Gokce Gurler

The Reduced Folate Carrier 1 (RFC1), also called solute carrier family 19 member 1 (SLC19A1/SLC19a1), is recognized for transporting folates across the blood-brain barrier (BBB). RFC1 has recently been defined as a hypoxia-immune related gene whose expression levels were induced by acute retinal ischemia, suggesting that RFC1 may have a role in the response of the brain to ischemic injury. Despite a recent human meta-analysis suggesting an association between certain RFC1 polymorphisms and the risk of silent brain infarctions, preclinical evidence concerning the potential role of RFC1 in acute ischemic stroke has yet to be presented. To investigate this, we first characterized RFC1 protein expression in mouse microvessels and pericytes which play significant roles in stroke pathophysiology. Then, we examined the temporal (1-h, 24-h, and 48-h) and spatial (infarct, periinfarct, contralateral) expression of RFC1 protein in the intraluminal transient middle cerebral artery occlusion mouse model. Finally, we knocked down RFC1 protein with RFC1-siRNA in the potential periinfarct region before induction of ischemia and investigated BBB integrity and infarct size in vivo via 7T-MRI. Moreover, we utilized a pharmacological modulation-methotrexate, a non-covalent inhibitor of RFC1- to further investigate the role of RFC1 in maintaining BBB integrity. Our study revealed that, i) RFC1 protein levels were dynamic throughout the acute phases of ischemic stroke, ii) RFC1 suppression aggravated the BBB leakage during ischemia. These results emphases the role of RFC1 in the pathophysiology of ischemic stroke and supports the evidence from human studies.

Purpose: Muscle weakness and delays in motor development are more common problems in children with neurofibromatosis type 1. Gross Motor Function Measurement-88 is widely used tool to evaluate motor functions in children with developmental disabilities. We aimed to investigate validity of the Gross Motor Function Measurement-88 in a sample of Turkish children with neurofibromatosis type 1. Methods: Aged between 5 to 17 years 40 (20 male/20 female) children with neurofibromatosis type 1. participated in this study. To asses validity of Gross Motor Function Measurement-88, Manual Muscle Test was done seven muscle groups in upper and lower limbs bilaterally by a physical therapist. Results: The mean age was 9.7 ± 3.81 years. A positive moderate to strong correlation was found between Manual Muscle Test and Gross Motor Function Measurement-88 subdomains (r = 0.317-0.668; p <0.05). Conclusion: Gross Motor Function Measurement-88 is a valid measurement for evaluating gross motor functions in children with neurofibromatosis type 1. Identifying motor developmental delays in children with neurofibromatosis type 1 will be a guide for establishing early intervention programs and determining symptom-specific rehabilitation goals. We recommend the use of Gross Motor Function Measurement-88 in children with neurofibromatosis type 1 for evaluating gross motor function.

Background: Reduced folate carrier 1 (RFC1; SLC19a1) is the main responsible transporter for the B9 family of vitamins named folates, which are essential for normal tissue growth and development. While folate deficiency resulted in retinal vasculopathy, the expression and the role of RFC1 in blood-retinal barrier (BRB) are not well known. Methods: We used whole mount retinas and trypsin digested microvessel samples of adult mice. To knockdown RFC1, we delivered RFC1-targeted short interfering RNA (RFC1-siRNA) intravitreally; while, to upregulate RFC1 we delivered lentiviral vector overexpressing RFC1. Retinal ischemia was induced 1-hour by applying FeCl ₃ to central retinal artery. We used RT-qPCR and Western blotting to determine RFC1. Endothelium (CD31), pericytes (PDGFR-beta, CD13, NG2), tight-junctions (Occludin, Claudin-5 and ZO-1), main basal membrane protein (Collagen-4), endogenous IgG and RFC1 were determined immunohistochemically. Results: Our analyses on whole mount retinas and trypsin digested microvessel samples of adult mice revealed the presence of RFC1 in the inner BRB and colocalization with endothelial cells and pericytes. Knocking down RFC1 expression via siRNA delivery resulted in the disintegration of tight junction proteins and collagen-4 in twenty-four hours, which was accompanied by significant endogenous IgG extravasation. This indicated the impairment of BRB integrity after an abrupt RFC1 decrease. Furthermore, lentiviral vector-mediated RFC1 overexpression resulted in increased tight junction proteins and collagen-4, confirming the structural role of RFC1 in the inner BRB. Acute retinal ischemia decreased collagen-4 and occludin levels and led to an increase in RFC1. Besides, the pre-ischemic overexpression of RFC1 partially rescued collagen-4 and occludin levels which would be decreased after ischemia. Conclusion: In conclusion, our study clarifies the presence of RFC1 protein in the inner BRB, which has recently been defined as hypoxia–immune-related gene in other tissues and offers a novel perspective of retinal RFC1. Hence, other than being a folate carrier, RFC1 is an acute regulator of the inner BRB in healthy and ischemic retinas.

Purpose: To assess physical fitness, gross motor capacity, and their relationship in children with neurofibromatosis type 1 (NF1). Materials and Methods: Children with NF1 (n=40, age 6-17, mean 9.70±3.8 years) and typically developing children (TDC) (n= 28, age 5,5-17,5, mean 11.35±3.0 years) were evaluated by the six-minute walking test, sit-up test, sit-and-reach test, flamingo balance test and body mass index. Gross motor capacity was assessed with the Gross Motor Function Measure D and E subdimensions. Results: Physical fitness and gross motor capacity differed significantly between NF1 and TDC (p<0.05). Physical fitness parameters correlated with gross motor capacity to a fair to moderate degree in children with NF1 (r:0.42-0.71; p<0.05). Conclusions: Physical fitness and gross motor capacity are correlated and both are impaired in children with NF1. Exercise programs aiming to increase these functions can be recommended: therefore, areas of intervention can be defined from tests described in this study. Amaç: Nörofibramatozis Tip 1 (NF1) tanılı çocuklarda kaba motor kapasite, ve fiziksel uygunluğu ve birbirleri arasındaki ilişkiyi değerlendirmektir. Yöntem: NF1'li çocuklar (n=40, yaş 6-17, ortalama 9,70±3.8 yıl) ve tipik gelişen çocuklar (TGÇ) (n= 28, yaş 5,5-17,5, ortalama 11,35±3,0 yıl) altı dakikalık yürüme testi, mekik testi, otur-uzan testi, flamingo denge testi ile değerlendirildi ve vücut kitle indeksi hesaplandı. Kaba motor fonksiyon, Kaba Motor Fonksiyon Ölçütü D ve E alt boyutları ile değerlendirildi. Sonuçlar: Fiziksel uygunluk ve kaba motor kapasite NF1 ve TDC arasında anlamlı farklılık gösterdi (p<0,05). Fiziksel uygunluk parametreleri, NF1'li çocuklarda kaba motor kapasitesi ile orta derecede korelasyon gösterdi (r:0,42-0,71; p<0,05). Tartışma: NF1 tanılı çocuklarda fiziksel uygunluk ve motor kapasite etkilenmiştir ve birbirleri ile ilişkilidirler. Etkilenen fonksiyonları arttırmaya yönelik egzersiz programları önerilebilir. Sonuç olarak; müdahale alanları çalışmamızda tanımlanmış testler ile belirlenebilir.

BackgroundThe responsibility of the medical faculties is to educate graduates who are aware and sensitive to the health problems of the society and who can provide preventive and therapeutic health services. All graduates who are expected to improve the health level of society should be provided with fundamental medical values and medical skills. The aim of this study is to evaluate the views of interns of Hacettepe University Faculty of Medicine on the level of achievement of fundamental medical skills stated in the National Medical Education Core Program (NMCP).MethodsIn the 2017-2018 academic year, 39.3% (n = 455) of senior medical students participated in the study. Their views on attitudes and habits related to medicine and their self-assessments about observing, performing and being able to do after graduation basic medical practices stated in the NMCP were evaluated with a survey consisting of 192 questions.ResultsAccording to the results of the survey, almost all of the students want to be a specialist and go to the commercial courses. Anxiety level about performing medical practices after graduation is quite high. When the total of the skills in the NMCP, is reviewed, it is seen that there is a loss of observing, performing and being able to do after graduation between 20-25%.ConclusionsThe study showed that some of the senior medical students who were a few months away from graduation were not sufficient for primary health care services according to the fundamental medical skills defined in the NMCP. It is necessary to investigate which skills are inadequate and the reasons for the inadequacy. It is also important to make the students' positive judgments about themselves and to give them motivation and self-confidence about their professional life.