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Öğe Adverse events in children and adolescents undergoing allergen immunotherapy for respiratory allergies-Report from the Allergen Immunotherapy Adverse Events Registry (ADER), a European Academy of Allergy and Clinical Immunology taskforce(Wiley, 2023) Asllani, Julijana; Mitsias, Dimitrios; Konstantinou, George; Mesonjesi, Eris; Xhixha, Fatmira; Shehu, Esmeralda; Christoff, GeorgeBackgroundAlthough it has been shown that allergen immunotherapy (AIT) is well-tolerated in children, systematic and prospective surveillance of AIT safety in real life settings is needed. MethodsThe multinational Allergen Immunotherapy Adverse Events Registry (ADER) was designed to address AIT safety in real life clinical practice. Data on children <= 18 years old with respiratory allergies undergoing AIT were retrieved. Patient- and AIT-related features were collected and analyzed. The characteristics of adverse events (AE) and risk factors were evaluated. ResultsA total of 851 patients, 11.3 +/- 3.4 years old, with rhinitis only (47.6%); asthma and rhinitis (44.5%); asthma (7.9%), receiving 998 AIT courses were analyzed. Sublingual immunotherapy (SLIT) accounted for 51% of the courses. In 84.5% of patients only one AIT treatment was prescribed. Pollen was the most frequent sensitizer (57.1%), followed by mites (53.4%), molds (18.2%) and epithelia (16.7%). Local and systemic AEs were reported in 85 patients (9.9%). Most AEs (83.1%) were mild and occurred in <30 min (87%). Respiratory and cutaneous symptoms were more frequent. Only 4 patients (0.47%) had severe AE (none after 6 weeks of maintenance). The risk of AE was higher in patients undergoing SCIT. ConclusionsAIT is safe and well tolerated in children and adolescents with respiratory allergies in real-life clinical practice. Though SCIT is more prone to AE compared to SLIT, overall severe reactions are rare and occur during build-up and early maintenance.Öğe Atrial Fibrillation Management in Acute Stroke Patients in Türkiye: Real-life Data from the NöroTek Study(Galenos Publ House, 2023) Topcuoglu, Mehmet Akif; Arsava, Ethem Murat; Ozdemir, Atilla Ozcan; Aykac, Ozlem; Cetiner, Mustafa; Gencer, Elif Sarioender; Gunes, AygulObjective: Atrial fibrillation (AF) is the most common directly preventable cause of ischemic stroke. There is no dependable neurology-based data on the spectrum of stroke caused by AF in Turkiye. Within the scope of NoroTek-Turkiye (TR), hospital-based data on acute stroke patients with AF were collected to contribute to the creation of acute-stroke algorithms.Materials and Methods: On May 10, 2018 (World Stroke Awareness Day), 1,790 patients hospitalized at 87 neurology units in 30 health regions were prospectively evaluated. A total of 929 patients [859 acute ischemic stroke, 70 transient ischemic attack (TIA)] from this study were included in this analysis.Results: The rate of AF in patients hospitalized for ischemic stroke/TIA was 29.8%, of which 65% were known before stroke, 5% were paroxysmal, and 30% were diagnosed after hospital admission. The proportion of patients with AF who received effective treatment [international normalization ratio >= 2.0 warfarin or non-vitamin K antagonist oral anticoagulants (NOACs) at a guideline dose] was 25.3%, and, either no medication or only antiplatelet was used in 42.5% of the cases. The low dose rate was 50% in 42 patients who had a stroke while taking NOACs. Anticoagulant was prescribed to the patient at discharge at a rate of 94.6%; low molecular weight or unfractionated heparin was prescribed in 28.1%, warfarin in 32.5%, and NOACs in 31%. The dose was in the low category in 22% of the cases discharged with NOACs, and half of the cases, who received NOACs at admission, were discharged with the same drug.Conclusion: NoroTekTR revealed the high but expected frequency of AF in acute stroke in Turkiye, as well as the aspects that could be improved in the management of secondary prophylaxis. AF is found in approximately one-third of hospitalized acute stroke cases in Turkiye. Effective anticoagulant therapy was not used in three-quarters of acute stroke cases with known AF. In AF, heparin, warfarin, and NOACs are planned at a similar frequency (one-third) within the scope of stroke secondary prophylaxis, and the prescribed NOAC dose is subtherapeutic in a quarter of the cases. Non-medical and medical education appears necessary to prevent stroke caused by AF.Öğe Congenital fibrinogen disorders: a retrospective clinical and genetic analysis of the Prospective Rare Bleeding Disorders Database(American Society of Hematology, 2024) Mohsenian, S.; Palla, R.; Menegatti, M.; Cairo, A.; Lecchi, A.; Casini, A.; Neerman-Arbez M.Congenital fibrinogen deficiency (CFD) is a rare bleeding disorder caused by mutations in FGA, FGB, and FGG. We sought to comprehensively characterize patients with CFD using PRO-RBDD (Prospective Rare Bleeding Disorders Database). Clinical phenotypes, laboratory, and genetic features were investigated using retrospective data from the PRO-RBDD. Patients were classified from asymptomatic to grade 3 based on their bleeding severity. In addition, FGA, FGB, and FGG were sequenced to find causative variants. A total of 166 CFD cases from 16 countries were included, of whom 123 (30 afibrinogenemia, 33 hypofibrinogenemia, 55 dysfibrinogenemia, and 5 hypodysfibrinogenemia) were well characterized. Considering the previously established factor activity and antigen level thresholds, bleeding severity was correctly identified in 58% of the cases. The rates of thrombotic events among afibrinogenemic and hypofibrinogenemic patients were relatively similar (11% and 10%, respectively) and surprisingly higher than in dysfibrinogenemic cases. The rate of spontaneous abortions among 68 pregnancies was 31%, including 86% in dysfibrinogenemic women and 14% with hypofibrinogenemia. Eighty-six patients received treatment (69 on-demand and/or 17 on prophylaxis), with fibrinogen concentrates being the most frequently used product. Genetic analysis was available for 91 cases and 41 distinct variants were identified. Hotspot variants (FGG, p.Arg301Cys/His and FGA, p.Arg35Cys/His) were present in 51% of dysfibrinogenemia. Obstetric complications were commonly observed in dysfibrinogenemia. This large multicenter study provided a comprehensive insight into the clinical, laboratory, and genetic history of patients with CFDs. We conclude that bleeding severity grades were in agreement with the established factor activity threshold in nearly half of the cases with quantitative defects. © 2024 by The American Society of Hematology.Öğe Hematological predictors of silent new cerebral ischemic lesions in carotid artery stenting: A retrospective study(Churchill Livingstone, 2024) Altunova, M.; Demir, Y.; Gulmez, R.; Evsen, A.; Aktemur, T.; Anil, Sahin, A.; Arslan E.Background: Silent new cerebral ischemic lesions (sNCIL) are a common complication of carotid artery stenting (CAS) that can lead to an increase in morbidity and mortality. We aimed to evaluate the impact of hematological parameters on sNCIL in patients undergoing CAS. Methods: We retrospectively evaluated 103 patients who underwent CAS, with a mean age of 70.5 ± 6.7 years, and 31 (20.1 %) of whom were female. Stents were placed for internal carotid artery revascularization. The presence of new hyperintense lesions on diffusion-weighted imaging (DWI) without neurological symptoms was considered as sNCIL in cases without apparent neurological findings. Patients were categorized into two groups based on DWI results: positive (29) and negative (74). Results: In the study population, sNCIL was observed in 29 patients (28.2 %). The DWI-positive group exhibited significantly higher Plateletcrit (PCT) levels, advanced age, and a lack of embolic protection device usage compared to the DWI-negative group. The Receiver Operating Characteristic (ROC) analysis identified a PCT value of 0.26 as the optimal threshold, detecting the development of sNCIL with a sensitivity of 75.9 % and specificity of 59.1 % (AUC: 0.700; 95 % CI: 0.594–0.806, p = 0.002). Conclusion: To be determined by a simple blood parameter, PCT can predict the risk of sNCIL before CAS and holds clinical value in the treatment of patients with carotid artery stenosis. © 2024 Elsevier LtdÖğe Implication of transcription factor FOXD2 dysfunction in syndromic congenital anomalies of the kidney and urinary tract (CAKUT)(Elsevier B.V., 2024) Riedhammer, K.M.; Nguyen, T.-M.T.; Koşukcu, C.; Calzada-Wack, J.; Li, Y.; Assia, Batzir, N.; Saygılı S.Congenital anomalies of the kidney and urinary tract (CAKUT) are the predominant cause for chronic kidney disease below age 30 years. Many monogenic forms have been discovered due to comprehensive genetic testing like exome sequencing. However, disease-causing variants in known disease-associated genes only explain a proportion of cases. Here, we aim to unravel underlying molecular mechanisms of syndromic CAKUT in three unrelated multiplex families with presumed autosomal recessive inheritance. Exome sequencing in the index individuals revealed three different rare homozygous variants in FOXD2, encoding a transcription factor not previously implicated in CAKUT in humans: a frameshift in the Arabic and a missense variant each in the Turkish and the Israeli family with segregation patterns consistent with autosomal recessive inheritance. CRISPR/Cas9-derived Foxd2 knockout mice presented with a bilateral dilated kidney pelvis accompanied by atrophy of the kidney papilla and mandibular, ophthalmologic, and behavioral anomalies, recapitulating the human phenotype. In a complementary approach to study pathomechanisms of FOXD2-dysfunction–mediated developmental kidney defects, we generated CRISPR/Cas9-mediated knockout of Foxd2 in ureteric bud–induced mouse metanephric mesenchyme cells. Transcriptomic analyses revealed enrichment of numerous differentially expressed genes important for kidney/urogenital development, including Pax2 and Wnt4 as well as gene expression changes indicating a shift toward a stromal cell identity. Histology of Foxd2 knockout mouse kidneys confirmed increased fibrosis. Further, genome-wide association studies suggest that FOXD2 could play a role for maintenance of podocyte integrity during adulthood. Thus, our studies help in genetic diagnostics of monogenic CAKUT and in understanding of monogenic and multifactorial kidney diseases. © 2023 International Society of NephrologyÖğe Short-term azithromycin use is associated with QTc interval prolongation in children with cystic fibrosis(Elsevier Masson s.r.l., 2024) Enhoş, A.; Doğuş, Kus, H.; Yozgat, C.Y.; Cakır, E.; Yazan, H.; Erol, A.B.; Erenberk U.Background: Azithromycin is used for children with cystic fibrosis (CF) for its immunomodulatory and anti-inflammatory action. This study investigated the short-term alterations in QTc interval associated with azithromycin prophylaxis in pediatric patients with CF. Methods: This study included 121 patients with mild CF, of whom 76 received azithromycin (patient group) and 45 did not receive azithromycin (control group). The patient and control groups were categorized according to age as under 12 years of age and over 12 years of age. The first presentation measured all the patient and control groups at basic QTc time intervals. The QTc intervals of all patients were then remeasured systemically at 1, 3, and 6 months. Age categories and QTc intervals that were calculated at each month in the patient and control groups were compared statistically. Results: A statistically significant difference was detected in the patient group between the initial QTc interval time and the electrocardiogram (ECG) findings in the first and third months after prophylaxis treatment (p < 0.001; p = 0.01). However, no statistically significant difference was detected in the sixth month (p > 0.05) in all groups. Almost all of the children's QTc intervals were within normal range and within the safety zone (under 0.44 s). No statistically significant difference was detected in the control group between the initial ECG and the QTc intervals measured at 1, 3, and 6 months. Conclusion: Short-term use of azithromycin prophylaxis in pediatric patients with mild CF slightly increased the QTc interval in the first and third months of follow-up. Nevertheless, all QTc interval changes fell within the safety zone. Notably, 1 month of follow-up treatment should be performed to check for any alteration in the QTc interval. If increased QTc interval duration is not detected in the first month, azithromycin prophylaxis can be safely prescribed. © 2024 French Society of PediatricsÖğe Concomitant amyloidosis is the primary cause of endothelial and coronary microvascular dysfunction in carpal tunnel syndrome(Elsevier Inc., 2024) İrgi, T.; Baycan, Ö.F.; Güvenç, T.S.; Özcan, F.B.; Atıcı, A.; Yılmaz, Y.; Çalişkan M.Study objectives: Patients with carpal tunnel syndrome (CTS) show manifestations of arterial abnormalities, including carotid intimal thickening and increased vascular stiffness. As carpal tunnel syndrome is associated with amyloidosis, we hypothesized that previously observed abnormalities can largely be related with concomitant amyloidosis rather than CTS itself. Design: Prospective observational study. Setting: Medeniyet University Goztepe Hospital Participants: 61 patients with CTS (of whom 32 had biopsy-proven amyloidosis) and 36 healthy controls. Interventions: Subjects underwent ultrasound examinations for the measurement of coronary flow velocity reserve (CFVR), flow-mediated vasodilatation (FMD) and carotid intimal-media thickness (CIMT). Main outcome measures: Comparison of CFVR, FMD and CIMT in CTS patients with or without amyloidosis. Results: Patients with either CTS or CTS with concomitant amyloidosis (CTS-A) had significantly lower FMD (9.7 % ± 4.0 % in CTS and 10.3 % ± 4.6 % in CTS-A groups, p < 0.05 for both) and CFVR (2.4 (2.1–2.8) in CTS and 1.8 (1.6–2.1) in CTS-A groups, p < 0.001 for both) as compared to controls, while CIMT was only increased in CTS-A group (0.70 (0.60–0.80), p < 0.001). The reduction in CFVR was solely related to an increased basal flow velocity in CTS patients while there was also a reduced hyperemic flow velocity in patients with CTS-A. Conclusion: Most arterial phenomena in CTS patients could be attributable to concomitant amyloidosis, although endothelial dysfunction was present even in patients with CTS without amyloidosis. © 2024 The Author(s)Öğe The cytotoxic effects of indoleamine 2, 3-dioxygenase inhibitors on triple negative breast cancer cells upon tumor necrosis factor ? stimulation(Wolters Kluwer Medknow Publications, 2023) Bilir, C.; Eskiler, G.G.; Bilir, F.Context: Overexpressed indoleamine 2,3-dioxygenase (IDO) has been observed in many types of cancer and plays an essential role in the tumor microenvironment through immune cells function. Aims: In our study, the therapeutic potentials of two different IDO inhibitors (Epacadostat [EPA] and 1-methyl-L-tryptophan [L-1MT]) in triple-negative breast cancer (TNBC) cells were assessed with and without tumor necrosis factor-? (TNF-?) stimulation. Materials and Methods: The anticancer activity of EPA and L-1MT alone and in combination with TNF-? was analyzed by WST-1, annexin V, cell cycle analysis, and acridine orange/ethidium bromide staining. In addition, the relationship between IDO1 and programmed death-ligand 1 (PD-L1) expressions in TNBC cells upon treatment with IDO inhibitors was evaluated by reverse transcription-polymerase chain reaction analysis. Statistical Analysis Used: SPSS 22.0 was conducted for statistical analysis. The one-way analysis of variance with Tukey's multiple comparison test was performed for multiple groups. Independent (unpaired) t -test was used for the comparison of two groups. Results: EPA and L-1MT alone significantly suppressed the TNBC cell viability through the induction of apoptotic cell death and G0/G1 arrest (P < 0.05). TNF-? alone induced the overexpression of IDO1 and PD-L1 in TNBC cells compared with MCF-10A control cells. However, IDO inhibitors significantly inhibited overexpressed IDO1 mRNA levels. Furthermore, EPA alone and co-treated with TNF-? suppressed the mRNA level of PD-L1 in TNBC cells. Therefore, TNF-? stimulation enhanced the therapeutic effects of IDO inhibitors on TNBC. Conclusions: Our findings showed that the efficacy of IDO inhibitors was mediated by pro-inflammatory cytokine. However, different molecular signaling pathways are associated with pro-inflammatory cytokines production, and the expression of IDO1 and PD-L1 calls for further investigations. © 2022 Journal of Cancer Research and Therapeutics | Published by Wolters Kluwer - Medknow.Öğe Can biomarkers predict myocardial iron overload in children with thalassemia major?(Cambridge Univ Press, 2023) Karakaş, Hasan; Eroğlu, Ayşe Güler; Akyel, Nazlı Gülsüm; Çiğ, Gülnaz; Adaletli, İbrahim; Özdemir, Gül Nihal; Türkkan, Emine; Celkan, Tülin TirajeAim:Beta-thalassemia major requires regular blood transfusions throughout life, which in turn leads to iron accumulation in the body. While cardiac T2* MRI is the gold standard in determining cardiac iron accumulation, it is not always feasible, which has led to the search for new biomarkers. Herein, the value of growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide in predicting cardiac iron accumulation is investigated in asymptomatic children with beta-thalassemia major. Materials and method:Forty-one patients aged 11-21 years and 41 age-, gender-, body mass index-matched healthy controls were included. Serum growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide levels were compared between the patients and controls. Additionally, the relations of these biomarkers with cardiac and liver T2 * MRI were investigated in the patients. Results:In the patients, growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide levels were higher than healthy controls (p < 0.001, p = 0.025, p < 0.001, respectively). There were no significant correlations of growth differentiation factor-15 and N-terminal pro-B-type natriuretic peptide levels with both cardiac and liver T2 * MRI measurements. While there was no significant correlation of serum galectin-3 with cardiac T2 * MRI measurements, a negative correlation was found with liver T2 * MRI measurements (p = 0.040, rho = -0.325). Conclusion:All three biomarkers investigated in this study failed to predict myocardial iron accumulation in asymptomatic children with beta-thalassemia major. However, a weak relation between serum galectin-3 level and hepatic iron accumulation was demonstrated.Öğe Gastrostomy in hospitalized patients with acute stroke: norotek Turkey point prevalence study subgroup analysis(Galenos Publ House, 2022) Topçuoğlu,Mehmet Akif; Özdemir, Atilla Özcan; Aykaç, Özlem; Milanoğlu, Aysel; Gökçe, Mustafa; Krespi, YakupObjective: Nutritional status assessment, dysphagia evaluation and enteral feeding decision are important determinants of prognosis in acute neurovascular diseases. Materials and Methods: NoroTek is a point prevalence study conducted with the participation of 87 hospitals spread across all health sub regions of Turkey conducted on 10-May-2018 (World Stroke Awareness Day). A total of 972 hospitalized neurovascular patients [female: 53%, age: 69 +/- 14; acute ischemic stroke in 845; intracerebral hematoma (ICH) in 119 and post-resuscitation encephalopathy (PRE) in 8] with complete data were included in this sub-study. Results: Gastrostomy was inserted in 10.7% of the patients with ischemic stroke, 10.1% of the patients with ICH and in 50% of the patients with PRE. Independent predictors of percutaneous endoscopic gastrostomy (PEG) administration were The National Institutes of Health Stroke Scale score at admission [exp (ss): 1.09 95% confidence interval (CI): 1.05-1.14, per point] in ischemic stroke; and mechanical ventilation in ischemic [exp (ss): 6.18 (95% CI: 3.16-12.09)] and hemorrhagic strokes [exp (ss): 26.48 (95% CI: 1.36-515.8)]. PEG was found to be a significant negative indicator of favorable (modified Rankin's scale score 0-2) functional outcome [exp (ss): 0.032 (95% CI: 0.004-0.251)] but not of in-hospital mortality [exp (ss): 1.731 (95% CI: 0.785-3.829)]. Nutritional and swallowing assessments were performed in approximately two-thirds of patients. Of the nutritional assessments 69% and 76% of dysphagia assessments were completed within the first 2 days. Tube feeding was performed in 39% of the patients. In 83.5% of them, tube was inserted in the first 2 days; 28% of the patients with feeding tube had PEG later. Conclusion: The NoroTek study provided the first reliable and large-scale data on key quality metrics of nutrition practice in acute stroke in Turkey. In terms of being economical and accurate it makes sense to use the point prevalence method.Öğe Turkish adaptation and validation of behavioral ınhibition questionnaire parent form(Aves, 2022) Kılınç, Saliha; Bilgiç, Ayhan; Görmez, VahdetBackground: Behavioral inhibition has been proposed as a temperamental risk factor for the development of childhood anxiety disorders universally; however, there is no validated instrument for, especially, its evaluation in Turkish children. This study aimed to examine reliability and validity of the Turkish version of Behavioral Inhibition Questionnaire parent form for children aged 3-7 years. Methods: Around 250 mothers or fathers of 3-7 years old children were recruited from non-clinical population to collect responses to the questionnaires. The sample was created by reaching 3 schools at preschool or elementary grade for the purpose of providing the questionnaires filled about the student and/or his/her little sisters and brothers by their parents; questionnaires were sent out to parents and then gathered. Parents were asked to fill sociodemographic data form, Behavioral Inhibition Questionnaire parent form, Children Behavior Questionnaire, and Strengths and Difficulties Questionaire parent form in order to perform convergent and divergent validity analyses. Results: As a result of reliability analysis, total Cronbach alpha coefficient for Behavioral Inhibition Questionnaire was determined as 0.92 with strong reliability. The internal consistency coefficients for Behavioral Inhibition Questionnaire subscales also showed strong reliability with alphas ranging between 0.81 and 0.87 except for the performance (a = 0.69) and physical challenges (a = 0.19) subscales of which some items were excluded due to item-total correlations and confirmatory factor analysis results. In the validity assessment analyses, confirmatory factor analysis demonstrated that Behavioral Inhibition Questionnaire has a construct validity with 5 factors loaded on the 2-second order main factors and one third-order final factor (root mean square error = 0.032, root mean square residual = 0.153, Comparative Fit Index = 0.978, Goodness of Fit Index = 0.915, and Turker-Lewis Index = 0.970). While the strongest correlations with the overall Behavioral Inhibition Questionnaire score were found for 2 main subscales, inhibition to social novelties (r = 0.926, P <.001) and situational novelties (r = 0.928, P <.001), similarly peers (r = 0.848, P <.001) and new situations (r = 0.898, P <.001) subscales, had strong correlations with the overall Behavioral Inhibition Questionnaire score. The weakest correlation with overall Behavioral Inhibition Questionnaire score was observed for physical challenges subscale even though this subscale displayed moderate association (r = 0.454, P <.001). A good convergent validity was determined accompanied by significant moderate positive correlations with Children Behavior Questionnaire shyness and Strengths and Difficulties Questionnaire internalizing scales. An adequate divergent validity was also demonstrated based on significant positive mild to moderate correlations with Children Behavior Questionnaire impulsivity, Children Behavior Questionnaire smiling/laugh, Strengths and Difficulties Questionnaire prosocial scales, and nonsignificant correlation with Strengths and Difficulties Questionnaire externalizing scale. Conclusion: The study demonstrated that the Turkish version of the Behavioral Inhibition Questionnaire parent form is an effective tool with good reliability and validity among 3-7 years old children.Öğe Pre-transplantation vitamin D deficiency increases acute graft-versus-host disease after hematopoietic stem cell transplantation in thalassemia major patients(WILEY, 2022) Daloğlu, Hayriye; Uygun, Vedat; Öztürkmen, Seda; Yalçın, Koray; Karasu, Gülsü; Yeşilipek, AkifBackground: Although there are many studies on the role of vitamin D deficiency (VDD) in hematopoetic stem cell transplantation (HSCT), outcomes have often reported conflicting results because of the heterogeneity of the patients in the studies. Methods: We investigated the association between VDD prior to HSCT and outcomes after HSCT in a relatively homogenous group of patients with thalassemia major (TM) who received identical treatment for TM before transplantation, and the same conditioning regimen and GVHD prophylaxis during and after transplantation. All patients, including the patients with normal vitamin D3 levels received 400 to 800 IU per day of vitamin D for the first 6 months after HSCT. Results: Pre-HSCT VDD increased the frequency of aGVHD after transplantation, particularly in HSCTs performed with PBSC for the stem cell source. Pre-transplant low vitamin D3 levels had no association with transplant outcomes such as engraftment, viral infections, alloimmunization, chronic GvHD, total days of hospitalization, and success in terms of transfusion independence. Conclusions: Low vitamin D3 levels before HSCT carry a significant risk for aGVHD. All patients with TM should be screened for VDD before HSCT, and every effort should be made to supplement vitamin D before the transplant in VDD patientsÖğe Enhancing effect of nicotine on electrical field stimulation elicited contractile responses in isolated rabbit bladder straight muscle; the role of cannabinoid and vanilloid receptors(Turkiye Klinikleri, 2022) İlhan, Sevil Özger; Fincan, Gökçe Sevim Öztürk; Okçay, Yağmur; Koç, Derya Sebile; Aşkin, Celil İlker; Kibar, Ayşe Kübra; Vural, İsmail Mert; Sarıoğlu, YusufBackground/aim: Nicotine acts as an agonist of nicotinic acetylcholine receptors (nAChR). These receptors belong to a superfamily of ligand-gated ion channels. We previously demonstrated that nicotine increased electrical field stimulation (EFS)-induced contractile or relaxation responses, possibly by facilitating neurotransmitter release from nerve terminals in various rabbit tissues. Studies have shown that there is an interaction between the endocannabinoid and nicotinic systems. This study aimed to investigate the interaction between nicotine and the endocannabinoid system in the rabbit urine bladder and also investigate the enhancing effect of nicotine on EFS-induced contractile responses in rabbit isolated bladder smooth muscle and its interaction with the endocannabinoid system. Materials and methods: The New Zealand albino male adult rabbits were used for this study. Following scarification, the urine bladder was rapidly excised, and then uniform strips were prepared. Each strip was mounted under 1 g isometric resting tension in an organ bath containing 20 mL of Krebs–Henseleit solution. After obtaining EFS-induced contractile responses, 10–4 M concentrations of nicotine were applied to the preparations, and EFS was stopped after 5 stimulations. Following washing, the same experimental procedure was performed with the same tissue in the presence of AM251 (a cannabinoid CB1R antagonist, 10–6 M), AM630 (a cannabinoid CB2R antagonist, 10–6 M), and capsazepine (a vanilloid receptor antagonist, 3 × 10–6 M). Results: Nicotine enhanced the EFS-induced contraction responses by 17.16% ± 2.81% at a 4-Hz stimulation frequency. Cannabinoid receptor antagonists AM251 and AM630 reduced this increasing effect of nicotine although it was not significant and vanilloid receptor antagonist capsazepine did not significantly alter the nicotines’ effect. Conclusion: These results show that enhancing effect of nicotine in the smooth muscle of the rabbit bladder, even though it was not significant endocannabinoid system possibly have a role in nicotines’ effect. © TÜBİTAK.Öğe Anti-amoebic activity of a series of benzofuran/benzothiophene derivatives against acanthamoeba castellanii belonging to the T4 genotype(2022) Akbar, Noor; El-Gamal, Mohammed, I; Zaraei, Seyed-Omar; Saeed, Balsam Qubais; Khan, Naveed Ahmed; Siddiqui, RuqaiyyahAims: To determine the anti-amoebic activity of benzofuran/benzothiophene-possessing compounds against Acanthamoeba castellanii of the T4 genotype. Method and results: A series of benzofuran/benzothiophene-possessing compounds were tested for their anti-amoebic activities, in particular, to block encystation and excystation processes in amoebae. Cytotoxicity of the compounds were evaluated using lactate dehydrogenase (LDH) assays. The amoebicidal assay results revealed significant anti-amoebic effects against A. castellanii. Compounds 1p and 1e showed the highest amoebicidal activity, eliminating 68% and 64% of the amoebae, respectively. These compounds remarkably repressed both the encystation and excystation processes in A. castellanii. Furthermore, the selected compounds presented minimal cytotoxic properties against human cells, as well as considerably abridged amoeba-mediated cytopathogenicity when compared to the amoebae alone. Conclusions: Our findings show that benzofuran/benzothiophene derivatives depict potent anti-amoebic activities; thus these compounds should be used as promising and novel agents in the rationale development of therapeutic strategies against Acanthamoeba infections.Öğe Quality of Life assessment with EORTC QLQ in patients with hodgkin lymphoma: multicenter study(Tr dizin, 2022) Gemici, Ali Ihsan; Serin, İstemi; Erol, Vedat Buğra; Doğu, Mehmet Hilmi; Karakuş, VolkanAim: The aim of our study is to obtain data on the quality of life (QoL) in Hodgkin lymphoma (HL) patients in a representative sample of the general population of Turkey with the help of the EORTC QLQ-C30 and QLQ-HL27 questionnaires. Material and Methods: A total of 68 patients from seven different centers diagnosed with HL between 2018-2020 were included in the study. The questionnaires were answered cross-sectionally by the patient under the control of a physician in the centers participating in the study. Results: Out of 68 patients, 42.6% (n=29) were female and 57.4% (n=39) were male. The ages of the patients ranged from 18 to 74 years, with a mean of 42.10±16.62 and with a median value of 40 years. There was no significant difference between age subgroups in terms of QLQ-C30 global health status/ QoL, functional or symptom scales and HL27 SB, PC, EI and WF scores (p>0.05, for all). It was determined that the constipation scores of females were higher than the scores of males (p=0.041). No statistically significant difference was found in terms of HL27 SB, PC, EI and WF sub-dimension scores according to gender (p>0.05). Conclusions: There was only a statistically significant difference in terms of QLQ-C30 constipation sub-dimension scores according to gender. The constipation scores of females were higher than the scores of men. More detailed and large population studies are needed to reveal the effectiveness of QoL assessment in HL patients.Öğe The effect of cord blood vitamin d level on bronchopulmonary dysplasia and other meonatal morbidities in preterm infants(GORM, 2022) Elif,Koç; Bolat, Fatih; Cihan, Meriç KaymakOBJECTIVES: We aimed to investigate the relationship between cord 25-hydroxyvitamin D level and bronchopulmonary dysplasia and other neonatal morbidities (sepsis, necrotizing enterocolitis, intraventricular hemorrhage, patent ductus arteriosus, respiratory distress syndrome, retinopathy of prematurity) in preterm neonates. STUDY DESIGN: Infants aged <32 gestational weeks who were admitted to the neonatal intensive care unit between March 2014 and November 2014 were enrolled in this prospective study. Cord blood samples were obtained during delivery. 25-hydroxyvitamin D level was measured using an automatic biochemical analyzer. Patients were divided into two groups according to their 25-hydroxyvitamin D levels: 25-hydroxyvitamin D <20 ng/mL and 25-hydroxyvitamin D ?20 ng/mL. We used descriptive statistics and multiple regression models to identify risk factors associated with bronchopulmonary dysplasia. RESULTS: Sixty premature infants were analyzed in this study. The mean cord 25-hydroxyvitamin D level was 13,8±6,8 ng/mL (range 3,5-30,7 ng/mL). Eighty percent of the patients (48/60) had 25-hydroxyvitamin D levels <20 ng/mL. Among the infants, 21 (35%) developed bronchopulmonary dysplasia. Infants with bronchopulmonary dysplasia had higher frequencies of 25-hydroxyvitamin D deficiency than the non-bronchopulmonary dysplasia group (p=0.028). Duration of hospitalization was also longer in infants with low levels of cord 25-hydroxyvitamin D. On the other hand, there was no significant difference between infants with and without vitamin D deficiency with respect to respiratory distress syndrome, patent ductus arteriosus, retinopathy of prematurity, necrotizing enterocolitis, sepsis, and intraventricular hemorrhage. CONCLUSION: This study shows the high rate of vitamin D deficiency in pregnant women in the central Anatolian region (Sivas) of Türkiye. Low cord 25-hydroxyvitamin D levels were associated with an increased risk of bronchopulmonary dysplasia and prolonged hospitalization in very preterm infants. These data strengthen the necessity for vitamin D supplementation during pregnancÖğe A case of bartonellosis mimicking systemic lupus erythematosus(SAGE PUBLICATIONS LTD, 2022) Kara, Emine Manolya; Özdemir, Gül Nihal; Taşdemir, Mehmet; Ata, Serap; Karini, Belma; Valiyev, Eldar; Tutkun, İlknur Tuğal; Köse, Gülşen; Özkaya, OzanBackground and aim: Cat-scratch disease (CSD) is a systemic bacterial infection caused by Bartonella henselae. The disease is typically characterized by regional lymphadenopathy developing after scratches from domestic or feral cats. Rarely, systemic involvement may be observed. The co-occurrence with glomerulonephritis and positive antinuclear antibody (ANA) tests have been reported before. In these cases, the disease can be misdiagnosed as systemic lupus erythematosus. Ocular involvement occurs in 5%-10% of the cases with CSD, and neuroretinitis is among the common manifestations. Administration of corticosteroids (CSs) in addition to antibiotics has been shown to improve prognosis in neuroretinitis cases. However, the optimal dose and duration, remain ill-defined. Case report: In this article, we present an 11-year-old girl with CSD and neuroretinitis with a positive ANA test and hematuria, who benefited from high-dose methyl-prednisolone and antibiotics. Conclusion: Further research is warranted in order to determine the dose and duration of CSs in the treatment of Bartonella neuroretinitis.Öğe Vajenden soyutlanan candida türlerinde biyofilm üretiminin iki farklı yöntemle araştırılması(2022) Aydınlı, Aydın; Vural, GürcanVajenden Soyutlanan Candida Türlerinde Biyofilm Üretiminin İki Farklı Yöntemle AraştırılmasıÖğe Hematopoietic stem cell transplantation in serine/threonine kinase 4 (stk4) deficiency: report of two cases and literature review(WILEY, 2022) Uygun, Vedat; Keleş, Sevgi; Daloğlu, Hayriye; Öztürkmen, Seda; Yalçın, Koray; Tezcan Karasu, Gülsün; Yeşilipek, AkifBackground Serine/threonine kinase 4 (STK4) deficiency is a combined immunodeficiency (CID) characterized by early onset recurrent bacterial, viral, and fungal infections. Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for CID; however, little is known about the necessity and benefits of HSCT in patients with STK4 deficiency. Methods We report two siblings with STK4 deficiency transplanted from two unrelated donors with the same conditioning regimen. Results In the conditioning regimen, rituximab was given on Day -11 (375 mg/m(2)), and sirolimus was added on the same day. Busulfan was administered at a myeloablative dose (3.2 mg/kg; Days -7 to -4) with 150 mg/m(2) of fludarabine (Days -7 to -3). They were transplanted with peripheral blood stem cells, and graft-versus-host disease (GVHD) prophylaxis was administered with 10 mg/m(2) methotrexate on Days 1, 3, and 6. In addition, mycophenolate mofetil (MMF) was started on Day 1 with ongoing use of sirolimus. We did not encounter veno-occlusive disease (VOD), high-grade acute GVHD, or significant organ toxicity in either patient. Both patients were well at the end of the first year after HSCT with complete donor chimerism. Conclusions Serine/threonine kinase 4 deficiency is a disease with high mortality post-HSCT; therefore, the conditioning regimen and GVHD prophylaxis strategies are important considerations in these patients. In our opinion, the conditioning regimen, which includes rituximab and busulfan and fludarabine (BU-FLU), GVHD prophylaxis with sirolimus and MMF, and short-term methotrexate, offers favorable outcomes and is well tolerated in our STK4-deficient patients.Öğe The relation of SYNTAX score with carotid plaque morphology in patients who undergoing coronary by-pass surgery(TRDizin, 2021) Aksoy, Süleyman Hilmi; Birdal, Oğuzhan; Yurdaışık, IşılThe Relation of SYNTAX Score with Carotid Plaque Morphology in Patients Who Undergoing Coronary By-pass Surgery
