The long-term outcomes of mepolizumab treatment at 100 mg dose on idiopathic chronic eosinophilic pneumonia: A real-life experience.

Background: The standard therapeutic regimen for idiopathic chronic eosinophilic pneumonia (ICEP) involves the administration of oral corticosteroids (OCS). However, a notable proportion of individuals experience recurrent episodes after the tapering or cessation of OCS during the course of ICEP. There has been a growing interest in exploring alternative treatment modalities for patients with ICEP at heightened risk of relapse. Objective: The aim of this study was to assess the efficacy of mepolizumab at a dose of 100 mg administered every 4 weeks in preventing relapses of ICEP and its impact on the clinical outcomes. Methods: This retrospective clinical observational study used real-world data to assess the impact of mepolizumab on patients diagnosed with ICEP accompanied by severe asthma. Demographic information and clinical characteristics were extracted from medical records. The study examined the effect of mepolizumab on the annual relapse rate, OCS dose, eosinophil count, and respiratory function parameters. Results: All patients included in the study, with a median (range) follow-up period of 19 months (4-40 months), the annual relapse rate decreased from 0.33 to 0 after the initiation mepolizumab. In addition, the maintenance OCS dose, expressed in methylprednisolone equivalents, declined from 4 mg/day to 0 mg/day. A reduction in the blood eosinophil count was observed, alongside a partial improvement in respiratory function test results among the patients. Conclusion: A dose regimen of 100 mg of mepolizumab administered every 4 weeks emerges as a promising and well-tolerated therapeutic approach for averting relapses of ICEP.

Gut microbiota-derived metabolite trimethylamine N-oxide and biomarkers of inflammation are linked to endothelial and coronary microvascular function in patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD), which is an umbrella term used for ulcerative colitis (UC) and Crohn's disease (CD), is associated with an increased risk for atherosclerotic cardiovascular disease (CVD). We aimed to investigate the association of local and systemic biomarkers of inflammation and gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) with endothelial and coronary microvascular dysfunction in IBD. METHODS: A total of 56 patients with IBD (20 with UC and 36 with CD) and 34 age and gender matched controls were included. For all participants, samples were collected to analyze faecal calprotectin, and TMAO concentrations. Ultrasound-based examinations were done to measure flow-mediated vasodilatation (FMD) and coronary flow velocity reserve (CFVR). RESULTS: Patients with IBD had lower CFVR (2.07 (1.82-2.40)) and FMD (8.7 ± 3.7) as compared to controls (2.30 (2.07-2.74), p = 0.005 and 11.9 ± 6.8, p = 0.03). In patients with IBD, TMAO concentration (r = -0.30, p = 0.03), C-reactive protein (r = -0.29, p = 0.03) and WBC count (r = -0.37, p = 0.006) had a significant negative correlation with CFVR, and TMAO (ß = -0.27, 95 % CI: -0.23 to -0.02) and WBC count (ß = -0.31, 95 % CI: -0.56 to -0.06) were significant predictors of CFVR after multivariate adjustment. None of the biomarkers of inflammation or TMAO showed significant correlations with FMD. In patients with UC, TMAO showed a significant correlation with both CFVR (r = -0.55, p = 0.01) and FMD (r = -0.60, p = 0.005) while only WBC count had a statistically significant correlation with CFVR (r = -0.49, p = 0.004) in patients with CD. CONCLUSIONS: Gut microbiota-derived metabolite TMAO and biomarkers of systemic inflammation are associated with measures of endothelial/coronary microvascular dysfunction in patients with IBD.

Coronary microvascular dysfunction is common in patients hospitalized with COVID-19 infection.

BACKGROUND AND AIMS: Microvascular disease is considered as one of the main drivers of morbidity and mortality in severe COVID-19, and microvascular dysfunction has been demonstrated in the subcutaneous and sublingual tissues in COVID-19 patients. The presence of coronary microvascular dysfunction (CMD) has also been hypothesized, but direct evidence demonstrating CMD in COVID-19 patients is missing. In the present study, we aimed to investigate CMD in patients hospitalized with COVID-19, and to understand whether there is a relationship between biomarkers of myocardial injury, myocardial strain and inflammation and CMD. METHODS: 39 patients that were hospitalized with COVID-19 and 40 control subjects were included to the present study. Biomarkers for myocardial injury, myocardial strain, inflammation, and fibrin turnover were obtained at admission. A comprehensive echocardiographic examination, including measurement of coronary flow velocity reserve (CFVR), was done after the patient was stabilized. RESULTS: Patients with COVID-19 infection had a significantly lower hyperemic coronary flow velocity, resulting in a significantly lower CFVR (2.0 ± 0.3 vs. 2.4 ± 0.5, p < .001). Patients with severe COVID-19 had a lower CFVR compared to those with moderate COVID-19 (1.8 ± 0.2 vs. 2.2 ± 0.2, p < .001) driven by a trend toward higher basal flow velocity. CFVR correlated with troponin (p = .003, r: -.470), B-type natriuretic peptide (p < .001, r: -.580), C-reactive protein (p < .001, r: -.369), interleukin-6 (p < .001, r: -.597), and d-dimer (p < .001, r: -.561), with the three latter biomarkers having the highest areas-under-curve for predicting CMD. CONCLUSIONS: Coronary microvascular dysfunction is common in patients with COVID-19 and is related to the severity of the infection. CMD may also explain the "cryptic" myocardial injury seen in patients with severe COVID-19 infection.

Quantitative assessment of left atrial functions by speckle tracking echocardiography in hypertensive patients with and without retinopathy.

PURPOSE: The association between hypertensive retinopathy and left atrial (LA) impairment is unknown. Accordingly, it was aimed to investigate the possible relationship between hypertensive retinopathy and LA phasic functions by means of two-dimensional speckle-tracking echocardiography (2D-STE). METHODS: A total of 124 hypertensive patients and 27 control subjects were included in the study. LA reservoir strain (LAS-S ), LA conduit strain (LAS-E ), and LA booster strain (LAS-A ) parameters were used to evaluate LA myocardial functions. RESULTS: Hypertensive patients (with and without retinopathy) displayed an obvious reduction in the LA reservoir strain (LAS-S ), and LA conduit strain (LAS-E ). Moreover, further impairment in LA reservoir and conduit strain was found in patients with hypertensive retinopathy than in the isolated hypertensive patients. There were no significant differences in LA booster strain (LAS-A ) among the three groups. Impaired LAS-S (OR: 0.764, CI: 0.657-0.888, and p < 0.001), LAS-E (OR: 0.754, CI: 0.634-0.897, and p = 0.001), and hypertension (HT) duration (OR: 2.345, CI: 1.568-3.507, and p < 0.001) were shown to be independent predictors of hypertensive retinopathy. CONCLUSION: Impaired LA reservoir and conduit strain may be used to predict hypertensive patients at higher risk of developing hypertensive retinopathy, and to determine which patients should be followed more closely for hypertensive retinopathy.

Implications of Childhood Trauma on Suicidal Behavior and Deliberate Self-Harm in Patients with Major Depressive Disorder.

BACKGROUND: Traumatic experiences in the first years of life have an important role in the occurrence of major depression as well as many psychiatric diseases. The aim of this study is to investigate the relationship between childhood trauma (CT), suicidal behavior and deliberate self-harm (DSH) behavior in patients who are diagnosed with major depressive disorder (MDD). SUBJECTS AND METHODS: 106 patients who were admitted with depressive complaints to the psychiatry outpatient clinic of Recep Tayyip Erdogan University Training and Research Hospital in Turkey were included in the study. Sociodemographic and clinical features data form, Hamilton Depression Rating Scale (HAD-D), Childhood Trauma Questionnaire (CTQ-28) and Intentional Self-harm Questionnaire (DSHI) were applied to all of the cases. RESULTS: 86 (81.1%) of the cases were female and 20 (18.9%) were male. It was determined that 68.9% of the patients had CT, 49.1% had a history of DSH, and 52.1% had a suicide attempt history. It was determined that 75% of those with DSH behavior had a history of suicide attempt. There was a significant difference between the groups (p˂0.001). When the subtypes of CT, suicide ideation, suicide attempt and DSH behavior, were compared to each other, a significant relationship was found for all of the subtypes. A significant correlation was found between the number of CT and suicide attempts and DSH (p˂0.001). CONCLUSIONS: In this study, high levels of CT and its subtypes were found in patients with MDD. In the presence of CT and all of its subtypes, suicide attempt and DSH were significantly higher. In the follow-up of cases diagnosed with MDD, questioning CT is important in terms of suicide attempt and prevention of DSH.

Combined past preeclampsia and gestational diabetes is associated with a very high frequency of coronary microvascular dysfunction.

BACKGROUND: A history of preeclampsia (pPE) and gestational diabetes (pGDM) are female-specific risk markers for atherosclerosis and future cardiovascular risk. In addition to increasing the risk of established risk factors for atherosclerosis, such as hypertension or diabetes, evidence suggests that pregnancy-related complications can also directly accelerate atherosclerosis by inducing endothelial dysfunction. A combination of both conditions is seen in a subset of patients with pregnancy, though it is not known whether this combination increases the overall risk for cardiovascular events. AIMS: Present study aimed to find the impact of combined pPE/pGDM on the prevalence of coronary microvascular dysfunction (CMD). METHODS: A total of 24 patients with combined pPE/pGDM, 19 patients with isolated pPE and 63 patients with pGDM were included to the present study and a further 36 healthy women with no previous pregnancy-related complications served as controls. Coronary flow reserve was measured using echocardiography and CMD was defined as a coronary flow reserve ≤2.5. RESULTS: Patients with combined pPE/pGDM had a high prevalence of CMD (91%), which was significantly higher than controls (5.6%, p < 0.001) and patients with pGDM (55%, p = 0.01). A history of pPE on top of pGDM was associated with an increased risk of CMD (HR:6.28, 95%CI:1.69-23.37, p = 0.006) after multivariate adjustment, but pGDM did not increase the odds for CMD in those with pPE. CONCLUSIONS: Combined pPE/pDM is associated with a very high prevalence of CMD, which may indicate an increased risk for future cardiovascular events.

Patients with cerebrotendinous xanthomatosis diagnosed with diverse multisystem involvement.

Cerebrotendinous xanthomatosis (CTX) is a lipid storage disease caused by deficiency of sterol 27-hydroxylase enzyme encoded by CYP27A1 gene. This multicenter, cross-sectional descriptive study aimed to document clinical characteristics of CTX patients of different ages, clinical presentations of early-diagnosed patients, and responses to short-term chenodeoxycholic acid (CDCA) treatment. Seven of 11 CTX patients were diagnosed in childhood. Three patients (27%) had neonatal cholestasis, seven (63%) patients had a history of frequent watery defecation started in infantile period, and eight (72.7%) patients had juvenile cataract. Four patients in the adult age group had pyramidal signs and parkinsonism symptoms. The mean Mignarri score at diagnosis was significantly lower in the pediatric patients (267.8 ± 51.4) than in the adult patients (450.0 ± 64.0, p = 0.001). No significant difference was determined between pediatric patients and adult patients regarding plasma cholestanol concentration at diagnosis (p = 0.482). The frequency of defecation decreased with treatment in six children, who had diarrhea at admission. Compared to pretreatment values, patients' body weight and standardized body mass index significantly increased at the 12th month of treatment. In conclusion, Mignarri scores are lower in the pediatric patients than in adult patients since the most determinative signs of the CTX disease are not apparent yet in the childhood. The disease is frequently overlooked in routine practice as the disease presents itself with different clinical combinations both in adults and in children. CTX is potentially a treatable disease; thereby, enhanced awareness is critically important for early diagnosis particularly in children.

Crochetage sign may predict late atrial arrhythmias in patients with secundum atrial septal defect undergoing transcatheter closure.

BACKGROUND: Atrial arrhythmias are well-known complications of atrial septal defect (ASD), and associated with substantial morbidity. After ASD closure, right atrial and ventricular enlargement regresses, however, the risk of atrial arrhythmia development continues. In this study, we aimed to investigate the relationship between the Crochetage sign, which is a possible reflection of heterogeneous ventricular depolarization due to long-term hemodynamic overload, and the development of late atrial arrhythmia after ASD closure. METHODS: This retrospective study included a total of 314 patients (mean age: 39.5 (30-50) years; male: 115) who underwent percutaneous device closure for secundum ASD. The study population was divided into two groups according to the presence or absence of the Crochetage sign. The Crochetage sign was defined as an M-shaped or bifid pattern notch on the R wave in one or more inferior limb leads. Cox-regression analysis was performed to determine independent predictors of late atrial arrhythmia development. RESULT: Fifty-seven patients (18.1%) presented with late atrial arrhythmia. Of these 57 patients, 30 developed new-onset atrial fibrillation/atrial flutter (AF/AFL), and 27 patients with pre-procedure paroxysmal AF/AFL had a recurrence of AF/AFL during follow-up. History of paroxysmal AF/AFL before the procedure (HR: 4.78; 95% CI 2,52-9.05; p < 0.001), the presence of Crochetage sign (HR: 3.90; 95% CI 2.05-7.76; p < 0.001), and older age at the time of ASD closure (HR: 1.03; 95% CI 1.01-1.06; p = 0.002) were found as independent predictors for late atrial arrhythmia. CONCLUSION: The presence of Crochetage sign may be used to predict the risk of late atrial arrhythmia development after transcatheter ASD closure.

Presence of fragmented QRS is associated with left ventricular systolic dysfunction after surgery in patients with severe aortic regurgitation.

BACKGROUND AND AIM OF THE STUDY: Chronic severe aortic regurgitation (AR) is associated with progressive accumulation of interstitial fibrosis and disruption of myocardial structure. After aortic valve replacement (AVR), the negative remodeling process reverses, and left ventricular ejection fraction (LVEF) improves but not in all patients. In this study, we aimed to investigate the association of fragmented QRS (F-QRS), which is a possible marker of myocardial fibrosis, with postoperative left ventricular (LV) systolic dysfunction. METHODS: A total of 147 consecutive patients with AVR were included in this study. F-QRS was identified by the presence of various RSR' patterns (QRS duration <120 ms) such as additional R wave (R prime)or notching of the R or S wave in at least two consecutive leads. Patients were compared in two groups based on the presence or absence of F-QRS. A logistic regression model was used to determine independent predictors of postoperative LV systolic dysfunction (LVEF <50%). RESULTS: Patients with F-QRS were associated with poor recovery of LV systolic function after AVR compared to the patients without F-QRS, regardless of preoperative LVEF (p = .008). F-QRS was found to be an independent predictor of postoperative LV systolic dysfunction (LVEF <50%). Lower preoperative LVEF and increased LV end diastolic diameter index were also found as independent risk factors for postoperative LV systolic dysfunction. CONCLUSIONS: As a possible marker of myocardial fibrosis, F-QRS was associated with postoperative LV systolic dysfunction. Therefore, as a simple and convenient clinical parameter, F-QRS may be used to predict poor recovery of LVEF after AVR.

Cytokine expression profiles in Autism spectrum disorder: A multi-center study from Turkey.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in communication and social interaction as well as restricted interests and repetitive behaviors. The pathogenesis of ASD is not completely understood, but a growing body of research has demonstrated that the immune response may be a contributing factor in the etiology and/ or ontogeny of ASD. The aim of this study was to determine the expression levels of IL-1ß, IL-1α, IL-4, IL-6, IL-17, TNF-α and TGF-ß in peripheral blood mononuclear cells of children with ASD and healthy controls in order to determine the contributions of cytokines to ASD. Within the study timeframe, 195 children with ASDs (80.5% male) and 162 controls (73.6% male) were enrolled. Most children with ASD had a comorbid disorder (n = 114, 58.5%), with the most common diagnoses as Intellectual Developmental Disorder (IDD, n = 64, 32.8%) and ADHD (n = 64, 32.8%). The majority of children with ASD had severe autistic symptoms as evaluated via Childhood Autism Rating Scale (CARS, n = 130, 64.6%). The mean CARS score in the ASD sample was 40.8 (S.D. = 7.6). The patients with ASD were found to have significantly higher levels of IL-6 (p < 0.001) and significantly lower levels of IL-17 (p < 0.05, all Bonferroni corrected). Treatment tended to affect IL-4 levels. Lastly, discriminant function analysis (DFA) revealed that a combination of IL-6, IL-17 and IL-1α correctly classified 56.6% of cases. Despite extensive immunological evidence suggesting immune system aberrations, further research is required to clarify the relationship between immune profiles and ASD symptoms.

The Relationship between Adaptation to Pregnancy and Prenatal Attachment in High-Risk Pregnancies.

BACKGROUND: Although pregnancy is a physiological process, there are various changes which need to be adapted to. Adaptation and prenatal attachment are important for both the mother's and baby's health. These situations are more crucial for women with high-risk pregnancy. The study aimed to determine the relationship between adaptation to pregnancy and prenatal attachment among women with high-risk pregnancy, as well as socio-demographic and obstetric parameters which affected this adaptation. SUBJECTS AND METHODS: This descriptive and analytic study's data were collected from high-risk pregnant women (n=479) who were receiving treatment at two public hospitals in Turkey using Prenatal Self-Evaluation Form (PSEQ) and Prenatal Attachment Inventory (PAI). Descriptive statistics, correlation and comparative analyses were used in data analyses. RESULTS: It was determined that adaptation to pregnancy was medium and prenatal attachment was high in high-risk pregnant (PSEQ mean score:159.43±27.05; PAI mean score: 63.79±10.75). There was a significant negative relationship between the scales (r=-0.556, p<0.01). This relationship showed that as adaptation to pregnancy increased, prenatal attachment also increased. There was significant difference in the PSEQ by age, educational status, employment status, marital status, year of marriage, spouse's educational and employment status, having health insurance, family type, income status, spouse's attitudes towards pregnancy, number of pregnancies, number of births, having living children, whether the pregnancy was planned, pregnancy week and prenatal attachment. CONCLUSION: According to results, there is relationship between adaptation to pregnancy and prenatal attachment in high-risk pregnancies and some sociodemographic and obstetric factors affects adaptation to pregnancy. Determining these factors can serve as a guide for preventing and reducing additional problems that may be encountered in pregnancy and postpartum period in high-risk pregnant women.

Mutations in the enzyme glutathione peroxidase 4 cause Sedaghatian-type spondylometaphyseal dysplasia.

BACKGROUND: Sedaghatian-type spondylometaphyseal dysplasia (SSMD) is a neonatal lethal form of spondylometaphyseal dysplasia characterised by severe metaphyseal chondrodysplasia with mild limb shortening, platyspondyly, cardiac conduction defects, and central nervous system abnormalities. As part of the FORGE Canada Consortium we studied two unrelated families to identify the genetic aetiology of this rare disease. METHODS AND RESULTS: Whole exome sequencing of a child affected with SSMD and her unaffected parents identified two rare variants in GPX4. The first (c.587+5G>A) was inherited from the mother, and the second (c.588-8_588-4del) was de novo (NM_001039848.1); both were predicted to impact splicing of GPX4. In vitro studies confirmed the mutations spliced out part of exon 4 and skipped exon 5, respectively, with both resulting in a frameshift and premature truncation of GPX4. Subsequently, a second child with SSMD was identified; although DNA from the child was not available, the two unaffected parents were found by Sanger sequencing to each carry the same heterozygous stop mutation in exon 3 of GPX4, c.381C>A, p.Tyr127* (NM_001039848.1). CONCLUSIONS: Our identification of truncating mutations in GPX4 in two families affected with SSMD supports the pathogenic role of mutated GPX4 in this very rare disease. GPX4 is a member of the glutathione peroxidase family of antioxidant defence enzymes and protects cells against membrane lipid peroxidation. GPX4 is essential for early embryo development, regulating anti-oxidative and anti-apoptotic activities. Our findings highlight the importance of this enzyme in development of the cardiac, nervous, and skeletal systems.

[Emotion Regulation and Emotional Vulnerability in Adolescents with Anxiety Disorders]. / Emotionsregulation und emotionale Verletzungssensitivität bei Jugendlichen mit Angststörungen.

From an attachment perspective, insecure attachment patterns in both infancy and adolescence are risk factors for the development of anxiety disorders in adolescence. Dysfunctional emotion regulation and biased social information processing are possible mediating processes. This study examines differences in emotion regulation, emotional vulnerability, and behaviour inhibition in adolescents with clinical diagnosis of anxiety disorder and healthy controls. Adolescents with anxiety disorder reported more maladaptive emotion regulation depending on the specific emotion and a higher incidence of reporting hurt feelings in social interactions. In contrast, behaviour inhibition did not explain additional variance. The results suggest that adolescents with anxiety disorders show a bias in the interpretation of social interactions as frequently emotionally hurting, and the use of dysfunctional emotion regulation strategies that minimize the possibility for effective social emotion regulation by close others or therapists. The results are interpreted within attachment framework.

Synthesis and carbonic anhydrase inhibitory properties of novel 1,4-dihydropyrimidinone substituted diarylureas.

Abstract A new series of 1,4-dihydropyrimidinone (DHPM) substituted diaryl urea and thiourea derivatives were synthesized and their inhibitory effects on the activity of purified human carbonic anhydrase (hCA) I and II were evaluated. 4-Nitrophenyl-1,4-DHPM was prepared with dimedone, nitrobenzaldehyde and urea or thiourea and nitro group was reduced to amine derivative. The compound was reacted with isocyanates and isothiocyanates to get the final products. The results showed that all the synthesized compounds inhibited the carbonic anhydrase isoenzyme activity; 4c (IC50=66.23 µM for hCA I) and 4f (IC50=63.09 µM for hCA II) have the most inhibitory effect. The synthesized compounds are very bulky to be able to bind near the zinc ion and they much more probably bind as the coumarins and activators.

Phenylketonuria from the perspectives of patients in Türkiye.

BACKGROUND: The present study aimed to determine the problems, unmet needs and expectations of phenylketonuria (PKU) patients in Türkiye regarding follow-up and treatment in order to provide data for future planning and implementations on PKU. METHODS: The study included patients diagnosed with PKU and/or their parents. They were informed about the study via phone calls and their verbal consents were obtained. Questions in the data collection forms, which were established separately for pediatric, adolescent, and adult age groups, were applied during the interviews and the answers were recorded. RESULTS: Among 182 classical PKU patients, 66 (36.3%) were in the pediatric group (0-12 years old), 44 (24.2%) were in the adolescent group (13-19 years old), and 72 (39.5%) were in the adult group (≥ 20 years old). In all patient groups, phenylalanine-restricted diet and medical nutrition products were the main options for treatment. The median of the last measured blood phenylalanine concentration (patient-reported) was 290 µmol/L, 425 µmol/L, and 750 µmol/L in the pediatric, adolescent, and adult groups, respectively. The frequency of blood testing for serum phenylalanine level according to the age groups was appropriate in nearly half of the patients. While the majority of the patients have been visiting the metabolism center they have been diagnosed with PKU for control, considerable proportion of the patients would like to change the center or the doctor they visit for control if they could. It was determined that nearly half of the patients had trouble in accessing the metabolism center. Treatment options' being limited and expensive were the major problems. The main requests of the patients and patient relatives included easier access to the metabolism centers and more options for treatment and diet. CONCLUSIONS: Access to the services should be easier to improve the patients' follow-up and treatment. There is need for low-cost, easily applicable, and accessible nutrition products and effective novel pharmacological agents. Focusing on these issues in health policies by providing pedagogic/psychological support, establishing support programs also comprising the families, and increasing the awareness activities were the key outcomes.

Elucidation of heavy metal content, phenolic profiles, and antioxidant activities of kale (Brassica oleracea L. var. acephala) and arugula (Brassica eruca L.) grown in urban gardens in Istanbul.

This study was conducted to evaluate the effect of two distances: close (0-10 m) and far (60 m) from the heavy traffic roadside, at three different cultivation sites (MS: Mevlanakapi-Silivrikapi, SB: Silivrikapi-Belgradkapi, and BY: Belgradkapi-Yedikule kapi) along the road line. First, the phenolic compounds, antioxidant activity, and physicochemical properties in kale and arugula vegetables were examined. Second, heavy metal concentrations in vegetables, soil, and irrigated water were investigated. In both vegetables, the highest total phenolic content was detected in samples obtained from far distance in SB site (3880.3 mg/kg) for kale and in BY site (1459.9 mg/kg) for arugula, whereas the lowest content was found at the close distance in MS site for both kale (448.5 mg/kg) and arugula (586.4 mg/kg). The antioxidant activity values [mg Trolox/kg (dw)] ranged from 366.74 to 586.10 and 2349.00 to 3757.4 for kale and from 520.00 to 945.60 and 3323.00 to 5814.70 for arugula in 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl methods, respectively. The levels of Cd and Hg in kale and arugula and Fe content in arugula exceeded FAO/WHO permissible limits, making them unsafe for human consumption. Meanwhile, the Pb content in kale and arugula and Fe content in kale were observed to be within acceptable limits set by FAO/WHO. In the irrigated water, the Pb value was below the permissible limit, whereas the Cd value was above it and no Hg and Fe were detected. In the soil samples, the Pb and Fe values were below the limit, whereas the Cd and Hg values were higher.

Are the promnestic effects of neurokinin 3 receptor mediated by hippocampal neurogenesis in a Aß-induced rat model of Alzheimer's disease?

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterised by cognitive dysfunction, memory loss and mood changes. Hippocampal neurogenesis has been suggested to play a role in learning and memory. Neurokinin 3 receptor (NK3R) has been shown to be prevalent in the hippocampus region. The aim of the project was to investigate the role of hippocampal neurogenesis in the promnestic effects of NK3R agonist administration in an amyloid beta-induced AD rat model. Wistar albino rats were divided into control, Alzheimer, NK3R agonist and Alzheimer + NK3R agonist groups. The open field (OF) test and Morris water maze (MWM) test were performed for locomotor activity and memory analysis. Peptide gene expression levels (Nestin, DCX, Neuritin, MASH1, Neun, BDNF) were analysed by quantitative reverse transcription polymerase chain reaction (RT-PCR). In the OF test, the group-time relationship was found to be statistically different in the parameters of distance travelled and percentage of movement (p < 0.05). In MWM, the time to reach the platform and the time spent in the target quadrant were statistically significant between the groups (p < 0.05). Statistically significant differences were observed in gene expression levels (Nestin, DCX, Neuritin, MASH1) in the hippocampal tissue of rats between the groups (p < 0.05). NK3 receptor agonism favourably affected hippocampal neurogenesis in AD model rats. It was concluded that NK3 receptor agonism in the hippocampus, which is the first affected region in the physiopathology of AD, may be effective in both the formation of neural precursor cells and the reduction of neuronal degeneration. The positive effect of NK3R on cognitive functions may be mediated by hippocampal neurogenesis.

Usefulness of triglyceride-glucose index and homeostatic model assessment for predicting coronary microvascular dysfunction.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a common occurrence in individuals with insulin resistance (IR). Homeostatic model assessment for insulin resistance (HOMA-IR) is a widely used surrogate marker of IR, although recent studies suggest Triglyceride-Glucose (TyG) index is a superior marker of IR that had a better accuracy to predict Type 2 Diabetes or cardiovascular outcomes than HOMA-IR. OBJECTIVES: We aimed to assess the accuracy and usefulness of TyG index and HOMA-IR for predicting CMD as assessed with echocardiographic coronary flow reserve (CFR) measurement. METHODS: All cases included in the institutional CFR registry were retrospectively reviewed, and 656 cases without epicardial coronary artery disease and without major risk factors for atherosclerosis were included. A CFR ≤2.0 was defined as CMD. RESULTS: TyG index was available in all cases, while HOMA-IR was available in 398 cases. Both TyG index and HOMA-IR were associated with CMD on univariate analyses, while after adjustment for potential confounders HOMA-IR (OR:1.38, 95 %CI:1.14-1.67, p = 0.001) but not TyG index(OR:1.48, 95 %CI:0.82-2.67, p = 0.19) was associated with CMD. The predictive accuracy of HOMA-IR (c-statistic:0.63, 95 %CI:0.54-0.72, p = 0.003) was higher than TyG index(c-statistic:0.55, 95 %CI:0.47-0.63, p = 0.13), although the difference was not statistically significant (DeLong p = 0.23). There was strong evidence favoring a true difference between CMD vs. non-CMD groups for HOMA-IR (BF10:3507) but not for TyG index(BF10:0.66). CONCLUSIONS: HOMA-IR, but not TyG index, is closely associated with CMD.

Cytokine expression profiles in children and adolescents with tic disorders.

The etiology of tic disorders (TDs) is not precisely known, although several lines of evidence suggest involvement of the immune system in pathogenesis. Here, we aimed to determine the expression levels of pro-inflammatory and anti-inflammatory cytokines in children with TD and compare them with those of healthy controls. Furthermore, we also evaluated their association with clinical variables in the TD group. Within the study period, 88 children with tic disorders and 111 healthy control children were enrolled. Most children with tic disorders were diagnosed with Tourette's disorder (n = 47, 53.4%) or persistent motor tic disorder (n = 39, 44.3%), while the remainder (n = 2, 2.3%) were diagnosed with persistent vocal tic disorder. We found that children with tic disorders had significantly elevated levels of IL-1ß, TNF-α, IL-6 and IL-4 expression, while we detected lower expression levels of IL-17 in children with tic disorders. Our findings provide a molecular landscape of cytokine expression in children with TD, which may suggest a proinflammatory state not affected by the presence of comorbidity and symptom severity. Delineating the contribution of alterations in the immune system to the pathogenesis of tic disorders may pave the way for better therapeutic interventions.

Cardiac Glycoside Oleandrin Suppresses EMT Ability in Endometrial Carcinoma Cells.

Endometrial carcinoma is one of the most common types of cancer among women. The progression of cancer occurs via the Epithelial- Mesenchymal Transition (EMT) pathway. Cells lose their epithelial properties and become mobile. For this reason, the EMT process is one of the most important step to be targeted in cancer treatment. Oleandrin is a cardiac glycoside and its use is limited due to its narrow therapeutic index. In this study, we aimed to evaluate effects of lower level Oleandrin doses on EMT process in endometrial carcinoma. Oleandrin was administrated to Ishikawa endometrial adenocarcinoma cells at different doses and times. IC50 dose was determined by XTT proliferation test. Expression analysis of EMT-related genes was then performed by qRT-PCR. Invasion and colony formation abilities of cells were examined microscopically. Finally, the migration analysis of cancer cells was determined by the Wound Healing Assay. The IC50 dose of Oleandrin applied to Ishikawa cells was determined as 75.3 nM at the 48 h. According to qRT-PCR analysis, expression levels of ZEB1, FN1, ITGB1, VIM, SMAD2, SNAI1, SNAI2, SNAI3, and TGFB3 genes significantly decreased, but TIMP2, TIMP3, ITGAV and GSK3B genes significantly increased. In addition, Oleandrin significantly reduced colony formation and invasion of Ishikawa cells. According to the Wound Healing analysis, the migratory abilities of the Oleandrin-treated cells were reduced compared to the control. Low dose Oleandrin suppresses the EMT pathway in Ishikawa cells. It has been shown that Oleandrin significantly suppresses the cell's colony formation, invasion and migration ability both in gene expression analyzes and microscopically.