Publications by authors named "Hulya Karatas"

40 Publications

Updated review on the link between cortical spreading depression and headache disorders.

Expert Rev Neurother 2021 Oct 17;21(10):1069-1084. Epub 2021 Sep 17.

Department of Neurology and Algology, Gazi University Faculty of Medicine, Besevler, Ankara, Turkey.

: Experimental animal studies have revealed mechanisms that link cortical spreading depression (CSD) to the trigeminal activation mediating lateralized headache. However, conventional CSD as seen in lissencephalic brain is insufficient to explain some clinical features of aura and migraine headache.: The importance of CSD in headache development including dysfunction of the thalamocortical network, neuroinflammation, calcitonin gene-related peptide, transgenic models, and the role of CSD in migraine triggers, treatment options, neuromodulation, and future directions are reviewed.: The conventional understanding of CSD marching across the hemisphere is invalid in gyrencephalic brains. Thalamocortical dysfunction and interruption of functional cortical network systems by CSD may provide alternative explanations for clinical manifestations of migraine phases including aura. Not all drugs showing CSD blocking properties in lissencephalic brains have efficacy in migraine headache and monoclonal antibodies against CGRP ligand/receptors which are effective in migraine treatment, have no impact on aura in humans or CSD properties in rodents. Functional networks and molecular mechanisms mediating and amplifying the effects of limited CSD in migraine brain remain to be investigated to define new targets.
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http://dx.doi.org/10.1080/14737175.2021.1947797DOI Listing
October 2021

Widespread brain parenchymal HMGB1 and NF-κB neuroinflammatory responses upon cortical spreading depolarization in familial hemiplegic migraine type 1 mice.

Neurobiol Dis 2021 08 10;156:105424. Epub 2021 Jun 10.

Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey. Electronic address:

Neuroinflammatory changes involving neuronal HMGB1 release and astrocytic NF-κB nuclear translocation occur following cortical spreading depolarization (CSD) in wildtype (WT) mice but it is unknown to what extent this occurs in the migraine brain. We therefore investigated in familial hemiplegic migraine type 1 (FHM1) knock-in mice, which express an intrinsic hyperexcitability phenotype, the extent of neuroinflammation without and after CSD. CSD was evoked in one hemisphere by pinprick (single CSD) or topical KCl application (multiple CSDs). Neuroinflammatory (HMGB1, NF-κB) and neuronal activation (pERK) markers were investigated by immunohistochemistry in the brains of WT and FHM1 mutant mice without and after CSD. Effects of NMDA receptor antagonism on basal and CSD-induced neuroinflammatory changes were examined by, respectively, systemically administered MK801 and ifenprodil or topical MK801 application. In FHM1 mutant mice, CSD caused enhanced neuronal HMGB1 release and astrocytic NF-κB nuclear translocation in the cortex and subcortical areas that were equally high in both hemispheres. In WT mice such effects were only pronounced in the hemisphere in which CSD was induced. Neuroinflammatory responses were associated with pERK expression indicating neuronal activation. Upon CSD, contralateral cortical and striatal HMGB1 release was reduced by topical application of MK801 in the hemisphere contralateral to the one in which CSD was induced. This study reveals that neuroinflammatory activation after CSD is widespread and extends to the contralateral hemisphere, particularly in brains of FHM1 mutant mice. Effective blockade of CSD-induced neuroinflammatory responses in the contralateral hemisphere in FHM1 mice by local NMDA receptor antagonism suggests that neuronal hyperexcitability-related neuroinflammation is relevant in migraine pathophysiology, but possibly also other neurological disorders in which spreading depolarization is involved.
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http://dx.doi.org/10.1016/j.nbd.2021.105424DOI Listing
August 2021

Migraine and neuroinflammation: the inflammasome perspective.

J Headache Pain 2021 Jun 10;22(1):55. Epub 2021 Jun 10.

Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.

Background: Neuroinflammation has an important role in the pathophysiology of migraine, which is a complex neuro-glio-vascular disorder. The main aim of this review is to highlight findings of cortical spreading depolarization (CSD)-induced neuroinflammatory signaling in brain parenchyma from the inflammasome perspective. In addition, we discuss the limited data of the contribution of inflammasomes to other aspects of migraine pathophysiology, foremost the activation of the trigeminovascular system and thereby the generation of migraine pain.

Main Body: Inflammasomes are signaling multiprotein complexes and key components of the innate immune system. Their activation causes the production of inflammatory cytokines that can stimulate trigeminal neurons and are thus relevant to the generation of migraine pain. The contribution of inflammasome activation to pain signaling has attracted considerable attention in recent years. Nucleotide-binding domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) is the best characterized inflammasome and there is emerging evidence of its role in a variety of inflammatory pain conditions, including migraine. In this review, we discuss, from an inflammasome point of view, cortical spreading depolarization (CSD)-induced neuroinflammatory signaling in brain parenchyma, the connection with genetic factors that make the brain vulnerable to CSD, and the relation of the inflammasome with diseases that are co-morbid with migraine, including stroke, epilepsy, and the possible links with COVID-19 infection.

Conclusion: Neuroinflammatory pathways, specifically those involving inflammasome proteins, seem promising candidates as treatment targets, and perhaps even biomarkers, in migraine.
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http://dx.doi.org/10.1186/s10194-021-01271-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192049PMC
June 2021

Arachidonic Acid Metabolites in Neurologic Disorders.

CNS Neurol Disord Drug Targets 2021 May 11. Epub 2021 May 11.

Selcuk University Faculty of Medicine Neurology, Turkey.

Background & Objective: Arachidonic acid (ARA) is essential for the fluidity, selective permeability, and flexibility of the cell membrane. It is an important factor for the function of all cells, particularly in the nervous system, immune system, and vascular endothelium. ARA, after docosahexaenoic acid, is the second most common polyunsaturated fatty acid in the phospholipids of the nerve cell membrane. ARA metabolites have many kinds of physiologic roles. The major action of ARA metabolites is the promotion of the acute inflammatory response, mediated by the production of pro-inflammatory mediators such as PGE2 and PGI2, followed by the formation of lipid mediators, which have pro-resolving effects. Another important action of ARA derivatives, especially COX, is the regulation of vascular reactivity through PGs and TXA2. There is significant involvement of ARA metabolites in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and neuropsychiatric disorders. ARA derivatives also make an important contribution to acute stroke, global ischemia, subarachnoid hemorrhage, and anticoagulation- related hemorrhagic transformation.

Conclusion: In this review, we discuss experimental and human study results of neurologic disorders related to ARA and its metabolites in line with treatment options.
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http://dx.doi.org/10.2174/1871527320666210512013648DOI Listing
May 2021

Depression, loneliness and factors influencing in Syrian refugee children.

Int J Clin Pract 2021 May 5;75(5):e14039. Epub 2021 Feb 5.

Department of Pediatrics, Faculty of Medicine, Harran University, Sanliurfa, Turkey.

Aims: About 3.5 million Syrian refugees are living within the borders of Turkey. This study examined depression, loneliness and factors influencing refugee children who live outside the camps and attend school in Turkey.

Methods: This was a descriptive study in Sanliurfa, which has the second highest refugee population in Turkey. The sample consisted of 535 students attending 6-8 grades in five schools randomly selected of 18 schools located in the city centre where the Syrian children received their education. Data were collected using the Sociodemographic Characteristics Question Form, the Depression Scale for Children and the UCLA Loneliness Scale. Data were analysed by IBM spss v23. The percentage, average and standard deviation were determined. A linear regression analysis was used to examine the independent variables affecting loneliness and depression scores, and the Backward method was used to include independent variables in the model. Significance level was considered as P < .05.

Results: The average age of the children was 13.22 ± 1.33 years and 57.9% female. The average UCLA Loneliness Scale score was 42.95 ± 7.77. About 42% of the children received ≥19 on the depression scale, and 65% of them received ≥40 on the UCLA Loneliness Scale. Independent variables affecting depression score and UCLA loneliness score were analysed by a linear regression analysis. The linear regression model established for depression and UCLA loneliness score was obtained as statistically significant (P < .001).

Conclusion: Depression and loneliness scores were relatively high in children, particularly those exposed to the devastating impacts of war. These results will make significant contributions to the planning of services to be provided for this group of children.
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http://dx.doi.org/10.1111/ijcp.14039DOI Listing
May 2021

KCl-induced cortical spreading depression waves more heterogeneously propagate than optogenetically-induced waves in lissencephalic brain: an analysis with optical flow tools.

Sci Rep 2020 07 30;10(1):12793. Epub 2020 Jul 30.

Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.

Although cortical spreading depolarizations (CSD) were originally assumed to be homogeneously and concentrically propagating waves, evidence obtained first in gyrencephalic brains and later in lissencephalic brains suggested a rather non-uniform propagation, shaped heterogeneously by factors like cortical region differences, vascular anatomy, wave recurrences and refractory periods. Understanding this heterogeneity is important to better evaluate the experimental models on the mechanistics of CSD and to make appropriate clinical estimations on neurological disorders like migraine, stroke, and traumatic brain injury. This study demonstrates the application of optical flow analysis tools for systematic and objective evaluation of spatiotemporal CSD propagation patterns in anesthetized mice and compares the propagation profile in different CSD induction models. Our findings confirm the asymmetric angular CSD propagation in lissencephalic brains and suggest a strong dependency on induction-method, such that continuous potassium chloride application leads to significantly higher angular propagation variability compared to optogenetically-induced CSDs.
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http://dx.doi.org/10.1038/s41598-020-69669-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393358PMC
July 2020

F-actin polymerization contributes to pericyte contractility in retinal capillaries.

Exp Neurol 2020 10 29;332:113392. Epub 2020 Jun 29.

Hacettepe University, Institute of Neurological Sciences and Psychiatry, Ankara, Turkey. Electronic address:

Although it has been documented that central nervous system pericytes are able to contract in response to physiological, pharmacological or pathological stimuli, the underlying mechanism of pericyte contractility is incompletely understood especially in downstream pericytes that express low amounts of alpha-smooth muscle actin (α-SMA). To study whether pericyte contraction involves F-actin polymerization as in vascular smooth muscle cells, we increased retinal microvascular pericyte tonus by intravitreal injection of a vasoconstrictive agent, noradrenaline (NA). The contralateral eye of each mouse was used for vehicle injection. The retinas were rapidly extracted and fixed within 2 min after injections. Polymeric/filamentous (F-actin) and monomeric/globular (G-actin) forms of actin were labeled by fluorescently-conjugated phalloidin and deoxyribonuclease-I, respectively. We studied 108 and 83 pericytes from 6 NA- and 6 vehicle-treated retinas and, found that F/G-actin ratio, a microscopy-based index of F-actin polymerization, significantly increased in NA-treated retinas [median (IQR): 4.2 (3.1) vs. 3.5 (2.1), p = .006], suggesting a role for F-actin polymerization in pericyte contractility. Shift from G-actin monomers to polymerized F-actin was more pronounced in 5th and 6th order contracted pericytes compared to non-contracted ones [7.6 (4.7) vs. 3.2 (1.2), p < .001], possibly due to their dependence on de novo F-actin polymerization for contractile force generation because they express α-SMA in low quantities. Capillaries showing F-actin polymerization had significantly reduced diameters compared to the ones that did not exhibit increased F/G-actin ratio in pericytes [near soma / branch origin diameter; 0.67 (0.14) vs. 0.81 (0.34), p = .005]. NA-responsive capillaries generally did not show nodal constrictions but a tide-like diameter decrease, reaching a maximum near pericyte soma. These findings suggest that pericytes on high order downstream capillaries have F-actin-mediated contractile capability, which may contribute to the vascular resistance and blood flow regulation in capillary bed.
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http://dx.doi.org/10.1016/j.expneurol.2020.113392DOI Listing
October 2020

12/15 Lipoxygenase as a Therapeutic Target in Brain Disorders.

Noro Psikiyatr Ars 2019 Dec 5;56(4):288-291. Epub 2019 Sep 5.

Hacettepe University, Institute of Neurological Sciences and Psychiatry, Ankara, Turkey.

Lipoxygenases are a family of lipid-oxidizing enzymes, which generate eicosanoids and related compounds from arachidonic acid and other polyunsaturated fatty acids. These metabolites play important roles in physiology and pathogenesis of host defense mechanisms, cardiovascular diseases, cancer, inflammatory, allergic and neurodegenerative diseases. The 12/15-lipoxygenase (LOX) is special in that it can directly oxidize lipid membranes containing polyunsaturated fatty acids, without the preceding action of a phospholipase, leading to the direct attack on membranous organelles, such as mitochondria. The cytotoxic activity of human 12/15-LOX is up-regulated in neurons and endothelial cells especially after a stroke and thought to contribute to both neuronal cell death and blood-brain barrier leakage. The discovery of inhibitors that selectively target recombinant 12/15-LOX , as well as possessing activity against the murine orthologous , could potentially support a novel therapeutic strategy for the treatment of stroke and other brain disorders related to 12/15-LOX. Here we reviewed 12/15-LOX chemistry shortly, and the diseases in which 12/15-LOX has a role in their pathophysiology and recent advances of 12/15-LOX inhibitors as a treatment option for neurological diseases.
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http://dx.doi.org/10.29399/npa.23646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927084PMC
December 2019

Contributions of 12/15-Lipoxygenase to Bleeding in the Brain Following Ischemic Stroke.

Adv Exp Med Biol 2019 ;1161:125-131

Neuroprotection Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.

Ischemic strokes are caused by one or more blood clots that typically obstruct one of the major arteries in the brain, but frequently also result in leakage of the blood-brain barrier and subsequent hemorrhage. While it has long been known that the enzyme 12/15-lipoxygenase (12/15-LOX) is up-regulated following ischemic strokes and contributes to neuronal cell death, recent research has shown an additional major role for 12/15-LOX in causing this hemorrhagic transformation. These findings have important implications for the use of 12/15-LOX inhibitors in the treatment of stroke.
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http://dx.doi.org/10.1007/978-3-030-21735-8_12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278041PMC
October 2019

Mouse Models of Familial Hemiplegic Migraine for Studying Migraine Pathophysiology.

Curr Neuropharmacol 2019 ;17(10):961-973

Institute of Neurological Sciences and Psychiatry, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey.

Migraine, an extremely disabling neurological disorder, has a strong genetic component. Since monogenic migraines (resulting from mutations or changes in a single gene) may help researchers discover migraine pathophysiology, transgenic mice models harboring gene mutations identified in Familial Hemiplegic Migraine (FHM) patients have been generated. Studies in these FHM mutant mice models have shed light on the mechanisms of migraine and may aid in the identification of novel targets for treatment. More specifically, the studies shed light on how gene mutations, hormones, and other factors impact the pathophysiology of migraine. The models may also be of relevance to researchers outside the field of migraine as some of their aspects are relevant to pain in general. Additionally, because of the comorbidities associated with migraine, they share similarities with the mutant mouse models of epilepsy, stroke, and perhaps depression. Here, we review the experimental data obtained from these mutant mice and focus on how they can be used to investigate the pathophysiology of migraine, including synaptic plasticity, neuroinflammation, metabolite alterations, and molecular and behavioral mechanisms of pain.
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http://dx.doi.org/10.2174/1570159X17666190513085013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052833PMC
February 2020

Brain Peptides for the Treatment of Neuropsychiatric Disorders.

Curr Pharm Des 2018 ;24(33):3905-3917

Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.

The realization of the importance of growth factors in adult CNS led to several studies investigating their roles in neuropsychiatric disorders. Based on the observations that chronic stress decreases brain-derived neurotrophic factor (BDNF) and antidepressant treatments reverse BDNF to normal levels, "neurotrophic hypothesis of depression" was proposed. Subsequent studies found that several other growth factors, including fibroblast growth factor (FGF), vascular endothelial growth factor, nerve growth factor were also decreased by chronic stress. Growth factors promote stem cell survival, angiogenesis and neurogenesis in addition to having anti-apoptotic and anti-inflammatory effects, all of which make them potential drug candidates as neuroprotective or neurorestorative agents. Indeed, certain peptides have consistently been shown to improve stroke outcome in experimental models of cerebral ischemia. Recent developments in nanotechnology appear promising in overcoming the blood-brain barrier and in delivering sufficient amounts of these large peptides to the brain after systemic administration. In addition to the translational potential resulting from application of nanotechnical approaches for delivering these large peptide growth factors, recent success obtained with small molecule and peptide antagonists of calcitonin gene-related peptide has created renewed enthusiasm to elucidate the role of neuropeptides in migraine headache, one of the most common health problems in the world. In this review, we will first focus on the role of FGF2 in mood disorders as well as in ischemic stroke. We will also introduce the nanomedicines developed to efficiently deliver FGF2 to the brain. In the last section, we will explore roles of the neuropeptides in migraine and its acute and prophylactic treatment.
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http://dx.doi.org/10.2174/1381612824666181112112309DOI Listing
November 2019

The Existing State Analysis of Working Children on the Street in Sanliurfa, Turkey.

Iran J Public Health 2018 Sep;47(9):1300-1307

Dept. of Public Health Nursing, School of Health, Harran University, Sanliurfa, Turkey.

Background: We aimed to determine the existing state analysis of children on the street and also attending to a school. The children's ages were between 13-18 yr, attending grades between 7-12 grade.

Methods: The sample group was 54,928 students in Sanliurfa, Turkey. The data were analyzed using Chi-square test (<0.05).

Results: 82.8% of working children were male. 92.5% were elder than 12 yr old and 85.8 % had more than 4 siblings. 52.7% of the families' income was less than 1,000 TL per month. 79.9% of the children had worked in different places before. The distribution of working places was 66.4% in an establishment, 9.5% in the fields, 7.5% in the bazaar and in the streets, 2.8% in bus terminal, 2.9% in industry, 2.5% in parks. The 46.3% of the children stated that they are working willingly. 50.7% were working 6 to 10 h a day. 64.4% were giving the money they earned to their families. 82.1% of the children stated that they liked to attend the school but 62.8% sometimes did not go to school. 20.6% went to work instead of school in those days. The 62.2% of the children answered the question; "According to you, should the children work?" with; "No".

Conclusion: The children started working at very early ages and they faced unfavorable situations. To avoid the children work in very early ages, it is suggested to make educational programs and to compose policies to resolve the problems that force the children to go to work.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174033PMC
September 2018

Nuclear expansion and pore opening are instant signs of neuronal hypoxia and can identify poorly fixed brains.

Sci Rep 2018 10 3;8(1):14770. Epub 2018 Oct 3.

Hacettepe University, Institute of Neurological Sciences and Psychiatry, Ankara, 06100, Turkey.

The initial phase of neuronal death is not well characterized. Here, we show that expansion of the nuclear membrane without losing its integrity along with peripheralization of chromatin are immediate signs of neuronal injury. Importantly, these changes can be identified with commonly used nuclear stains and used as markers of poor perfusion-fixation. Although frozen sections are widely used, no markers are available to ensure that the observed changes were not confounded by perfusion-induced hypoxia/ischemia. Moreover, HMGB1 was immediately released and p53 translocated to mitochondria in hypoxic/ischemic neurons, whereas nuclear pore complex inhibitors prevented the nuclear changes, identifying novel neuroprotection targets.
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http://dx.doi.org/10.1038/s41598-018-32878-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170374PMC
October 2018

Prevalence of war-related adverse events, depression and anxiety among Syrian refugee children settled in Turkey.

Eur Child Adolesc Psychiatry 2018 Nov;27(11):1513-1517

Department of Pediatry, School of Medicine, Harran University, Şanlıurfa, Turkey.

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http://dx.doi.org/10.1007/s00787-018-1178-0DOI Listing
November 2018

Improving Microcirculatory Reperfusion Reduces Parenchymal Oxygen Radical Formation and Provides Neuroprotection.

Stroke 2018 05 18;49(5):1267-1275. Epub 2018 Apr 18.

From the Institute of Neurological Sciences and Psychiatry (A.T.-S., M.Y., Y.G.-O., S.E.E., H.K., T.D.)

Background And Purpose: Reperfusion is the most significant determinant of good outcome after ischemic stroke. However, complete reperfusion often cannot be achieved, despite satisfactory recanalization. We hypothesized that microvascular protection was essential for achieving effective reperfusion and, hence, neuroprotection. To test this hypothesis, we have developed an in vivo model to differentially monitor parenchymal and vascular reactive oxygen species (ROS) formation. By comparing the ROS-suppressing effect of N-tert-butyl-α-phenylnitrone (PBN) with its blood-brain barrier impermeable analog 2-sulfo-phenyl-N-tert-butylnitrone (S-PBN), we assessed the impact of vascular ROS suppression alone on reperfusion and stroke outcome after recanalization.

Methods: The distal middle cerebral artery was occluded for 1 hour by compressing with a micropipette and then recanalized (n=60 Swiss mice). ROS formation was monitored for 1 hour after recanalization by intravital fluorescence microscopy in pial vasculature and cortical parenchyma with topically applied hydroethidine through a cranial window. PBN (100 mg/kg) or S-PBN (156 mg/kg) was administered shortly before recanalization, and suppression of the vascular and parenchymal hydroethidine fluorescence was examined (n=22). Microcirculatory patency, reperfusion, ischemic tissue size, and neurological outcome were also assessed in a separate group of mice 1 to 72 hours after recanalization (n=30).

Results: PBN and S-PBN completely suppressed the reperfusion-induced increase in ROS signal within vasculature. PBN readily suppressed ROS produced in parenchyma by 88%. S-PBN also suppressed the parenchymal ROS by 64% but starting 40 minutes later. Intriguingly, PBN and S-PBN comparably reduced the size of ischemic area by 65% and 48% (>0.05), respectively. S-PBN restored the microvascular patency and perfusion after recanalization, suggesting that its delayed parenchymal antioxidant effect could be secondary to improved microcirculatory reperfusion.

Conclusions: Promoting microvascular reperfusion by protecting vasculature can secondarily reduce parenchymal ROS formation and provide neuroprotection. The model presented can be used to directly assess pharmacological end points postulated in brain parenchyma and vasculature in vivo.
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http://dx.doi.org/10.1161/STROKEAHA.118.020711DOI Listing
May 2018

Inadequate brain glycogen or sleep increases spreading depression susceptibility.

Ann Neurol 2018 01;83(1):61-73

Department of Neurology, Faculty of Medicine and Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.

Objective: Glycogen in astrocyte processes contributes to maintenance of low extracellular glutamate and K concentrations around excitatory synapses. Sleep deprivation (SD), a common migraine trigger, induces transcriptional changes in astrocytes, reducing glycogen breakdown. We hypothesize that when glycogen utilization cannot match synaptic energy demand, extracellular K can rise to levels that activate neuronal pannexin-1 channels and downstream inflammatory pathway, which might be one of the mechanisms initiating migraine headaches.

Methods: We suppressed glycogen breakdown by inhibiting glycogen phosphorylation with 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) and by SD.

Results: DAB caused neuronal pannexin-1 large pore opening and activation of the downstream inflammatory pathway as shown by procaspase-1 cleavage and HMGB1 release from neurons. Six-hour SD induced pannexin-1 mRNA. DAB and SD also lowered the cortical spreading depression (CSD) induction threshold, which was reversed by glucose or lactate supplement, suggesting that glycogen-derived energy substrates are needed to prevent CSD generation. Supporting this, knocking down the neuronal lactate transporter MCT2 with an antisense oligonucleotide or inhibiting glucose transport from vessels to astrocytes with intracerebroventricularly delivered phloretin reduced the CSD threshold. In vivo recordings with a K -sensitive/selective fluoroprobe, Asante Potassium Green-4, revealed that DAB treatment or SD caused a significant rise in extracellular K during whisker stimulation, illustrating the critical role of glycogen in extracellular K clearance.

Interpretation: Synaptic metabolic stress caused by insufficient glycogen-derived energy substrate supply can activate neuronal pannexin-1 channels as well as lower the CSD threshold. Therefore, conditions that limit energy supply to synapses (eg, SD) may predispose to migraine attacks, as suggested by genetic studies associating glucose or lactate transporter deficiency with migraine. Ann Neurol 2018;83:61-73.
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http://dx.doi.org/10.1002/ana.25122DOI Listing
January 2018

A Study of Bullying Against Nursing Students.

J Nurs Res 2017 Jun;25(3):198-202

1PhD, RN, Assistant Professor, Department of Pediatric Nursing, School of Health, Harran University, Turkey 2PhD, RN, Professor, Faculty of Health, Department of Nursing, Near East University, TRNC 3PhD, RN, Associate Professor, Faculty of Nursing, Dokuz Eylul University, Turkey.

Background: Many institutions have conducted research on the subject of bullying. The literature includes many studies of the effects of widespread bullying among primary and secondary school students. Bullying against hospital nurses and also bullying against university students are well-known and frequently discussed research topics. Yet, the exposure of nursing students to bullying has not been sufficiently explored, and few studies have focused on the issue of bullying against nursing students.

Purpose: The aim of this study is to examine bullying against nursing students, including the rate of bullying, types of bullying, and responses to the negative effects of bullying.

Methods: This study was conducted on 202 nursing students (including sophomores, juniors, and seniors) during the 2013-2014 academic year. The participation rate was 88.5%. The Negative Attitudes Scale was used to collect data, and descriptive statistics were used in data analysis.

Results: Participants were evenly distributed between women (49.5%) and men (50.5%). The median age of participants was 21.58 ± 2.28 years; the frequency of bullying was 78.1%. The types of bullying were pejorative statements about the nursing profession (11.3%); low grades used as a form of punishment (9.9%); work, homework, and job rotation used as punishment in lieu of training (9.4%); impossible workloads (9.0%); and the spreading of rumors and gossip (7%).

Conclusions/implications For Practice: This study indicates that the participants were exposed to high levels of bullying. As exposure to bullying negatively affects the job attitudes of nursing students, further studies are necessary to develop strategies to prevent horizontal bullying.
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http://dx.doi.org/10.1097/JNR.0000000000000144DOI Listing
June 2017

Refractory Lesional Parietal Lobe Epilepsy: Clinical, Electroencephalographic and Neurodiagnostic Findings.

Noro Psikiyatr Ars 2016 Sep 1;53(3):213-221. Epub 2016 Mar 1.

Department of Neurology, Hacettepe University School of Medicine, Ankara, Turkey.

Introduction: Specialized centers, in the management and surgical treatment of medically refractory epilepsy, emphasize the importance of differentiating the varieties of localization related epilepsies. There has been considerable recent interest in temporal and frontal lobe epileptic syndromes and less attention has been paid to parietal and occipital lobe epilepsies.

Methods: Here we report the clinical, electroencephalographic and neuroimaging characteristics of 46 patients with medically refractory lesional parietal lobe epilepsy who have been followed up for 1-10 years.

Results: In this study auras were reported in 78.3% of the patients and included sensory symptoms (72.2%), headache (36.1%), nausea and vomiting (36.1%), psychic symptoms (36.1%) and visual symptoms (16.6%). The most common ictal behavioral changes were paresthesia (69.6%) and focal clonic activity (39.1%). Tonic posture, various automatisms, head deviation, staring, sensation of pain and speech disturbances occurred to a lesser extent. Simple partial seizures were present in 69.6%. Complex partial seizures occurred in 43.5% and secondary generalized tonic clonic seizures were reported in 58.7% of the patients. Interictal routine EEG disclosed abnormal background activity in 1/3 of the patients. Nonlocalising epileptiform abnormalities were found in 34.8% of the patients. EEG findings were normal in 34.8% of the patients. The most common presumed etiologic factors were as follows: posttraumatic encephalomalacia, stroke, tumor, malformation of cortical development, atrophy, and arteriovenous malformation.

Conclusion: Clinical, electrophysiological and neuroimaging features of the lesional symptomatic partial epilepsy patients may help us to localize the seizure focus in some patients with cryptogenic partial epilepsy. So that, the timing decision of the parietal lobe sampling with more invasive techniques like intracranial electrodes prior to epilepsy surgery would be easier.
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http://dx.doi.org/10.5152/npa.2016.13790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378203PMC
September 2016

12/15-Lipoxygenase Inhibition or Knockout Reduces Warfarin-Associated Hemorrhagic Transformation After Experimental Stroke.

Stroke 2017 02 5;48(2):445-451. Epub 2017 Jan 5.

From the Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown (Y.L., Y.Z., H.K., X.W., E.H.L., K.v.L.); Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, China (Y.L.); and Department of Neurology, Goethe University, Frankfurt am Main, Germany (C.F.).

Background And Purpose: For stroke prevention, patients with atrial fibrillation typically receive oral anticoagulation. The commonly used anticoagulant warfarin increases the risk of hemorrhagic transformation (HT) when a stroke occurs; tissue-type plasminogen activator treatment is therefore restricted in these patients. This study was designed to test the hypothesis that 12/15-lipoxygenase (12/15-LOX) inhibition would reduce HT in warfarin-treated mice subjected to experimental stroke.

Methods: Warfarin was dosed orally in drinking water, and international normalized ratio values were determined using a Coaguchek device. C57BL6J mice or 12/15-LOX knockout mice were subjected to transient middle cerebral artery occlusion with 3 hours severe ischemia (model A) or 2 hours ischemia and tissue-type plasminogen activator infusion (model B), with or without the 12/15-LOX inhibitor ML351. Hemoglobin was determined in brain homogenates, and hemorrhage areas on the brain surface and in brain sections were measured. 12/15-LOX expression was detected by immunohistochemistry.

Results: Warfarin treatment resulted in reproducible increased international normalized ratio values and significant HT in both models. 12/15-LOX knockout mice suffered less HT after severe ischemia, and ML351 reduced HT in wild-type mice. When normalized to infarct size, ML351 still independently reduced hemorrhage. HT after tissue-type plasminogen activator was similarly reduced by ML351.

Conclusions: In addition to its benefits in infarct size reduction, 12/15-LOX inhibition also may independently reduce HT in warfarin-treated mice. ML351 should be further evaluated as stroke treatment in anticoagulated patients suffering a stroke, either alone or in conjunction with tissue-type plasminogen activator.
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http://dx.doi.org/10.1161/STROKEAHA.116.014790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5263178PMC
February 2017

The Level of Professionalism of Nurses Working in a Hospital in Turkey.

J Caring Sci 2016 1;5(2):95-102. Epub 2016 Jun 1.

Department of Nursing, School of Health, Abant Izzet Baysal University, Turkey.

Introduction: Professionalism is characterized by the degree of dedication displayed by individuals regarding the values and behavioral attributes of a specific career identity. Professionalism indicates attitudes that represent high levels of identification with and commitment to a specific profession. In the process of the professional development of nursing, various factors affect these obstacles which may impede the professional development of nurses and their professional behaviors. This study was carried out with the aim of determining the professional behavior of nurses in a hospital in Turkey.

Methods: In this descriptive exploratory study a total of 89 nurses working in a public hospital in northwestern of Turkey were participated. Data were collected using a demographic questionnaire and Behavioral Inventory Form for Professionalism in Nursing (BIPN).

Results: The result showed that mean scores on the BIPN were 5.07 (3.47). The areas with the highest levels of professional behavior were competence and continuing education 1.88 (0.34). The professionalism levels for nurses were the lowest in the areas of autonomy 0.06 (0.34), publication 0.10 (0.25), and research 0.25 (0.60). There was a statistically significant difference between the total BIPN scores and the education levels of the nurses and the working of nurses.

Conclusion: The professional behavior of nurses is at a low level. Since the arrangement of the nurses' working conditions affects their professional behaviors; therefore, development in the field of professional behaviors in nursing must be assessed and supported to increase the quality of patient care.
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http://dx.doi.org/10.15171/jcs.2016.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923842PMC
June 2016

Determination of Nursing Diagnoses in Children of Agricultural Laborer Families in South Eastern Regions of Turkey.

Int J Nurs Knowl 2018 Jan 30;29(1):29-37. Epub 2016 May 30.

Professor in Child Health Nursing, Department of Nursing, Faculty of Health Science, Near East University, Nicosia, Turkey.

Purpose: Identifying functional health patterns and nursing diagnoses of migrant agricultural laborer families.

Methods: Interpretative-qualitative study based on interviews with 162 mothers of 0- to 2-year-old children in two Turkish provinces.

Findings: Health perception-health management: growth and development, risk for being delayed; health maintenance, ineffective; health behavior, risk-prone; risk for contamination; risk for sudden infant death syndrome; and risk for injury. Nutritional-metabolic: Risk for infection; and breastfeeding, interrupted. Self-perception: risk for chronic low self-esteem, disturbed self-esteem; and powerlessness. Role-relationship: impaired parenting; and dysfunctional family process. Coping-stress tolerance: coping, disabled family; violence, risk for other-directed. Cognitive-perceptive: knowledge deficit CONCLUSIONS: Nursing diagnoses of this population were reported for the first time.

Implications: Addressing agricultural laborer families' diagnoses will positively affect maternal-child health.
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http://dx.doi.org/10.1111/2047-3095.12144DOI Listing
January 2018

STAT-dependent upregulation of 12/15-lipoxygenase contributes to neuronal injury after stroke.

J Cereb Blood Flow Metab 2015 Dec 15;35(12):2043-51. Epub 2015 Jul 15.

Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.

Oxidative stress is a major brain injury mechanism after ischemic stroke. 12/15-lipoxygenase (12/15-LOX) is a key mediator of oxidative stress, contributing to neuronal cell death and vascular leakage. Nonetheless, the mechanism leading to its upregulation is currently unknown. We show here that Signal Transducers and Activators of Transcription (STATs), specifically STAT6 and possibly STAT1, increase transcription of 12/15-LOX in neuronal cells. Both p-STAT6 and -1 bound to specific STAT binding sites in the mouse 12/15-LOX promoter. Small interfering RNA (siRNA) knockdown showed STAT6 to be the dominant regulator, reducing 12/15-LOX promoter activation and cell death in oxidatively stressed HT22 cells. STAT6 siRNA efficiently prevented the increase of 12/15-LOX in murine primary neurons, both after induction of oxidative stress and after oxygen-glucose deprivation. Early activation of STAT6 and STAT1 in mice was consistent with a role in regulating 12/15-LOX in focal ischemia. Brains of human stroke patients showed increased p-STAT6 and p-STAT1 in the peri-infarct region, along with 12/15-LOX and markers of apoptosis. These results link STAT6 and STAT1 to the 12/15-LOX damage pathway and suggest disregulation of STAT-dependent transcription as injury mechanism in stroke. Selectively targeting STATs may thus be a novel therapeutic approach to reducing brain injury after a stroke.
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http://dx.doi.org/10.1038/jcbfm.2015.169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671126PMC
December 2015

Complementary and alternative medicine in pediatrics in Turkey.

World J Pediatr 2014 Nov 17;10(4):299-305. Epub 2014 Dec 17.

Faculty of Health Sciences, Istanbul Sabahattin Zaim University, Istanbul, Turkey.

Background: Complementary and alternative medicine (CAM) is applied both to children and adults widely throughout the world. A previous pan-European survey showed a surprisingly high CAM-use in Turkish children. This review aimed to survey information on the use of CAM in pediatrics in Turkey.

Data Sources: A narrative, non-systematic review was conducted by melding expert opinions with a thorough and balanced review of available evidence. An unrestricted literature search using the key words, "alternative", "complementary", "integrative", "prevalence" and "pediatric" or "children" and "Turkey" was performed by internet search in March, 2012 using PubMed and Google Scholar.

Results: CAM use was examined in general pediatrics, pediatric oncology, patients with asthma, and patients with diabetes. A frequency of CAM use was 87% in Turkish pediatric patients, with a mean of 60%. The primary sources of information about CAM are family and friends. Communication with patients/parents and health care professionals showed that most parents do not speak about CAM use with their physicians or nurses.

Conclusions: CAM is extensively used in Turkish pediatric patients. This might be due to Turkey's status as a developing country in which a traditional medical system still dominates in comparison to developed countries. Thus, larger studies are required to prove an extensive use of CAM in Turkey, as this review article does not have the capacity for in-depth analysis. Knowledge about CAM and its related topics is essential for physicians and nurses in order to meet the patients' wish for a competent consultation concerning all aspects of a possible therapy.
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http://dx.doi.org/10.1007/s12519-014-0507-8DOI Listing
November 2014

Poloxamer-188 and citicoline provide neuronal membrane integrity and protect membrane stability in cortical spreading depression.

Int J Neurosci 2015 4;125(12):941-6. Epub 2014 Dec 4.

c Institute of Neurological Sciences and Psychiatry, Hacettepe University , Ankara , Turkey.

Under pathological conditions such as brain trauma, subarachnoid hemorrhage and stroke, cortical spreading depression (CSD) or peri-infarct depolarizations contribute to brain damage in animal models of neurological disorders as well as in human neurological diseases. CSD causes transient megachannel opening on the neuronal membrane, which may compromise neuronal survival under pathological conditions. Poloxamer-188 (P-188) and citicoline are neuroprotectants with membrane sealing properties. The aim of this study is to investigate the effect of P-188 and citicoline on the neuronal megachannel opening induced by CSD in the mouse brain. We have monitored megachannel opening with propidium iodide, a membrane impermeable fluorescent dye and, demonstrate that P-188 and citicoline strikingly decreased CSD-induced neuronal PI influx in cortex and hippocampal dentate gyrus. Therefore, these agents may be providing neuroprotection by blocking megachannel opening, which may be related to their membrane sealing action and warrant further investigation for treatment of traumatic brain injury and ischemic stroke.
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http://dx.doi.org/10.3109/00207454.2014.979289DOI Listing
August 2016

Effects of student perceptions of social skills on their perception of smoking.

Asian Pac J Cancer Prev 2014 ;15(14):5937-40

Department of Pediatric Nursing, Faculty of Nursing, Dokuz Eylul University, Istanbul, Turkey E-mail :

Background: This study was conducted as a descriptive-correlational exercise with the aim of determining the effect of student perceptions of social skills on their pro and con perceptions of smoking.

Materials And Methods: The study sample comprised 106 students at 6th, 7th and 8th grades in three primary schools. The data were collected through socio-demographic data collection form, Social Skill Perception Form and Child Decisional Balance Scale. Data were evaluated by percentage calculation, Student t test and correlation analysis.

Results: While the point average of pro perception of smoking of the students with a high point average of social skill perception, was 8.6±3.1, in those with a low social skill perception point average it was 10.7±4.2, the difference being significant(p=0.012). The respective point averages of con perceptions were 26.8±3.7 and 23.5±3.3, again significant (p=0.000). While a positive medium level (r=0.410) relationship was determined between the point average of social skill perception and con perception of smoking, a negative low level (r=0.281) relationship was determined with the pro perception of smoking.

Conclusions: As the social skill perception point average increases, children's con perceptions of smoking increase and their pro perceptions decrease.
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http://dx.doi.org/10.7314/apjcp.2014.15.14.5937DOI Listing
June 2015

Imaging of contrast medium extravasation in anticoagulation-associated intracerebral hemorrhage with dual-energy computed tomography.

Stroke 2013 Oct 6;44(10):2883-90. Epub 2013 Aug 6.

From the Department of Neurology, Goethe-University, Frankfurt am Main, Germany (S.-Y.W., F.S., A.L., H.S., C.F.); Neuroprotection Research Laboratory, Massachusetts General Hospital, Charlestown (S.-Y.W., F.S., H.K., W.L., K.H., E.L.); and Department of Radiology, Massachusetts General Hospital, Boston (J.D., R.G.).

Background And Purpose: Contrast medium extravasation (CE) in intracerebral hemorrhage (ICH) is a marker of ongoing bleeding and a predictor of hematoma expansion. The aims of the study were to establish an ICH model in which CE can be quantified, characterized in ICH during warfarin and dabigatran anticoagulation, and to evaluate effects of prothrombin complex concentrates on CE in warfarin-associated ICH.

Methods: CD1-mice were pretreated orally with warfarin, dabigatran, or vehicle. Prothrombin complex concentrates were administered in a subgroup of warfarin-treated mice. ICH was induced by stereotactic injection of collagenase VIIs into the right striatum. Contrast agent (350 μL Isovue 370 mg/mL) was injected intravenously after ICH induction (2-3.5 hours). Thirty minutes later, mice were euthanized, and CE was measured by quantifying the iodine content in the hematoma using dual-energy computed tomography.

Results: The optimal time point for contrast injection was found to be 3 hours after ICH induction, allowing detection of both an increase and a decrease of CE using dual-energy computed tomography. CE was higher in the warfarin group compared with the controls (P=0.002). There was no significant difference in CE between dabigatran-treated mice and controls. CE was higher in the sham-treated warfarin group than in the prothrombin complex concentrates-treated warfarin group (P<0.001).

Conclusions: Dual-energy computed tomography allows quantifying CE, as a marker of ongoing bleeding, in a model of anticoagulation-associated ICH. Dabigatran induces less CE in ICH than warfarin and consequently reduces risks of hematoma expansion. This constitutes a potential safety advantage of dabigatran over warfarin. Nevertheless, in case of warfarin anticoagulation, prothrombin complex concentrates reduce this side effect.
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http://dx.doi.org/10.1161/STROKEAHA.113.001224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985727PMC
October 2013

Identification of the traditional methods of newborn mothers regarding jaundice in Turkey.

J Clin Nurs 2014 Feb 28;23(3-4):524-30. Epub 2013 May 28.

Balikesir University, Bandirma School of Health, Pediatric Nursing Department, Balikesir.

Aims And Objectives: To detect traditional methods applied for the treatment of newborn jaundice by mothers in Turkey.

Background: Traditional methods are generally used in our society. Instead of using medical services, people often use already-known traditional methods to treat the disease. In such cases, the prognosis of the disease generally becomes worse, the treatment period longer and healthcare costs higher, and more medicine is used.

Design: A cross-sectional descriptive study.

Methods: The participants of this study were 229 mothers with newborn babies aged 0-28 days in one university hospital and one public children's hospital in Sanliurfa. The study was conducted between March and May 2012. In this research, the Beliefs and Traditional Methods of Mothers for Jaundice Questionnaire, which was formed by searching the relevant literature, is used as a data collection tool. The data are evaluated by percentage distributions.

Results: Mothers apply conventional practices in cases of health problems such as jaundice, and application of these methods is important to mothers. Moreover, mothers reported applying hazardous conventional methods in cases of neonatal jaundice, such as cutting the area between the baby's eyebrows with a blade, cutting the back of the ear and the body and burning the body, which are not applied in different cultures.

Conclusions: Education regarding the effects of conventional methods being applied in families should be provided, and the results of this study should serve to guide further studies in assessing the effects of such education.

Relevance To Clinical Practice: This approach can support beneficial practices involving individual care and prevent the negative health effects of hazardous practices.
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http://dx.doi.org/10.1111/jocn.12150DOI Listing
February 2014

Spreading depression triggers headache by activating neuronal Panx1 channels.

Science 2013 Mar;339(6123):1092-5

Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.

The initial phase in the development of a migraine is still poorly understood. Here, we describe a previously unknown signaling pathway between stressed neurons and trigeminal afferents during cortical spreading depression (CSD), the putative cause of migraine aura and headache. CSD caused neuronal Pannexin1 (Panx1) megachannel opening and caspase-1 activation followed by high-mobility group box 1 (HMGB1) release from neurons and nuclear factor κB activation in astrocytes. Suppression of this cascade abolished CSD-induced trigeminovascular activation, dural mast cell degranulation, and headache. CSD-induced neuronal megachannel opening may promote sustained activation of trigeminal afferents via parenchymal inflammatory cascades reaching glia limitans. This pathway may function to alarm an organism with headache when neurons are stressed.
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http://dx.doi.org/10.1126/science.1231897DOI Listing
March 2013

Inhibition of 12/15-lipoxygenase as therapeutic strategy to treat stroke.

Ann Neurol 2013 Jan 28;73(1):129-35. Epub 2012 Nov 28.

Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, USA.

Targeting newly identified damage pathways in the ischemic brain can help to circumvent the currently severe limitations of acute stroke therapy. Here we show that the activity of 12/15-lipoxygenase was increased in the ischemic mouse brain, and 12/15-lipoxygenase colocalized with a marker for oxidized lipids, MDA2. This colocalization was also detected in the brain of 2 human stroke patients, where it also coincided with increased apoptosis-inducing factor. A novel inhibitor of 12/15-lipoxygenase, LOXBlock-1, protected neuronal HT22 cells against oxidative stress. In a mouse model of transient focal ischemia, the inhibitor reduced infarct sizes both 24 hours and 14 days poststroke, with improved behavioral parameters. Even when treatment was delayed until at least 4 hours after onset of ischemia, LOXBlock-1 was protective. Furthermore, it reduced tissue plasminogen activator-associated hemorrhage in a clot model of ischemia/reperfusion. This study establishes inhibition of 12/15-lipoxygenase as a viable strategy for first-line stroke treatment.
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http://dx.doi.org/10.1002/ana.23734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563836PMC
January 2013

Relationship between bullying and health problems in primary school children.

Asian Nurs Res (Korean Soc Nurs Sci) 2011 Jun 8;5(2):81-7. Epub 2011 Jul 8.

Associate Professor of Nursing, School of Nursing, Dokuz Eylul University, Izmir, Turkey.

Purpose: The aim of this study is to analyze the relationship between bullying and exposure to bullying and the health problems in the primary school children.

Methods: This study was conducted on 92 parents and 92 students who were sixth grade students in two primary schools in Izmir. The data were collected using the Peer Bullying Scale Adolescent Form and the Identification of Health Problems Form. The data were analyzed through χ(2) analysis and odds ratios with a 95% confidence interval.

Results: About forty-nine percent of the students (48.9%) was male, 51.1% of them was female and the average age was 11.6 ± 0.53 years. It was found that students who had high scores for being exposed to bullying were significantly more likely to experience headache, feeling bad, crying restlessness, nervousness, sleeping problems, dizziness; whereas students who had high bullying scores were significantly more likely to experience only poor appetite.

Conclusions: Students exposed to bullying have more health problems than the bullying students. It is recommended that programs designed to prevent the negative effects of bullying be developed.
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http://dx.doi.org/10.1016/S1976-1317(11)60016-9DOI Listing
June 2011
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