to determine whether similar protective effects can be achieved when ranolazine is administered after ovarian torsion or following surgical detorsion.
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Review ArticleYalnız künye2026/r/ebyu/10559
A Meta-Analysis of Applied Behavior Analysis-Based Interventions for Individuals with Autism Spectrum Disorders (ASD) in Turkey
Sulu, Mehmet D.; Aydin, Orhan; Martella, Ronald C.; Erden, Emine; Ozen, Zafer
Interventions based on the principles of applied behavior analysis (ABA) have been determined to be evidenced-based practices and are widely used with individuals with autism spectrum disorders (ASD) across the world. Originally developed in the USA, implementation of these interventions has become widespread in the last decade in Turkey. Given the significance of culture in guiding ABA practices, this meta-analysis investigated the prevalence and the magnitude effects of ABA-based interventions and whether specific participant and intervention characteristics moderated such effects in Turkey. Seventy-one ABA-based intervention studies were assessed based on What Works Clearinghouse (WWC, Kratochwill et al., Remedial and Special Education, 34(1), 26–38, 2013) design standards (DSs) including (a) systematic manipulation of independent variables, (b) interrater reliability, (c) three demonstrations of the intervention effect, and (d) adequate number of data points collected for each condition. Forty-three studies that met WWC (Kratochwill et al., Remedial and Special Education, 34(1), 26–38, 2013) DSs were analyzed and calculated with baseline-corrected tau (Tarlow, Behavior Modification, 41(4), 427–467, 2017). Furthermore, performance-criteria-based effect size values (PCES; Aydin and Tanious, Journal of Applied Behavior Analysis, 2021) were calculated for 27 studies that had mastery criteria. While the overall tau appeared to be large 0.71 (p = 0.072, se = 0.254), the overall effect size for PCES revealed a small effect of 0.73. The comparisons of all sub-categories’ effect sizes of moderator variables were not statistically significant based on Kruskal Wallis or Mann Whitney U tests. Additionally, findings revealed that studies were predominantly implemented by highly trained researchers in segregated one-on-one settings, and did not include adults with ASD nor challenging behavior. Overall, there has been significant growth in ABA-based interventions in Turkey that show promise in improving the lives of individuals with ASD. However, further research and cultural considerations are essential for a comprehensive understanding of their impact in the Turkish context. Findings from two different effect size analyses and recommendations for future studies are discussed.
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ArticleAçık Erişim2026/r/ebyu/10557
Managing diagnostic uncertainty in primary care: a mixed-methods study of family physicians’ experiences in Türkiye
Nas, Mehmet Akif; Karahan, Harun; Gürsoy, Ersan
Background: Clinical uncertainty is an inherent component of primary care practice. Family physicians frequently face diagnostic ambiguity, time pressure, and limited access to diagnostic resources, which may affect decision-making and patient outcomes. However, evidence on how family physicians in Türkiye manage diagnostic uncertainty remains limited. Methods: This mixed-methods study included 20 family physicians practicing in primary care settings in Türkiye. Quantitative data were collected using the Physicians’ Reactions to Uncertainty Scale (PRUS) and the Melbourne Decision-Making Questionnaire I-II (MDMQ). Semi-structured interviews were then conducted and analyzed thematically using the Braun and Clarke framework. Results: Quantitative findings showed moderate-to-high emotional reactions to uncertainty and variation in decision-making styles among participants. Thematic analysis of the interviews revealed six key themes: diagnostic challenges and systemic barriers as major sources of uncertainty; specialist consultation, peer support, and patient communication as the main coping strategies; and the significant influence of patient compliance, physicians’ experience, and time pressure on decision-making. High patient load, referral difficulties, and inadequate digital systems were identified as major health system challenges. Physicians consistently emphasized the importance of case-based training and professional development, while also highlighting the role of transparent physician–patient communication in reducing uncertainty. Conclusions: Diagnostic uncertainty is a multifaceted challenge in primary care in Türkiye, influenced by individual, systemic, and patient-related factors. Strengthening case-based educational programs, improving referral processes, and reducing patient load may enhance physicians’ ability to manage uncertainty and improve patient outcomes. Clinical trial number: Not applicable.
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ArticleAçık Erişim2026/r/ebyu/10553
Understanding the relationship between lung GABAA receptors and aquaporin-1: a new therapeutic approach for acute lung injury
Halici, Hamza; Karakoy, Zeynep; Cadirci, Elif; Halici, Zekai; Ozdemir, Bengul; Toktay, Erdem
Background: This study aimed to investigate the effects of the GABAA receptor and the potential relationship between GABA/ GABAA receptor signalling and aquaporin-1 in acute lung injury (ALI). Methods: Fifty-six male Wistar albino rats (220–240 g) were divided into seven groups. Two groups received intraperitoneal diazepam at 5 or 10 mg/kg. In two other groups, 0.1 mg/kg flumazenil was administered five minutes after diazepam. Thirty minutes after the final treatment, all groups except the healthy controls were subjected to an LPS- induced ALI model. Lung tissue were collected 24 h after LPS administration and analysed using histopathological, molecular, and biochemical methods. Results: In the present study, it was found that aquaporin-1, which plays an important regulatory role in LPS-damaged lung tissue, decreased and the weight of lung tissue increased in wet/dry analysis of a murine model of ALI. The levels of IL-1β, IL-6, and TNF-α were found to be elevated. Additionally, in groups treated with the GABAA receptor modulator diazepam, the levels of these inflammatory cytokines were significantly reduced and in parallel a significant increase in aquaporin-1 expression was observed. Conclusion: Diazepam, acting as a GABAA receptor modulator, may alleviate ALI by reducing inflammation and enhancing aquaporin-1 expression via GABAA receptor activation.
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ArticleAçık Erişim2026/r/ebyu/10552
Factors Affecting the Use of Colchicine in FMF Patients and Alternative Treatments in FMF Management: Limits of Colchicine and Solutions
Karataş, Beliz
Objective: The main medication for treating Familial Mediterranean Fever (FMF) is colchicine. We aimed to identify situations that affect the response to colchicine in the treatment of FMF, such as ineffectiveness and side effects, and to discuss alternative treatments, with anti-IL-1 (anti-interleukin-1) agents being at the forefront in these situations. Material and Methods: Our research is a descriptive case series. The age, gender, disease duration, MEFV gene mutation, colchicine preparation used, doses, duration, anti-IL-1 preparation and doses used, duration, reason for intolerance to domestic and/or imported colchicine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum amyloid A (SAA) values at baseline and 3rd and 6th month visits in patients diagnosed with FMF followed and treated on an outpatient or inpatient basis in the internal medicine rheumatology clinic of our university, the presence and frequency of FMF attacks, their clinical status during attacks, and FMF complications (proteinuria, chronic kidney damage, dialysis status) were recorded retrospectively for 25 patients diagnosed with FMF. Results: During colchicine treatment, non-response was present in 19 patients (76%), diarrhea in four patients (16 liver dysfunction in six patients (24%), and myopathy in 1 patient (4%). For these reasons, treatment with anti-IL-1 agents was continued. Conclusion: Side effects such as diarrhea, elevated liver enzymes, myopathy, cytopenia or unresponsiveness limit the use of this medication. In this case, changing the colchicine preparation or switching to anti-IL-1 agents will help us overcome the difficulties in treatment and protect the patient from complications, such as secondary amyloidosis. As part of our continuing mission to enrich the sharing of ideas between medical and scientific communities around the world, the Yale Journal of Biology and Medicine is published Open Access on PubMed Central (PMC). Any user may read, download, or reproduce a digital copy of any article, so long as proper credit is given to the authors and to the Journal as the place of original publication. Al
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