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Objective: A global approach to factors responsible for functional impairment in patients with BD is necessary., Method: Ninety-three euthymic patients with BD [49 patients with SD (subthreshold depression) and 44 patients without SD] and 48 healthy controls were invited for evaluation of demographic, clinical, and cognitive characteristics. To define SD, the lower limit was HDRS ≥4 points and the upper limit was HDRS <9 points. Stroop test, California verbal learning test, digit-span test, controlled word association test, and clock drawing test were performed. Serum BDNF levels were measured. Additionally in the BD group; blood drug (lithium, valproic acid), leukocyte, C-reactive protein (CRP), TSH, and vitamin B12 levels were measured., Results: We found no difference between serum BDNF levels of BD ( n  = 93) and controls. The cognitive performances of the BD group were worse than the control group ( p  < 0.001). Attention, working memory, and stroop performance of patients with SD were worse than patients without SD ( p  < 0.05). Verbal fluency, stroop test, and planning performance decreased as serum CRP level increased in patients with BD ( p  < 0.05)., Conclusions: Although the patient group with SD was in euthymia, their cognitive performance was worse than the group without SD. Poor cognitive performance in BD was associated with serum CRP levels.

Objective: This study aimed at investigating whether there is a relationship between 7- or 30-day mortality and mean platelet volume, platelet distribution width, platelet count-to-total lymphocyte count ratio, or red cell distribution width in patients with traumatic brain injury., Methods: We retrospectively analyzed intensive care unit patients with traumatic brain injury. We recorded patients' ages; genders; diagnoses; Glasgow Coma Scale scores; length of intensive care unit stay (in days); mean platelet volume, platelet distribution width, platelet count-to-total lymphocyte count ratio, and red cell distribution width values upon hospital admission; and health on the 7th and 30th days of their stays., Results: We analyzed data from 110 patients. Of these, 84 (76.4%) were male and 26 (23.6%) were female. On the 7- and 30-day mortality evaluations, compared to the living patients, the deceased patients had a significantly higher median age and a significantly lower median Glasgow Coma Scale. Thus, increased age and lower Glasgow Coma Scale scores were associated with increased 7- and 30-day mortality rates. mean platelet volume and platelet distribution width values were similar in living and deceased patients. platelet count-to-total lymphocyte count ratio values were lower in deceased patients, but this difference was not statistically significant. Within 30 days after traumatic brain injury, deceased patients' red cell distribution width values were significantly elevated in deceased patients compared to those of living patients., Conclusion: Mean platelet volume, platelet distribution width, and platelet count-to-total lymphocyte count ratio values were not associated with 7- and 30-day mortality, whereas only elevated red cell distribution width was associated with 30-day mortality.

Competing Interests: There are no conflicts of interest.

Objective: Unipolar mania is not included in the diagnostic and statistical manual of mental disorders-5 (DSM-5) as a separate diagnosis, although it is defined by widely accepted diagnostic criteria. The aim of this study was to investigate the differences between unipolar mania and bipolar disorder in terms of clinical and inflammatory parameters., Methods: The data of 495 hospitalised patients with bipolar disorder diagnoses were analysed retrospectively. Forty met the diagnostic criteria for unipolar mania. Two patients refused to participate in the study. Thirty-eight unipolar mania patients and 42 randomly selected patients with bipolar disorder diagnosis were included in the study. The two groups were compared in terms of sociodemographic, clinical characteristics, serum brain-derived neurotrophic factor, C-reactive protein (CRP), leucocyte and cytokine levels., Results: A total of 40 (8.08%) of 495 patients diagnosed with bipolar disorder met the unipolar mania diagnostic criteria. The number of manic episodes and the number of hospitalisations were statistically higher in the unipolar mania group than in the bipolar disorder group. Among all the manic symptoms, the incidence of symptoms such as euphoria, increased sexual interest, grandiosity and delusions were found to be statistically higher in the unipolar mania group. Interleukin (IL)-6 and CRP levels were significantly higher in the unipolar mania group than in the bipolar disorder group., Conclusion: Unipolar mania differs from bipolar disorder in terms of clinical features and serum IL-6 and CRP levels.

Background: Chronic postsurgical pain is an important problem for both children and adults. This study aims to investigate the prevalence of chronic postappendectomy pain (CPAP) in children and its social and physical effects., Methods: This prospective observational study was conducted on children aged 8-18 years who had undergone open appendectomies. In the sixth month after the surgical procedure, the presence of chronic pain was examined in the lower right abdominal area. CPAP and its effects on children's daily life activities were assessed using the numeric rating scale (NRS) and the Pediatric Quality of Life Scale (PedsQL)., Results: Analysis was performed on 158 children, 97 of whom were boys (61.4%) and 61 were girls (38.6%). The average age was 12.8 ± 3 years, the average NRS was 4.48 ± 1.1, and the average scar length was 6.09 ± 1.6 cm. Twenty-nine children described CPAP, and its prevalence at six months after the surgery was 18.4%. Of these, 16 (55.2%) complained of pain only during exercise and 13 (44.8%) experienced pain while resting. The rate of CPAP was significantly higher in girls. Female gender and longer scar length were associated with the development of chronic pain. The PedsQL scores from the children's self-reports and their parents' reports were significantly lower for children who described CPAP as compared to those without CPAP., Conclusion: CPAP occurs quite frequently in children, especially in girls, and negatively affects children's quality of life., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Onur Palabiyik and Gurkan Demir.)

In the setting of acute myocardial infarction (AMI), adverse myocardial remodeling (AMR) has been universally regarded as an early-onset phenomenon generally arising within the first few weeks (usually within days in the infarct zone) following myocardial injury. On the other hand, onset of cardiac morphological changes in this setting may potentially extend far beyond this time frame (usually beyond several months after the index AMI), suggesting a prolonged latent period in certain cases. In clinical practice, this delayed form of post-AMI remodeling, namely late AMR, has emerged as an interesting and underrecognized phenomenon with poorly understood mechanisms. Notably, systemic inflammation and associated growth factors seem to play a pivotal role in this setting. Accordingly, the present article primarily aims to discuss potential mechanisms and clinical implications of late AMR (in a comparative manner with its classical early counterpart) among AMI survivors along with a particular emphasis on potential benefits of certain anti-inflammatory strategies in this setting.

Athletes misuse recombinant human growth hormone (r-hGH) to enhance their performance. Although r-hGH is known to increase cardiac hypertrophy, the underlying molecular mechanism remains unclear. The aim of the present study was to investigate the role of r-hGH in cardiac intracellular signaling pathways and of miR-21 and miR-133 expression in rat hearts during exercise. A total of 36 adult male Sprague-Dawley rats were divided into sedentary control (SC, n=9), swimming exercise (SE, n=8), r-hGH (GH, n=10) and swimming exercise plus r-hGH (SE-GH, n=9) groups. The exercise groups completed a 1-h swimming exercise 5 times a week for 8 weeks. Subcutaneous r-hGH was administered as 0.3 mg/kg/day. Phosphoinositide-3-kinase (PI3K), serine/threonine protein kinase 1 (AKT1), extracellular signal-regulated kinase (ERK), microRNA (miR)-21 and miR-133 expression was evaluated in ventricular muscle by real-time quantitative polymerase chain reaction. Protein expression of PI3K, AKT1, ERK and mechanistic target of rapamycin (mTOR) was also assessed by immunohistochemistry. Statistical differences were analyzed by two-way ANOVA. PI3K and AKT1 expression and the gene and protein levels was notably increased in the SE-GH group compared with in SC ventricular tissues (P<0.05). mTOR protein expression was higher in the GH, SE and SE-GH groups compared with in the SC group (P<0.05, <0.05 and <0.001, respectively). ERK gene/protein expression was similar across all groups. miR-21 and miR-133 levels in ventricular muscle were higher in the SE and GH groups than those in the SC group. In summary, growth hormone application coupled with swimming exercise appeared to affect the PI3K/AKT/mTOR signaling pathway in the left ventricular tissue of rats; however, ERK signaling pathway appeared inactive in physiological left ventricular hypertrophy caused by swimming and GH administration over 8 weeks. Furthermore, GH treatment resulted in increased miR-21 and miR-133 expression. Future study by our group will aim to assess the effects of higher dose GH treatment.

Over recent decades, the prevalence of aortic valve stenosis (AVS) has been constantly increasing possibly owing to the aging of general population. Severe AVS as determined by an aortic valve area (AVA) of <1 cm 2 has been regarded as a serious clinical condition potentially associated with a variety of adverse outcomes, including sudden cardiac death (SCD). However, patients with severe AVS (in the absence of overt high-risk features) are usually evaluated and managed exclusively based on symptomatology or imperfect prognostic tools including exercise testing and biomarkers, with a potential risk of mismanagement, suggesting the need for further objective risk stratifiers in this setting. Within this context, copeptin (C-terminal pro-vasopressin), a novel neurohormone widely considered as the surrogate marker of the arginine-vasopressin (AVP) system, may potentially serve as a reliable prognostic and therapeutic guide (e.g. timing of aortic valvular intervention) in patients with severe AVS largely based on its hemodynamic, fibrogenic as well as autonomic implications in these patients. Accordingly, the present paper aims to discuss clinical and pathophysiological implications of copeptin in the setting of AVS along with a summary of biomarkers and other prognostic tools used in this setting.

Background: The aim of this study is to assess the effect of sugammadex on postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic cholecystectomy., Methods: Eighty patients who were scheduled for elective laparoscopic cholecystectomy surgery were enrolled in this prospective study. Patients were randomly assigned to neostigmine (group N) or sugammadex (group S) for neuromuscular antagonism at the end of anesthesia. The incidence of PONV and antiemetic consumption were recorded., Results: Nausea and vomiting were observed in 60% of the patients given sugammadex and 77.5% given neostigmine during the initial 24 hours postoperatively. The incidence of nausea and the need for rescue antiemetic were lower in group S than group N during all time intervals but there were no significant differences between the groups., Conclusions: Sugammadex seems to be effective in decreasing the incidence of PONV, severity of nausea, number of patients who suffered from nausea and vomiting, and need for rescue antiemetic, although there were no significant differences.

The aim of the study is to determine the effect of nursing students making short films about mental health disorders in preventing stigmatization of the mentally disordered patient. Students, under the supervision of the faculty member who taught the course, worked in groups; each group wrote the script for and then produced and showed the film. Each student performed in one film. Students wrote scenarios about preventing stigmatization of the mentally disordered patient after receiving theoretical education about this topic. The films were completed in a month. Short films made by students were evaluated based on their titles. The titles reveal that the films were mainly concerned with social problems. It is remarkable that students performed in an empathetic way particularly when discussing psychopathology and that they emphasized the attitudes of the families. Students wrote themselves scenarios, performed role-sharing, and employed visual displays, which showed that they were against stigmatization. This study concluded that short films about mental health disorders made by students have a positive effect on preventing stigmatization of the mentally disordered patient., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Differentiated thyroid carcinomas (DTC) account for most of the thyroid cancers. The emergence of DTC may be affected by various predisposing genetic alterations and environmental factors The aim of this study was to investigate the role of VEGF C936T and IL-8 A251T gene polymorphisms in the pathogenesis and metastasis of differentiated thyroid cancer., Methods: The study consisted of 101 patients DTC patients and 109 healthy controls. The parameters of the stage of cancer of the DTC patients at the time of diagnosis (TNM) were recorded. DNA was isolated from blood using a DNA isolation kit. VEGF C936T and IL-8 A251T gene polymorphisms were determined using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. Distributions of gene polymorphisms were evaluated according to the Hardy-Weinberg principle., Results: The TT genotype from the VEGF C936T genotype distributions was higher in the control group than in the DTC group (p < 0.05). In contrast, the IL-8 A-251T genotype distributions were similar in both groups. No relationship was found between either cytokine gene polymorphism or the DTC stages. The frequency of IL-8 TT was higher in the DTC group with lymph gland metastasis (TT 92%) than in the group without lymph gland metastasis (TT 45.9%) (p < 0.05)., Conclusions: We consider that the VEGF 936 TT genotype may play a protective role in the development of DTC and that the IL-8 A-251 TT genotype may contribute to the DTC lymph node metastasis. Therefore, these genotypes may hold a key to the evaluation of thyroid nodules and the metastasis of DTC.

High-protein (HP) diets are commonly consumed by athletes despite their potential health hazard, which is postulated to enforce a negative effect on bone and renal health. However, its effects on heart have not been known yet. Aquaporin-7 (AQP7) is an aquaglyceroporin that facilitates glycerol and water transport. Glycerol is an important cardiac energy production substrate, especially during exercise, in conjunction with fatty acids and glucose. Glucose transporter 4 (GLUT4) is an insulin-sensitive glucose transporter in heart. We aimed to investigate the effect of HPD on AQP7 and GLUT4 levels in the rat heart subjected to exercise. Male Sprague-Dawley rats were divided into control (n = 12), exercise (E) training (n = 10), HPD (n = 12), and HPD-E training (n = 9) groups. The HPD groups were fed a 45 % protein-containing diet 5 weeks. The HPD-E and E groups were performed the treadmill exercise during the 5-week study period. Real-time polymerase chain reaction and immunohistochemistry techniques were used to determine the gene expression and localization of AQP7 and GLUT4 in heart tissue. Results of relative gene expression were calculated by the 'Pfaffl' mathematical method using the REST program. Differences in AQP7 and GLUT4 gene expression were expressed as fold change compared to the control group. Heart weight/tibia ratio and ventricular wall thickness were evaluated as markers of cardiac hypertrophy. Further, serum glucose, glycerol, and insulin levels were also measured. AQP7 gene expression was found to be increased in the E (3.47-fold, p < 0.001), HPD (5.59-fold, p < 0.001), and HPD-E (3.87-fold, p < 0.001) groups compared to the control group. AQP7 protein expression was also increased in the HPD and HPD-E groups (p < 0.001). Additionally, cardiac mRNA expression levels of GLUT4 showed a significant increase in the E (2.16-fold, p < 0.003), HPD (7.14-fold, p < 0.001), and HPD-E (3.43-fold, p < 0.001) groups compared to the control group. GLUT4 protein expression was significantly increased in the E, HPD, and HPD-E groups compared to the control group (p = 0.024, p < 0.001, and p < 0.001, respectively). Furthermore, Serum glucose levels were significantly different between groups (p < 0.005). This difference was observed between the HPD groups and normal-protein diet groups (C and E). Serum insulin levels were higher for HPD groups compared with the normal-protein diet groups (p < 0.001), whereas no differences were observed between the exercise and sedentary groups (p = 0.111). Serum glycerol levels were significantly increased in the HPD groups compared with control and E groups (p < 0.05 and p < 0.05, respectively). Consumption of HPD supplementation caused the increased effects on AQP7 and GLUT4 expression in rat heart.

The aim of this study was to investigate the effect of controlled hypotension on cerebral oxygen saturation (rSO2) using near infrared spectroscopy (NIRS) and evaluation of postoperative cognitive function in patients undergoing rhinoplasty. Fifty adult patients who were scheduled for elective rhinoplasty surgery and required controlled hypotension were enrolled in this prospective study. Controlled hypotension was provided using a combination of propofol and remifentanil infusion supplemented with nitroglycerin infusion as necessary. rSO2 was evaluated during controlled hypotension by NIRS. Cerebral desaturation was observed in 5 out of 50 patients (10 %) during hypotensive anesthesia. The greatest decrease from baseline was 28 % when MAP was 57 mmHg. In both non-desaturated and desaturated patients, postoperative MMSE scores were significantly lower than preoperative scores. There was a 4 % decrease in the non-desaturated patients and a 7 % decrease in the desaturated patients when preoperative and postoperative MMSE scores were compared. A decline in cognitive function 1 day after surgery was observed in 23 patients (46 %) and in all patients with intraoperative cerebral desaturation. The current study showed that even if SpO2 is in the normal range, there might be a decrease of more than 20 % in cerebral oxygen saturation during controlled hypotension.

Long-term effects of high protein diets (HPDs) on kidneys are still not sufficiently studied. Irisin which increases oxygen consumption and thermogenesis in white fat cells was shown in skeletal muscles and many tissues. Nitric oxide synthases (NOS) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. We aimed to investigate the effects of HPD, irisin and NO expression in kidney and relation of them with exercise and among themselves. Animals were grouped as control, exercise, HPD and exercise combined with HPD (exercise-HPD). Rats were kept on a HPD for 5 weeks and an exercise program was given them as 5 exercise and 2 rest days per week exercising on a treadmill with increasing speed and angle. In our study, while HPD group had similar total antioxidant capacity (TAC) levels with control group, exercise and exercise-HPD groups had lower levels (p < 0.05). Kidneys of exercising rats had no change in irisin or eNOS expression but their iNOS expression had increased (p < 0.001). HPD-E group has not been observed to cause kidney damage and not have a significant effect on rat kidney irisin, eNOS, or iNOS expression. Localization of irisin, eNOS, and iNOS staining in kidney is highly selective and quite clear in this study. Effects of exercise and HPD on kidney should be evaluated with different exercise protocols and contents of the diet. İrisin, eNOS, and iNOS staining localizations should be supported with various research studies.

Background and Objectives: Laparoscopic surgery has become a popular surgical tool when compared to traditional open surgery. There are limited data on pediatric patients regarding whether pneumoperitoneum affects cerebral oxygenation although end-tidal CO2 concentration remains normal. Therefore, this study was designed to evaluate the changes of cerebral oxygen saturation using near-infrared spectroscope during laparoscopic surgery in children., Methods: The study comprised forty children who were scheduled for laparoscopic (Group L, n=20) or open (Group O, n=20) appendectomy. Hemodynamic variables, right and left regional cerebral oxygen saturation (RrSO2 and LrSO2), fraction of inspired oxygen, end-tidal carbon dioxide pressure (PETCO2), peak inspiratory pressure (Ppeak), respiratory minute volume, inspiratory and end-tidal concentrations of sevoflurane and body temperature were recorded. All parameters were recorded after anesthesia induction and before start of surgery (T0, baseline), 15min after start of surgery (T1), 30min after start of surgery (T2), 45min after start of surgery (T3), 60min after start of surgery (T4) and end of the surgery (T5)., Results: There were progressive decreases in both RrSO2 and LrSO2 levels in both groups, which were not statistically significant at T1, T2, T3, T4. The RrSO2 levels of Group L at T5 were significantly lower than that of Group O. One patient in Group L had an rSO2 value <80% of the baseline value., Conclusions: Carbon dioxide insufflation during pneumoperitoneum in pediatric patients may not affect cerebral oxygenation under laparoscopic surgery., (Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Background: Neostigmine, the currently commonly used agent for reversal of neuromuscular blockade. Sugammadex is a novel and unique compound designed as an antagonist of steroidal neuromuscular blockers. In this study, we evaluated the effects of sugammadex or neostigmine on kidney functions in patients scheduled for elective surgery., Material/methods: Patients scheduled for a surgical procedure under desflurane/opioid anesthesia received an intubating dose rocuronium. Patients were divided into 2 groups receiving either sugammadex or neostigmine atropine to reverse neuromuscular blockade. Cystatin C, creatinine, urea, blood urea nitrogen, sodium, potassium, and calcium levels in the blood and α1microglobulin, β2microglobulin, and microalbumin levels in the urine were measured., Results: There was no significant difference between the groups with regard to the demographic data. In the Neostigmine Group, although β2microglobulin and microalbumin were similar, a significant increase was found in the postoperative α1microglobulin and cystatin C values. In the Sugammadex Group, although β2-microglobulin and cystatin C were similar, a significant increase was found in the postoperative α1-microglobulin and microalbumin values. The only significant difference was cystatin C value variation in the Neostigmine Group compared to the Sugammadex Group., Conclusions: We believe that the use of more specific and sensitive new-generation markers like cystatin C to evaluate kidney function will provide a better understanding and interpretation of our results. Sugammadex has more tolerable effects on kidney function in patients than does neostigmine. However, when compared to preoperative values, there is a negative alteration of postoperative values. Neostigmine and sugammadex do not cause renal failure but they may affect kidney function.

Background/aim: Atrial natriureticpeptide (ANP) is known as a protective agent against ischemia-reperfusion injuryfor cardiomyocytes. We compared the hemodynamic effects of ANP and isatin, which is known as an ANP receptor blocker, in ischemia followed by reperfusion in exercised rat hearts with nonexercised ones., Materials and Methods: Isolated hearts were perfused in 4 exercised (E) groups after a running protocol for 5 days and 4 nonexercised (NE) groups. In the first protocol, ANP was added to the perfusion solution before ischemia in an E and NE group. In the second protocol, different doses of isatin (0.1, 10, 100 µM/L) were added to the perfusion solution before ANP in 3 E and 3 NE groups. Left ventricular developed pressure (LVDP) and maximum and minimum rates of change in left ventricular pressure (dP/dtmax and dP/dtmin) were recorded., Results: Higher LVDP and dP/dtmin values were observed in the E group than the NE group following addition of ANP before ischemia. Values of dP/dtmax were higher in the E group at the first minute of reperfusion period. Hemodynamic difference was not observed between groups given the same amount of isatin before ANP., Conclusion: This study indicated that higher ANP concentrations before ischemia were more effective on the left ventricle contractility and relaxation functions in the hearts that were exposed to exercise.

Coronary artery disease (CAD) is one of the frequent cardiovascular mortality causes in the world. Common risk factors explain only about half the risk of CAD. The healthy familial predisposition to CAD, combined with advances in genetic analysis, has led to a number of studies in recent years making an effort to identify the genetic factors that influence the risk. The approach taken by most studies was to examine the association of naturally occurring genetic polymorphisms in candidate genes with risk of or severity of CAD. Endothelial nitric oxide synthase (eNOS) is important for vascular and tissue protection and is found in endothelial cells that encompass the entire vasculature, including the vessels in the heart. Nitric oxide (NO) is produced in a catabolic reaction in the endothelial cells, neurons, glia and macrophages by nitric oxide synthase (NOS) isoenzymes. eNOS is a subgroup of this family of enzymes that catalyses the production of nitric oxide (NO) from L-arginine and oxygen, which leads to vascular relaxation by activating the guanylate cyclase. This finally induces smooth muscle relaxation. The aim of this study was to investigate the allelic frequency and the genotypic distribution of the variable number of tandem repeat 27 (27 VNTR) gene polymorphism in intron 4 of the eNOS (eNOS 4a/b) gene in Thrace region, to compare CAD patients with appropriate healthy controls and to correlate the genetic findings with CAD subtypes. The study group included 281 (153 subjects with CAD and 128 controls) patients. The eNOS polymorphism was identified with a polymerase chain reaction. Genotypes were defined as aa, ab and bb according to the presence of a and b alleles. In this case-control study, we found that there was sensible correlation between eNOS gene intron 4a/b VNTR polymorphism and the risk of CAD in Thrace region of Turkey. However, there was no major difference for the genotype distribution and the allelic frequency among the CAD subtypes. Further studies on the interaction of such genes are needed to clarify the association between eNOS 4a/b polymorphism and CAD patients.

Introduction: In this study, we investigated the association of migraine with the Variable Number of Tandem Repeats (VNTR), repeated as 27 base pair, gene polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) and the insertion/deletion of angiotensin converting enzyme (ACE) gene polymorphisms., Methods: One hundred and five migraine and ninety seven healthy female control subjects were enrolled in the study. The patients were subdivided as migraine with aura and without aura, and the frequency and severity of migraine headaches were recorded. The eNOS VNTR (eNOS 4 a/b) and ACE insertion/deletion gene polymorphisms (ACE I/D) were assessed by polymerase chain reactions., Result: The allele and genotype frequencies of eNOS 4 a/b gene polymorphism showed no difference between the migraine and control groups. The genotypic distribution of the ACE I/D gene polymorphism in the migraine group significantly differed from that in the control group. The DD and ID genotype increased the risk of migraine as much as 2.571 (95% CI-1.138-5.811) and 4.453 (95% CI-2.006-9.883) compared to the II genotype. The same increased risk sustained for both genotypes in the migraine with aura subgroup, but only the ID genotype remained as the risk factor in the migraine without aura subgroup (OR-3.750, 95% CI-1.493-9.420). No association of gene polymorphisms with migraine frequency and severity was observed., Conclusion: Our findings support the relationship between migraine and the ACE I/D gene polymorphism. However, no association was found between migraine and the eNOS 4 a/b gene polymorphism., Competing Interests: Conflict of interest: The authors reported no conflict of interest related to this article. Çıkar çatışması: Yazarlar bu makale ile ilgili olarak herhangi bir çıkar çatışması bildirmemişlerdir.