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Understanding cellular metabolism often involves an accurate estimation of metabolic fluxes-the rates at which metabolites are converted in biochemical pathways. Flux Variability Analysis (FVA) is the gold standard for computing reaction flux intervals. However, its reliance on linear programming makes it computationally intensive, often requiring hours or days for large cohorts on complex genome-scale metabolic network models. To address this limitation, we propose mFLIP, a machine learning-based framework for predicting flux intervals across metabolic pathways. The models were trained using large-scale metabolomics datasets comprising over 22,000 samples obtained from Metabolomics Workbench and MetaboLights. Multiple machine learning and deep learning approaches, including Random Forest, XGBoost, CNN, GNN, VAE, and FT-Transformer, were evaluated. Model performance was independently validated across six independent cancer datasets (Breast, Colon, Pancreatic, Prostate, and two stages of Clear Cell Renal Carcinoma). The proposed approach significantly reduces computation time from minutes to under a second during inference. Among the evaluated models, Random Forest and XGBoost achieved the best overall performance, with the lowest regression errors and highest classification scores. Deep learning models, particularly CNN and FT-Transformer, also demonstrated competitive results. Overall, all proposed methods outperformed the state-of-the-art baseline in terms of both accuracy and computational efficiency. mFLIP provides a fast and accurate alternative to traditional FVA-based approaches for metabolic flux interval estimation. By leveraging supervised learning on FVA-derived data, it enables scalable analysis of large cohorts while maintaining high predictive performance, making it a practical tool for large-scale metabolic studies.
Parkinson's Disease (PD) represents the second most prevalent neurodegenerative condition which leads to the progressive destruction of dopaminergic neurons in the substantia nigra through oxidative stress mechanisms. The research evaluated Gallic Acid (GA) as a natural polyphenol with proven antioxidant properties for its ability to protect cells from 1-methyl-4-phenylpyridinium (MPP⁺)-induced neurotoxicity in SH-SY5Y dopaminergic cell models. The research used SH-SY5Y cells which received 1 mM MPP⁺ treatment alongside different GA concentrations (25, 50 and 100 µM) for 24 and 48 h. The CCK-8 assay measured cell viability while flow cytometry evaluated apoptosis and SOD and MDA levels determined oxidative status through SOD and Catalase and NO measurements. The addition of MPP⁺ resulted in a 32.74% decrease in cell viability at 48 h while simultaneously decreasing SOD and Catalase and NO levels and increasing MDA levels. The addition of 25 µM GA protected cells from damage by increasing their viability to 86.53% at 48 h and decreasing apoptotic cell numbers. Our results revealed that co-treatment with 25-50 µM GA effectively mitigated oxidative damage by preventing the depletion of catalase and NO levels. Furthermore, GA successfully reduced lipid peroxidation; specifically, 25 µM GA decreased MDA levels from 21.18 to 9.64 nM/mg protein at 48 h, thereby restoring the cellular antioxidant defense system against MPP+-induced oxidative stress. In conclusion, the present study demonstrates that GA exerts a significant neuroprotective effect in an in vitro PD model by modulating the endogenous antioxidant network and alleviating lipid peroxidation. By effectively reversing the depletion of crucial enzymes and reducing apoptosis, GA shows potential therapeutic efficacy against oxidative stress-associated neurodegeneration. These findings suggest that GA is a promising phytochemical candidate warranting further in vivo evaluation to clarify its long-term bioavailability and translational value.
This paper presents a practical implementation of relative primary radiation thermometry (RPRT) together with MultiFixRadSoft, an open-source software package developed in accordance with the Mise-en-Pratique for the kelvin (MeP-K) for realization of the thermodynamic temperature scale and uncertainty evaluation under the new definition of the kelvin. The software enables realization of temperature scales using ITS-90 metal fixed points as well as metal-carbon and metal-carbide-carbon eutectic high-temperature fixed points (HTFPs) for both radiation thermometers and radiometers. It incorporates automated routines for melting plateau analysis, including determination of the point of inflection, liquidus point, and melting range, together with correction modules for size-of-source effect, detector nonlinearity, emissivity, and temperature drop. Validation is demonstrated through experimental realization using six fixed points (Cu, Fe-C, Co-C, Pd-C, Ru-C, and WC-C) and a linear radiation thermometer. The software also supports ITS-90 extrapolation procedures and flexible calibration schemes (n = 1 to n ≥ 3), with automated Sakuma-Hattori fitting and full uncertainty propagation compliant with MeP-K requirements. The results show excellent agreement with manual analyses and published data, confirming the correctness of the implemented algorithms. By integrating data processing, scale realization, and uncertainty analysis within a unified and transparent framework, MultiFixRadSoft provides a robust and accessible tool for traceable radiometric thermometry, supporting emerging NMIs and industrial laboratories while promoting the wider adoption of primary thermodynamic temperature realization methods.
Obesity is common in rheumatoid arthritis (RA), but its prognostic value at first recorded advanced-therapy initiation is incompletely defined. We examined whether baseline body mass index (BMI) was associated with early DAS28-ESR remission and Health Assessment Questionnaire Disability Index (HAQ-DI)-based functional recovery after first recorded advanced therapy. Adults with clinician-diagnosed RA initiating first recorded advanced therapy between 2013 and 2020 were studied retrospectively. BMI was analyzed continuously and categorically. Outcomes were assessed at the eligible visit closest to 9 months within 6-12 months. Complete-case multivariable logistic regression was supplemented by robust Poisson and sensitivity analyses. Of 581 screened patients, 574 had baseline BMI data, including 235 (40.9%) with obesity. DAS28-ESR remission was evaluable in 258 patients and occurred in 125 (48.4%); remission was less frequent with obesity than with BMI < 25.0 or 25.0-29.9 kg/m² (38.7% vs. 55.8% and 54.7%). In the primary adjusted remission model (n = 208), BMI was not conventionally significant (OR 1.048 per 1 kg/m², 95% CI 0.999-1.100; P = 0.056). HAQ-DI response was evaluable in 228 patients; 226 entered the primary adjusted model. Higher BMI was associated with poor HAQ-DI response (OR 1.056, 95% CI 1.006-1.110; P = 0.029), attenuating after hypertension/diabetes adjustment. Higher BMI showed its most consistent adjusted association with less complete early HAQ-DI-based functional recovery, whereas the DAS28-ESR remission signal was weaker and model-sensitive. Findings are associative and prognostic rather than causal.
Congested tournament schedules impose substantial physiological stress in team sports; however, the integrated endocrine and inflammatory responses to real competitive match load in female handball players remain insufficiently characterized. This study aimed to characterize the acute biochemical responses, including hormonal, inflammatory, muscle damage, and bone metabolism markers, elicited by competitive tournament load in female handball players and to provide practical insights for optimizing recovery strategies and load management during short-term competitive periods. In a pre-post study design, venous blood samples were collected from competitive female athletes (n = 8; age 20.83 ± 2.93 years) before the first match and after the fourth consecutive match of an official university qualification tournament. Biochemical analyses included cortisol, insulin, IL-6, creatine kinase (CK), IGF-1, irisin, lactate dehydrogenase (LDH), osteocalcin, and testosterone. Pre-to-post changes were assessed using paired t-tests and effect sizes. Tournament load induced substantial multisystem physiological perturbations. Significant increases were observed in cortisol (p < 0.001), insulin (p = 0.044), IL-6 (p < 0.001), CK (p < 0.001), and osteocalcin (p = 0.005), indicating activation of the hypothalamic-pituitary-adrenal axis, systemic inflammation, muscle membrane disruption, and enhanced bone turnover. Conversely, IGF-1 (p < 0.001) and testosterone (p = 0.004) significantly decreased, reflecting suppression of anabolic signaling and a shift toward a catabolic hormonal environment under cumulative match stress. LDH significantly decreased (p = 0.002), while irisin showed no significant change (p > 0.05). These findings demonstrate that congested tournament schedules provoke an integrated endocrine-inflammatory stress response in female handball players. Importantly, the observed anabolic-catabolic imbalance highlights the need for individualized recovery strategies, optimized load management, and adequate recovery periods to mitigate maladaptation and reduce injury risk during short-term competitive tournaments.
Micro(nano)plastics (MNPs) are emerging environmental contaminants, yet pharmaceuticals and medical procedures represent a distinct, direct exposure pathway that bypasses primary physiological barriers. This access, via intravenous administration, implants, or injections, is hypothesized to alter toxicokinetic profiles compared to environmental ingestion, representing a unique but unquantified risk. This review synthesizes current knowledge on MNPs introduced via pharmaceutical and clinical routes through a systematic analysis of 27 core studies identified from Web of Science, PubMed, Scopus, and Google Scholar. Our analysis reveals a bifurcated research landscape: one domain focuses on the intentional engineering of particles for drug delivery systems, while the other investigates unintentional contamination from clinical applications. A critical finding is the disconnection between exposure confirmation and hazard characterization. While studies confirm significant iatrogenic exposure, ranging from thousands of particles in intravenous fluids to millions released from degrading sutures, regulatory-relevant toxicological data linking these exposures to adverse human health outcomes are largely lacking. Furthermore, we identify a lack of standardization in analytical processes; methods vary between direct characterization of engineered particles and inconsistent isolation protocols for detecting contaminants in clinical matrices. Consequently, current evidence establishes the presence of iatrogenic MNPs but remains insufficient for robust risk assessment, underscoring the need for standardized analytical methods and foundational toxicological research to bridge the gap between exposure detection and safety management in healthcare.
Alzheimer's disease is characterized by progressive cognitive decline driven by oxidative stress, neuroinflammation, and synaptic dysfunction. This study investigated the neuroprotective effects of vitexin in a scopolamine (Sco)-induced rat model of cognitive impairment. Forty-two male Wistar rats were randomly assigned to six groups (n = 7 per group): saline, Sco (2 mg/kg/day, i.p.), Sco + vitexin (30 mg/kg/day, oral), Sco + donepezil (1.5 mg/kg/day, i.p.), vitexin alone, and donepezil alone. All treatments were administered for 14 consecutive days. Behavioral assessments using the morris water maze and elevated plus maze revealed that Sco significantly impaired spatial learning and memory while increasing anxiety-like behaviors. Vitexin treatment markedly improved these deficits, with efficacy comparable to donepezil. Biochemically, Sco elevated acetylcholinesterase activity, lipid peroxidation, and oxidative/nitrosative stress markers (TOS, OSI, MDA, Peroxynitrite, NO, and NOS) while decreasing total antioxidant status (TAS). Vitexin reversed these changes. Western blot and immunofluorescence analyses demonstrated that Sco reduced hippocampal BDNF, GDNF, PSD95, and synaptophysin levels and increased GFAP, IL-6, TNF-α, NF-κB p65, and COX-2 expression. Vitexin restored neurotrophic and synaptic proteins, suppressed astrocyte activation and inflammatory signaling, and activated the Nrf2/HO-1 pathway. These findings were further supported by qRT-PCR analysis of BDNF, GDNF, GPX4, and NF-κB. In conclusion, vitexin exerts significant neuroprotective and synaptoprotective effects against Sco-induced cognitive impairment by simultaneously restoring redox balance, suppressing neuroinflammation, and preserving synaptic integrity. These results position vitexin as a promising therapeutic candidate for neurodegenerative disorders, including Alzheimer's disease.
The role of traction radiographs in the preoperative evaluation of intertrochanteric femur fractures remains controversial, with inconsistent evidence regarding their impact on fracture classification, stability assessment, and surgical decisionmaking. This nationwide simulation-based study aimed to investigate how orthopedic trauma surgeons use and interpret traction radiographs and to determine their influence on surgical planning across different levels of clinical experience. A nationwide, cross-sectional simulation-based study was conducted among actively practicing orthopedic and trauma surgeons between October 14 and November 15, 2025, using a structured questionnaire containing simulated cases. The questionnaire included demographic characteristics, clinical experience, perceptions of traction radiographs, and case-based assessments of 15 AO Foundation/Orthopaedic Trauma Association (AO/OTA)-classified intertrochanteric fractures (31-A1, 31-A2, 31-A3). A total of 133 surgeons participated, yielding 1,995 individual case evaluations. Changes in surgical decisions before and after traction radiographs were analyzed using McNemar tests, while independent predictors were identified using generalized estimating equations (GEE). Traction radiographs were requested in 59.5% of all assessments, with significantly higher request rates in unstable patterns (31-A2: 75%; 31-A3: 68.2%) compared with 31-A1 fractures (30%). Overall, traction imaging resulted in a 12.4% change in surgical planning, increasing to 21% among cases in which traction radiographs were obtained. Decision changes were most common in 31-A2.3 (14.9%) and 31-A3.3 (16.9%) patterns. The most frequent implant transition was from short to long proximal femoral nail (PFN) (40.8%), followed by conversion to arthroplasty (18.8%). GEE analysis demonstrated that both fracture type and requesting traction radiographs were independent predictors of surgical plan modification (odds ratio [OR]=1.55-2.40 for unstable fracture types; OR=1.60 for traction radiograph request; p<0.05 for all). Surgeon title, institutional setting, years of experience, and case volume were not associated with decision changes. Traction radiographs provide clearer visualization of fragment configuration and medial and lateral wall integrity, leading to improved recognition of fracture instability and a measurable shift toward more durable fixation strategies. Their impact on surgical planning is most pronounced in complex or borderline-unstable fracture patterns and remains consistent across experience levels. As a low-cost and readily accessible adjunct, traction radiography represents a valuable tool in the preoperative assessment of intertrochanteric fractures. Routine use is recommended, particularly when instability is suspected or when standard radiographs provide insufficient clarity. Traksiyon grafilerinin intertrokanterik femur kırıklarının preoperatif değerlendirilmesindeki yeri halen tartışmalıdır. Literatürde kırık sınıflandırması, stabilite değerlendirmesi ve cerrahi planlama üzerindeki etkisine ilişkin bulgular kesinleşmemiştir. Bu ulusal ölçekli çalışma, ortopedi ve travmatoloji uzmanlarının traksiyon grafisi kullanımına yönelik yaklaşımlarını ve bu görüntülemenin cerrahi karar verme sürecine etkisini, klinik deneyimden bağımsız olarak değerlendirmeyi amaçlamıştır. 14 Ekim–15 Kasım 2025 tarihleri arasında aktif olarak çalışan ortopedi ve travmatoloji hekimlerine çevrimiçi vaka temelli bir değerlendirme uygulanmıştır. Bu değerlendirme; demografik bilgiler, klinik deneyim, traksiyon grafisine yönelik algı ve 15 AO/OTA sınıflandırılmış intertrokanterik kırık vakasına (31-A1, A2, A3) ilişkin vaka temelli soruları içermiştir. Toplam 133 katılımcıdan 1995 gözlem elde edilmiştir. Cerrahi karar değişiklikleri McNemar testi ile analiz edilmiş, bağımsız belirleyiciler Genelleştirilmiş Tahmin Denklemleri (GEE) ile değerlendirilmiştir. Traksiyon grafisi istem oranı tüm değerlendirmelerin %59.5’ini oluşturmuş olup, bu oran instabil kırık tiplerinde anlamlı biçimde yükselmiştir (31-A2: %75; 31-A3: %68.2; 31-A1: %30). Traksiyon grafisi sonrası genel cerrahi plan değişikliği oranı %12.4, traksiyon grafisi istenen olgularda ise %21 olarak bulunmuştur. Karar değişikliği özellikle 31-A2.3 (%14.9) ve 31-A3.3 (%16.9) kırıklarında belirginleşmiştir. En sık implant geçişi kısa PFN’den uzun PFN’ye (%40.8), ardından artroplastiye geçiş (%18.8) şeklinde olmuştur. GEE analizinde kırık tipi ve traksiyon grafisi istemi cerrahi karar değişikliğinin bağımsız belirleyicileri olarak saptanmıştır (OR=1.55–2.40 ve OR=1.60; p<0.05). Katılımcının unvanı, kurum tipi, deneyim yılı ve vaka hacminin karar değişikliği üzerinde anlamlı etkisi bulunmamıştır. Traksiyon grafileri fragman konfigürasyonunun ve medial/lateral duvar bütünlüğünün daha net değerlendirilmesine olanak sağlayarak kırık instabilitesinin daha doğru tanınmasına ve daha dayanıklı implant tercihlerine yönelimde artışa neden olmaktadır. Bu etkinin özellikle kompleks veya sınırda instabil kırıklarda belirgin olduğu ve cerrah deneyiminden bağımsız olarak korunduğu gösterilmiştir. Traksiyon grafisinin düşük maliyetli, uygulanabilir ve klinik karar sürecine anlamlı katkı sağlayan bir yöntem olarak intertrokanterik kırıkların preoperatif değerlendirilmesinde rutin kullanımının, özellikle instabiliteden şüphelenilen durumlarda, faydalı olabileceği düşünülmektedir.
This study aimed to evaluate the impact of different intra-abdominal pressure (IAP) levels on oxidative stress, as measured by thiol-disulfide homeostasis parameters, in geriatric patients undergoing laparoscopic cholecystectomy. A total of 62 patients aged 65 years and older diagnosed with cholelithiasis were included. Patients were randomly assigned to either the low-pressure group (10 mmHg) or the high-pressure group (15 mmHg). Standard laparoscopic cholecystectomy was performed under general anesthesia by the same surgical team. Preoperative and postoperative blood samples were collected to evaluate oxidative stress parameters (native thiol, total thiol, disulfide), as well as basic biochemical markers (AST, ALT, urea, creatinine) and hematological indices (WBC, hemoglobin, hematocrit, platelet count). Postoperative AST levels were significantly higher in the high-pressure group compared to the low-pressure group (p = 0.031), while ALT differences were not statistically significant. Although disulfide and oxidized thiol ratios were higher in the high-pressure group preoperatively, no significant differences were observed between the groups postoperatively. While higher intra-abdominal pressure may be associated with mild hepatic stress, it does not appear to cause significant oxidative imbalance in geriatric patients. Both low and high-pressure pneumoperitoneum levels can be used safely during laparoscopic cholecystectomy in elderly individuals, provided that appropriate perioperative management is ensured.
We aimed to assess the presence of microplastics in nasal irrigation methods commonly used in the treatment of sinusitis and rhinitis, and to evaluate human exposure. A total of 150 samples were included in the study, consisting of nasal wash bottles containing nasal irrigation solution, seawater spray, syringes for nasal irrigation with isotonic solution. The amount of microplastics per millilitre in the samples and patient exposure during single use were assessed separately for each method and product. All samples were filtered using a stainless steel vacuum filter on filter paper with a pore size of 1.2 μm, washed at least three times with distilled water and incubated at 45 °C for 24 h to prevent mould growth. Identification and counting of microplastics was performed using a Leica Flexacam C1 camera connected to an M80 stereomicroscope. The presence of microplastics was confirmed by the hot needle method and Nile red staining. An average of 6.49 ± 13.08 microplastics/product was detected in all filtered samples. The lowest microplastic count was 0 microplastics/product in syringes and the highest was 92 microplastics/product in nasal wash bottles. Significant differences in the amount of microplastics individuals were exposed to during a single use were found between nasal wash bottles and seawater brands, while no significant differences were found between syringe brands. When nasal wash kits, seawater sprays and isotonic nasal rinses were evaluated separately, significant differences were found in the number of microplastics, the microplastics/ml ratio and the number of microplastics exposed during a single use. The highest microplastic exposure was found in nasal irrigation bottles. The exposure of individuals to microplastics increases with medical support treatments, regardless of intranasal or intravenous administration. Due to the inflammation, oxidative stress and proliferation caused by microplastics, new regulations and inspections of production conditions should be implemented worldwide to reduce exposure.
Tularemia is a zoonosis caused by the bacterium Francisella tularensis. F.tularensis is a small pleomorphic, non-motile, obligate aerobe, gram-negative bacterium that shows facultative intracellular parasitism. It is known to cause disease in both humans and animals and is one of the most infectious bacteria known. The disease has different clinical forms depending on the route of bacterial entry into the body. The routes of transmission of the disease include drinking water contaminated with the bacteria, tick bites, consuming game meat, handling tissues or fluids from infected animals and inhaling infected aerosols. While there is a potential for pregnant animals to miscarry, the frequency of this risk in humans remains uncertain due to the low number of tularemia cases during pregnancy. F.tularensis has four subspecies, which differ in virulence and geographical distribution. The subspecies found in Türkiye is F.tularensis subspecies holarctica, which has a better clinic. In the treatment of tularemia, aminoglycosides (streptomycin, amikacin), quinolones and tetracyclines are used. However, due to the fetotoxicity of these agents, their use during pregnancy is problematic. The World Health Organization recommends using gentamicin or ciprofloxacin for the treatment of tularemia during pregnancy. In this case report, tularemia infection that developed in the second trimester of pregnancy was presented and the relevant literature was reviewed., A 23-year-old patient in the 16th week of her pregnancy presented with painful swelling in the neck. Following the detection of a microagglutination test titer of over 1/1280 for tularemia in her blood sample sent to General Directorate of Public Health National High Risk Pathogens Reference Laboratories, the patient was diagnosed as tularemia. Gentamicin treatment was planned for the patient who had glandular tularemia however, due to the refusal of this treatment by the patient and her relatives, oral azithromycin (500 mg/day for six weeks) was initiated instead. The patient was closely monitored with clinical, laboratory findings, and obstetric ultrasonography until delivery. A complicationfree birth occurred at the 39th week of pregnancy. Postnatal follow-up for two months revealed that both the mother and the baby were in good health. A PubMed search using the keywords “tularemia, pregnancy, azithromycin” identified case reports from three different countries (Austria, France and the United States of America) in which tularemia cases during pregnancy were successfully treated with azithromycin. To our knowledge, the presented case is the fourth case successfully treated with azithromycin in the literature. While tularemia cases during pregnancy have previously been reported in Türkiye, this case report represents the first documented experience with the use of azithromycin for the treatment within the country.
The heterogeneity of symptoms among patients with fibromyalgia (FM) makes the development of standardized diagnostic criteria challenging. No imaging technique has reliably shown FM-related muscle changes to aid clinical assessment. This study aimed to quantitatively analyze the upper trapezius muscle in FM patients using B-mode ultrasonography and blob analysis and to examine its correlation with clinical parameters. A total of 34 female FM patients and 34 healthy controls were included in this cross-sectional study. B-mode ultrasonography was used to image the dominant-side upper trapezius muscle, and MATLAB-based blob analysis was performed to assess blob size, blob count, and echointensity. These measurements were correlated with disease severity indices, including the Central Sensitization Inventory (CSI), Visual Analog Scale (VAS) for pain, Fibromyalgia Impact Questionnaire (FIQ), 36-Item Short Form Survey (SF-36), and Beck Depression and Anxiety Inventories (BDI, BAI). FM patients had significantly higher total blob size (p < 0.001) and blob size per mm² (p < 0.001) than controls. Echointensity was significantly increased in the FM group (p = 0.009). Total blob size showed a moderate positive correlation with CSI scores (p = 0.002). Regression analysis indicated that pain-VAS was a significant predictor of total blob size per mm² (p < 0.001). Blob analysis demonstrated quantifiable muscle alterations in FM, supporting its potential role as an objective assessment tool. Given the correlation between muscle echotexture and FM severity, quantitative ultrasonography may contribute to a better understanding of FM pathophysiology.
HOXB13 is a lineage-specific transcription factor that plays a critical role in initiation and progression of prostate cancer (PCa). While most research has focused on the role of HOXB13 on androgen receptor (AR) activity, here we demonstrate that HOXB13 is frequently expressed in AR-negative tumors and is essential for the proliferation of both AR-positive and -negative PCa models. Strikingly, HOXB13 is remarkably selective and has almost no effect on nonprostatic tissues. Despite this common essentiality in PCa, HOXB13 activity is markedly different in AR-negative stem cell-like tumors, where interactions with the AP-1 change the HOXB13 cistrome and interactome. Yet despite these distinct activities, HOXB13 activity is commonly mediated by SMARCD2, a member of the mSWI/SNF chromatin remodeling complex. The HOXB13/SMARCD2 interaction alters chromatin accessibility at HOXB13-binding sites, causing increased proliferation in AR-negative PCa. Overall, this work demonstrates a distinct mechanism of action for HOXB13 and highlights its critical role in AR-negative castration-resistant PCa.
In this study, the structure of a new boron compound obtained using 3-methoxy catechol and 4-methoxy phenyl boronic acid was characterized by 1H, 13C NMR, LC-MS-IT-TOF, UV-Vis and FTIR spectroscopy. The antioxidant activities of the newly synthesized compound were evaluated by DPPH free radical scavenging, ABTS quation radical scavenging and CUPRAC copper reducing capacity methods. Anticholinesterase activities were determined by acetylcholinesterase and butyrylcholinesterase enzyme inhibitor assays. Antiurease and antithyrosinase enzyme inhibition activities were also examined. Cytotoxic effects were evaluated on healthy cell lines and breast and colon cancer cell lines using MTT method. The results showed that the synthesized compound has high antioxidant activity. Especially the average antioxidant activity values obtained at 10 μg/mL concentration were found to be statistically significantly (p < 0.05) higher than the reference values of α-TOC and BHT. When the antioxidant activity data (IC50) were compared separately with α-TOC and BHT reference values, the new compound was found to be more effective. In acetylcholinesterase enzyme inhibition, the average activity values were found to be statistically significantly (p < 0.05) higher than the galantamine reference value. However, no statistically significant difference was observed at BChE (% inhibition) level with galantamine reference value. In terms of urease and tyrosinase enzyme inhibition activities, the urease activity of the synthesized compound was statistically significantly (p < 0.05) lower than the thiurea reference value. Tyrosinase activity was statistically significantly (p < 0.05) lower than kojic acid reference values. The synthesized and characterized compound was found to have no toxic effect on healthy cell lines and did not show any cytotoxic effect on breast cancer (MCF-7) and colon cancer (HT-29) cell lines.
After liver transplantation, recipients continue to receive immunosuppressive drug regimens at varying doses for years to ensure graft function and survival. Although liver transplant recipients are aware of the importance of immunosuppressive drug regimens, treatment compliance may decrease over time due to low motivation, putting recipients at risk of organ rejection. Acceptance and commitment therapy (ACT) appears to be an ideal solution for increasing motivation and, indirectly, treatment compliance. The aim of this study was to investigate the effect of ACT on adherence to immunosuppressive medication and motivation in liver transplant recipients. This study was conducted at an organ transplant hospital with the participation of recipients who had completed at least 6 months post-liver transplant. The sample included n = 140 liver transplant recipients (n = 70 experimental, n = 70 control). The study was randomized and controlled. The control group received no intervention, while the experimental group underwent an eight-session ACT program administered by a psychologist. Data collection utilized a personal characteristics form, the Adherence to Immunosuppressive Drug Regimen Scale (AIDRS), the Mindfulness Scale (MS), and the Adult Motivation Scale (AMS). Data analysis was performed using descriptive statistical methods and tests of significance for differences between variables. According to the homogeneity tests of this study, there was no statistically significant difference between the control and experimental groups in terms of individual characteristics (age, time since transplantation, immunosuppressive drugs, comorbidities, etc.). In the experimental group, the level of adherence to the immunosuppressive drug regimen after ACT was very close to the maximum AIDRS score. In the control group, the level of compliance with the immunosuppressive drug regimen was close to the mean value of the AIDRS. The differences mentioned in both groups were statistically significant (p < 0.05). In addition, the scores obtained from the MS and YMS were higher than those in the pretest. When the experimental and control groups were compared, the experimental group's final test YMS score was almost twice that of the control group, and this difference was statistically significant (p < 0.05). The importance of full compliance with the immunosuppressive drug regimen in improving graft function after liver transplantation is well known. The results of this study showed that liver transplant recipients who underwent ACT demonstrated higher adherence to the immunosuppressive drug regimen due to increased motivation and conscious awareness. We recommend the use of ACT to increase adherence to the immunosuppressive medication due to its effectiveness.
Alcohol-impaired driving is a well-established and preventable cause of road traffic deaths and injuries. This study examined national time trends in the relative burden of alcohol-related fatal-and-injury road traffic crashes in Türkiye between 2015 and 2024 and interpreted the findings within an ecological policy and enforcement context. We conducted a national ecological time-trend analysis using annual aggregate road traffic crash statistics from the Turkish Statistical Institute for 2015-2024. The outcome was the annual count of alcohol-related crashes resulting in death or injury. To estimate changes in the relative burden over time, the natural logarithm of the annual total number of fatal-and-injury crashes was included as an offset. Temporal trends were first assessed using Poisson regression; after overdispersion was identified, estimates were re-evaluated using negative binomial regression. Results are reported as incidence rate ratios (IRR) with 95% confidence intervals (CI). The proportion of alcohol-related fatal-and-injury crashes among all fatal-and-injury crashes declined from 2.13% in 2015 to 0.72% in 2024. In the Poisson model, calendar year was negatively associated with the relative burden (IRR 0.883; 95% CI 0.880-0.887; p < 0.001), although model fit indicated overdispersion. In the negative binomial model, the direction of the association remained negative but was not statistically significant (IRR 0.883; 95% CI 0.709-1.097; p = 0.260). Sensitivity analyses excluding 2020 alone and excluding both 2019 and 2020 yielded nearly identical estimates, indicating that the negative but non-significant trend was not materially driven by potentially atypical pandemic-period observations. Descriptive data showed a marked decline in the relative burden of alcohol-related fatal-and-injury road traffic crashes in Türkiye from 2015 to 2024. However, negative binomial regression did not confirm a statistically significant temporal trend, indicating that model-based evidence should be interpreted cautiously. Interpretation should consider the ecological nature of the data and the possibility of time-varying enforcement intensity, detection, and reporting practices.
To evaluate the applicability and clinical effectiveness of a modified clamp-rod internal fixation (M-CRIF) system compared with conventional locking plate osteosynthesis in the treatment of feline corpus ilium fractures. Prospective, controlled clinical study. Thirty-six client-owned cats with corpus ilium fractures. Cats were randomly assigned to two groups: Group I (M-CRIF, n = 18) and Group II (locking plate, n = 18). All fractures were stabilized with a lateral approach. Radiographic healing, sacral index (SI), and complications were assessed at postoperative days 21, 45, 60, and 120. Long-term outcomes were assessed using owner questionnaires addressing mobility and defecation. Fracture union was achieved in all cats. Healing scores increased over time in both groups (p < .05). At day 45, Group I showed higher healing scores than Group II (p = .002). Sacral index narrowing was lower in Group I (p = .005). Implant-related complications occurred in 22.2% (4/18) of cats in the plate group, including screw loosening and one revision surgery, whereas no screw loosening was observed in the M-CRIF group. Preoperative neurological deficits were present in 22.2% of cats, decreasing to 5.5% postoperatively. Owner questionnaires indicated satisfactory mobility, although some discrepancies with clinical and radiographic findings were observed. The M-CRIF system provided greater stability, fewer complications, and better preservation of the pelvic canal than locking plates. This study is the first clinical evaluation of the M-CRIF system in feline ilial fractures and demonstrates favorable outcomes, supporting its use as a reliable alternative to conventional plating.
Psilocybin and MDMA produce rapid, enduring therapeutic effects in posttraumatic stress disorder (PTSD); however, the underlying cellular mechanisms remain incompletely understood. In this study, we investigated whether adult myelin plasticity contributes to the therapeutic actions of psilocybin and MDMA in a rat model of contextual fear conditioning. Adult male Wistar rats (N = 210) received repeated low doses of psilocybin (0.5 mg/kg, intraperitoneally [i.p.], for 4 days) or MDMA (0.1 mg/kg/day, i.p., for 4 days). Behavioral tests assessed anxiety-like behaviors and spatial memory. Following local and global manipulations of myelin integrity, we assessed the drugs' effects on myelination by quantifying myelin sheath thickness; oligodendrocyte-lineage cell densities; and transcriptomic, proteomic, and metabolomic profiles in the dentate gyrus. Both compounds reduced anxiety-like behaviors. These improvements coincided with oligodendroglial changes and multiomic signatures of myelin-related remodeling; however, mean g-ratio measures of myelin thickness did not differ significantly between intact fear-conditioned animals with or without psychedelic treatment. Myelin disruption abolished these anxiolytic effects, and integrative multiomics revealed convergent upregulation of myelin-related proteins following administration of psilocybin or MDMA. Psilocybin preferentially induced early oligodendroglial gene programs, while MDMA enhanced markers of mature myelin. Notably, 5-HT2A receptor blockade completely abolished the myelin and behavioral enhancements induced by both psilocybin and MDMA. Psilocybin and MDMA promote adult oligodendrocyte and myelin plasticity. Enhancing myelination may be a viable strategy to augment or sustain the therapeutic effects of psychedelic-assisted treatments for PTSD and related disorders.
Biomarkers play a pivotal role in disease diagnosis and prognosis by offering molecular insights into biological states. The rapid growth of high-throughput omics technologies has enabled the generation of large-scale biomarker datasets, yet analyzing these complex, high-dimensional data remains a major challenge-particularly for researchers lacking advanced computational expertise. While numerous tools exist for omics data analysis, many fall short in providing an integrated, user-friendly environment tailored specifically for biomarker discovery and interpretation. To address this gap, we present BioMark, a web-based platform designed to streamline biomarker analysis across diverse omics types. BioMark integrates robust statistical methods with widely used machine learning algorithms to support key workflows including statistical analysis, dimensionality reduction, classification, and subsequent model explanation. The platform emphasizes accessibility, offering intuitive visualizations and automated reporting to facilitate interpretation and dissemination of results. Notably, BioMark also offers a feature-ranking strategy that consolidates outputs from multiple analytical methods, enhancing the robustness of biomarker identification. By lowering the barrier to advanced biomarker analytics, BioMark empowers a broader range of researchers to uncover clinically relevant molecular signatures and accelerate translational research. Biomark is available online at https://bioinf.itu.edu.tr/biomark .