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Publication Metadata only 1200 nm pumped Tm3+:Lu2O3 ceramic lasers(Optical Soc Amer, 2018) Özharar, Sarper; N/A; Department of Physics; Toker, Işınsu Baylam; Sennaroğlu, Alphan; PhD Student; Faculty Member; Department of Physics; N/A; College of Sciences; N/A; 23851We report on an experimental demonstration of a 1200-nm pumped Tm3+:Lu2O3 ceramic laser. By using a gain-switched, tunable Cr4+:forsterite laser, the excitation spectrum was measured, with optimum pumping bands centered near 1198 nm, 1204 nm, and 1211 nm. The highest slope efficiency of 21.5% was obtained at the pump wavelength of 1204 nm. Comparative energy efficiency measurements performed near 1200-nm and 800-nm pumping further showed that nearly 40% improvement was obtained in slope efficiency measured with respect to the incident pump energy for 1200-nm pumping. A transition was further observed from single-wavelength operation at 2066 nm to dual-wavelength operation near 2066 nm and 1967 nm for absorbed pump energies above 50 mu J. In this regime, two consecutive output pulses were observed in the time domain. The shortest temporal duration of the first pulse was 1.1 mu s at the incident pulse energy of 105 mu J. The duration and build-up time of the second pulse remained around 5.9 mu s and 18.5 mu s. We believe that the improved energy efficiency demonstrated for the 1.5% Tm3+:Lu2O3 ceramic with 1200-nm pumping can be used as an alternative scheme for the excitation of Tm3+:Lu2O3 ceramic lasers.Publication Metadata only 18F-FDG PET/CT mean suv and metabolic tumor volume for mean survival time in non-small cell lung cancer(Lippincott Williams and Wilkins, 2015) Kurtipek, Ercan; Çaycı, Mustafa; Düzgün, Nuri; Esme, Hıdır; Terzi, Yüksel; Bakdık, Süleyman; Ünlü, Yaşar; Burnik, Cengiz; Bekçi, Taha Tahir; N/A; Aygün, Murat Serhat; Teaching Faculty; School of Medicine; Koç University Hospital; 291692Objective: The study was designed to determine the relationship between survival time of standardized uptake value (SUVmax and SUVmean) and metabolic tumor volume (MTV) in patients with non-small cell lung cancer (NSCLC), and examine the impact of demographic, clinical, and radiological data of these patients on survival. Materials and Methods: We performed a retrospective analysis of the records of 79 patients with NSCLC who presented to our hospital between May 2010 and March 2013, received a final diagnosis, and underwent 18F-FDG PET/CT for staging. Clinical, radiological, and 18F-FDG PET/CT parameters with an impact on prognosis such as the SUVmax of the primary tumor as calculated by the volumetric region of interest in the 18F-FDG PET/CT scans during initial diagnosis, mean SUV of the tumor, and MTV obtained with a threshold of SUVmax greater than 2.5 were recorded and statistically analyzed. A statistical analysis was carried out based on the clinical, radiological, and PET/CT findings of the patients who were divided into 2 groups: survivors and nonsurvivors. Results: Seventy patients (88.6%) were men, and 9 (11.4%) were women. The mean age was 63.65 ± 11.51 years in the nonsurvivor group (n = 40) versus 62.74 ± 10.60 years in the survivor group (n = 39) (Table 1). The mean survival time from diagnosis was 7.9 ± 6.52 months in the nonsurvivor group versus 14.09 ± 7.41 months in the survivor group. The mean survival time was 12.9 ± 7.9 months for those aged 60 or younger, whereas it was 9.9 ± 7.2 years for those aged 60 or older. According to the Cox regression analysis, higher MTV [relative risk (RR), 1.006; P = 0.03] and mean SUVmax (mSUV) (RR, 1.302; P = 0.03) had a significant impact on shortening of the mean survival time. However, no statistical significance was reached for SUVmax measurements (RR, 0.970; P = 0.39). Furthermore, there was a significant relationship between increased tumor size (andlt;2 cm, 2-4 cm, and ≥4 cm) and shortened mean survival time (P = 0.03). Conclusion: The present study showed that MTV and mSUV of FDG PET/CT scans of the tumor, but not SUVmax, had a significant impact on survival time of patients with NSCLC. Based on this result, we believe that we might have more accurate information about the survival time of our patients if we also evaluate mSUV and MTV in combination with mSUV, which is frequently used for diagnosis and monitoring of patients with NSCLC during our daily practice. © 2015 Wolters Kluwer Health, Inc. All rights reserved.Publication Metadata only 18F-FDG PET/CT texture analysis of anthracotic lymph nodes detected with EBUS and comparison with cytological findings(P.Ziti and Co, 2022) N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; Çağlayan, Benan Niku; Fırat, Pınar Arıkan; Seymen, Hülya; Bulutay, Pınar; Falay, Fikri Okan; Demirtaş, Elif; Demirkol, Mehmet Onur; Meriçöz, Çisel Aydın; Faculty Member; Faculty Member; Teaching Faculty; Teaching Faculty; Teaching Faculty; Master Student; Faculty Member; Teaching Faculty; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Graduate School of Health Sciences; School of Medicine; School of Medicine; 230719; 207545; 350778; 133565; 246484; N/A; 196946; 162418Objective: Lymph node metastasis is the most important factor both in the selection of treatment since many alternatives have been created in recent years, and in the evaluation of prognosis in lung cancer. The most unpredictable cause of lymph node false positivity in fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is anthracosis. The aim of this study is to compare 18F-FDG PET/CT texture information of anthracotic (ALN) and metastatic (MLN) lymph nodes, after re-evaluation of the cytological samples obtained from anthracotic lymph nodes by EBUS-TBNA. Subjects and Methods: Ninety nine patients, 78 of whom had primary lung cancer were included in the study. Two hundred and three lymph nodes from 99 patients sampled by EBUS-TBNA and diagnosed cytologically as ALN or MLN were evaluated retrospectively. All ALN were classified as grades 1, 2 and 3 cytologically. Volume of interest (VOI) of 203 lymph nodes was re-drawn and maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) values were recorded. Results: There was a statistically significant difference in MTV and TLG values in MLN and all ALN grades. However, only grade 1-2 ALNs could be differentiated from MLNs with SUVmax, and no statistically significant difference was found in grade 3 ALN and MLN. Metabolic tumor volume and TLG values over 4.10cm3 and 26.57 showed 60% and 59% sensitivity and 83% and 94 specificity respectively for the identification of MLN. Conclusion: The contribution of MTV and TLG values of 18F-FDG PET/CT to the differential diagnosis of ALN is much more valuable than SUVmax values, especially for grade 3 anthracosis. It was thought that cytological reporting of only grade 3 ALN could make a better contribution to the 18F-FDG PET/CT evaluation analysis.Publication Metadata only 2.3-μm Tm3+: YLF laser passively Q-switched with a Cr2+: ZnSe saturable absorber(Optical Soc Amer, 2017) N/A; N/A; Canbaz, Ferda; Yorulmaz, İsmail; Sennaroğlu, Alphan; PhD Student; PhD Student; Faculty Member; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Sciences; N/A; N/A; 23851We report, what is to our knowledge, the first passively Q-switched operation of a 2.3-mu m Tm3+ : YLF laser by using a Cr2+ : ZnSe saturable absorber. In the experiments, a tunable Ti3+ : sapphire laser was used to end pump the Tm3+ : YLF gain medium inside an x cavity. A Cr2+ : ZnSe saturable absorber was also included in the cavity to initiate passive Q switching. At all pump power levels above lasing threshold, passively Q-switched operation of the Tm3+ : YLF laser could be obtained at 2309 nm with pulse durations and repetition frequencies in the ranges of 1.21.4 mu s and 0.3-2.1 kHz, respectively. Analysis of power dependent repetition rate data further gave an estimated value of 3.1% for the round-trip saturable loss of the Cr2+ : ZnSe saturable absorber.Publication Metadata only 21 fs Cr:LiSAF laser mode locked with a single-walled carbon nanotube saturable absorber(Optical Soc Amer, 2019) Bae, Ji Eun; Rotermund, Fabian; Demirbaş, Ümit; N/A; N/A; N/A; Department of Physics; Tanısalı, Gökhan; Toker, Işınsu Baylam; Taşçı, Mısra; Sennaroğlu, Alphan; PhD Student; PhD Student; Undergraduate Student; Faculty Member; Department of Physics; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; School of Medicine; College of Sciences; N/A; N/A; N/A; 23851We report the shortest femtosecond pulses directly generated from a solid-state laser that is mode locked by using a single-walled carbon nanotube saturable absorber (SWCNT-SA). In the experiments, we used a 660 nm diode-pumped, low-threshold extended-cavity Cr:LiSAF laser operating around 850 nm with a repetition rate of 47.9 MHz. The SWCNT-SA mode-locked Cr:LiSAF laser produced 21 fs pulses with a time-bandwidth product of 0.56 by using only 210 mW of pump power. Pump-probe spectroscopy measurements showed that the SWCNT-SA exhibited saturable absorption with slow and fast decay times of 2.7 ps and 0.4 ps. The single-pass modulation depth and saturation fluence of the SWCNT-SA were further determined as 0.3% and 45 mu J/cm(2) at the pump wavelength of 850 nm.Publication Metadata only 268th ENMC workshop - Genetic diagnosis, clinical classification, outcome measures, and biomarkers in Facioscapulohumeral Muscular Dystrophy (FSHD): Relevance for clinical trials(Elsevier B.V., 2023) Montagnese F, de Valle K, Lemmers RJLF, Mul K, Dumonceaux J, Voermans N; 268th ENMC workshop participants.; Oflazer, Piraye; ; School of Medicine;Highlights This ENMC workshop has seen the participation of many important stakeholders working together to improve trial readiness in FSHD: patients and patients’ organizations (FSHD-Europe, FSHD-Society and FSHD Global), neuromuscular clinicians, geneticists, basic researchers, representatives of the TREAT-NMD network, the FSHD-CTRN and EMA. COMs represent useful tools for the standardized collection of clinical features but need to be selected to match the clinical setting of use. For patient care, they need to be informative, with practical and time efficient utility so as not to detract from clinical care. For clinical trial purposes, the need to be reliable, valid, meaningful and sensitive to change to better depict therapeutic responses. An optimized clinical evaluation and genetic test form is one of the goals of WG1 and 2. A diagnostic flowchart for FSHD1 and FSHD2 has been proposed. Another important unmet need for clinical trial readiness in FSHD is the identification of good therapeutic biomarkers, which ideally should be quantitative, non-invasive, applicable across the entire range of disease severity, sensitive to change, reliable and clinically meaningful. The WG 3 will produce standard operating procedures (SOPs) for DUX4 detection. Similarly, large differences in the reporting of studies performed on animal models, thus hindering interpretation, repeatability and comparison of the results need to be addressed. Guidelines regarding minimum information for publication of work including animal models for FSHD will therefore be published.Publication Metadata only 3D printed biodegradable polyurethaneurea elastomer recapitulates skeletal muscle structure and function(American Chemical Society (ACS), 2021) Gokyer, Seyda; Berber, Emine; Vrana, Engin; Orhan, Kaan; Abou Monsef, Yanad; Guvener, Orcun; Zinnuroglu, Murat; Oto, Cagdas; Huri, Pinar Yilgor; Department of Chemistry; Department of Chemistry; Yılgör, Emel; Yılgör, İskender; Researcher; Faculty Member; Department of Chemistry; College of Sciences; College of Sciences; N/A; 24181Effective skeletal muscle tissue engineering relies on control over the scaffold architecture for providing muscle cells with the required directionality, together with a mechanical property match with the surrounding tissue. Although recent advances in 3D printing fulfill the first requirement, the available synthetic polymers either are too rigid or show unfavorable surface and degradation profiles for the latter. In addition, natural polymers that are generally used as hydrogels lack the required mechanical stability to withstand the forces exerted during muscle contraction. Therefore, one of the most important challenges in the 3D printing of soft and elastic tissues such as skeletal muscle is the limitation of the availability of elastic, durable, and biodegradable biomaterials. Herein, we have synthesized novel, biocompatible and biodegradable, elastomeric, segmented polyurethane and polyurethaneurea (TPU) copolymers which are amenable for 3D printing and show high elasticity, low modulus, controlled biodegradability, and improved wettability, compared to conventional polycaprolactone (PCL) and PCL-based TPUs. The degradation profile of the 3D printed TPU scaffold was in line with the potential tissue integration and scaffold replacement process. Even though TPU attracts macrophages in 2D configuration, its 3D printed form showed limited activated macrophage adhesion and induced muscle-like structure formation by C2C12 mouse myoblasts in vitro, while resulting in a significant increase in muscle regeneration in vivo in a tibialis anterior defect in a rat model. Effective muscle regeneration was confirmed with immunohistochemical assessment as well as evaluation of electrical activity produced by regenerated muscle by EMG analysis and its force generation via a custom-made force transducer. Micro-CT evaluation also revealed production of more muscle-like structures in the case of implantation of cell-laden 3D printed scaffolds. These results demonstrate that matching the tissue properties for a given application via use of tailor-made polymers can substantially contribute to the regenerative outcomes of 3D printed tissue engineering scaffolds.Publication Metadata only 3D printed kombucha biomaterial as a tissue scaffold and L929 cell cytotoxicity assay(Wiley, 2024) Yanbakan, Edaguel; Tuncel, Tugba; Kocak Sezgin, Ayse; Bozoglan, Emirhan; Berikten, Derya; Kar, Fatih; Department of Molecular Biology and Genetics; Bağlan, İlkyaz; Department of Molecular Biology and Genetics; College of SciencesTissue engineering includes the construction of tissue-organ scaffold. The advantage of three-dimensional scaffolds over two-dimensional scaffolds is that they provide homeostasis for a longer time. The microbial community in Symbiotic culture of bacteria and yeast (SCOBY) can be a source for kombucha (kombu tea) production. In this study, it was aimed to investigate the usage of SCOBY, which produces bacterial cellulose, as a biomaterial and 3D scaffold material. 3D printable biomaterial was obtained by partial hydrolysis of oolong tea and black tea kombucha biofilms. In order to investigate the usage of 3D kombucha biomaterial as a tissue scaffold, "L929 cell line 3D cell culture" was created and cell viability was tested in the biomaterial. At the end of the 21st day, black tea showed 51% and oolong tea 73% viability. The cytotoxicity of the materials prepared by lyophilizing oolong and black tea kombucha beverages in fibroblast cell culture was determined. Black tea IC50 value: 7.53 mg, oolong tea IC50 value is found as 6.05 mg. Fibroblast viability in 3D biomaterial + lyophilized oolong and black tea kombucha beverages, which were created using the amounts determined to these values, were investigated by cell culture Fibroblasts in lyophilized and 3D biomaterial showed viability of 58% in black tea and 78% in oolong tea at the end of the 7th day. In SEM analysis, it was concluded that fibroblast cells created adhesion to the biomaterial. 3D biomaterial from kombucha mushroom culture can be used as tissue scaffold and biomaterial.Publication Metadata only 3D printed poly(lactic acid) scaffolds modified with chitosan and hydroxyapatite for bone repair applications(Elsevier, 2020) N/A; N/A; N/A; N/A; Department of Chemistry; Department of Chemical and Biological Engineering; Department of Chemistry; Nazeer, Muhammad Anwaar; Önder, Özgün Can; Sevgili, İlkem; Yılgör, Emel; Kavaklı, İbrahim Halil; Yılgör, İskender; PhD Student; PhD Student; PhD Student; Researcher; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Department of Chemistry; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Sciences; College of Engineering; College of Sciences; N/A; N/A; N/A; N/A; 40319; 241813D printed poly(lactic acid) (PLA) scaffolds surface modified with chitosan (CS) and hydroxyapatite (HA) to produce a novel bioactive composite scaffold is reported. Excellent mechanical properties of PLA, the bioactivity of CS, and osteogenic characteristics of HA are combined to fabricate composite scaffolds using a simple desktop 3D printer. Scaffolds were characterized through attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray (EDX) spectroscopy, X-ray diffraction (XRD) and water contact angle measurements before and after modification. Formic acid was used as a solvent to prepare stable CS/HA dispersions and was found to be a suitable solvent for producing PLA/CS/HA composites. Surface properties of modified scaffolds were superior in terms of hydrophilicity and bioactivity, which resulted in enhanced attachment and proliferation of human osteosarcoma cells in vitro compared to the unmodified PLA scaffolds.Publication Metadata only 3D printed styrax liquidus (liquidambar orientalis miller)-loaded poly (l-lactic acid)/chitosan based wound dressing material: fabrication, characterization, and biocompatibility results(Elsevier, 2023) Cakmak, Hanife Yuksel; Ege, Hasan; Yilmaz, Senanur; Agturk, Gokhan; Enguven, Gozde; Sarmis, Abdurrahman; Cakmak, Zeren; Gunduz, Oguzhan; Ege, Zeynep Ruya; Yöntem, Fulya Dal; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of MedicineThe medicinal plant of Styrax liquidus (ST) (sweet gum balsam) which extracted from Liquidambar orientalis Mill tree, was loaded into the 3D printed polylactic acid (PLA)/chitosan (CS) based 3D printed scaffolds to investigate its wound healing and closure effect, in this study. The morphological and chemical properties of the ST loaded 3D printed scaffolds with different concentrations (1 %, 2 %, and 3 % wt) were investigated by Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FT-IR), respectively. In addition, the me-chanical and thermal properties of the materials were investigated by Tensile test and Differential Scanning Calorimetry (DSC), respectively. The antimicrobial activities of the ST loaded 3D printed scaffolds and their incubation media in the PBS (pH 7.4, at 37 degrees C for 24 h) were investigated on two Gram-positive and two Gram -negative standard pathogenic bacteria with the agar disc diffusion method. The colorimetric MTT assay was used to determine the cell viability of human fibroblast cells (CCD-1072Sk) incubated with free ST, ST loaded, and unloaded 3D printed scaffolds. The 1 % and 2 % (wt) ST loaded PLA/CS/ST 3D printed scaffolds showed an increase in the cell number. Annexin V/PI double stain assay was performed to test whether early or late apoptosis was induced in the PLA/CS/1 % ST and PLA/CS/2 % ST loaded groups and the results were consistent with the MTT assay. Furthermore, a wound healing assay was carried out to investigate the effect of ST loaded 3D printed scaffolds on wound healing in CCD-1072Sk cells. The highest wound closure compared to the control group was observed on cells treated with PLA/CS/1 % ST for 72 h. According to the results, novel biocompatible ST loaded 3D printed scaffolds with antimicrobial effect can be used as wound healing material for potential tissue engineering applications.Publication Metadata only 3D printing of cytocompatible gelatin-cellulose-alginate blend hydrogels(Wiley-V C H Verlag Gmbh, 2020) Erkoc, Pelin; Uvak, Ileyna; Odeh, Yazan Nitham; Akdogan, Ozan; Odeh, Yazan Nitham; Akdogan, Ozan; N/A; Department of Chemistry; Department of Chemical and Biological Engineering; Nazeer, Muhammad Anwaar; Batool, Syeda Rubab; Kızılel, Seda; PhD Student; Researcher; Faculty Member; Department of Chemistry; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of Sciences; College of Engineering; N/A; N/A; 283763D bioprinting of hydrogels has gained great attention due to its potential to manufacture intricate and customized scaffolds that provide favored conditions for cell proliferation. Nevertheless, plain natural hydrogels can be easily disintegrated, and their mechanical strengths are usually insufficient for printing process. Hence, composite hydrogels are developed for 3D printing. This study aims to develop a hydrogel ink for extrusion-based 3D printing which is entirely composed of natural polymers, gelatin, alginate, and cellulose. Physicochemical interactions between the components of the intertwined gelatin-cellulose-alginate network are studied via altering copolymer ratios. The structure of the materials and porosity are assessed using infrared spectroscopy, swelling, and degradation experiments. The utility of this approach is examined with two different crosslinking strategies using glutaraldehyde or CaCl2. Multilayer cylindrical structures are successfully 3D printed, and their porous structure is confirmed by scanning electron microscopy and Brunauer-Emmett-Teller surface area analyses. Moreover, cytocompatibility of the hydrogel scaffolds is confirmed on fibroblast cells. The developed material is completely natural, biocompatible, economical, and the method is facile. Thus, this study is important for the development of advanced functional 3D hydrogels that have considerable potential for biomedical devices and artificial tissues.Publication Metadata only 3D-printed micrometer-scale wireless magnetic cilia with metachronal programmability(American Association for the Advancement of Science, 2023) Zhang, Shuaizhong; Hu, Xinghao; Li, Meng; Bozüyük, Uğur; Zhang, Rongjing; Suadiye, Eylül; Han, Jie; Wang, Fan; Onck, Patrick; Department of Mechanical Engineering; Sitti, Metin; Faculty Member; Department of Mechanical Engineering; College of Engineering; 297104Biological cilia play essential roles in self-propulsion, food capture, and cell transportation by performing coordinated metachronal motions. Experimental studies to emulate the biological cilia metachronal coordination are challenging at the micrometer length scale because of current limitations in fabrication methods and materials. We report on the creation of wirelessly actuated magnetic artificial cilia with biocompatibility and metachronal programmability at the micrometer length scale. Each cilium is fabricated by direct laser printing a silk fibroin hydrogel beam affixed to a hard magnetic FePt Janus microparticle. The 3D-printed cilia show stable actuation performance, high temperature resistance, and high mechanical endurance. Programmable metachronal coordination can be achieved by programming the orientation of the identically magnetized FePt Janus microparticles, which enables the generation of versatile microfluidic patterns. Our platform offers an unprecedented solution to create bioinspired microcilia for programmable microfluidic systems, biomedical engineering, and biocompatible implants.Publication Metadata only 3D-printed micrometer-scale wireless magnetic cilia with metachronal programmability(Amer Assoc Advancement Science, 2023) Zhang, Shuaizhong; Hu, Xinghao; Li, Meng; Bozuyuk, Ugur; Zhang, Rongjing; Suadiye, Eylul; Han, Jie; Wang, Fan; Onck, Patrick; Department of Mechanical Engineering; Sitti, Metin; Department of Mechanical Engineering; College of Engineering; School of MedicineBiological cilia play essential roles in self-propulsion, food capture, and cell transportation by performing coor-dinated metachronal motions. Experimental studies to emulate the biological cilia metachronal coordination are challenging at the micrometer length scale because of current limitations in fabrication methods and ma-terials. We report on the creation of wirelessly actuated magnetic artificial cilia with biocompatibility and meta-chronal programmability at the micrometer length scale. Each cilium is fabricated by direct laser printing a silk fibroin hydrogel beam affixed to a hard magnetic FePt Janus microparticle. The 3D-printed cilia show stable actuation performance, high temperature resistance, and high mechanical endurance. Programmable meta-chronal coordination can be achieved by programming the orientation of the identically magnetized FePt Janus microparticles, which enables the generation of versatile microfluidic patterns. Our platform offers an unprecedented solution to create bioinspired microcilia for programmable microfluidic systems, biomedical en-gineering, and biocompatible implants.Publication Metadata only 5-HT causes splanchnic venodilation(Amer Physiological Soc, 2017) Seitz, Bridget M.; Krieger-Burke, Teresa; Darios, Emma S.; Thompson, Janice M.; Fink, Gregory D.; Watts, Stephanie W.; N/A; Orer, Hakan S.; Faculty Member; School of Medicine; 53477Serotonin [5-hydroxytryptamine (5-HT)] causes relaxation of the isolated superior mesenteric vein, a splanchnic blood vessel, through activation of the 5-HT7 receptor. As part of studies designed to identify the mechanism(s) through which chronic (>= 24 h) infusion of 5-HT lowers blood pressure, we tested the hypothesis that 5-HT causes in vitro and in vivo splanchnic venodilation that is 5-HT7 receptor dependent. In tissue baths for measurement of isometric contraction, the portal vein and abdominal inferior vena cava relaxed to 5-HT and the 5-HT1/7 receptor agonist 5-carboxamidotryptamine; relaxation was abolished by the 5-HT7 receptor antagonist SB-269970. Western blot analyses showed that the abdominal inferior vena cava and portal vein express 5-HT7 receptor protein. In contrast, the thoracic vena cava, outside the splanchnic circulation, did not relax to serotonergic agonists and exhibited minimal expression of the 5-HT7 receptor. Male SpragueDawley rats with chronically implanted radiotelemetry transmitters underwent repeated ultrasound imaging of abdominal vessels. After baseline imaging, minipumps containing vehicle (saline) or 5-HT (25 mu g.kg(-1).min(-1)) were implanted. Twenty-four hours later, venous diameters were increased in rats with 5-HT-infusion (percent increase from baseline: superior mesenteric vein, 17.5 +/- 1.9; portal vein, 17.7 +/- 1.8; and abdominal inferior vena cava, 46.9 +/- 8.0) while arterial pressure was decreased (similar to 13 mmHg). Measures returned to baseline after infusion termination. In a separate group of animals, treatment with SB-269970 (3 mg/kg iv) prevented the splanchnic venodilation and fall in blood pressure during 24 h of 5-HT infusion. Thus, 5-HT causes 5-HT7 receptor-dependent splanchnic venous dilation associated with a fall in blood pressure. NEW & NOTEWORTHY This research is noteworthy because it combines and links, through the 5-HT7 receptor, an in vitro observation (venorelaxation) with in vivo events (venodilation and fall in blood pressure). This supports the idea that splanchnic venodilation plays a role in blood pressure regulation.Publication Metadata only 5-hydroxytryptamine does not reduce sympathetic nerve activity or neuroeffector function in the splanchnic circulation(Elsevier, 2015) Darios, Emma S.; Barman, Susan M.; Morrison, Shaun F.; Davis, Robert P.; Seitz, Bridget M.; Burnett, Robert; Watts, Stephanie W.; N/A; Orer, Hakan S.; Faculty Member; School of Medicine; 53477Infusion of 5-hydroxytryptamine (5-HT) in conscious rats results in a sustained (up to 30 days) fall in blood pressure. This is accompanied by an increase in splanchnic blood flow. Because the splanchnic circulation is regulated by the sympathetic nervous system, we hypothesized that 5-HT would: 1) directly reduce sympathetic nerve activity in the splanchnic region; and/or 2) inhibit sympathetic neuroeffector function in splanchnic blood vessels. Moreover, removal of the sympathetic innervation of the splanchnic circulation (celiac ganglionectomy) would reduce 5-HT-induced hypotension. In anaesthetized Sprague-Dawley rats, mean blood pressure was reduced from 101 ± 4 to 63 ± 3 mm Hg during slow infusion of 5-HT (25 μg/kg/min, i.v.). Pre- and postganglionic splanchnic sympathetic nerve activity were unaffected during 5-HT infusion. In superior mesenteric arterial rings prepared for electrical field stimulation, neither 5-HT (3, 10, 30 nM), the 5-HT1B receptor agonist CP 93129 nor 5-HT1/7 receptor agonist 5-carboxamidotryptamine inhibited neurogenic contraction compared to vehicle. 5-HT did not inhibit neurogenic contraction in superior mesenteric venous rings. Finally, celiac ganglionectomy did not modify the magnitude of fall or time course of 5-HT-induced hypotension when compared to animals receiving sham ganglionectomy. We conclude it is unlikely 5-HT interacts with the sympathetic nervous system at the level of the splanchnic preganglionic or postganglionic nerve, as well as at the neuroeffector junction, to reduce blood pressure. These important studies allow us to rule out a direct interaction of 5-HT with the splanchnic sympathetic nervous system as a cause of the 5-HT-induced fall in blood pressure. © 2015 Elsevier B.V. All rights reserved.Publication Metadata only A 3-year-old child with multi-drug resistant epilepsy responding to pharmacological and nonpharmacological treatments(Taylor & Francis, 2022) Yıldırım, Canan; N/A; Coşkun, Yeşim; Doctor; N/A; Koç University Hospital; N/AIntroduction: Despite the development of new antiseizure drugs (ASDs), around one third of epilepsy patients become refractory to treatment or experience adverse events due to ASDs. Therefore, discovery of new ASDs and new therapy options are crucial to improve the quality of life. Herein, we report a 3-year-old child with multi-drug resistant epilepsy caused by perinatal asphyxia whose seizures were reduced by 90% after the introduction of ketogenic diet, vagal nerve stimulation (VNS) AspireSR (SR-seizure response) and oral cannabidiol.Case presentation: A 9-month-old female infant had a history of multidrug resistant epilepsy due to perinatal asphyxia. At admission, she was experiencing up to 20-25 seizures per day lasting for 2-3 minutes. In addition to antiseizure drugs (ASDs), she was put on ketogenic diet (KD), vagal nerve stimulation (VNS) aspire seizure response (AspireSR) was inserted and oral cannabidiol (CBD) was started sequentially. Using pharmacological and nonph armacological therapies, her seizures have been reduced by 90%.Conclusion: The concurrent use of pharmacological and nonpharmacological therapies may be beneficial to improve seizures in infants with multi- Furthermore, our patient is the youngest child inserted VNS AspireSR in Turkey.Publication Metadata only A 52-year-old man with progressive weakness and incontinence(Sage, 2022) Danyeli, Ayca Ersen; Bozkurt, Subutay Berke; Uysal, Sanem Pinar; Akpek, Sergin; Kahyaoglu, Bulent; Peker, Selcuk; Altıntaş, Ayşe; Aygün, Murat Serhat; Akay, Olga Meltem; Üre, Ümit Barbaros; Ferhanoğlu, Ahmet Burhan; Faculty Member; Teaching Faculty; Faculty Member; Faculty Member; Faculty Member; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; 11611; 291692; 170966; N/A; 18320Here we report a challenging case of a 52-year-old man presenting with subacute constipation, urinary retention, impotence, absent Achilles reflexes, and hypoesthesia in S2-S5 dermatomes. We review the clinical decision-making as the symptoms evolved and diagnostic testing changed over time. Once the diagnosis is settled, we discuss the sign and symptoms, additional diagnostic tools, treatment options and prognosis.Publication Metadata only A Bayesian network analysis to examine the effects of HIV stigma processes on self-concept and depressive symptoms among persons living with HIV(Wiley, 2024) Pala, Andrea Norcini; Department of Psychology; Turan, Bülent; Department of Psychology; College of Social Sciences and HumanitiesObjective: This study examines the relationships between HIV stigma dimensions, self-related mechanisms, and depressive symptoms among persons living with HIV. Background: HIV stigma hinders the well-being of individuals living with HIV, which is linked to depressive symptoms and increased risk of poor clinical outcomes. However, the mechanisms underlying stigma's impact on depression are poorly understood. Psychosocial theories propose that experiencing HIV stigma leads to internalized stigma, impacting self-concept and mental health. Method: Using Bayesian network analysis, we explored associations among HIV stigma processes (experienced, anticipated, internalized, perceived community stigma, and HIV status disclosure) and self-related mechanisms (self-esteem, fear of negative evaluation [FNE], self-blame coping, and social exclusion), and depressive symptoms. Results: Our diverse sample of 204 individuals, primarily men, gay/bisexual, Black, and lower-middle SES, who experienced stigma showed increased anticipated, internalized, and perceived community stigma, FNE, and depressive symptoms. Internalized stigma contributed to self-blame coping and higher depressive symptoms. Anticipated and perceived community stigma and FNE correlated with increased social exclusion. Discussion: This study investigates potential mechanisms through which HIV stigma may impact depression. Identifying these mechanisms establishes a foundation for future research to inform targeted interventions, enhancing mental health and HIV outcomes among individuals living with HIV, especially from minority backgrounds. Insights gained guide evidence-based interventions to mitigate HIV stigma's detrimental effects, ultimately improving overall well-being and health-related outcomes for people with HIV.Publication Metadata only A biallelic ANTXR1 variant expands the anthrax toxin receptor associated phenotype to tooth agenesis(Wiley, 2018) Dinckan, Nuriye; Du, Renqian; Akdemir, Zeynep C.; Bayram, Yavuz; Jhangiani, Shalini N.; Doddapaneni, Harsha; Hu, Jianhong; Muzny, Donna M.; Guven, Yeliz; Aktoren, Oya; Boerwinkle, Eric; Gibbs, Richard A.; Posey, Jennifer E.; Lupski, James R.; Uyguner, Zehra O.; Letra, Ariadne; N/A; Kayserili, Hülya; Faculty Member; School of Medicine; 7945Tooth development is regulated by multiple genetic pathways, which ultimately drive the complex interactions between the oral epithelium and mesenchyme. Disruptions at any time point during this process may lead to failure of tooth development, also known as tooth agenesis (TA). TA is a common craniofacial abnormality in humans and represents the failure to develop one or more permanent teeth. Many genes and potentially subtle variants in these genes contribute to the TA phenotype. We report the clinical and genetic impact of a rare homozygous ANTXR1 variant (c.1312C>T), identified by whole exome sequencing (WES), in a consanguineous Turkish family with TA. Mutations in ANTXR1 have been associated with GAPO (growth retardation, alopecia, pseudoanodontia, and optic atrophy) syndrome and infantile hemangioma, however no clinical characteristics associated with these conditions were observed in our study family. We detected the expression of Antxr1 in oral and dental tissues of developing mouse embryos, further supporting a role for this gene in tooth development. Our findings implicate ANTXR1 as a candidate gene for isolated TA, suggest the involvement of specific hypomorphic alleles, and expand the previously known ANTXR1-associated phenotypes.Publication Metadata only A biallelic mutation links myorg to autosomal-recessive primary familial brain calcification(Oxford University Press (OUP), 2019) Forouhideh, Yalda; Mueller, Kathrin; Ruf, Wolfgang; Assi, Muhannad; Seker, Tuncay; Knehr, Antje; Strom, Tim M.; Gorges, Martin; Schradt, Falk; Meitinger, Thomas; Ludolph, Albert C.; Pinkhardt, Elmar H.; Kassubek, Jan; Uttner, Ingo; Weishaupt, Jochen H.; N/A; Tunca, Ceren; Başak, Ayşe Nazlı; Researcher; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; School of Medicine; N/A; 1512N/A