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Article Citation - WoS: 16Citation - Scopus: 19A Pumpless Monolayer Microfluidic Device Based on Mesenchymal Stem Cell-Conditioned Medium Promotes Neonatal Mouse in Vitro Spermatogenesis(Bmc, 2023) Onen, Selin; Atik, Ali Can; Gizer, Merve; Kose, Sevil; Yaman, Onder; Kulah, Haluk; Korkusuz, PetekBackgroundChildhood cancer treatment-induced gonadotoxicity causes permanent infertility/sub-infertility in nearly half of males. The current clinical and experimental approaches are limited to cryopreservation of prepubertal testicular strips and in vitro spermatogenesis which are inadequate to achieve the expanded spermatogonial stem/progenitor cells and spermatogenesis in vitro. Recently, we reported the supportive effect of bone marrow-derived mesenchymal cell co-culture which is inadequate after 14 days of culture in static conditions in prepubertal mouse testis due to lack of microvascular flow and diffusion. Therefore, we generated a novel, pumpless, single polydimethylsiloxane-layered testis-on-chip platform providing a continuous and stabilized microfluidic flow and real-time cellular paracrine contribution of allogeneic bone marrow-derived mesenchymal stem cells.MethodsWe aimed to evaluate the efficacy of this new setup in terms of self-renewal of stem/progenitor cells, spermatogenesis and structural and functional maturation of seminiferous tubules in vitro by measuring the number of undifferentiated and differentiating spermatogonia, spermatocytes, spermatids and tubular growth by histochemical, immunohistochemical, flow cytometric and chromatographic techniques.ResultsBone marrow-derived mesenchymal stem cell-based testis-on-chip platform supported the maintenance of SALL4(+) and PLZF(+) spermatogonial stem/progenitor cells, for 42 days. The new setup improved in vitro spermatogenesis in terms of c-Kit(+) differentiating spermatogonia, VASA(+) total germ cells, the meiotic cells including spermatocytes and spermatids and testicular maturation by increasing testosterone concentration and improved tubular growth for 42 days in comparison with hanging drop and non-mesenchymal stem cell control.ConclusionsFuture fertility preservation for male pediatric cancer survivors depends on the protection/expansion of spermatogonial stem/progenitor cell pool and induction of in vitro spermatogenesis. Our findings demonstrate that a novel bone marrow-derived mesenchymal stem cell-based microfluidic testis-on-chip device supporting the maintenance of stem cells and spermatogenesis in prepubertal mice in vitro. This new, cell therapy-based microfluidic platform may contribute to a safe, precision-based cell and tissue banking protocols for prepubertal fertility restoration in future.Article Citation - WoS: 7Citation - Scopus: 8Communities for Healthy Living (chl) a Community-Based Intervention To Prevent Obesity in Low-Income Preschool Children: Process Evaluation Protocol(Bmc, 2020) Beckerman-Hsu, Jacob P.; Aftosmes-Tobio, Alyssa; Gavarkovs, Adam; Kitos, Nicole; Figueroa, Roger; Kalyoncu, Z. Begum; Davison, Kirsten K.BackgroundProcess evaluation can illuminate barriers and facilitators to intervention implementation as well as the drivers of intervention outcomes. However, few obesity intervention studies have documented process evaluation methods and results. Community-based participatory research (CBPR) requires that process evaluation methods be developed to (a) prioritize community members' power to adapt the program to local needs over strict adherence to intervention protocols, (b) share process evaluation data with implementers to maximize benefit to participants, and (c) ensure partner organizations are not overburdened. Co-designed with low-income parents using CBPR, Communities for Healthy Living (CHL) is a family-centered intervention implemented within Head Start to prevent childhood obesity and promote family well-being. We are currently undertaking a randomized controlled trial to test the effectiveness of CHL in 23 Head Start centers in the greater Boston area. In this protocol paper, we outline an embedded process evaluation designed to monitor intervention adherence and adaptation, support ongoing quality improvement, and examine contextual factors that may moderate intervention implementation and/or effectiveness.MethodsThis mixed methods process evaluation was developed using the Perez et al. framework for evaluating adaptive interventions and is reported following guidelines outlined by Grant et al. Trained research assistants will conduct structured observations of intervention sessions. Intervention facilitators and recipients, along with Head Start staff, will complete surveys and semi-structured interviews. De-identified data for all eligible children and families will be extracted from Head Start administrative records. Qualitative data will be analyzed thematically. Quantitative and qualitative data will be integrated using triangulation methods to assess intervention adherence, monitor adaptations, and identify moderators of intervention implementation and effectiveness.DiscussionA diverse set of quantitative and qualitative data sources are employed to fully characterize CHL implementation. Simultaneously, CHL's process evaluation will provide a case study on strategies to address the challenges of process evaluation for CBPR interventions. Results from this process evaluation will help to explain variation in intervention implementation and outcomes across Head Start programs, support CHL sustainability and future scale-up, and provide guidance for future complex interventions developed using CBPR.Trial registrationClinicalTrials.gov, NCT03334669. Registered on October 10, 2017Article Citation - WoS: 2Citation - Scopus: 22-Ag and Bone Marrow-Targeted Pcl Nanoparticles as Nanoplatforms for Hematopoietic Cell Line Mobilization(Bmc, 2024) Kose, Sevil; Varan, Cem; Onen, Selin; Nemutlu, Emirhan; Bilensoy, Erem; Korkusuz, PetekBackgroundThe use of mobilizing agents for hematopoietic stem cell (HSC) transplantation is insufficient for an increasing number of patients. We previously reported lipid made endocannabinoid (eCB) ligands act on the human bone marrow (hBM) HSC migration in vitro, lacking long term stability to be therapeutic candidate. In this study, we hypothesized if a novel 2-AG-loaded polycaprolactone (PCL)-based nanoparticle delivery system that actively targets BM via phosphatidylserine (Ps) can be generated and validated.MethodsPCL nanoparticles were prepared by using the emulsion evaporation method and characterized by Zetasizer and scanning electron microscopy (SEM). The encapsulation efficiency and release profile of 2-AG were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The presence of cannabinoid receptors (CBRs) in HSCs and monocytes was detected by flow cytometry. Cell morphology and viability were assessed using transmission electron microscopy (TEM), SEM, and the WST-1 viability assay. The migration efficacy of the 2-AG and 2-AG-loaded nanoparticle delivery system on HSCs and HPSCs (TF-1a and TF-1) and monocytes (THP-1) was evaluated using a transwell migration assay.ResultsThe 140-225 nm PCL nanoparticles exhibited an increasing polydispersity index (PDI) after the addition of Ps and 2-AG, with a surface charge ranging from - 25 to -50 mV. The nanoparticles released up to 36% of 2-AG within the first 8 h. The 2-AG-Ps-PCL did not affect cellular viability compared to control on days 5 and 10. The HSCs and monocytes expressed CB1R and CB2R and revealed increased migration to media containing 1 mu M 2-AG-Ps-PCL compared to control. The migration rate of the HSCs toward monocytes incubated with 1 mu M 2-AG-Ps-PCL was higher than that of the monocytes of control. The 2-AG-Ps-PCL formulation provided a real time mobilization efficacy at 1 mu M dose and 8 h time window via a specific CBR agonism.ConclusionThe newly generated and validated 2-AG-loaded PCL nanoparticle delivery system can serve as a stable, long lasting, targeted mobilization agent for HSCs and as a candidate therapeutic to be included in HSC transplantation (HSCT) protocols following scale-up in vivo preclinical and subsequent clinical trials.Article Association Between Rutherford Classification and Cha2ds2< Chads2 and Ascvd Scores in Peripheral Artery Disease Patients(Bmc, 2020) Karaduman, Bilge Duran; Ayhan, Huseyin; Keles, Telat; Bozkurt, EnginBackground and Aim: The classification system is important in assessing the severity of Peripheral Artery Disease (PAD) and making the treatment decision. However, classification systems may not be sufficient and scoring systems developed to predict cardiovascular and cerebrovascular events can also be useful to assess the severity of PAD. In this study, our aim was to investigate the association of the Rutherford classification and CHADS(2), CHA(2)DS(2)-VASc and ASCVD scores in PAD patients. Method: A total of 65 consecutive patients with PAD (males 92.3%, mean age 63.0 +/- 9.2 years), who underwent percutaneous peripheral intervention were included in our retrospective study. Results: There were 16 patients in Category 2, 31 patients in Category 3, and 10 patients in Category 4 and eight patients in Category 5. The CHADS(2), CHA(2)DS(2)-VASc and ASCVD scores were found to be significantly different among the Rutherford categories and between each other. From Category 1 to 5, CHADS(2), CHA(2)DS(2)-VASc and ASCVD scores were significantly increased. When we grouped the scores as CHADS 2 <2 and <2 and CHA(2)DS(2)-VASc<4 and >= 4, it was determined that as the category increased the score group also increased. There was significantly correlation between CHADS(2), CHA(2)DS(2)-VASc and ASCVD scores with the Rutherford categories in correlation analyses. Conclusion: As far as we know, in this study which is the first study about the association of Rutherford classification and scoring systems, the major finding of the present study is that the CHADS(2), CHA(2)DS(2)-VASc and ASCVD scores was independently correlated with the severity of Rutherford Category in patients with PAD. (C) 2020 Association for Research into Arterial Structure and Physiology. Publishing services by Atlantis Press International B.V.Article Citation - WoS: 48Citation - Scopus: 58Determinants of Mortality in a Large Group of Hemodialysis Patients Hospitalized for Covid-19(Bmc, 2021) Turgutalp, Kenan; Ozturk, Savas; Arici, Mustafa; Eren, Necmi; Gorgulu, Numan; Islam, Mahmut; Ates, KenanBackground: Maintenance hemodialysis (MHD) patients are at increased risk for coronavirus disease 2019 (COVID-19). The aim of this study was to describe clinical, laboratory, and radiologic characteristics and determinants of mortality in a large group of MHD patients hospitalized for COVID-19. Methods: This multicenter, retrospective, observational study collected data from 47 nephrology clinics in Turkey. Baseline clinical, laboratory and radiological characteristics, and COVID-19 treatments during hospitalization, need for intensive care and mechanical ventilation were recorded. The main study outcome was in-hospital mortality and the determinants were analyzed by Cox regression survival analysis. Results: Of 567 MHD patients, 93 (16.3%) patients died, 134 (23.6%) patients admitted to intensive care unit (ICU) and 91 of the ones in ICU (67.9%) needed mechanical ventilation. Patients who died were older (median age, 66 [57-74] vs. 63 [52-71] years, p = 0.019), had more congestive heart failure (34.9% versus 20.7%, p = 0.004) and chronic obstructive pulmonary disease (23.6% versus 12.7%, p = 0.008) compared to the discharged patients. Most patients (89.6%) had radiological manifestations compatible with COVID-19 pulmonary involvement. Median platelet (166 x 10(3) per mm(3) versus 192 x 10(3) per mm(3), p = 0.011) and lymphocyte (800 per mm(3) versus 1000 per mm(3), p < 0.001) counts and albumin levels (median, 3.2 g/dl versus 3.5 g/dl, p = 0.001) on admission were lower in patients who died. Age (HR: 1.022 [95% CI, 1.003-1.041], p = 0.025), severe-critical disease clinical presentation at the time of diagnosis (HR: 6.223 [95% CI, 2.168-17.863], p < 0.001), presence of congestive heart failure (HR: 2.247 [95% CI, 1.228-4.111], p = 0.009), ferritin levels on admission (HR; 1.057 [95% CI, 1.006-1.111], p = 0.028), elevation of aspartate aminotransferase (AST) (HR; 3.909 [95% CI, 2.143-7.132], p < 0.001) and low platelet count (< 150 x 10(3) per mm(3)) during hospitalization (HR; 1.864 [95% CI, 1.025-3.390], p = 0.041) were risk factors for mortality. Conclusion: Hospitalized MHD patients with COVID-19 had a high mortality rate. Older age, presence of heart failure, clinical severity of the disease at presentation, ferritin level on admission, decrease in platelet count and increase in AST level during hospitalization may be used to predict the mortality risk of these patients.Article Citation - WoS: 2Citation - Scopus: 2Chronic Pregabalin Treatment Reduced Anxiety, and Acute Pregabalin Treatment Increased Depression-Like Behaviors in Rats(Bmc, 2024) Caliskan, Hasan; Akat, Firat; Dursun, Ali Dogan; Zaloglu, NezahetBackgroundPregabalin is an antiepileptic drug that binds to the alpha-2/delta unit at presynaptic voltage-dependent calcium channels. We aimed to investigate the effect of acute and chronic pregabalin administration on anxiety and depression-like behaviors.MethodsFifty-six male Wistar albino rats were divided into seven groups: control, vehicle, and five different dose groups (5, 10, 30, 60, and 100 mg/kg). Pregabalin was administered for two weeks. Depression-like behaviors were evaluated by Forced swimming test. Anxiety-like behavior (ALB) was evaluated by Open field test (OFT), Elevated Plus Maze (EPM), and light-dark box. Subjects underwent the forced swimming test (FST) after the first dose, while the open field test (OFT), elevated plus maze (EPM), and light-dark box (LDB) were performed after two weeks of treatment. Further sucrose preference test was conducted to evaluate anhedonia until the end of the experiment.ResultsIn the forced swimming test, depression-like behaviors increased after acute single-dose administration of 10, 30, 60, 100 mg/kg pregabalin. According to OFT results, chronic 100 mg/kg pregabalin showed anxiolytic effects by decreasing grooming, and freezing behaviors. In addition, 100 mg/kg chronic pregabalin administration significantly increased the time spent in the central region, the number of entries to the center, and the unsupported rearing number without causing any change in locomotor activity. According to EPM results, both chronic 60 and 100 mg/kg pregabalin treatments showed anxiolytic effects by increasing open arm time and head dipping behavior. In addition, 60 and 100 mg/kg chronic pregabalin administration significantly decreased stretch attend posture. All pregabalin administrations between 5 and 100 mg/kg displayed anxiolytic effects in the LDB. Sucrose preference was above 65% for the duration of all experiments and subjects did not show anhedonia.ConclusionAcute pregabalin treatment triggered depression-like behaviors. Anhedonia, which may be associated with depression, was not observed during chronic treatment. Moreover, chronic treatment with pregabalin revealed potent anxiolytic effects in different behavior patterns and doses for all tests of unconditional anxiety. In particular, 100 mg/kg chronic pregabalin administration decreased anxiety-like behaviors in all experiment setups. Although the anxiolytic effect was demonstrated in chronic treatment, acute treatment of pregabalin induced depression-like behaviors, and thus in clinical practice should be done with caution, especially in patients with anxiety-depression comorbidity.Article Citation - WoS: 31Citation - Scopus: 36Predicting the Outcome of Covid-19 Infection in Kidney Transplant Recipients(Bmc, 2021) Oto, Ozgur Akin; Ozturk, Savas; Turgutalp, Kenan; Arici, Mustafa; Alpay, Nadir; Merhametsiz, Ozgur; Yildiz, AlaattinBackgroundWe aimed to present the demographic characteristics, clinical presentation, and outcomes of our multicenter cohort of adult KTx recipients with COVID-19.MethodsWe conducted a multicenter, retrospective study using data of patients hospitalized for COVID-19 collected from 34 centers in Turkey. Demographic characteristics, clinical findings, laboratory parameters (hemogram, CRP, AST, ALT, LDH, and ferritin) at admission and follow-up, and treatment strategies were reviewed. Predictors of poor clinical outcomes were analyzed. The primary outcomes were in-hospital mortality and the need for ICU admission. The secondary outcome was composite in-hospital mortality and/or ICU admission.ResultsOne hundred nine patients (male/female: 63/46, mean age: 48.412.4years) were included in the study. Acute kidney injury (AKI) developed in 46 (42.2%) patients, and 4 (3.7%) of the patients required renal replacement therapy (RRT). A total of 22 (20.2%) patients were admitted in the ICU, and 19 (17.4%) patients required invasive mechanical ventilation. 14 (12.8%) of the patients died. Patients who were admitted in the ICU were significantly older (age over 60years) (38.1% vs 14.9%, p=0.016). 23 (21.1%) patients reached to composite outcome and these patients were significantly older (age over 60years) (39.1% vs. 13.9%; p=0.004), and had lower serum albumin (3.4g/dl [2.9-3.8] vs. 3.8g/dl [3.5-4.1], p=0.002), higher serum ferritin (679 mu g/L [184-2260] vs. 331 mu g/L [128-839], p=0.048), and lower lymphocyte counts (700/mu l [460-950] vs. 860 /mu l [545-1385], p=0.018). Multivariable analysis identified presence of ischemic heart disease and initial serum creatinine levels as independent risk factors for mortality, whereas age over 60years and initial serum creatinine levels were independently associated with ICU admission. On analysis for predicting secondary outcome, age above 60 and initial lymphocyte count were found to be independent variables in multivariable analysis.Conclusion Over the age of 60, ischemic heart disease, lymphopenia, poor graft function were independent risk factors for severe COVID-19 in this patient group. Whereas presence of ischemic heart disease and poor graft function were independently associated with mortality.Article Citation - WoS: 3Citation - Scopus: 3The Relationship Between Glomerular Igg Staining and Poor Prognostic Findings in Patients With Iga Nephropathy: the Data From Tsn-Gold Working Group(Bmc, 2021) Turgutalp, Kenan; Cebeci, Egemen; Turkmen, Aydin; Derici, Ulver; Seyahi, Nurhan; Eren, Necmi; Ozturk, SavasBackground Galactose-deficient IgA1 (Gd-IgA1) has an increased tendency to form immunocomplexes with IgG in the serum, contributing to IgAN pathogenesis by accumulating in the glomerular mesangium. Several studies showed that glomerular IgG deposition in IgAN is an important cause of mesangial proliferation and glomerular damage. This study aims to determine the association of the positivity of IgG and the intensity of IgG staining with a poor renal prognosis. Methods A total of 943 IgAN patients were included in the study. Glomerular IgG staining negative and positive patients were compared using Oxford classification scores, histopathological evaluations, proteinuria, eGFR, albumin, blood pressures. IgG positive patients were classified as (+), (++), (+++) based on their staining intensity, and the association with the prognostic criteria was also evaluated. Results 81% (n = 764) of the patients were detected as IgG negative, while 19% (n = 179) were positive. Age, gender, body mass index, blood pressure, proteinuria, eGFR, uric acid values were similar in IgG positive and negative patients who underwent biopsy (p > 0.05). Intensity of glomerular IgG positivity was not found to be associated with diastolic and systolic blood pressure, urea, uric acid, age, eGFR, albumin, proteinuria (p > 0.05 for all, r = - 0.084, r = - 0.102, r = - 0.006, r = 0.062, r = 0.014, r = - 0.044, r = - 0.061, r = - 0.066, r = 0.150, respectively). There was no difference for histopathological findings between IgG (+), IgG (++), IgG (+++) groups (for all, p > 0.05). Conclusion Glomerular IgG negativity and positivity detected by routine IFM in IgAN patients is not associated with poor renal prognostic risk factors.Article Citation - Scopus: 1Systemic Iodine Levels Increase With Povidone-Iodine Irrigation, but Does This Affect Thyroid Functions? a Case-Control Study(Bmc, 2024) Ertan, Mehmet Batu; Basarir, Kerem; Kocaoglu, Hakan; Aydugan, Mehmet Yagiz; Guengoer, ErdalBackgroundIntraoperative irrigation with diluted povidone iodine (PI) can be used to reduce the incidence of infection-related complications in arthroplasty surgeries. Since PI is associated with many interventions, especially skin antisepsis, its systemic effects are being studied. The aim of our study is to evaluate the systemic effects of PI, which we use as an irrigation solution, by means of urine iodine and thyroid function tests.MethodsIn this case-control study, 96 patients who underwent knee or hip arthroplasty were included and divided into two groups according to the irrigation solution. In the first group, PI was added to the standard irrigation. The second group was considered as the control group and only standard irrigation was applied. Urine iodine, thyroid stimulating hormone, free T3 and free T4 values were compared in the preoperative and postoperative periods of these two groups. In this way, the effect of absorbed iodine on thyroid functions was investigated.ResultsIn the diluted PI group, urinary iodine levels were measured at maximum levels (450 mu g/L) in the early postoperative period in most of the patients. The statistically significant difference in urinary iodine levels between the PI group and the control group, which started in the early postoperative period, continued until the last follow-up on the 14th postoperative day. In terms of thyroid functions, the observed differences were not statistically significant.ConclusionStudies to reduce periprosthetic infection show that PI can be preferred for irrigation before the closure of the joint area in total joint arthroplasty. Although the success of this treatment in periprosthetic infection has been investigated, its systemic examination has not been demonstrated. It was determined that PI treatment, which was seen to decrease in the systemic circulation within 14 days, did not show a statistically significant change in terms of thyroid functions when used at the determined concentration and duration. These results should be evaluated with larger and longer-term studies.Trial registrationClinical trials ID no. NCT05599841.Article Citation - WoS: 5Citation - Scopus: 6Adaptation of Food Craving Inventory To Turkish Culture: a Validity and Reliability Study(Bmc, 2022) Ozel, Irem Cagla; Yabanci Ayhan, Nurcan; Cetiner, OzlemPlain English Summary This study was carried out to adapt the Food Craving Inventory to Turkish. The English version of inventory consists of 4 sub-factors that measure cravings for high-fat foods, carbohydrates/starches, sweets, and fast food fats, and creates a total score. The sample of the study consists of 621 individuals between the ages of 19-50 who voluntarily agree to participate in an online survey. This study revealed that FCI-TR is a valid instrument of specific food cravings in the Turkish adult population. Turkish version of the FCI also consist of 4 sub-factors. Women experienced more food craving for sweets than men. While the most craved food by women was chocolate, men scored significantly higher on bread than women. In addition, a relationship was found between food craving and body weight. Introduction The Food Craving Inventory is a 28-item self-report measure of specific food cravings. The inventory consists of 4 factors: high fats, sweets, carbohydrates/starches and fast-food fats. Purpose This study was carried out to evaluate the Turkish validity and reliability of the Food Craving Inventory, and to determine the psychometric properties and factor structure of the Turkish version. Methods The sample of the study consists of 621 individuals between the ages of 19-50 who voluntarily agree to participate in online survey. Validity and reliability analyses were performed for the Turkish version of Food Craving Inventory (FCI-TR). Confirmatory factor analysis was performed to evaluate the factor structure of the Turkish version of FCI. Results Confirmatory factor analysis yielded a four-factor structure as "sweets," "high-fats," "carbohydrates/starches" and "fast food fats". The Cronbach-alpha coefficient for the total score was 0.84; subfactors were calculated as 0.74 for "sweets", 0.64 for "high-fat foods", 0.65 for "carbohydrates/starches", and 0.66 for "fast-food fats". The scores of the FCI-TR factors and its total score significantly correlated with the sub-factors of Three Factor Eating Questionnaire (TFEQ). A significant correlation was found between body mass index (BMI) and high fats and fast-food fats factor score. Also total and factor scores of the FCI-TR were different between BMI groups. Conclusions This study demonstrates that the Turkish version of the FCI is a valid and reliable tool to measure food cravings in the Turkish population. FCI is also correlated with sub-factors of TFEQ.
