Research Outputs
Permanent URI for this communityhttps://hdl.handle.net/20.500.14288/2
Browse
317 results
Filters
Advanced Search
Filter by
Settings
Search Results
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 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 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/APublication Metadata only A case of drop foot due to piriformis syndrome(Springer Heidelberg, 2015) Yıldırım, Pelin; Güler, Tuba; Özer, Tülay; Gündüz, Osman Hakan; N/A; Mısırlıoğlu, Tuğçe Özekli; Doctor; N/A; Koç University Hospital; 175999N/APublication Metadata only A case-control candidate gene study on base excision repair mechanism (BER) as a novel therapeutic target in bipolar disorder(Wiley, 2022) Ozerdem, Aysegul; Veldic, Marin; Singh, Balwinder; Frye, Mark; Schulze, Thomas; Biernacka, Joanna; Winham, Stacey J.; N/A; Ceylan, Deniz; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 137755N/APublication Metadata only A combined clinical and computational approach to understand the SOD1(A4T)-mediated pathogenesis of rapidly progressive familial amyotrophic lateral sclerosis(Springer Heidelberg, 2022) Diker, Sevda; Gelener, Pınar; Teralı, Kerem; Ergören, Mahmut Çerkez; Ersin, Tan; N/A; 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; 1512Here, we aim to provide a comprehensive clinical and biomolecular description of familial amyotrophic lateral sclerosis (fALS) in a 25-year-old female patient with respect to the SOD1(A4T) genotype. The clinical diagnosis of the disease was based on family history, neurological examination, electroneurophysiological studies, and revised El Escorial criteria. The heterozygous presence of the A4T mutation in the proband was confirmed by PCR coupled with Sanger sequencing of exon 1 of the SOD1 gene. The mutation was introduced in silico into the three-dimensional structure of the native protein. After energy minimization and quality assessment, non-covalent interactions around threonine-4 and changes in protein stability were calculated computationally. The patient differed widely in age at onset, initial neurological symptoms and findings, and survival time from her kindred, in which several members are affected. SOD1(A4T)-linked fALS in this case had bulbar involvement at onset, a combination of lower and upper motor neuron signs and showed rapid progression. Unlike alanine-4, threonine-4 failed to engage in hydrophobic interactions with the vicinal non-polar amino acids. The overall fold of the modeled SOD1(A4T) mutant remained intact, but unfolding free energy estimations disclosed a decrease in the protein's stability. We report a phenotypically distinct patient with fALS due to the SOD1(A4T) mutation and further expand the largest pedigree ever published for SOD1(A4T)-linked fALS. Genotype-phenotype correlation in fALS is complex, and it demands detailed clinical investigation and advanced scientific research. Awareness of the broadened phenotypic spectrum might potentially enhance the diagnosis and genetic counseling of fALS.Publication Metadata only A combined clinical and computational approach to understand the sod1a4t-mediated pathogenesis of rapidly progressive familial amyotrophic lateral sclerosis(Wiley, 2019) Gelener, P.; Diker, S.; Ergoren, M. C.; Terali, K.; Tan, E.; N/A; Başak, Ayşe Nazlı; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 1512Here, we aim to provide a comprehensive clinical and biomolecular description of familial amyotrophic lateral sclerosis (fALS) in a 25-year-old female patient with respect to the SOD1A4T genotype. The clinical diagnosis of the disease was based on family history, neurological examination, electroneurophysiological studies, and revised El Escorial criteria. The heterozygous presence of the A4T mutation in the proband was confrmed by PCR coupled with Sanger sequencing of exon 1 of the SOD1 gene. The mutation was introduced in silico into the three-dimensional structure of the native protein. After energy minimization and quality assessment, non-covalent interactions around threonine-4 and changes in protein stability were calculated computationally. The patient difered widely in age at onset, initial neurological symptoms and fndings, and survival time from her kindred, in which several members are afected. SOD1A4T-linked fALS in this case had bulbar involvement at onset, a combination of lower and upper motor neuron signs and showed rapid progression. Unlike alanine-4, threonine-4 failed to engage in hydrophobic interactions with the vicinal non-polar amino acids. The overall fold of the modeled SOD1A4T mutant remained intact, but unfolding free energy estimations disclosed a decrease in the protein’s stability. We report a phenotypically distinct patient with fALS due to the SOD1A4T mutation and further expand the largest pedigree ever published for SOD1A4T-linked fALS. Genotype‒phenotype correlation in fALS is complex, and it demands detailed clinical investigation and advanced scientifc research. Awareness of the broadened phenotypic spectrum might potentially enhance the diagnosis and genetic counseling of fALS.Publication Metadata only A comparative study on thyroid function in alzheimer's disease: results from a Turkish multi-centre study(Journal Neurological Sciences, 2015) Yılmaz, Gökhan; Erbayraktar, Zübeyde; Evlice, Ahmet; Genç, Metin; Aras, Sevgi; Avcı, Aslıhan; Yener, Görsev; Ulusu, Nuriye Nuray; Faculty Member; School of Medicine; 6807Alzheimer's disease is a very severe degenerative disease that affects brain function. Neuronal loss, accumulation of extracellular amyloid beta containing plaques and accumulation of intracellular (tau) neurofibrillary tangles are the hallmarks of this disease. We aim to investigate serum thyroid function tests in Alzheimer's disease, in addition to other dementias, and geriatric Turkish patients. We evaluated patients from Ankara, Dokuz Eylul, Cukurova University Hospitals. 357 female and male geriatric subjects were enrolled. All the cases were selected from three different geographical regions irrespective of sex and socioeconomic status. In this study, we evaluated the results of thyroid functions in Alzheimer disease patients as well as in other dementias and geriatric patients. In patients from Ankara, Central Anatolia region, no significant difference between groups regarding the routine control of biochemical parameters was observed. However, thyroid function results revealed that hypothyroidism in Alzheimer's disease patients from Mediterranean region, Adana and Aegean region, Izmir is a recurrent medical condition and is often an embedded side of the normal aging process. We concluded that currently, routine thyroid functions tests should be a part of all geriatric patients for screening presymptomatic Alzheimer's disease. There might be an interplay between reduced thyroid function and Alzheimer's disease that could be exploited for diagnostic purposes.Publication Metadata only A decision model of timing(Elsevier Science Bv, 2016) Simen, Patrick; Department of Psychology; Balcı, Fuat; Faculty Member; Department of Psychology; College of Social Sciences and Humanities; 51269The fundamental assumption of pacemaker accumulator models of interval timing is that timed behavior relies on the accumulation of brain-derived clock signals. Following this theoretical tradition, a recent series of interval timing models has formulated the processing dynamics of timing behavior within the drift-diffusion decision theoretic framework, which has been traditionally applied to explain accuracy and response times in perceptual decision making. The generative processes assumed by these models and their key features can be implemented by neural populations given simple assumptions, and their predictions have received recent support from electrophysiological studies. This paper discusses the conceptual links of the diffusion model of interval timing to other prominent timing models and interprets recent electrophysiological evidence in relation to its predictions.Publication Metadata only A developmental study of glutamatergic neuron populations in the ventrobasal and the lateral geniculate nucleus of the thalamus: Comparing Genetic Absence Rats from Strasbourg (GAERS) and normal control wistar rats(Elsevier, 2017) Kirazhi, Ozlem; Yildizel, Sercan; Onat, Filiz; Kaptanoglu, Erkan; Çavdar, Safiye; Faculty Member; School of Medicine; 1995An imbalance of GABAergic inhibition and glutamatergic excitation is suspected to be the cause of absence epileptic seizures. Absence seizures are known to be generated in thalamocortical circuitry. In the present study we used light microscopy immunohistochemistry to quantify the density of glutamate+ve neurons at two developmental stages (P10 and P60) in two thalamic nuclei, the ventrobasal (VB) and lateral geniculate nucleus (LGN) in Wistar rats and compared the results with similar data obtained from genetic absence epilepsy rats from Strasbourg (GAERS). Rats were perfused transcardially with glutaraldehyde and paraformaldehyde fixative, then samples from VB and LGN were removed from each animal and sectioned. The glutamatergic neurons were labelled using light-microscopic glutamate immunohistochemistry. The disector method was used to quantify the glutamate+ve neurons in VB and LGN of GAERS and Wistar rats. The data were statistically analyzed. The distribution of the glutamate+ve neurons in the VB thalamic nucleus showed a significant reduction in the neuronal profiles per unit thalamic area from P10 to P60 in both Wistar and GAERS. The decrease was greater in the GAERS compared to the Wistar animals. However, in the LGN no reduction was observed either in the Wistar or in the GAERS. Comparing the density of glutamate+ve neurons in the VB thalamic nucleus of P10 of Wistar animals with of P10 GAERS showed statistically significant greater densities of these neurons in GAERS than in the Wistar rats. However no significant difference was present at P60 between the Wistar and GAERS animals. The disproportional decrease in GAERS may be related to the onset of absence seizures or may be related to neurogenesis of absence epilepsy. (C) 2016 ISDN. Published by Elsevier Ltd. All rights reserved.