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Tigecycline therapy for multidrug-resistant bacteria: is it the right choice for pediatric patients
Introduction: The incidence of infections caused by multidrug-resistant pathogens is increasing worldwide, resulting in significant morbidity and mortality. Tigecycline has become a good option because it has a broad spectrum of antibacterial activity. This study aimed to reveal the clinical, microbiological, and laboratory outcomes of hospitalized children treated with tigecycline. Methodology: We retrospectively collected the medical records of the hospitalized pediatric patients treated with tigecycline from April 1, 2018, to Apr 30, 2023, at Ege University Children's Hospital. Demographic features and clinical and laboratory findings were evaluated to determine the efficacy and safety of tigecycline therapy. Results: Sixty-seven patients (65.7% male) with a median age of 6 years (2.5 months-17.5 years) were included. There was an underlying condition in 83.5% of the patients, and 55.2% were immunosuppressed. The most common infections were; lower respiratory tract infections (29.8%), intra-abdominal infections (20.9%), bloodstream infections (17.9%), and soft tissue infections (13.4%), respectively. Acinetobacter spp. (28.4%) was the most isolated microorganism, followed by Klebsiella spp. (19.4%) and Enterococcus spp. (14.9%). Tigecycline was used as a targeted treatment in 76.1% of the patients and was often used as a combination therapy (80.6%) with a median duration of 12 days (range, 2-60 days). Clinical response was achieved in 65.6% of patients, microbiologic response in 62.6%, and treatment failure in 34.3%. No major adverse events were noted during the therapy. Conclusions: Tigecycline, which was mostly preferred in combination therapy, had high clinical response and microbiologic eradication rates, but these rates varied according to infection sites and microorganism species
Raising Acoustic, Mechanical, and Thermal Properties of Flexible Polyurethane Foams via Hazelnut Shell and Hemp Fiber Hybrid Fillers
The growing demand for sustainable materials drives the integration of natural fillers into flexible polyurethane foams. This study explores a novel hybrid filler system using hazelnut shell powder (HSP) and industrial hemp fibers to enhance acoustic, mechanical, and thermal properties while reducing petroleum-based components. Flexible foams were produced with filler loadings of 1.5%, 3%, and 6% for each material. Samples were analyzed using Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), scanning electron microscopy (SEM), compression testing, and acoustic measurements. Results show that foams with 3% hazelnut and 3% hemp achieved an 8% increase in compressive strength at a density of 168 kg/m3. Acoustic tests revealed that 1.5% blends improved sound transmission loss at 250 Hz by 4.13 dB, while 3% blends enhanced performance at 6300 Hz by 13%. Thermal stability showed marginal improvement with filler addition. These findings demonstrate that combining hazelnut shell powder and hemp fibers can significantly enhance foam properties while reducing reliance on petroleum-derived components. The dual-filler strategy offers a novel route toward more sustainable polyurethane foams.Turkiye Bilimsel ve Teknolojik Arastimath;rma KurumuThis work was supported by Turkiye Bilimsel ve Teknolojik Arast & imath;rma Kurumu
Experiences of Intern Nurses Returning From Distance Education to Clinical Practice During the COVID-19 Pandemic: A Qualitative Study
Rationale: The present study aimed to understand the experiences of intern nurses returning to clinical practice after a year-long distance education during the pandemic. Methods: The study was conducted using the qualitative content analysis method. The participants were 32 intern nurses. The data included specific narratives on the experience of intern nurses returning from distance education to clinical practice during the pandemic. Data were collected through a total of four focus group interviews. Data analysis was conducted using an inductive qualitative analysis approach. Results: The content analysis identified three main categories. The category ‘Feelings during Clinical Practice’ included the subcategories ‘fear’, ‘uncertainty’ and ‘intolerance’. The category ‘Challenges during Clinical Practice’ included the subcategories ‘sleep problems’, ‘alienation from clinical placement’, ‘lack of knowledge and experience’, ‘hospital staff’, ‘difficulty reaching nurse educator’ and ‘lack of protective equipment’. The category ‘Suggestions for Clinical Practice’ included the subcategories ‘psychological support’, ‘case discussion and academic counselling’ and ‘protective equipment support’. Conclusions: The study revealed that intern nurses faced various challenges in clinical settings following their year-long distance education. The results may help nurse educators understand the experiences of intern nurses returning to clinical practice after a year-long distance education and determine the teaching strategies to be followed in specific situations like pandemics in the future. © 2025 Elsevier B.V., All rights reserved
Baba-yi Emir dergisinde hiciv yazıları üzerine bir inceleme
Baba-yi Emir dergisi üzerinde yapılan bu çalışmada, dergi Azerbaycan Türkçesinden Türkiye Türkçesine aktarılmış ve derginin Azerbaycan'daki önemi değerlendirilmiştir. Çalışma boyunca birincil kaynaklar temel alınmıştır. Tezin giriş bölümünde Rusya'nın Türk toplumlarına uyguladığı yayılmacı politikadan ve bu politikayı Azerbaycan topraklarında sürdürürken Baba-yi Emir dergisinde bu politikaların nasıl ele alındığından ve eleştirildiğinden bahsedilmiştir. Birinci bölümde Baba-yi Emir dergisi mizah çerçevesinde incelenmiştir. İkinci bölümde ise derginin basın ve yayın hayatındaki yerinden, dilinden, biçim özelliklerinden ve yayın sürecinden bahsedilmiştir. Üçüncü bölümde ise seçili örnekler üzerinden derginin din, kadın, eğitim ve uluslararası meseleler üzerine getirmiş olduğu eleştirel bakış açısı incelenmiştir. Dördüncü bölümde söz konusu derginin 1915 yılında yayımlanmış sayılarının izahlı bibliyografyası çıkarılmıştır. Sonuç bölümünde Babayi Emir dergisi hakkında değerlendirme yapılmış ve yapılan çalışma hakkında genel bilgi verilmiştir.In this study on the Baba-yi Emir journal, the text has been transcribed from Azerbaijani Turkish into Turkey Turkish, and the significance of the journal within Azerbaijan has been assessed. The research is grounded primarily in first-hand sources. The introduction section discusses the expansionist policies implemented by Russia toward Turkic communities and how these policies were continued on Azerbaijani territory. It further examines how Baba-yi Emir critically addressed and responded to these policies. The first chapter analyzes Baba-yi Emir within the framework of satire. The second chapter focuses on the journal's role in the press and publishing life, addressing its language, formal characteristics, and publication process. In the third chapter, selected examples are used to explore the journal9s critical perspective on religion, women, education, and international issues. The fourth chapter presents an annotated bibliography of the journal9s issues published in 1915. The conclusion offers an overall evaluation of Baba-yi Emir and summarizes the findings of the study
Caspofungin in the treatment of Candida auris candiduria in Hemato-oncological Patients: An observational retrospective cohort study
Candiduria is a common problem especially in advanced stage oncology/hematology cases. Herein, we aimed to analyze the efficacy of caspofungin treatment in Candida auris isolated from urine culture. We conducted an observational retrospective study in a tertiary-care educational hema-to-oncology hospital from October 2021 to November 2022. The patients hospitalized in our center and having at least two consecutive urine cultures that yielded C. auris with significant pyuria were included in the study. The effectiveness of caspofungin was evaluated based on clinical and microbiological outcomes. In total, 10 patients (two female, aged 55.3 ± 15) were included in the study. Four (40%) patients had urinary tract infections, and six (60%) patients had asymptomatic C. auris candiduria which required antifungal therapy. Nine cases had urinary instrumentation: two nephrostomy, one suprapubic catheter, and six urinary catheters. The 10 cases received a mean of 13.4 ± 3.5 days of caspofungin. Four of 10 cases (40%) had at least 1 negative culture between day 1 and the end of caspofungin treatment. Relapse and re-infection rates 30 days after the end of therapy in microbiologically successful cases were 3/4 and 2/4. Caspofungin resistance developed in three cases (30%) within 30 days after treatment. Overall day-30 mortality was 3/10 (30%) while overall success (microbiological success + no relapse/reinfection during 30 days follow up after end of therapy) was 10%. Caspofungin demonstrated limited efficacy in treating C. auris-related urinary tract infection/colonization in hospitalized cancer patients. © 2025 Elsevier B.V., All rights reserved
Üzümsü meyvelerden sirke üretiminde farklı teknolojik uygulamaların biyoaktif bileşikler üzerine etkilerinin incelenmesi
Üzümsü meyveler, fenolik bileşikler ve antioksidanlar açısından zengin, değerli bir gıda grubudur. Bu çalışmada; yaban mersini (YM), frenk üzümü (FÜ) ve böğürtlenden (B) elde edilen meyve sularıyla, %7 etanol ilaveli (B grubu) ve ilavesiz (A grubu) olarak uygulanan 0, 5, 10 ve 15 dakikalık ultrason işlemleriyle sirke üretilmiştir. Elde edilen sirke örneklerinde toplam fenolik madde, toplam flavonol, antioksidan kapasite (DPPH), pH, asitlik, yoğunluk, absorbans, ve renk özellikleri açısından analiz edilmiştir. Analizler sonucunda, en yüksek toplam fenol değeri 1078,48 mg/L GAE ile BA3, en yüksek flavonol içeriği 168,421 mg/L kuersetin ile BB2 örneğinde belirlenmiştir. DPPH açısından en yüksek antioksidan aktivite FÜB3 (141,8 mg TE/100 mL), en yüksek asitlik değeri (%6,01) ise FÜA1, FÜB1 ve BA2 örneklerinde saptanmıştır. Renk analizinde en yüksek kroma değeri FÜB1 (896,17), en düşük Hue değeri BB4 (3,22) örneğine aittir. 520 nm ve 620 nm absorbansındaki artış, renk yoğunluğunun ultrason süresiyle paralel olduğunu göstermektedir. Sonuçlar, %7 etanol içeren substratlar ve ultrason işlemlerinin sirke üretiminde yenilikçi ve etkili bir yaklaşım sunduğunu göstermektedir. Asetik fermantasyonun hızlandırılmasına ve biyoaktif bileşiklerin artmasına katkı sağlarken, renk ve duyusal kaliteyi de artırmıştır. Ultrason süresi ve etanol oranı gibi parametrelerin yanıt yüzey metodolojisi ile optimize edilmesi, fonksiyonel sirke üretiminde kalite standardının sağlanması açısından önem arz etmektedir.Berry fruits are a valuable food group rich not only in essential nutrients but also in phenolic compounds, flavonoids, anthocyanins, and other antioxidants. In this study, vinegar was produced using fresh blueberry (YM), blackcurrant (FÜ), and blackberry (B) juices, applying ultrasound treatments of 0, 5, 10, and 15 minutes with (group B) and without 7% ethanol (group B) addition. A total of 24 samples were analyzed for total phenolic content, total flavonol, antioxidant capacity (DPPH), pH, titratable acidity, density, absorbance , and color properties. According to the analyses, the highest total phenolic content was found in sample BA3 (1078.48 mg/L GAE), and the highest flavonol content in BB2 (168.421 mg/L quercetin). The highest antioxidant activity (DPPH) was observed in FÜB3 (141.8 mg TE/100 mL), while the highest In color analysis, FÜB1 showed the highest chroma value (896.17), and BB4 had the lowest Hue value (3.22). Increases in absorbance at 520 nm and 620 nm indicated that color intensity rose in parallel with ultrasound duration. The results demonstrate that using substrates with 7% ethanol and ultrasound treatments offers an innovative and effective approach to vinegar production. This method contributes to the acceleration of acetic fermentation, enhances bioactive compound content, and improves color and sensory quality. Optimization of parameters such as ultrasound duration and ethanol concentration via responce surface methodology is important for ensuring quality standards in functional vinegar production
Farkli ejeksiyon fraksiyonlu kalp yetmezliğinde atriyum dokularında kontraktil yanıtlar SERCA2a fosfolamban ve SIRT enzim ilişkisinin incelenmesi
Amaç: Çalışmada, Ege Üniversitesi Tıp Fakültesi Kalp ve Damar Cerrahisi Anabilim Dalı'nda kardiyopulmoner bypass ameliyatına giren kalp yetmezliği (KY) tanısı koyulmuş hastalardan elde edilen atriyum doku örneklerinde Beta 1 reseptörler üzerinden gelişen fonksiyonel yanıtların izoproterenol ile değerlendirilmesi, hücre içi Ca++ regülasyonundan sorumlu SERCA2a ve fosfolamban ekspresyonlarının ve Sirtuin enzim aktivitesinin kalp yetmezliğindeki rollerinin araştırılması amaçlanmıştır. Kalp yetmezliği hastaları ejeksiyon fraksiyonuna göre düşük (n=10), orta derecede azalmış (n=2) ve korunmuş (n=4) ejeksiyon fraksiyonlu hastalar olarak 3 gruba ayrılmıştır. Atriyum dokularından trabeküller izole edildikten sonra Tyrode çözeltisi içeren, %95 O2 ve %5 CO2 ile gazlandırılan organ banyolarına asılmıştır. Dokular Tyrode çözeltisi ile yıkamalar yapılarak stabilize edildikten sonra dokulara kümülatif izoproterenol dozları uygulanmış, konsantrasyon-yanıt eğrileri alınmıştır. Dokular daha sonra homojenize edilmiş ve Bikinkoninik asit (BCA) analizleri yapılmıştır. SERCA2a, fosfolamban ve Sirtuin enzimlerinin protein ekspresyon düzeyleri, primer ve uygun sekonder antikorlar kullanılarak Western Blot tekniği ile saptanmıştır. Deneyler sonucunda elde edilen veriler istatiksel açıdan değerlendirilmiştir. İzole organ banyosu deneyleri, isoproterenole karşı kasılma yanıtının, düşük ejeksiyon fraksiyonlu kalp yetmezliği (KYdEF) grubunda, korunmuş ejeksiyon fraksiyonlu kalp yetmezliği (KYkEF) grubuna göre istatistiksel olarak anlamlı şekilde arttığını göstermiştir. (Sırasıyla Emax, 0,16±0,23; 0,86±0,17, p%50 (KYkEF) hasta grubuna kıyasla anlamlı derecede azaldığı saptanmıştır. Benzer şekilde, SIRT-6 protein ekspresyon düzeyinin de KYdEF grubunda KYkEF grubuna göre istatistiksel olarak anlamlı şekilde azaldığı belirlenmiştir.Çalışmada SERCA2a protein ekspresyon seviyeleri açısından iki grup arasında anlamlı bir farklılık tespit edilmemiştir. Buna karşılık, fosfolamban protein ekspresyon düzeylerinin KYdEF grubunda KYkEF grubuna kıyasla anlamlı biçimde azaldığı görülmüştür. Bu çalışmada elde edilen veriler, ejeksiyon fraksiyonuna göre ayrılan kalp yetmezliği gruplarında kontraktil yanıtlar ve hücresel düzenleyici mekanizmalar arasında anlamlı farklılıklar bulunduğunu ortaya koymuştur. Özellikle düşük ejeksiyon fraksiyonlu kalp yetmezliği grubunda, SIRT-1 ve SIRT-6 ekspresyon düzeylerinde belirgin bir azalma gözlenmesi, bu enzimlerin kalp yetmezliğinde enerji metabolizması, oksidatif stres ve hücresel yaşlanma süreçleriyle ilişkili kritik roller üstlenebileceğini düşündürmektedir. Benzer şekilde, fosfolamban ekspresyonundaki azalmanın, kalsiyum homeostazındaki bozulma yoluyla kontraktil disfonksiyona katkıda bulunabileceği değerlendirilmektedir. Buna karşın SERCA2a protein ekspresyonunda anlamlı bir farklılık saptanmamış olması, bu proteininin ekspresyon düzeyinden daha çok fonksiyonel aktivitesinin veya düzenleyici proteinlerle etkileşimlerinin daha belirleyici olabileceğine işaret etmektedir. İzoproterenol uygulaması sonrasında düşük ejeksiyon fraksiyonlu grupta gözlenen farklı kontraktil yanıtlar ise, adrenerjik uyarıya verilen cevabın hastalığın seyrinde önemli bir parametre olabileceğini göstermektedir. Bulgular genel olarak, düşük ejeksiyon fraksiyonlu ve korunmuş ejeksiyon fraksiyonlu kalp yetmezliği alt tiplerinin patofizyolojik açıdan farklı biyokimyasal mekanizmalarla karakterize olabileceğini ortaya koymaktadır. Bu bağlamda, sirtuin enzimleri ve fosfolambanın kalp yetmezliğinde potansiyel biyobelirteçler veya yeni tedavi hedefleri olarak değerlendirilebileceği düşünülmektedir.Backgrounds: Heart failure is a complex clinical syndrome characterized by structural and/or functional abnormalities of the heart, which impair its ability to pump blood effectively. The diagnosis and management of heart failure present significant clinical challenges due to its heterogeneous presentation and overlapping symptoms with other conditions. As a result, the disease is associated with high rates of hospitalization and mortality. Globally, heart failure has emerged as a major public health concern, affecting an estimated 60 million individuals. In this study, it was aimed to evaluate the functional responses mediated by Beta-1 receptors using isoproterenol and to examine the roles of SERCA2a, phospholamban and SIRT enzymes in atrial tissue samples obtained from patients diagnosed with heart failure who underwent cardiopulmonary bypass surgery at Ege University Faculty of Medicine, Department of Cardiovascular Surgery. The patients were categorized into three groups: Group I – patients with heart failure with reduced ejection fraction (HFrEF); Group II – patients with heart failure with preserved ejection fraction (HFpEF); and Group III – patients with heart failure with mildly reduced ejection fraction (HFmrEF). Atrial appendage tissues were obtained intraoperatively from patients undergoing open-heart surgery with cardiopulmonary bypass. Immediately after excision, the tissues were placed in Tyrode's solution and transported to the laboratory under suitable physiological conditions. Trabeculae within the atrial tissue were carefully isolated and attached in isolated organ bath systems for functional analyses. During the isolated organ bath experiments, the trabeculae were suspended in baths containing Tyrode's solution, continuously aerated with a gas mixture of 95% O₂ and 5% CO₂, and maintained at appropriate physiological temperature. Following an equilibration period, cumulative concentration–response curves to isoproterenol were generated. Contractile responses were recorded, and parameters such as maximum contraction amplitude and sensitivity (pD₂ values) were calculated. Subsequently, the tissues were homogenized, and protein concentrations were quantified using the bicinchoninic acid (BCA) assay. The expression levels of SERCA2a, phospholamban, and sirtuin enzymes were analyzed via Western blotting, employing specific primary and appropriate secondary antibodies. The experimental data were subjected to statistical analysis to determine significance. Results: Isolated organ bath experiments have shown that the contractile response to isoproterenol increases statistically significantly in the group of patients patients with heart failure with reduced ejection fraction (HFrEF) compared to the group with preserved ejection fraction heart failure (HFpEF) (Emax respectively, 0,16±0,23 vs 0,86±0,17, p50% (HFrEF) patient group. Similarly, it was determined that SIRT-6 protein expression levels were also statistically significantly reduced in the KYdEF group compared to the KYkEF group. No significant difference was detected between the two groups in terms of SERCA2a protein expression levels. In contrast, phospholamban protein expression levels were found to be significantly reduced in the KYdEF group compared to the KYkEF group. The findings of this study demonstrate significant differences in contractile responses and regulatory mechanisms among heart failure groups classified according to ejection fraction. In particular, the marked reduction of SIRT-1 and SIRT-6 expression levels in the reduced ejection fraction group suggests that these enzymes may play critical roles in energy metabolism, oxidative stress, and cellular aging processes in heart failure. Similarly, the decrease in phospholamban expression may contribute to impaired calcium homeostasis, thereby exacerbating contractile dysfunction. In contrast, the absence of significant changes in SERCA2a protein expression implies that its functional activity or interaction with regulatory proteins, rather than expression levels alone, may be more determinant in disease progression. Furthermore, the distinct contractile responses to isoproterenol observed in the reduced ejection fraction group indicate that adrenergic responsiveness could represent an important parameter influencing the course of heart failure. Overall, these results highlight that reduced and preserved ejection fraction heart failure subtypes may be characterized by different pathophysiological mechanisms. In this context, sirtuin enzymes and phospholamban may serve as potential biomarkers or therapeutic targets in the management of heart failur
A dual-nonconjugated polymer-based laser-printed ?PAD for chromogenic sensing of halitosis-related salivary biomarkers
Biogenic amines play a critical role in oral malodor and metabolic disorders, yet their detection remains challenging due to the need for rapid, non-invasive, and cost-effective diagnostic methods. This study presents a laser-printed microfluidic paper-based analytical device (LP-mu PAD) for dual-confirmatory detection of biogenic amines in saliva, integrating polyesters grafted with maleic anhydride units (poly(propylene succinate) and poly(propylene citraconic)) and crystal violet dye. The novelty of this work lies in the integration of a dual-polymer chromogenic sensing system into an LP-mu PAD, specifically optimized to account for the inherent biogenic amine content in saliva, thus improving selectivity and diagnostic relevance for halitosis detection. The device exhibited strong linearity (R-2 > 0.98), low limits of detection (0.43-1.25 mu g/mL), and high recovery rates (98-111 %) in saliva samples, ensuring accuracy in real biological conditions. Compared to plate-based assays, the LP-mu PAD improved amine detection efficiency, minimized pH effects, and reduced salivary interference (<6 %), enabling reliable measurements across pH 5.5-8.5. The sensor demonstrated rapid analysis (<5 min) and reproducibility (RSD < 10 %), highlighting its potential for real-time, point-of-care halitosis diagnostics. The laser-printing approach facilitates low-cost, scalable fabrication, making the LP-mu PAD a promising alternative to conventional laboratory techniques for biogenic amine monitoring in oral and metabolic health applications. Future work will focus on expanding biomarker detection and integrating smartphone-based imaging for enhanced diagnostic accessibility.COST (European Cooperation in Science and Technology) [CA21140]; Scientific and Technological Research Council of Turkiye (TUEBITAK) [124Z632]; Health Institutes of Tuerkiye (TUESEB) [124Z632, 39245]The authors thank the Health Institutes of Tuerkiye (TUESEB) for their support (Project number: 39245) . The COST Action CA21140 - INTERCEPTOR supported by COST (European Cooperation in Science and Technology- www.cost.eu) and The Scientific and Technological Research Council of Turkiye (TUEBITAK) (Project number: 124Z632) are also thanked for their support
Batı Anadolu kırsalında üretim ilişkileri: (1740-1922)
Çalışmanın temel amacı, kırsalın üretim ilişkilerinin dönüşümünde oynadığı rolü görünür kılmaktır. Araştırma alanı olarak, Osmanlı İmparatorluğu döneminde Batı Anadolu bölgesinde yer alan Büyük Menderes Havzası belirlenmiştir. Söz konusu araştırma alanı, 1740-1922 yılları arasını kapsayan dönemde, büyük oranda Devlet Arşivleri Başkanlığı Osmanlı Arşivi’ndeki muhtelif fonlardan yararlanılarak incelenmiştir. Odaklanılan bölge ve dönemdeki üretim ilişkilerinin dönüşümü, arşiv belgeleri elverdiği ölçüde, büyük çiftlik sahipliği ve sınıf mücadeleleri merkeze alınarak çözümlenmiştir. Çalışmada öncelikle âyan ailelerinin servet ve nüfuz sahibi olmalarını sağlayan araçların ve bölgede cereyan eden sınıf mücadelelerinin arkasındaki temel dinamiklerin neler olduğu irdelenmiştir. Akabinde çiftliklerdeki üretim ilişkileri ele alınmış, emekçi sınıfların durumu ayrıca tahlil edilmiştir. Bölgenin uzun dönemli incelenmesi sonucunda ise genel literatürün aksine, 18. yüzyıldaki bazı âyan ailelerinin servetlerini kaybetmediği; farklı araçlarla 19. yüzyıldan 20. ve hatta 21. yüzyıla kadar bölgedeki varlıklarını ve nüfuzlarını sürdürdüğü tespit edilmiştir. Bu mesele çalışmada, Cihanzade ve İlyaszade ailesi üzerinden ele alınmıştır. İki ailenin, 18. yüzyıl ile 19. yüzyılın ikinci çeyreğine kadar olan dönemde kırsalın ve köylülerin sömürülmesi üzerinden elde ettikleri servetlerini artırmada ve nüfuzlarını sürdürmede sınıf ittifaklarını/ sınıf evliliklerini birer araç olarak kullandığı saptanmıştır. Örneğin, İlyaszade ailesinin 19. yüzyılın üçüncü çeyreğiyle kırsalda görünür olmaya başlayan toprak sahibi yeni "girişimci" sınıfla kurduğu sınıf ittifakının/sınıf evliliğinin ortaya çıkarılması, bu durumun kanıtlarından birini teşkil etmiştir. Toprak sahibi yeni "girişimci" sınıfın ise Batı Anadolu kırsalında nüfuzunu ve servetini artırmada hangi araçları kullandığı ve köylü sınıfıyla mücadelesinin üretim ilişkilerinin dönüşümüne doğrudan nasıl etki ettiği arşiv belgeleri temelinde çözümlenmiştir.The main purpose of the study is to illuminate the role of the rural in the transformation of production relations. The Great Meander Basin, located in the Western Anatolia region during the Ottoman Empire, was chosen as the research area. This research area was examined for the period between 1740 and 1922, largely by using the various fonds in the Ottoman Archives of the Directorate of State Archives. The transformation of production relations in the focused region and period was analyzed, to the extent that archival documents allowed, by centering on large estates (çiftlik) ownership and class struggles. The study primarily examines the fundamental dynamics that enabled the âyan families to acquire wealth and influence, as well as the underlying factors behind the class struggles that took place in the region. Subsequently, the production relations on the large estates (çiftlik) are discussed, and the situation of the peasants is analyzed specifically. A long-term examination of the region revealed that, contrary to the general literature, some âyan families from the 18th century did not lose their wealth. Instead, they maintained their existence and influence in the region through different means, extending into the 19th, 20th, and even the 21st century. This issue is addressed in the study through the case of the Cihanzade and İlyaszade families. It has been determined that these two families, in the period from the 18th century to the second quarter of the 19th century, used class alliances/class marriages as means to increase their wealth and sustain their influence, which they obtained through the exploitation of the rural areas and the peasants. For instance, the uncovering of the class alliance/class marriage formed by the İlyaszade family with the new land-owning "entrepreneur" class, which began to rise to prominence in the rural areas in the third quarter of the 19th century, constitutes one of the proofs of this situation. Furthermore, the study, based on archival documents, analyzes the means that the new land-owning "entrepreneur" class used to increase its influence and wealth in rural Western Anatolia and how its struggle with the peasant class directly impacted the transformation of production relations
Unraveling the influence of astrocytes on endothelial cell transcription: Towards understanding blood-brain barrier in vitro models' dynamics
In recent years, considerable advancements have been made in developing in vitro models to better understand the complex dynamics of the blood-brain barrier (BBB) and its critical role in neurological health and disease. Incorporating astrocytes into these models introduces an essential layer of complexity, allowing for a more comprehensive investigation of the cellular interactions and regulatory mechanisms that maintain BBB integrity and functionality. Despite these advances, the specific influence of astrocytes on endothelial cells in in vitro systems remains inadequately explored. This study addresses this gap by examining the transcriptional changes in primary human brain microvascular endothelial cells (HBMECs) cocultured with human astrocytes (HAs). Our findings demonstrate that astrocytes profoundly modulate endothelial pathways involved in cell cycle regulation and division while upregulating genes associated with BBB integrity, protective mechanisms, and transporter activity. Furthermore, astrocytes significantly enhanced transendothelial electrical resistance (TEER) and reduced permeability to tracer Cascade Blue dye, confirming their functional impact on BBB models. By providing a comprehensive human primary cell dataset, this research underscores the pivotal role astrocytes play in shaping endothelial cell gene expression and function in contact coculture systems. These results emphasize the necessity of incorporating astrocytes into in vitro BBB models to accurately replicate neurovascular interactions. Ultimately, this study advances our understanding of BBB physiology and highlights the importance of refining in vitro models to better reflect the complexity of the human neurovascular environment, with potential implications for studying neurological disorders and drug delivery strategies.Sao Paulo Research Foundation (FAPESP); National Council for Scientific and Technological Development (CNPq); TUBITAK 2214-A International Research Fellowship Programme; Swedish Research Council [2022-01362]; Knut and Alice Wallenberg Stiftelse [2020.0206]; Eurostars-3 project; European unions research and innovation program Horizion Europe [E!5304]; AIMES - Center for the Advancement of Integrated Medical and Engineering Sciences; Karolinska Institutet [1-249/2019]; KTH Royal Institute of Technology [VF-2019-0110]; Getinge AB [4-1599/2018]; [2021/14327-8]; [2022/16296-5]; [202895/2019-0]; Swedish Research Council [2022-01362] Funding Source: Swedish Research CouncilLNZ acknowledges funding from the Sao Paulo Research Foundation (FAPESP) , grant numbers 2021/14327-8 and 2022/16296-5, and the National Council for Scientific and Technological Development (CNPq) , grant number 202895/2019-0. BG acknowledges financial support to TUBITAK 2214-A International Research Fellowship Programme. AH acknowledges funding from Hjarnfonden 2022-0151, Swedish Research Council 2022-01362, Knut and Alice Wallenberg Stiftelse 2020.0206. This work received support from Eurostars-3 project with co-financing from the European unions research and innovation program Horizion Europe (E!5304, GBA-CONNECT) . This work was supported by AIMES - Center for the Advancement of Integrated Medical and Engineering Sciences (www.aimes.se) , Karolinska Institutet (1-249/2019) , KTH Royal Institute of Technology (VF-2019-0110) and Getinge AB (4-1599/2018)