Browsing by Author "Yilmaz, Ekrem"

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The Butterfly Effect in Psychiatry: a Case Example
(Yerkure Tanitim & Yayincilik Hizmetleri A S, 2014) Ozdemir, Osman; Ozdemir, Pinar Guzel; Yilmaz, Ekrem
The butterfly effect is that a small change at one place in a complex dynamic system can lead to large and unexpected consequences. In modern science, the theory can have applications in physics, mathematics, engineering, as well as biology, psychology, and cognitive science. The dynamic approach to cognition emphasizes the complex process of human development including mental, behavioral, neural and social systems interacting with each other over the life course. Emotion-related experiences as the result of interaction between person and his environment have been useful for explaining the butterfly effect in psychiatry practice. Here, we report a patient with depressive episode that has developed after psychosocial stress and has been treated with electroconvulsive therapy.
Comparison of Paraoxonase, Prolidase Activities and Hs-Crp, Bdnf Levels in Patients With Autogenous and Reactive Subtypes of Obsessive Compulsive Disorder
(Cumhuriyet Univ Tip Fak Psikiyatri Anabilim Dali, 2019) Guzel Ozdemir, Pinar; Yilmaz, Ekrem; Yilmaz, Emine
Objective: Obsessions have been categorized as autogenous obsessions and reactive obsessions on the original of the cognitive theory and this study aimed to evaluate whether differences are found between obsessive compulsive disorder (OCD) subgroups in terms of biochemical markers. Methods: Thirty patients with obsessions defined as autogenous, 30 patients with obsessions defined as reactive group and 30 healthy volunteers were consisted the sample of the study. Sociodemographic Data Form, Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) were filled to the participants. The activity of paraoxanase, prolidase and Hs-CRP and brain-derived neurotrophic factor (BDNF) levels were detected. Results: There was no any statistically significant difference between autogenous and reactive obsession groups in terms of total mean score of Y-BOCS, BDI and BAI. Paraoxanase activity did not statistically significant difference between all groups. Prolidase activity showed significantly higher in reactive group than autogenous obsession and control groups. Serum Hs-CRP levels were not statistically different among participants of autogenous group, reactive group and control groups. Serum BDNF levels were significantly lower in autogenous obsession group rather than reactive obsession and control groups. Conclusion: This finding indicates that neurobiological processes have important role in the pathophysiology of autogenous obsessions.
Comparison of Venlafaxine Alone Versus Venlafaxine Plus Bright Light Therapy Combination for Severe Major Depressive Disorder
(Physicians Postgraduate Press, 2015) Ozdemir, Pinar Guzel; Boysan, Murat; Smolensky, Michael H.; Selvi, Yavuz; Aydin, Adem; Yilmaz, Ekrem
Objective: Phototherapy, ie, bright light therapy, is an effective and safe treatment of major depressive disorder (MDD). It exerts rapid mood-elevating activity, similar to antidepressant medications, most likely mediated through both monoaminergic and circadian system melatonergic mechanisms. We assessed the efficiency of bright light therapy as an adjuvant treatment to antidepressant pharmacotherapy in patients with severe MDD randomized by Hamilton Depression Rating Scale (HDRS) score to either (1) 150 mg venlafaxine hydrochloride daily at 7: 00 am or (2) 150 mg venlafaxine plus 60-minute light of 7000 lux the initial week of clinical management (venlafaxine + bright light therapy) daily at 7: 00 am. Method: 50 inpatients with severe MDD at the Psychiatry Clinic of Yuzuncu Yil University Training and Education Hospital participated. The study, which was conducted from January 2013 through June 2014, entailed patients diagnosed with severe MDD based on DSM-IV-TR for the first time. Mood states were assessed by the HDRS, Profile of Mood States (POMS), and Beck Depression Inventory (BDI) before treatment and at 1, 2, 4, and 8 weeks of treatment. Results: On the basis of the HDRS score as the primary outcome variable, both strategies significantly improved depression and negative mood states already at the first treatment week (P < .001). Differences in therapeutic effects by treatment strategy were remarkable at the second and fourth weeks of clinical management (P = .018 and P = .011, respectively), with beneficial effects continuing until trial Conclusion. Those treated with venlafaxine + bright light therapy evidenced significantly lower HDRS depression scores (P < .05) as well as BDI scores (P < .05) and POMS negative mood states scores (depression-dejection, tension-anxiety, anger-hostility, fatigue-inertia, and confusion-bewilderment subscales; all P < .05) after the second week. At week 4 of the trial, 19 (76%) of the 25 venlafaxine + bright light therapy patients versus just 11 (44%) of the 25 venlafaxine patients (P < .05) attained the target goal of treatment, a HDRS score = 13, indicative of mild depression, and, although not statistically significant in our small sample study (P = .36), at week 8, 76% of venlafaxine + bright light therapy patients (n = 19) versus just 64% of the venlafaxine patients (n = 16) experienced complete remission of depression (HDRS score = 7). Conclusions: Both venlafaxine and venlafaxine + bright light therapy treatment strategies significantly reversed the depressive mood of patients with severe MDD; however, the latter induced significantly stronger and more rapid beneficial effects. Future longer-term studies with large sample sizes, nonetheless, are required to confirm and generalize these results to patients of diverse ethnicities and cultures with both severe and mild MDD. (C) Copyright 2015 Physicians Postgraduate Press, Inc.
Dissociative Experiences in Patients With Epilepsy
(Assoc Arquivos Neuro- Psiquiatria, 2016) Ozdemir, Osman; Cilingir, Vedat; Ozdemir, Pinar Guzel; Milanlioglu, Aysel; Hamamci, Mehmet; Yilmaz, Ekrem
A few studies have explored dissociative experiences in epilepsy patients. We investigated dissociative experiences in patients with epilepsy using the dissociative experiences scale (DES). Ninety-eight patients with epilepsy and sixty healthy controls were enrolled in this study. A sociodemographic questionnaire and the Dissociative Experiences Scale (DES), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) were administered to the participants. The DES scores were significantly higher for the patients with epilepsy than the healthy individuals. The number of individuals with pathological dissociation (DES >= 30) was higher in the epilepsy group (n = 28) than in the control group (n = 8). Also, higher levels of dissociation were significantly associated with frequency of seizures, but were not associated with duration of epilepsy and age at onset of the disorder. These findings demonstrate that patients with epilepsy are more prone to dissociation than controls. The high rate of dissociative experiences among patients with epilepsy suggest that some epilepsy-related factors are present.
Evaluation of Plasma Agmatine Level and Its Metabolic Pathway in Patients With Bipolar Disorder During Manic Episode and Remission Period
(Taylor & Francis Ltd, 2019) Yilmaz, Emine; Sekeroglu, M. Ramazan; Yilmaz, Ekrem; Cokluk, Erdem
Objectives: Agmatine is a cationic amine resulting from the decarboxylation of l-arginine. Agmatine has neuroprotective, anti-inflammatory, anti-stress, and anti-depressant properties. In this study, plasma agmatine, arginine decarboxylase, and agmatinase levels were measured during manic episode and remission period in patients with bipolar disorder. Methods: Thirty healthy volunteers and 30 patients who meet Bipolar Disorder Manic Episode diagnostic criteria were included in the study. Additionally, the changes in the patient group between manic episode and remission period were examined. We evaluated the relationship between levels of l-arginine and arginine decarboxylase in the agmatine synthesis pathway, and level of agmatinase that degrades agmatine. Results: Levels of agmatine and l-arginine were significantly increased than control group during manic episode (p < .01). All parameters were increased during manic episode compared to remission period (p < .05). Agmatinase was significantly decreased both during manic episode (p < .01) and remission period (p < .05) in comparison to the control group. Arginine decarboxylase levels did not show a significant difference between the groups (p > .05). Conclusions: This study indicate that there may be a relationship between bipolar disorder and agmatine and its metabolic pathway. Nonetheless, we believe more comprehensive studies are needed in order to reveal the role of agmatine in etiology of bipolar disorder.
Family History in Patients With Bipolar Disorder
(Aves, 2016) Ozdemir, Osman; Coskun, Salih; Aktan Mutlu, Elif; Ozdemir, Pinar Guzel; Atli, Abdullah; Yilmaz, Ekrem; Keskin, Siddik
Introduction: In this study, we aimed to better understand the genetic transmission of bipolar disorder by examining the family history of patients. Methods: Sixty-three patients with bipolar disorder and their families were included. The final sample comprised 156 bipolar patients and their family members. An inclusion criterion was the presence of bipolar disorder history in the family. The diagnosis of other family members was confirmed by analyzing their files, hospital records, and by calling them to the hospital. Results: Sixty-five patients were women (41.6%) and 91 were men (58.3%) (ratio of men/women: 1.40). When analyzing the results in terms of the transition of disease from the mother's or father's side, similar results were obtained: 25 patients were from the mother's side and 25 patients were from the father's side in 63 cases. Conclusion: The results of our study support the fact that a significant relationship exists between the degree of kinship and the heritability of bipolar disorder and, furthermore, that the effect of the maternal and paternal sides is similar on the transmission of genetic susceptibility.
Family Patterns of Psychopathology in Psychiatric Disorders
(W B Saunders Co-elsevier inc, 2015) Ozdemir, Osman; Boysan, Murat; Ozdemir, Pinar Guzel; Coskun, Salih; Ozcan, Halil; Yilmaz, Ekrem; Atilla, Ercan
Objective: Familial loading and crucial outcomes of family history of psychopathology in psychiatric disorders have long been recognized. There has been ample literature providing convincing evidence for the importance of family psychopathology in development of emotional disturbances in children as well as worse outcomes in the course of psychiatric disorders. More often, maternal psychopathology seems to have been an issue of interest rather than paternal psychopathology while effects of second-degree familiality have received almost no attention. In this study, we addressed the relations between affected first- and second-degree relatives of probands and categories of psychiatric disorders. METHOD: Subjects were 350 hospitalized psychiatric inpatients, consecutively admitted to psychiatry clinics in Van, Turkey. Mean age was 34.16 (SD +/- 12) and 51.4% of the sample consisted of male patients. Assessment of psychopathology in psychiatric probands was conducted based on DSM-IV TR. Familial loading of psychiatric disorders amongst first- and second-degree relatives of patients were initially noted primarily relying on patients' retrospective reports, and confirmed by both phone call and following official health records via the Medical Knowledge System. We analyzed the data using latent class analysis approach. RESULTS: We found four patterns of familial psychopathology. Latent homogeneous subsets of patients due to familial characteristics were as paternal kinship psychopathology with schizophrenia, paternal kinship psychopathology with mood disorders, maternal kinship psychopathology and core family psychopathology. CONCLUSION: Family patterns were critical to exerting variation in psychiatric disorders of probands and affected relatives. Probands with a core family pattern of psychopathology exhibited the most colorful clinical presentations in terms of variation in psychopathology. We observed a specificity of intergenerational transmission of psychiatric disorders when family patterns of psychopathology were taken into consideration, even second-degree relatives of psychiatric probands. Copyright (C) 2014 Elsevier Inc. All rights reserved
Psychometric Properties of the Turkish Version of the Clinician-Administered Ptsd Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (Turkish Caps-5)
(Aves, 2017) Boysan, Murat; Ozdemir, Pinar Guzel; Yilmaz, Ekrem; Selvi, Yavuz; Ozdemir, Osman; Kefeli, Mehmet Celal
Background: In the subsequent revision of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5; American Psychiatric Association, 2013) symptoms of diagnostic criteria for post-traumatic stress disorder (PTSD) are defined in four clusters and the number of PTSD symptoms was expanded to 20. The Clinician-Administered PTSD Scale (CAPS) is the most widely used structured clinical interview and recognized as the golden standard in PTSD diagnosis. The final revision of the clinical interview form as the CAPS for DSM-5 (CAPS-5) was advanced in line with the recent revisions in DSM-5 with regards to the PTSD definition. The aim of this study was to examine the psychometric properties of the Turkish version of CAPS-5 in clinical samples and healthy controls. Methods: In the present study, 30 inpatients with PTSD and 30 inpatients with major depressive disorder consecutively presented to the Psychiatry Outpatient Clinic Yuzuncu Yil University Research Hospital, and 30 healthy controls were enrolled. All participants were included if only they reported an index trauma in the Life Events Checklist for DSM-5 (LEC-5) that bothered them during the past month. Subjects were administered a socio-demographic questionnaire, the Dissociative Experiences Scale (DES), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) along with the LEC-5, CAPS-5 and PTSD Checklist for DSM-5 (PCL-5). We used confirmatory factor analysis to compare a structured clinical interview (CAPS-5) and a self-report measure, the PCL-5 and to examine DSM-5 implied four-symptom clusters and several factor structures proposed in the literature to understand which model best represents the latent factor structure of PSTD symptoms. Using multivariate analysis of covariance, concurrent validity of both self-report and structured clinical interview was evaluated. Receiver operating characteristics (ROC) curve was utilized to obtain an optimal cut-off value of the PCL-5 scores in order to use in demarcating cases with non-cases. Results: Even though DSM-5 implied four-factor model adequately fit to either data collected using self-report or clinician-administered measures of PTSD, the latent structure of PTSD symptoms measured by either CAPS-5 or PCL-5 were best represented by six-factor Externalizing Behaviors model, particularly compared to seven-factor Hybrid model. In comparison to depressive and control groups, PTSD patients reported greater scores on the PCL-5, DES, BDI, and BAI and McNemar.2 values between two applications with two weeks interval were unsubstantial. Additionally, PTSD patients exhibited greater symptom endorsement on B, C, D, E, F, G symptom clusters and dissociative subtype than depressive patients and controls. Using signal detection analysis, a significant area under the curve (AUC) was calculated for the PCL-5 (AUC = 0.87 p < 0.001 asymptotic 95% Confidence Interval = 0.798-0.942). The PCL-5 had excellent diagnostic utility with 0.90 sensitivity and 0.80 specificity on a cut-off score >= 47. Conclusion: Turkish versions of the CAPS-5 and PCL-5 are demonstrated to have very good psychometric properties. Implications regarding the findings are discussed.
Psychometric Properties of the Turkish Version of the Ptsd Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (pcl-5)
(Aves, 2017) Boysan, Murat; Ozdemir, Pinar Guzel; Ozdemir, Osman; Selvi, Yavuz; Yilmaz, Ekrem; Kaya, Nuray
Objective: The posttraumatic stress disorder (PTSD) Checklist is one of the most widely used screening tool in assessing PTSD symptomatology. Several changes to PTSD definition were made in the recent revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The aim of the study was to assess psychometric properties of the Turkish version of the PTSD Checklist for DSM-5 (PCL-5), the revised version conforming to the advances in DSM-5. Method: Psychiatric outpatients with PTSD (n = 29) and major depressive disorder (n = 73) and a community group (n = 360) included in the study. Respondents completed the PCL-5, Trauma Symptom Checklist-40, Life Events Checklist for DSM-5, Dissociative Experiences Scale, Beck Anxiety Inventory, Beck Depression Inventory and Posttraumatic Cognitions Inventory. Results: We found a four-factor solution best fit to the data providing support for the vast array of PTSD research. The PCL-5 demonstrated good reliability with composite reliability coefficients of re-experiencing (.79-.92), avoidance (.73-.91), negative alterations (.85-.90) and hyper-arousal (.81-.88) and temporal reliability with two-week test retest intra-correlation coefficients of .70, .64, .78, and .76, respectively. Strong associations of the total and sub-scale scores of the PCL-5 with other measures of trauma-related symptoms were indicative of construct validity of the screening tool. The current investigation suggested a cut-off score >= 47 for PTSD diagnosis, with .76 sensitivity and .69 specificity. Conclusion: The PCL-5 is a promising screening tool with sound psychometric properties.
Psychometric Properties of the Turkish Version of the Sleep Hygiene Index in Clinical and Non-Clinical Samples
(W B Saunders Co-elsevier inc, 2015) Ozdemir, Pinar Guzel; Boysan, Murat; Selvi, Yavuz; Yildirim, Abdullah; Yilmaz, Ekrem
Objective: Sleep is one of the most significant of human behaviors, occupying roughly one third of human life. Sleep is a process the brain requires for proper functioning. Sleep hygiene can be described as practices to ease sleep and to avoid factors which decrease sleep quality. Inadequate sleep hygiene generally results in disturbance of daily life activities due to inability to sustain sleep quality and daytime wakefulness. Therefore, the importance of development and utilization of measures of sleep hygiene increases. The aim of the study was to assess psychometric properties of the Sleep Hygiene Index (SHI) in clinical and non-clinical Turkish samples. Method: Data were collected from 106 patients with major depression consecutively admitted to the psychiatry clinic of Yuzuncu Yil University School of Medicine and 200 were volunteers recruited from community sample who were enrolled at the university. The SHI, Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI) and Epworth Sleepiness Scale (ESS) were administered to the subjects. Factor structure of the SHI was evaluated with explanatory and multi-sample confirmatory factor analyses. Pearson product-moment correlation coefficients of the SHI with the PSQI, IST and ESS were computed. Item analyses, internal consistency coefficients and intra-class correlations between two repeated applications in both patient and healthy subjects were calculated. Results: The Sill revealed a unidimensional factor structure. Significant strong partial associations of the SHI with depression, insomnia and poor sleep quality and a modest partial association with sleepiness were detected. Cronbach's alphas for the SHI in community sample and patients with major depression were 0.70 and 0.71, respectively. Additionally, we found acceptable three-week temporal reliability in terms of intra-correlation coefficients of r = 0.62, p < 0.01 for the community sample and of r = 0.67, p < 0.01 among patients with major depression. Conclusion: The SHI revealed adequate validity and reliability to be used by researchers in Turkish sample. Current results were discussed in light of previous findings and theoretical considerations. (C) 2015 Elsevier Inc. All rights reserved.
Relations Between Post-Traumatic Stress Disorder, Dissociation and Attention-deficit/Hyperactivity Disorder Among Earthquake Survivors
(Aves, 2015) Ozdemir, Osman; Boysan, Murat; Ozdemir, Pinar Guzel; Yilmaz, Ekrem
Introduction: There is a burgeoning interest in relations between posttraumatic stress disorder (PTSD) and attention-deficit/hyperactivity disorder (ADHD). Although few studies were conducted, weak evidence was found supporting the hypothesis that ADHD may be a risk factor for the development of PTSD. In addition, there is a paucity of research addressing the relations between dissociation and ADHD. In this study, our aim was to examine the relations between PTSD and ADHD combined with the mediating effect of dissociative psychopathology. Methods: The participants were 317 undergraduate students, a greater proportion of whom experienced the 2011 Van earthquake (66%). The participants were administered the Posttraumatic Diagnostic Scale, Dissociative Experiences Scale, Adult ADHD Self-Report Scale, Beck Depression Inventory and Beck Anxiety Inventory. Results: We found that ADHD symptoms and dissociation were significantly associated with PTSD. Considering the multivariate relations between ADHD, PTSD and dissociation, significant associations between PTSD and ADHD resulted from symptom overlaps. However, pathological dissociation mediated the relations between PTSD and ADHD. Conclusion: We concluded that ADHD comorbidity was not a predominant vulnerability factor for the development of post-traumatic stress response but may be an exacerbating factor after the development of PTSD.
The Relationship Between Atypical Depression and Insulin Resistance in Patients With Polycystic Ovary Syndrome and Major Depression
(Elsevier Ireland Ltd, 2017) Ozdemir, Osman; Kurdoglu, Zehra; Yildiz, Saliha; Ozdemir, Pinar Guzel; Yilmaz, Ekrem
In this study, we aimed to examine the relationship between atypical depression and insulin resistance (IR) in patients with polycystic ovary syndrome (PCOS) and major depression. A total of 176 subjects (69 patients with PCOS, 58 patients with depression, and 49 healthy controls) were included in the study. The Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAT), the Beck Hopelessness Scale (BHS), and the Scale for Suicide Ideation (SSI) were administered. Data concerning their height, weight, fasting a.m. serum levels of insulin, glucose level, and total testosterone level were collected from all participants. The body mass index (BMI) and the Homeostasis Model Assessment Insulin Resistance index (HOMA-IR) were both calculated. 34 (49.3%) of the PCOS patients met the criteria for depression. 26 (76.5%) of them had atypical depression, 8 (23.5%) had non-atypical depression. 27 (46.6%) of the 58 depressed patients had atypical depression. Insulin resistance was higher in the PCOS patients than in the control subjects and the depression patients. There was no association between atypical depression and IR in patients with PCOS and depression. We concluded that there is no relationship between IR and atypical depression.
The Relationships Between Dissociation, Attention, and Memory Dysfunction
(Turkish Neuropsychiatry Assoc-turk Noropsikiyatri dernegi, 2015) Ozdemir, Osman; Ozdemir, Pinar Guzel; Boysan, Murat; Yilmaz, Ekrem
Introduction: Dissociation is a disruption in the integrated functions of consciousness, memory, identity, and perception. Dissociative symptoms include derealization/depersonalization, absorption, and amnesia. These experiences can cause a loss of control over mental processes, including memory and attention. In literature, there is a paucity of research concerning the relationships between dissociation and memory performance. In this study, our aim was to investigate the relationships between dissociative experiences, attention, and memory performance in a non-clinical community sample. Methods: In this study, we examined the relationship between dissociation and cognitive dysfunction among 60 healthy volunteers. We administered the Wechsler Memory Scale-Revised, Auditory Verbal Learning Test, Stroop Color Word Interference Test, and Dissociative Experience Scale. Here we examined the relationships between the subtypes of dissociation and memory performance as assessed by neuropsychological tests. Results: We found that verbal memory was negatively associated with dissociative experiences. Pathological dissociation, particularly amnesia and depersonalization/derealization, was reversely linked to general memory performance and long-term memory. Moreover, low dissociators reported higher scores on verbal memory, general memory performance, and long-term memory but lower scores on recognition than high dissociators. Conclusion: The results of our study suggested that there are significant linkages between dissociative experiences and memory performance.
Relationships Between Posttraumatic Stress Disorder (Ptsd), Dissociation, Quality of Life, Hopelessness, and Suicidal Ideation Among Earthquake Survivors
(Elsevier Ireland Ltd, 2015) Ozdemir, Osman; Boysan, Murat; Ozdemir, Pinar Guzel; Yilmaz, Ekrem
Researches have demonstrated that Posttraumatic stress disorder (PTSD) is one of the most common stress reactions in the face of disasters and significantly associated with a broad range of trauma-induced sequelaes including anxiety, depression, suicidality as well as functional impairments. To date, though many aspects of risk factors with respect to the development and maintenance of PTSD have been addressed, mediating role of dissociation has received relatively less attention. In the present study, we examined relations of PTSD with quality of life, hopelessness, suicidal ideation, and mediational effect of pathological dissociation in these connections. 583 subjects most of whom experienced a severe earthquake participated in the study after two years of the disaster. We found that being female, being single, earthquake exposure, and having greater suicidal ideation were significant predictors of PTSD symptom severity. Role-Physical, Bodily-Pain, General Health and Role-Emotional subscales of the SF-36 were inversely associated with PTSD symptom severity. Pathological dissociation significantly mediated the substantial associations between predictors and PTSD symptom clusters. Chronic dissociation appears to put trauma exposed individuals in jeopardy of prolonged posttraumatic reactions by mediating the negative influences of risk factors in the face of experienced earthquake. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
White Matter Hyperintensity in Patient With Treatment Resistant Obsessive Compulsive Disorder: a Case Report
(Cumhuriyet Univ Tip Fak Psikiyatri Anabilim Dali, 2015) Ozdemir, Osman; Guzel Ozdemir, Pinar; Cilingir, Vedat; Yilmaz, Ekrem; Bulut, Mehmet Deniz
Neurobiological models of obsessive compulsive disorder (OCD) suggest that there are structural and functional abnormalities in frontal-striatal-thalamic-cortical circuits. These cortical and subcortical microcircuits are physically and functionally connected through the white matter. Therefore, the disrupted white matter microstructure may be implicated in the pathophysiology of OCD. Neuroanatomical studies have reported various regional white matter abnormalities in patients with OCD. In this case, we present subcortical white matter lesions or hyperintensities in a patient with treatment resist ant OCD.