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Amaç: Parametrik kovaryans analizi (ANCOVA) varsayımlarının sağlanamaması ve/veya bağımlı değişkenin iki değerli/sıralayıcı ölçekli olması durumunda, parametrik olmayan ANCOVA yaklaşımlarından yararlanılmaktadır. Parametrik olmayan ANCOVA metodolojisinde Quade, Puri & Sen ve McSweeney & Porter metotları, Ranklı ANCOVA yöntemleri olarak bilinmektedir. Ancak yaygın kullanılan programlarda, bu metotların uygulanmasına yönelik modül(ler) bulunmamaktadır. Bu çalışmanın amacı Ranklı ANCOVA yaklaşımlarını tanıtmak, yazarlar tarafından geliştirilen web tabanlı bir programda uygulamasını yapmak ve bu yaklaşımların avantajlarından bahsetmektedir.Gereç ve Yöntemler: Ranklı ANCOVA yaklaşımlarının teorik özellikleri ve uygulama adımları tanımlanmış ve her bir yaklaşımın uygulanmasına yönelik web tabanlı bir program oluşturulmuştur. Sigara kullanma durumunun biyokimyasal tetkik sonuçları üzerindeki etkisinin incelendiği sağlık alanındaki bir çalışmadan simüle edilen veriler yardımıyla web tabanlı bir program üzerinde her bir yaklaşımın uygulamasına da yer verilmiştir.Bulgular: Her ne kadar, bu çalışmada açıklanan yaklaşımlar için yaygın kullanılan istatistik programlarında özel bir modül olmasa da, bu yaklaşımların kolaylıkla uygulanabileceği simüle verilerle oluşturulmuş klinik bir çalışma üzerinde gösterilmiş, yaklaşımların sonuçları verilmiştir.Sonuç: Birçok araştırmada örneklem genişliğinin kısıtlı olması ve/veya bağımlı değişkenin normal dağılım göstermemesi durumunda, faktöriyel modeller için parametrik yöntemlerin kullanılması, Tip I hata oranının artmasına ve testin gücünün azalmasına neden olmaktadır. Bu hatayı azaltmak için çalışmada önerilen yaklaşımların kullanılması tavsiye edilmektedir. Bu yaklaşımların, web tabanlı program sayesinde de yaygın kullanıma ulaşacağı düşünülmektedir.

Amaç: Yüksek çalışma performansı gerektiren tıp eğitiminde başarıyı etkileyen çok sayıda faktör mevcut olabilir. Bu araştırmanın amacı, Düzce Üniversitesi Tıp Fakültesi öğrencilerinde cinsiyet, yatay geçişle gelme ve yabancı uyruklu olmanın başarı üzerine etkisini incelemektir.Gereç ve Yöntemler: Düzce Üniversitesi Tıp Fakültesinde, 2014-2015 eğitim-öğretim yılında ilk üç sınıfta eğitime devam eden 365 ve 2015-2016 eğitim-öğretim yılında 400 öğrencinin notları incelenmiştir. Birey bazında incelenen öğrenci sayısı 505 olup 217’si erkek ve 288’i kızdır.Bulgular: Dönem sonunda başarılı olarak bir üst sınıfa geçme oranları genel olarak kız öğrencilerde (%95,0) erkek öğrencilere (%86,5) göre anlamlı düzeyde daha yüksek bulunmuştur. Yatay geçişle gelen öğrencilerde başarı oranı (%74,2), ilk yerleştirmeyle Düzce Üniversitesi Tıp Fakültesi’ne yerleşen öğrencilere (%92,2) kıyasla daha düşük çıkmıştır. Yabancı uyruklu öğrencilerde ise bu fark daha da artmış ve başarı oranı %39,5 olmuştur.Sonuç: Genel başarı oranının oldukça iyi düzeyde olduğu Düzce Üniversitesi Tıp Fakültesi’nde ilk üç yıllık süreçte, kız öğrencilerin erkek öğrencilerden daha başarılı, yatay geçiş yapan öğrencilerde beklenenin aksine başarı oranının daha düşük ve yabancı uyruklu öğrencilerin başarı oranının ciddi manada düşük olduğu görülmüştür. Bu çalışmada incelenen yabancı uyruklu olmanın ciddi, yatay geçişle üniversite değiştirmenin orta ve erkek cinsiyetin ise düşük düzeyde de olsa tıp eğitiminde başarıyı olumsuz etkileyen risk faktörleri olduğu saptanmıştır.

Amaç: Bu araştırmanın amacı Düzce Üniversitesi Tıp Fakültesi Dönem I, Dönem II ve Dönem III öğrencilerine uygulanan sınav sorularının geçerlik ve güvenirlik analizlerini yapmaktır.Gereç ve Yöntemler: Düzce Üniversitesi Tıp Fakültesi Öğrenci İşlerinden 2014-2015 ve 2015-2016 eğitim-öğretim yıllarına ait Dönem I, Dönem II ve Dönem III öğrencilerine uygulanan sınav sonuçları elde edilmiştir. 2014-2015 ve 2015-2016 eğitim-öğretim yıllarında Dönem I, Dönem II ve Dönem III öğrencilerine uygulanan toplam 38 kurul sınavı ve 6 dönem sonu sınavı olmak üzere 44 sınav sonucu incelenmiştir. Her bir sınav için 100 soru seçilmiş ve incelenen toplam soru sayısı 4400 adettir. Sınava giren her birey analize dahil edilmiştir. Sınav sorularının geçerlik ve güvenirliğini değerlendirmek için her bir sınava ayrı ayrı “Madde Yanıt Analizi” uygulanmıştır. Her bir sınavın güvenirliğini değerlendirmek için Kuder-Richardson 20 (KR20), KR21 ve Spearman-Brown güvenirlik katsayıları hesaplanmıştır.Bulgular: Çalışma sonucunda, 2014-2015 ve 2015-2016 eğitim-öğretim yıllarında Dönem I ve Dönem II ders kurul sınavlarına ait soruların oldukça kolay düzeyde olduğu ve ayırt edici sorulardan oluştuğu, Dönem III ders kurul sınavına ait soruların oldukça kolay düzeyde olduğu ve düzeltilmesi gereken sorular olduğu söylenebilir. Dönem I, Dönem II final sınavlarına ait soruların ise orta düzeyde zor oldukları ve düzeltilmesi gereken sorular olduğu gözlenmiştir. Dönem III final sınavına ait soruların oldukça zor düzeyde olduğu ve çok zayıf nitelikte yani sınavda yer almaması gereken sorular olduğu söylenebilir.Sonuç: Sınav niteliğini ve öğrenci başarısını değerlendirmek için uygulanan sınavların hem genel hem de soru bazında farklı teknikler kullanılarak değerlendirilmesi önerilmektedir. Ayrıca sınav sorularının kalitesini artırmak amacıyla tıp fakültesi öğretim üyelerine Tıp Eğitiminde Ölçme ve Değerlendirme konularında eğitimlerin verilmesi tavsiye edilmektedir.

Introduction: Repetitive wheezing in children today is an important problem. It isimportant to identify preventable risk factors in children with recurrentwheezing complaints. Asking for risk factors and making suggestions can preventboth recurrent admission and persistent bronchial damage. The present research was conducted to evaluate therisk factors of recurrent wheezing in children. Methods: Thiscross-sectional study was performed with 50 children with recurrent wheezing.Previous medical history and sociodemographic features of children weresearched.Results: The60%(n=30) of participants were male , %40 (n=20) were female. The mean age andbirth weight of children were calculated 49.1 ± 48 months and 3227.2 ± 680.6 grrespectively. Children with recurrent wheezing had significantly diverse ratiosin terms of the type of delivery (p=0,007),breast feding (p lt;0.001),vaccinations (p lt;0.001),atopic dermatitis (p lt;0.001),child care (p=0.003),natal and postnatal maternal smoking (p lt;0.001, p=0.007), asthma history of the parents and siblings(p lt;0.001), rural-urbansettlement (p=0.021), andmoisture and warming shape of family house (p=0.002).Conclusion: Recurrentwheezing is an important health problem in childhood. Sociodemographic, environmental preventiveapproaches must be considered in the treatment modalities of patients.

Aim: The aim of this study is to determine the Turkish validity reliability and newborns’ adaptation to Pediatric Peripheral Intravenous Infiltration Scale. Materials and Methods: This study is methodological and was conducted on 54 newborns with the simultaneous evaluation of two observers. Each infant was monitored 8 times with hourly observations from when the vein path was changed, and a total of 864 observational outcomes were assessed with scale. SPSS program was used for statistical evaluations. Results: A total of 54 newborns were taken into the study and the proportions of cases at each care level in neonatal intensive care unit were similar (level 1: 16 patients, level 2: 23 patients, level 3: 15 patients (p=0.348). The most commonly used fluid was found to be dextrose 10% in 63%, and total parenteral nutritional fluid in 26%. The newborns’ postnatal age was median 3 days (minimum: 1, maximum: 27). A total of 864 observations were made for 8 hours and in the 35% (n=19) of 54 babies, the vein pathway was changed after the first observation. 69% of the infants whose vascular accesses were changed, were identified in the first stage (1 point), 25% in the second stage (2 points), and vascular accesses were renewed. The Krippendorff’s alpha reliability coefficient showing the integration between the two evaluators was 1.00 (p

INTRODUCTION: The research was conducted in order to evaluate the alterations in vocational self-esteem of nurses and social workers before and after graduation. METHODS: The study is descriptive. The research began with 112 students before graduation and 40 of the participants were reached after their graduation. In the study, the pre-and-post graduate data of these 40 students were evaluated. The 'Professional Self-Esteem Scale' was used as a data collection means. The scale was carried out to the students twice; first before graduation and second, after one year of their graduation. While analyzing the research data; the Mann-Whitney U test was used to compare quantitative variables between groups and Pearson Chi-square and Fisher' Exact for the relations between categorical variables. RESULTS: In this study when the participants' scores of Professional Self-Esteem Scale were analyzed; the average score was determined as 114,72+-17,32 for the students in the Nursing Department and 121,18+-17,63 for the students in Social Work Department. After graduation score of Nursing and Social Work Department students from the Professional Self-Esteem Scale was significantly lower than the score measured before graduation (p

Özet: Yapılan çalışmada, doğal bir polimer olan kitosan polimeri ile polivinil alkol (PVA) polimeri kullanılarak elektrostatik lif çekim (elektrospinning) yöntemi ile nananolif eldesi gerçekleştirilmiştir. Çapraz bağlayıcı olarak çözeltiye gluteraldehit (GA) ilave edilmiştir. Çekilen nanoliflerin arasına nanokil konularak PVA/Kitosan nanolif-nanokil yüzey elde edilmiştir. Elde edilen nanokil katkılı PVA/Kitosan nanolif yüzeyin taramalı elektron mikroskobu (SEM) görüntüleri alınarak lif morfolojisi ve lif boyutları incelenmiş ve lif çaplarının 110-140 nm arasında oluştuğu görülmüştür. FT-IR analizleri ile elde edilen yüzeyin yapısındaki fonksiyonel gruplar incelenmiş, çapraz bağların oluştuğu gözlenmiştir. TGA (termal gravimetrik analiz) yöntemi kullanılarak sıcaklık değişimi ile numunedeki ağırlık kaybı incelenmiş ve iki aşamalı bozunmanın gerçekleştiği görülmüştür. Anahtar kelimeler: Nanolif, PVA, kitosan, elektrostatik lif çekim, nanokil Synthesis and Characterization of PVA/Chitosan Nanofiber Added Nanoclay Abstract: In this study, nanofibers have been prepared through the electrospinning method in which chitosan- a natural polymer- and polyvinyl alcohol (PVA) polymers were used. Gluteraldehide (GA) was added into the solution as cross-linker. A certain amount of nanoclay was added between the layers of the electrospun nanofibers to obtain PVA/Chitosan nanofiber and nanoclay layer. After that, the fiber morphology and fiber dimensions of the PVA/Chitosan nanofiber and nanoclay were examined by scanning electron microscope (SEM). As a result, it was determined that the diameter of the fiber was between 110 and 140 nm. By FT-IR analysis, the functional groups in the structure of the nanofiber-nanoclay layer and whether the cross-linkers formed were examined. Finally, the change of temperature and the weight loss in the sample were examined through TGA (thermal gravimetric analysis) and it was observed that two-stage degradation occurred. Key words : Nanofiber, PVA, chitosan, electrospinning, nanoclay

Özet: Bu çalışmada, nanolif elde etme yöntemlerinden en yaygın yöntem olan elektrolif çekim (electrospinning) yöntemi kullanılarak, poliakrilonitril (PAN) polimeri ile nanolif üretilmiştir. Üretilen nanolifler arasına daha sonraki çalışmalarda adsorpsiyon amaçlı kullanılabileceği düşünülerek nanokil serpilerek nanokil katkılı PAN nanolif yüzey elde edilmiştir. Üretilen nanokil katkılı PAN nanoliflerin, taramalı elektron mikroskobu (SEM) ile nanolif boyutları ve lif morfolojileri incelenerek, yaklaşık 950 nm çaplarında oldukları görülmüştür. FT-IR ile kimyasal yapı aydınlatılmaya çalışılmış ve bileşimindeki fonksiyonel grupların varlığı incelenmiştir. Nanoliflerin yapısında PAN ve nanokile ait piklerin oldukları belirlenmiştir. Termal gravimetrik analiz yöntemi (TGA) kullanılarak nanokil katkılı PAN nanolifler termal olarak karakterize edilmeye çalışılmıştır. Çalışılan sıcaklık aralığında iki aşamalı bozunmanın gerçekleştiği ve termal bozunmanın tamamlanmadığı görülmüştür. Nanokil katkılı PAN nanoliflerinden sentezlenen yüzeyin, alternatif bir adsorban madde olarak kullanılabileceği tespit edilmiştir. Anahtar kelimeler: Nanolif, nanokil, PAN (poliakrilonitril), elektrolif çekim , SEM. Synthesis and Characterization of PAN Nanofiber Added Nanoclay Abstract: In this study, nanofibers have been prepared from polyacrylonitril (PAN) polymer by using electrospinnig method which is the most common method to obtain nanofibers. Nanoclay doped PAN nanofiber webs were prepared by sprinkled nanoclay in spinning process of nanofibers which may be used to purpose of adsorption in other study. Diameter sizes and morphology of the produced PAN nanofibers including nanoclay were examined through SEM and it was observed that nanofibers have about 950 nm diameters. The chemical structure has been tried to be illuminated by using FT-IR and the presence of functional groups in this composition have been investigated. It was observed that there were peak belonging to PAN and nanoclay within the structure of nanofibers. PAN nanofibers included nanoclay have been tried to be characterized thermally by using the TGA (thermal gravimetric analysis) method. In the studied range of temperature, it was observed that two-stage degradation occurred and the thermal degradation was not completed. It was determined that the PAN nanofibers were electrospun with nanoclay could be used as a new alternative adsorbent. Key words: Nanofibers, nanoclay, PAN(Polyacrylonitrile), electrospinning, SEM.

Toxoplasma gondii is a protozoon parasite that causes congenital toxoplasmosis, as well as other serious clinical presentations, in immune compromised humans. Analyses of the prevalence and genotyping of strains from the definitive host and intermediate hosts will help to understanding the circulation of the different strains and elucidating the role of the genotype(s) in human toxoplasmosis. Turkey has a specific geographic location bridging Africa, Europe, and Asia. We hypothesized that T. gondii strains may have been transferred to Turkey from these continents via migratory birds or vice versa. The present study aimed to assess the prevalence of toxoplasmosis in wild birds of prey of İzmir and Manisa provinces as well as genetically characterize T. gondii strains from these wild birds to show the relation between bird strains and neighboring stray cats as well as human strains previously isolated in Turkey. Tissues obtained from 48 wild birds were investigated for the presence of T. gondii DNA and then bioassayed in mouse. Isolated strains were genotyped using 15 microsatellite markers. The prevalence of T. gondii DNA was found to be 89.6% (n: 43/48) in wild birds. Out of 43 positive samples, a total of 14 strains were genotyped by 15 microsatellite markers. Among them, eight were type II, three were type III and three were mixture of genotypes (two type II/II and one was II/III). These are the first data that showed the presence of T. gondii and types II and III genotypes in wild birds of Turkey. Moreover, Africa 1 was not detected. In addition, cluster analysis showed that T. gondii strains within type II and III lineage have close relation with strains previously isolated from stray cats in İzmir. Further studies are required to isolate more strains from human cases, other intermediate hosts, and water sources to reveal this relation.

Background and objectives: Cryotherapy is a method of treatment using cold application. This study aimed to evaluate postoperative clinical and hematological parameters and pain associated with total knee arthroplasty in patients and compared cryotherapy to the conventional method of cold ice pack compressions. Materials and Methods: Between January 2015 and January 2016, 90 patients who underwent total knee arthroplasty for grade 4 gonarthrosis were prospectively evaluated. The patients were divided into three groups (n = 30, each): Group 1, cryotherapy was applied in the pre- and postoperative periods; Group 2, cryotherapy was applied only in the postoperative period; and Group 3 (control group), only a cold pack (gel ice) was applied postoperatively. In all groups, pre- and postoperative evaluations at 6, 24, and 48 h, hemorrhage follow-up, knee circumference measurement, visual analog scale pain score, knee circumference, and temperature measured by thermal camera were recorded. Results: Of the 90 patients, 10% were men and 90% were women. The mean age was 64.3 ± 8.1 (range: 46−83) years. The patella upper end diameter values were significantly lower in the postoperative period in Groups 1 and 2 than in Group 3 (p = 0.003). Hemoglobin levels at 24 and 48 h postoperatively were significantly lower in Group 3 than in Group 1 (p < 0.001, each) and Group 2 (p = 0.038, p < 0.001). At 6, 24, and 48 h follow-ups, pain values were significantly lower in Group 2 than in Group 3 (p < 0.001). Preoperative 6, 24, and 48 h temperature values were significantly lower in Group 1 than in Group 3 (p < 0.001 for each). It was found that the difference between preoperative and postoperative knee flexion measurements was significantly different in both groups or the difference between the groups was changed in each period (p < 0.001). Conclusions: Postoperative cryotherapy is a potentially simple, noninvasive option and beneficial for the reduction of reducing pain, bleeding, length of stay, analgesic requirement and swelling after total knee arthroplasty. Moreover, there was no early or late prosthesis infection in cryotherapy groups, which may be considered as an additional measure to prevent prosthesis infection.

Background and objectives: Hallux valgus is a complex deformity of the first metatarsophalangeal joint characterized by varus deformity of the first metatarsal bone, valgus deformity of the big toe, and lateral deviation of the extensor tendons and sesamoid bones. Several surgical methods have been described for correction of the deformity. Different materials have been used for the fixation of osteotomy. We compared the functional, radiological, and pain results of intramedullary self-locked plates and Herbert screws for the treatment of a hallux valgus deformity. Materials and Methods: Distal metatarsals were treated with self-locking intramedullary plate−screw systems in 18 feet from 12 patients (Group 1) and with Herbert screws in 18 feet from 12 patients (Group 2). The hallux valgus angle (HVA) and intermetatarsal angle (IMA) in patients of Group 1 and 2 were examined radiologically during the pre- and postoperative periods. We also determined the American Orthopedic Foot and Ankle Society (AOFAS), EQ-5D General Life Quality Scale, and Visual Analogue Scale (VAS) scores during the pre- and postoperative periods and compared the scores between groups. Results: Post hoc test results of HVA and IMA angles measured after the operation were significantly higher in Group 2 than in Group 1. In each group, the AOFAS scores during the preoperation period were significantly lower than those during the postoperation period (p < 0.001). According to the post hoc test results, the VAS scores after the operation were significantly higher in Group 2 than in Group 1 (p < 0.001). Conclusions: For the surgical treatment of hallux valgus, operations using self-locked plates compared to a single screw are superior in terms of providing rigid stability and for functional, radiological, and pain scores.

The developments in conversational AI raised urgent questions about the future direction of many aspects of society, including computing education. The first reactions to the fast-paced evolution of conversational agents were varied: Some announced "the end of programming," while others considered this "premature obituary of programming." Some adopted a defensive approach to detecting the use of conversational AI and avoiding an increase in plagiarism, while others questioned, "So what if ChatGPT wrote it?" Nevertheless, questions arise about whether computing education in its current form will still be relevant and fit for purpose in the era of conversational AI. Recognizing these diverse reactions to the advent of conversational AI, this paper aims to contribute to the ongoing discourse by exploring the current state through three perspectives in a dedicated literature review: adoption of conversational AI in (1) software engineering education specifically and (2) computing education in general, and (3) a comparison with software engineering practice. Our results show a gap between software engineering practice and higher education in the pace of adoption and the areas of use and generally identify preliminary research on student experience, teaching, and learning tools for software engineering., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could potentially create a conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Sengul, Neykova and Destefanis.)

Objective: Hyperbilirubinemia is associated with protection against various oxidative stress-mediated diseases. We aimed to investigate the association between bilirubin and novel electrocardiography (ECG)-based ventricular repolarization parameters., Methods: We enrolled 201 healthy men with mild hyperbilirubinemia (group 1) and 219 healthy men with normal bilirubin levels (group 2). The Tpeak-Tend (Tp-e) interval (defined as the interval from the peak of the T wave to the end of the T wave), corrected (c) Tp-e interval, QT interval, cQT interval, and Tp-e interval/QT interval ratio were measured from leads V5 and V6 with 20 mm/mV amplitude and 50 mm/second rate., Results: The Tp-e interval, cTp-e interval, and Tp-e interval/QT interval ratio were significantly lower in group 1 compared with group 2. The cTp-e interval showed a significant negative correlation with total bilirubin, conjugated bilirubin, and unconjugated bilirubin. The cTp-e interval (odds ratio [OR], 0.900; P =.002) and Tp-e interval/QT interval ratio (OR, 0.922; P =.04) were significantly associated with mild hyperbilirubinemia., Conclusion: We showed the association of mild hyperbilirubinemia with decreased novel ECG-based ventricular repolarization parameters., (© American Society for Clinical Pathology 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: T-wave inversion in lead III was linked to displacement of the base of the heart due to abdominal adipose tissue in early electrocardiography (ECG) trials. The observation of T-wave inversion in lead III in some of the pathological and physiological conditions other than obesity suggests the possibilities of different mechanisms. We aimed to investigate the prevalence and correlates of T-wave inversion in lead III in non-obese men., Method: A total of 1240 men underwent ECG, blood pressure measurement, hepatic ultrasonography, and biochemical tests from January 2019 to December 2019. We excluded 220 subjects due to predetermined criteria. The eligible 105 non-obese men with T-wave inversion in lead III and 915 non-obese men without T-wave inversion in lead III were compared with each other in terms of clinical, demographic and laboratory parameters., Results: The mean age was 27.9 years with a range of 20 to 46 years. The prevalence of T-wave inversion in lead III was 10.3%. Body mass index (BMI), blood urea nitrogen, creatinine, alanine aminotransferase, hematocrit, and the percentage of non-alcoholic fatty liver disease (NAFLD) were significantly higher in Group with T-wave inversion while alkaline phosphatase was significantly higher in Group without T-wave inversion. In multivariable analysis, NAFLD was the best independent correlate of inverted T-wave in lead III (β = 6.215, p < 0.0001). BMI (β = 1.448, p < 0.001) and hematocrit (β = 1.179, p = 0.021) were the other independent correlates of T-wave inversion in lead III., Conclusion: We demonstrated the association of T-wave inversion in lead III with NAFLD, BMI, and hematocrit in non-obese men., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Alcohol dependence (AD) is a neuropsychiatric disorder to which both genetic and environmental factors contribute. Especially, multiple genetic factors are promising to explain the etiology of AD. microRNAs (miRNAs) are members of a family of noncoding small RNAs, which are thought to be responsible for the altered gene expression in neuropsychiatric disorders. We hypothesized that single nucleotide polymorphisms (SNPs) in the miRNA biogenesis pathway may result in dysregulation of miRNA levels inside the cell. The aim of this study was to test an association between miRNA biogenesis gene variants and AD risk. Real-time polymerase chain reaction genotyping experiment was conducted on DNA samples from 123 alcohol-dependent patients and 135 healthy controls. We found that AGO1 rs595961 (χ(2) = 9.066, p = 0.003; odds ratio [OR] = 0.459, 95% confidence interval [CI]: 0.275-0.768) and AGO2 rs4961280 (χ(2) = 4.111, p = 0.043; OR = 0.590, 95% CI: 0.353-0.986) G alleles have significantly altered the risk for AD, and also there is a significant association of GEMIN4 rs910924 (χ(2) = 5.291, p = 0.021; OR = 1.913, 95% CI: 1.094-3.344) T allele with the risk for AD. We also found statistically significant difference in AGO1 rs595961 (χ(2) = 11.139, p = 0.001) and DGCR8 rs1640299 (χ(2) = 13.001, p = 0.002) genotype frequencies between case-control groups. This is the first study to investigate the effects of SNPs in the miRNA biogenesis pathway on AD risk. In conclusion, we identified a significant association of miRNA biogenesis genes with altered AD risk, and these results could be a guide to research on the role of miRNAs in AD in the future.

Background: Non-alcoholic fatty liver disease (NAFLD) has been considered as a benign disease often associated with central obesity and insulin resistance and, in general, with factors of the metabolic syndrome. Heart rate recovery after exercise is a function of vagal reactivation, and its impairment is an independent prognostic indicator for cardiovascular and all-cause mortality. The aim of our study was to evaluate the heart rate recovery index in patients with NAFLD., Material and Methods: The study population included 59 patients with NAFLD (mean age=42.3±9.3 years) and 22 healthy subjects as controls (mean age=40.7±6.5 years). Basal electrocardiography, echocardiography, and treadmill exercise testing were performed on all patients and controls. The heart rate recovery index was defined as the reduction in the heart rate from the rate at peak exercise to the rate at the 1st minute (HRR1), 2nd minute (HRR2), 3rd minute (HRR3), and 5th minute (HRR5) after stopping exercise stress testing., Results: There were significant differences in HRR1 and HRR2 indices between patients with ED and the control group (19.9±8.2 vs. 34.1±9.6; p<0.001 and 24.3±5.4 vs. 40.5±9.1; p=0.006, respectively). Similarly, HRR indices after the 3rd and 5th minutes of the recovery period were significantly lower in patients with NAFLD compared with those indices in the control group (32.3±8.5 vs. 58.4±6.5; p=0.001 and 58±18.2 vs. 75.1±15.8; p<0.001). Effort capacity was markedly lower (11±1.9 vs. 12.5±1.5 METs; p=0.001) among the patients with NAFLD., Conclusions: The heart rate recovery index is deteriorated in patients with NAFLD. When the prognostic significance of the heart rate recovery index is considered, these results may help explain the increased occurrence of cardiac death. It points to the importance of the heart rate recovery index in the identification of high-risk patients.

Objective: The relationship between menstruation disorders and antidepressant drugs usage in women remains unclear. In this study, we aimed to investigate the incidence rate of antidepressant-related menstruation disorders and to examine whether or not antidepressant use is associated with menstrual disorders in women., Methods: The study sample was gathered from three centers and four hospitals. A total of 1432 women who met the criteria of inclusion were included in the study. The sample was divided into two groups: the antidepressant group (n=793) and the control group (n=639). The menstruation disorders were established with reports from the study participants on the basis of related gynecological descriptions., Results: The prevalence of menstrual disorders was significantly higher in the antidepressant group (24.6%) than the control group (12.2%). The incidence of antidepressant-induced menstruation disorder was 14.5%. The antidepressants most associated with menstrual disorders were paroxetine, venlafaxine, sertraline and their combination with mirtazapine. Overall, the incidence rate was similar in women receiving selective serotonin reuptake inhibitors and serotonin noradrenaline reuptake inhibitors., Conclusions: The results of the present study suggest that menstruation disorders are frequently observed in women taking antidepressants and that it appears to be associated with antidepressant use at least in some women., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Atrial electromechanical delay (EMD) parameters predict the development of atrial fibrillation. We investigated the effect of telmisartan treatment on atrial EMD parameters in patients with newly diagnosed essential hypertension., Methods: Thirty-six patients with essential hypertension were treated with telmisartan (80 mg/day) for 6 months. Baseline electrocardiographic P-wave measurements and echocardiographic atrial EMD parameters were compared with the 6-month follow-up., Results: Pmax and Pd were significantly decreased (108.4 ± 6.1 vs 93.9 ± 6.2 milliseconds, 33.4 ± 8.6 vs 19.5 ± 7.0 milliseconds, respectively, P = .0001 for each) after 6-month telmisartan therapy. The atrial EMD parameters were decreased from baseline (mitral EMD, 68.9 ± 4.9 vs 53.8 ± 4.9 milliseconds; septum EMD, 51.6 ± 7.1 vs 42.6 ± 7. milliseconds1; tricuspid EMD, 48 ± 6.9 vs 39 ± 6.9 milliseconds; interatrial EMD, 20.9 ± 5.5 vs 14.8 ± 5.7 milliseconds; P = .0001 for each parameter). The reduction of interatrial EMD was correlated with the reduction in systolic BP nighttime and the increase in mitral E wave velocity/mitral A wave velocity ratio., Conclusion: Telmisartan decreased the atrial EMD parameters in patients with newly diagnosed essential hypertension., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Epicardial fat tissue reflects visceral adiposity and is a suggested cardiometabolic risk factor. Patients with abdominal obesity have an increased prevalence of the non-dipper blood pressure (BP) pattern, but it is unclear whether the same is true of patients with increased epicardial fat thickness (EFT). The association between EFT and circadian BP changes in patients with recently diagnosed essential hypertension was examined., Methods: Sixty hypertensive patients underwent echocardiography, treadmill stress testing, and 24 hours of ambulatory BP monitoring. Epicardial fat thickness and left ventricular mass (LVM) index were measured by using transthoracic echocardiography. The patients were categorized into two groups according to their BP pattern (group 1, non-dippers; group 2, dippers)., Results: The mean EFT and LVM of patients in group 1 (n = 24) (EFT, 7.6 ± 2.1 mm; LVM, 130 ± 31.2 g/m(2)) were significantly greater than those of group 2 (n = 36) (EFT, 5.5 ± 1.2 mm, P = .0001; LVM, 107 ± 23.7 g/m(2), P = .002). The average systolic BP over 24 hours (BP(s) 24) and average diastolic BP over 24 hours (BP(d) 24) of group 1 (BP(s) 24, 151.1 ± 17.6 mm Hg; BP(d) 24, 94.1 ± 16.5 mm Hg) were significantly higher than those of group 2 (BP(s) 24, 136.7 ± 11.9 mm Hg, P = .0001; BP(d) 24, 84.6 ± 10.6 mm Hg; P = .008). Multivariate backward logistic regression analysis demonstrated that the non-dipper BP pattern was associated with EFT (standardized β coefficient = 0.87, P = .005) and LVM (standardized β coefficient = 0.43, P = .016). An EFT ≥ 7 mm was associated with the non-dipper BP pattern with 44% sensitivity and 94% specificity (receiver operating characteristic area under curve of 0.72, 95% CI [0.59-0.83], P = .0007)., Conclusions: Epicardial fat thickness was above average in newly diagnosed, untreated hypertensive patients with non-dipper BP pattern. The echocardiographic measurement of EFT may be used to indicate increased risk of hypertension-related adverse cardiovascular events.

Background: Coronary artery ectasia (CAE) is associated with increased sympathetic activity, plasma levels of inflammatory markers, and oxidative stress. These factors can also cause arrhythmias such as atrial fibrillation. Atrial conduction abnormalities in patients with CAE have not been investigated in terms of atrial electromechanical delay obtained by tissue Doppler echocardiography., Methods: Ninety patients with pure CAE (n = 30), nonobstructive coronary artery disease (NO-CAD) (n = 30), and angiographically normal coronary arteries "controls" (n = 30) were compared in terms of electrocardiographic P-wave measurements, echocardiographic atrial electromechanical coupling (AEC) parameters, and interatrial conduction delay., Results: The mean left atrium diameter in the CAE group was similar to the NO-CAD group but significantly greater than the control group (3.62 ± 0.28 vs 3.46 ± 0.32 vs 3.41 ± 0.31 cm, P = 0.021). P maximum and P-wave dispersion were significantly increased in the CAE group compared to the NOCAD group and the control group (108.6 ± 6.6 vs 97.9 ± 6.6 vs 93.5 ± 6.2, P = 0.0001; 34.4 ± 7.6 vs 23.2 ± 7.8 vs 19.4 ± 7.7 ms, P < 0.0001). Mitral AEC, septal AEC, and tricuspid AEC were significantly higher in the CAE group than the NO-CAD group and the control group (68 ± 4.5 vs 57 ± 4.5 vs 53 ± 4.6 ms, P < 0.0001; 50.7 ± 7 vs 42.7 ± 7 vs 41.7 ± 7.2 ms, P = 0.0001; 47 ± 6.7 vs 39.1 ± 6.7 vs 38.1 ± 6.6 ms, P < 0.0001). Interatrial conduction delay was significantly increased in the CAE group compared to the NO-CAD group and the control group (21 ± 5.5 vs 17.8 ± 5.6 vs 15 ± 5.6 ms, P < 0.0001).The correlation analysis demonstrated that the interatrial conduction delay and P-wave dispersion (Pd) were positively correlated with number of ectatic segments (ESN) (r = 0.41, P = 0.024 vs r = 0.49, P = 0.006). Stepwise multiple linear regression analysis revealed that the ESN was the only independent determinants of interatrial conduction delay (P = 0.024)., Conclusion: Pd and interatrial conduction delay are prolonged in patients with CAE compared to NO-CAD patients and the healthy controls.

Objective: Hypertensive response at peak exercise and blunted blood pressure (BP) recovery, altered BP responses obtained from exercise stress testing, have been suggested as risk factors for future onset of hypertension in previous studies. Epicardial fat, a new cardiometabolic risk factor, has been linked to hypertension in some recent studies. In this study, we tested the primary hypothesis suggesting that the epicardial fat thickness (EFT) is related to altered BP responses to treadmill exercise testing. We also evaluated the sensitivity and specificity of the EFT as a predictor of hypertensive response to peak exercise., Methods: Normotensive subjects underwent to treadmill stress testing and transthoracic echocardiography. Hypertensive response to peak treadmill exercise testing was defined as ≥ 210/105 mmHg and ≥ 190/105 mmHg at peak exercise in males and females, respectively. BP recovery index (BPRI) was defined as the ratio of the BP at the 3rd minute of the recovery phase to BP at peak exercise. EFT was measured by echocardiography. Thirty-two subjects with hypertensive response to peak exercise constituted Group 1 and 48 subjects with normal response constituted Group 2., Results: The mean EFT of subjects in Group 1 was significantly higher (8.2 ± 1.1 mm vs 5.1 ± 1.5 mm; p = 0.0001) than subjects in Group 2. In correlation analysis performed in Group 1, EFT was found to be significantly correlated with BPRI (r = 0.51, p < 0.003). An EFT of ≥ 6.5 mm predicted the hypertensive response to peak exercise test with 68.8% sensitivity and 87.5% specificity (receiving operator characteristic area under curve: 0.879, 95% CI 0.793-0.965, p < 0.001). Patients with EFT ≥ 6.5 mm showed a significantly increased BPRI (0.89 ± 0.07 vs 0.74 ± 0.09, p < 0.0001) and peak systolic BP (198.4 ± 15.3 mmHg vs 169.4 ± 19.8 mmHg, p < 0.0001). There were significant differences in metabolic equivalents, maximum heart rate, homeostatic model assessment of insulin resistance, high-density lipoprotein-cholesterol, waist circumference and age values between two patients groups dichotomized according to the cut-off value of EFT. BPRI was the only independent variable related to EFT in the multivariate analysis (odds ratio = 1.4, 95% CI 2.75-7.16, p = 0.001)., Conclusions: EFT was found to be related to altered BP responses to exercise stress testing. The echocardiographic measurement of EFT may serve as a useful non-invasive indicator of heightened risk of future hypertension.

Background: Carotid intima-media thickness (CIMT) is a potential indicator of subclinical atherosclerosis in patients with metabolic syndrome (MetS). Epicardial fat thickness (EFT) is suggested as a new cardiometabolic risk factor. We investigated the association between EFT and CIMT in patients with MetS., Methods: Forty patients with MetS were compared with 40 age- and sex-matched subjects without MetS in terms of echocardiographic EFT, CIMT, anthropometric measurements, and metabolic profile in this cross-sectional study., Results: The waist circumference, total and LDL-cholesterol, fasting glucose, triglycerides, systolics and diastolic blood pressure levels, hs-CRP, and homeostasis model assessment index for insulin resistance (HOMA-IR) were significantly increased in patients with MetS. The EFT and CIMT were also increased significantly in patients with MetS compared to controls (7.2 ± 2 mm vs. 5.7 ± 1.9 mm; P = 0.001, 0.74 ± 0.1 mm vs. 0.59 ± 0.1 mm; P < 0.01, respectively). Echocardiographic EFT was the only independent predictor of CIMT in the multivariate analysis (standardized β coefficient = 0.74, P < 0.001)., Conclusion: EFT is associated with increased CIMT in patients with MetS., (© 2011, Wiley Periodicals, Inc.)

Epicardial fat tissue has unique endocrine and paracrine functions that affect the cardiac autonomic system. Epicardial fat thickness (EFT) and blunted heart rate recovery (HRR) are newly identified cardiovascular risk factors in patients with metabolic syndrome (MS). The objective of this study is to evaluate the association between EFT and HRR in patients with MS. Forty patients with MS and 36 healthy controls were included in the study. Echocardiographic EFT and HRR at 1min after exercise termination (HRR-1) are measured and compared between the two groups. HRR-1 equal to or lower than 18 beats is considered as blunted HRR. EFT was increased (7.2 ± 2 vs. 5.6 ± 1.8 mm; p = 0.001) and HRR-1 was significantly reduced in patients with MS compared to control group (21 ± 8 vs. 26 ± 9; p = 0.006). Among the MS patients, subjects with blunted HRR had increased EFT compared to patients without blunted HRR (8.5 ± 2.0 vs. 5.9 ± 1.1 mm, p < 0.001). In multivariate analysis, EFT was the only independent predictor of blunted HRR in patients with MS (95% confidence interval = 1.42-3.87, OR = 2.34, p = 0.001). Furthermore, EFT of equal to or thicker than 5.5 mm was associated with the blunted HRR with 84% sensitivity and 52% specificity (ROC area under curve: 0.84, 95% confidence interval = 0.70-0.96, p < 0.001). In conclusion, EFT is an independent predictor of blunted HRR, a novel cardiovascular risk factor, in patients with MS.

Background: Acute alcohol consumption can cause atrial fibrillation in patients with, and without, heart disease. Increased atrial electromechanical delay (EMD) has been associated with atrial fibrillation. We evaluated the atrial conduction properties by tissue Doppler imaging (TDI) echocardiography in healthy men following acute alcohol intake., Methods: Thirty healthy male volunteers were included in this study. Baseline ECG, heart rate, blood pressure, and TDI echocardiographic findings were compared to readings taken one hour after drinking six 12-oz cans of beer (76.8 g of ethanol)., Results: Although the blood pressure and heart rate remained similar before and one hour after alcohol intake, Pmax and Pd values were significantly prolonged (114.2 ± 10.4 vs 100.8 ± 10.6, p = 0.002; 50.6 ± 9.6 vs 34.5 ± 8.8, p < 0.0001). Interatrial EMD was significantly increased after drinking alcohol compared to the baseline (19.8 ± 9.2 vs 14.0 ± 5.5 ms, p < 0.0002)., Conclusions: Acute moderate alcohol intake was associated with an increased interatrial EMD obtained by TDI echocardiography. This finding may help explain how these patients express increased susceptibility to atrial fibrillation.

The authors present two cases of advanced Coats' disease having total exudative retinal detachment, in which the disease regressed spontaneously. The patients were a 4-year-old girl and 3-year-old boy with total retinal detachment with widespread vascular anomalies. In the follow-up, fundus examination revealed spontaneous regression. At this stage, photocoagulation and cryotherapy were applied. In case 1, the eye was stable during 2 months but recurrence started thereafter, which ended with phthisis. In case 2, the retina was still attached 6 months following surgery. The authors emphasize the possibility of spontaneous regression, even in advanced Coats' disease., (Copyright 2010, SLACK Incorporated.)

Aim: The aim of the present study was to investigate the differences in the antioxidant-oxidant balance (AO-OB) between schizophrenic patients and healthy individuals and to explore the relationship of AO-OB with illness subtypes and symptom profiles., Methods: After a 15-day drug-free period, schizophrenia patients (n = 50) in a clinical sample, and age- and sex-matched healthy subjects (n = 49) were enrolled. Total antioxidant potentials (TAOP) and total peroxide levels (TPEROX) of all participants were measured and the oxidative stress index (OSI) was calculated. The assessment included structured measurements, including the Positive and Negative Syndrome Scale (PANSS), and the Brief Psychiatric Rating Scale (BPRS)., Results: TAOP had a significant positive correlation with age at onset of schizophrenia (P = 0.013), a negative correlation with the PANSS negative subscale scores (P = 0.008), a negative correlation with the PANSS total scores (P < 0.001), and a significant negative correlation with BPRS scores (P = 0.001). OSI had a significant negative correlation with age at onset (P = 0.046) and a significant positive correlation with PANSS negative subscale (P = 0.015). A multiple regression model indicated a significant linear combination of age, gender, duration of illness, subtype of schizophrenia, and PANSS scores, in which only the subtype of schizophrenia made a statistically significant contribution to predicting mean OSI (F[5,35] = 2.44, P = 0.04)., Conclusion: Several parameters in the pathogenesis of schizophrenia, such as age of onset, level of negative symptoms, and subtype of illness, but not the presence of the illness itself, are associated with the level of oxidative stress.

Background: Multiple primary malignant tumors are rarely seen. Tobacco is one of the factors in their etiology. We report the case of a heavy smoker with metachronous triple primary cancer occurring in the prostate, kidney and urinary bladder., Case Report: A 70-year-old man with prostate cancer presented with the complaint of hematuria. Computed tomography (CT) showed increased wall thickness of the urinary bladder with an enlarged prostate. After the trans-urothelial resection operation pathological diagnosis was consistent with transitional cell carcinoma of the urinary bladder. After 9 months of follow-up, the control CT showed metastatic lesions in the right and left kidneys and in the right lung. Bilateral partial nephrectomy was performed. Interestingly, renal cell carcinoma (RCC) was diagnosed. Rightsided video-assisted thoracoscopic surgery was also performed. The results of the histopathological examination were consistent with metastatic RCC., Conclusions: Although the patient presented with triple carcinoma, there was no familial cancer history suggesting a genetic association. The patient was a heavy smoker, and tobacco usage may be the underlying cause of the detected cancers. This is one of the rare cases in the published literature with triple primary urogenital cancer., (Copyright 2009 S. Karger AG, Basel.)

P-glycoprotein (P-gp), an efflux transporter protein, is an ABC transporter encoded by the multidrug resistance 1 gene (MDR1, ABCB1). The common synonymous C3435T polymorphism in exon 26 is reported to associate with lower P-gp functional expression and drug uptake. Many extended pharmacogenomics, functional, and complex disease association studies focused mainly on this polymorphism. We investigated the association of exon 26 C3435T genetic variants of MDR1 gene with susceptibility to bipolar disorder and serum valproic acid concentration. Totally, 104 patients meeting DSM-IV criteria for bipolar disorder and 169 controls were admitted to the study. There was statistically significant difference between the genotypes of bipolar patients (CT 91.2%, TT 6.8%, and CC 2%) and controls (CT 52.7%, TT 26%, CC 21.3%) although their allelic distribution was similar. The serum valproic acid concentrations of the patients with CT, TT and CC genotypes were 72.92 +/- 20.55, 80.47 +/- 14.01 and 68.29 +/- 12.17 microg/ml, respectively, and there was no significant difference between the C3435T genotypes.

Background: Most published data on the characteristics and direct hospital costs of deliberate self-poisoning (DSP) were collected from developed countries. This study was conducted to investigate hospital costs of DSP cases and relevant factors in a university-based emergency department (ED) in Turkey., Material/methods: All patients referred to the ED due to DSP in the one-year period between October 1, 2005, and September 30, 2006, were investigated prospectively. Clinical and demographic features were analyzed., Results: The female-to-male ratio was 6.3 (189/30). Mean age of the patients was 24.5+/-5.7 years. Medical drugs comprised 93.6% (n=205) of the substances ingested in admissions due to DSP. The mean cost of patients with DSP was calculated to be $144.06+/-90.83. Treatment costs constituted 36.2% of the total figure ($52.27). Total costs showed statistically significant differences with respect to sex, type of intoxicants, and location of treatment. Venipuncture, monitoring, nasogastric tube insertion, and gastric lavage were the procedures most commonly applied. Activated charcoal was administered to 66.9% (n=146) of the study sample., Conclusions: The study sample had many differences in demographic and clinical outcomes of patients with DSP as well as hospital costs compared with global reports. Gender, ingestion of non-medical substances, and treatment location affected the total hospital costs of these patients. Strategies focusing on high-risk subgroups and conditions may help to reduce unnecessary expenses.

Objective: Long-term inhalation of thinners may cause damage, both to the lungs and to other organ systems. It causes cellular damage via formation of reactive oxygen species. The lung is protected from oxidative stress by the glutathione (GSH) antioxidant system which can be augmented by the thiol drug, N-acetylcysteine (NAC). This study investigated the protective effect of NAC on peroxidative changes in rat lungs exposed to inhalation of thinners for 8 weeks., Methodology: Seventy-two male Wistar albino rats were used and divided into two groups: one group inhaled only thinners (TI), while the other inhaled TI plus NAC. Rats in the TI and TI + NAC groups were divided into four subgroups (each consisting of eight rats) according to the duration of exposure to TI: 2, 4, 6 and 8 weeks. A control group (n = 7) of rats inhaled neither TI nor NAC. Malondialdehyde (MDA) and GSH levels, and superoxide dismutase (SOD) activities were determined in the lung tissues. Histopathological findings were evaluated as acute and chronic changes in the alveoli and interstitium in the TI and TI + NAC groups and compared with those in the control group., Results: While tissue MDA levels in the groups inhaling TI for 4, 6 and 8 weeks were significantly higher than those in the control groups (P < 0.01, P < 0.01, P < 0.0001, respectively), GSH levels were significantly lower (P < 0.05, P < 0.01, P < 0.01, respectively). Tissue SOD activities in the groups inhaling TI for 6 and 8 weeks were significantly lower than those in the control group (P < 0.05, P < 0.01, respectively). In the TI group, MDA levels were significantly increased (P < 0.01) with increasing duration of inhalation (from the second week through to the eighth week), while GSH levels and SOD activities were significantly decreased (P < 0.01, P < 0.01). Tissue MDA levels were significantly lower in the TI + NAC groups across all inhalation periods, when compared with the TI groups (P < 0.01, P < 0.0001, P < 0.0001, P < 0.0001, respectively). Tissue GSH levels in the TI + NAC groups were significantly higher than those of the TI groups (respective values: P < 0.05, P < 0.01, P < 0.01, P < 0.0001). Tissue SOD activities in the TI + NAC groups were significantly higher than those of the TI groups (respective values: P < 0.05, P < 0.0001, P < 0.05, P < 0.0001). Pathological examinations with light microscopy did not show any beneficial effect of NAC application in terms of deferring or alleviating the negative effects of TI., Conclusions: Thinners are agents that cause imbalance between oxidants and antioxidants produced by aerobic cellular systems. This imbalance between oxidant and antioxidant systems is decreased by the effect of NAC. However, ultrastructural studies may be needed to substantiate this evidence morphologically, as light microscopy was inconclusive.

Background: Recent years' usage of thinner by the young generation as a drug constitutes a serious problem in the society. Due to common usage in the industrial sector, most people are affected from the manufacturing process to the consuming phase., Aim: Because of these reasons, this project has been preferred to research the effects of thinner on oxidant and antioxidant status., Methods: Totally 46 rats were included in the study. Thirty six rats were separated into six groups with 10 rats in a control group. The first group inhaled thinner for 2 weeks, and the other groups were exposed to thinner for 4, 6, 8, 10 and 12 weeks for 1 h twice a day. On the mentioned duration, rats were autopsied. Lung tissues malondialdehyde (MDA), glutathione (GSH) levels and superoxide dismutase (SOD) activities were determined to designate the oxidant-antioxidant balance., Results: We observed an increase in MDA values both in the acute and the subacute periods. In the chronic period by the consuming of lipid peroxidation products, MDA values decreased and as the oxidative stress continued MDA values again increased. We observed that especially GSH values that has antioxidant feature, decreased until 6 weeks in order to compensate lipid peroxidation products. In the consuming period of lipid peroxidation, the values became fixed and later, these values again increased. There was no relationship between the changing values of MDA and SOD., Conclusions: Thinner is an agent that causes oxidative stress and inhalation of high doses of thinner causes harm to the respiratory system. As there are few reports in the literature on long-term effects of thinner inhalation, more studies might be necessary.