Design, synthesis, and enzyme inhibition evaluation of some novel Mono- and Di-O-ß-D-Glycopyranosyl Chalcone analogues with molecular docking studies.

In this study, some novel mono- and di-O-ß-D-glycopyranosyl chalcone analogs were designed, synthesized, and characterized. The chalcone derivatives were synthesized with good yields by base-catalyzed Claisen-Schmidt condensation in EtOH solution. Then these chalcones were reacted with TAGBr (2,3,4,6-tetra-O-acetyl-α-D-glucopyranosylbromide) in dry acetone under the anhydrous condition at 0-5 °C. Deacylated was carried out by the Zemplen's method with NaOCH3 in dry methanol results in substituted chalcone-O-glycosides (mono- and di-O-ß-D-glycopyranosyl chalcone analogs). The chemical structures of all synthesized compounds were elucidated based on IR, NMR spectral data, and mass spectrometry. Further, the compounds (7a-c, 8a-c, 12a-c, 16a-c, and 17a-c) were tested for their enzyme inhibition activity against α-glycosidase, tyrosinase, and AChE with in vitro and in silico analysis. Amongst them, compounds 12a-c, 16a-c, and 17a-c displayed moderate or less enzyme inhibition activity against α-glycosidase while other compounds 7a-c and 8a-c) were not active. Remarkably interesting enzyme inhibition effects, with IC50 values below 30.59 ± 0.30 µM were recorded with 7c (IC50=11.07 ± 0.55 µM) against tyrosinase.

Role of calcium metabolism in ADHD: The relationship between parathyroid hormone and ADHD symptom severity.

Background: Vitamin D has been found to be associated with the pathogenesis of attention deficit hyperactivity disorder (ADHD). However, the potential role of parathyroid hormone (PTH) is still unclear. Aim: We aimed to investigate the association between calcium metabolism and ADHD symptomatology. Methods: We included 106 participants aged between 7 and 13 years old (51 ADHD patients, mean age: 9.54 ± 1.77, 55 healthy controls mean age: 9.97 ± 0.94) to this study. K-SADS-PL and Conners' Parent/Teacher Rating Scales, Stroop Test were performed. Blood samples to measure serum levels of Vitamin D, PTH, calcium (Ca), magnesium (Mg), phosphorus (P), and alkaline phosphatase (ALP) were collected in the spring (March-April-May) to prevent seasonal variability. Results: PTH, P, and ALP values were significantly lower and Vitamin D, Ca, and Mg values were significantly higher in the ADHD group (P < 0.05, for all). Both groups had Vitamin D deficiency. Control group has lower Vitamin D levels than the ADHD group (respectively; 17.66 ± 9.07, 21.99 ± 10.99, P < 0.05). There was a negative correlation between PTH and CTRS hyperactivity, CGI-RI and CGI-EL sub-scores, CGI-Total, DSM-IV-Inattention, DSM-IV Hyperactivity/Impulsivity, DSM-IV-Total scores (P < 0.05, for all). Conclusions: We found lower PTH levels in ADHD patients and a strong and negative correlation between PTH and symptom severity. Future studies are needed to clarify if these findings are due to the key role of PTH in ADHD pathology or PTH's function in activating vitamin D.

Evaluation of child marriage in a Turkish sample: 8 years' data.

This study aims to examine 167 adolescents who were referred by courts between 2008 and 2016 to prepare medical-legal reports on their suitability for marriage. Most were illiterate or graduates of primary/secondary school; only 17 (10.2%) were still at high school. A total of 95 girls (56.9%) had a religious marriage without a civil certificate, 63 girls (37.7%) were pregnant, and 15 (9%) had a child. According to medical reports, 91 of the girls were considered unsuitable for marriage; 76 girls who were pregnant and/or had a child were also considered unsuitable, so it was necessary to let the judge decide.

Synthesis of hydroxy benzoin/benzil analogs and investigation of their antioxidant, antimicrobial, enzyme inhibition, and cytotoxic activities.

In this study, hydroxy benzoin ( 1-7 ), benzil ( 8-14 ), and benzoin/benzil-O-ß-D-glucosides ( 15-25 ) were synthesized to investigate their biological activities. An efficient method for synthesizing hydroxy benzoin compounds ( 1 - 7 ) was prepared from four different benzaldehydes using an ultrasonic bath. Then, antioxidant (FRAP, CUPRAC, and DPPH), antimicrobial (3 Gram (-), 4/6 Gram (+), one tuberculosis and one fungus), and enzyme inhibition (acetylcholinesterase, butyrylcholine esterase, tyrosinase, α-amylase, and α- glucosidase) for the all synthesized compounds ( 1-25 ) were evaluated. And also, four most active compounds ( 4 , 12 , 18a+b , and 25 ) from each group were evaluated to the human cervical cancer cell line (HeLa) and anticancer screening tests against the human retinal normal cell line (RPE). Compound 4 showed HeLa and RPE cancer cell activities as much as cisplatin. The synthesized compounds were characterized by spectroscopic methods (NMR, FT-IR, UV, LC-QTOF-MS) and the ACD NMR program's help.

Nutritional and herbal supplements in the treatment of obsessive compulsive disorder.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder that is characterised by obsessions and compulsions. The recommended treatments for OCD are cognitive- behavioural therapy using exposure and response prevention and/or pharmacotherapy. On the other hand, some nutritional and herbal supplements may be effective in the treatment of OCD. Nutritional and herbal supplements in OCD treatment will be reviewed in this paper. PubMed (Medline), Cochrane Library and Google Scholar databases were reviewed for the topic. There are some supplements that have been researched in OCD treatment studies such as vitamin D, vitamin B12, folic acid, homocysteine, trace elements, N-acetyl cysteine, glycine, myoinositol, St John's wort, milk thistle, valerian root, curcumin and borage. The effectiveness of herbal and nutritional supplements in the treatment of OCD should be supported with more conclusive evidence.

Gender Identity and Assignment Recommendations in Disorders of Sex Development Patients: 20 Years' Experience and Challenges

Objective: Gender assignment in infants and children with disorders of sex development (DSD) is a stressful situation for both patient/families and medical professionals. Methods: The purpose of this study was to investigate the results of gender assignment recommendations in children with DSD in our clinic from 1999 through 2019. Results: The mean age of the 226 patients with DSD at the time of first admission were 3.05±4.70 years. 50.9% of patients were 46,XY DSD, 42.9% were 46,XX DSD and 6.2% were sex chromosome DSD. Congenital adrenal hyperplasia (majority of patients had 21-hydroxylase deficiency) was the most common etiological cause of 46,XX DSD. In 46,XX patients, 87 of 99 (89.7%) were recommended to be supported as a female, 6 as a male, and 4 were followed up. In 46,XY patients, 40 of 115 (34.8%) were recommended to be supported as a female, and 70 as male (60.9%), and 5 were followed up. In sex chromosome DSD patients, 3 of 14 were recommended to be supported as a female, 9 as a male. The greatest difficulty in making gender assignment recommendations were in the 46,XY DSD group. Conclusion: In DSD gender assignment recommendations, the etiologic diagnosis, psychiatric gender orientation, expectation of the family, phallus length and Prader stage were effective in the gender assignment in DSD cases, especially the first two criteria. It is important to share these experiences among the medical professionals who are routinely charged with this difficult task in multidisciplinary councils.

Synthesis and characterization of some new pyrazolines and their inhibitory potencies against carbonic anhydrases.

The inhibition of the two human cytosolic carbonic anhydrase (hCA; EC 4.2.1.1) isozymes I and II with some new pyrazoline derivatives was investigated for the first time. The structures of the newly synthesized pyrazoline derivatives were characterized by Fourier transform-infrared spectroscopy, 1 H-/13 C-nuclear magnetic resonance, and mass spectrometry, and elemental analysis. Compounds 1-6 showed Ki values in the range of 16.4-205.9 nM for hCA I and of 6.08-93.21 nM against hCA II. These hydroxyl and amino group-containing compounds generally were competitive inhibitors. The compounds investigated here showed effective hCA I and II inhibitory effects, in the same range as the clinically used acetazolamide, and might be used as leads for generating enzyme inhibitors, possibly targeting other CA isoforms that have not yet been assayed for their interactions with such agents.

Technological addictions in attention deficit hyperactivity disorder: Are they associated with emotional intelligence?

BACKGROUND: The impaired regulation of emotional responses has significant social consequences for patients with attention deficit hyperactivity disorder (ADHD) and can be thought to increase the risk for technological addictions. AIM: Ditto objective of the present research is to investigate the relationship between technological addictions and trait emotional intelligence (EI) in adolescents with ADHD. METHODS: This cross-sectional study was conducted in 150 treatment-naïve adolescents with ADHD, aged 12-18 years. The sociodemographic information form, the Emotional Quotient-Inventory: Youth Version (EQ-i: YV), Internet Addiction Test, Smartphone Addiction Scale, and Conners' Parent Rating Scales were used for data collection. RESULTS: The findings revealed that ADHD-C and female patients have lower mean stress management scores on EQ-i: YV. Patients who have smartphone addiction (SA)/problematic internet usage have lower total EI and stress management scores. The oppositional, hyperactivity, and DSM-total scores were negatively correlated with stress management scores. Intrapersonal and stress management scores were negatively correlated to SA symptoms. CONCLUSION: The stress management dimension was the strongest factor related to ADHD and technological addictions. In adolescents with ADHD, stress management may be the key factor to cope with daily problems. Therefore, the interventions to develop EI can be a therapeutic option in ADHD and technological addictions.

Symptomatic multifocal avascular necrosis in an adolescent with neuropsychiatric systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by malar rash, oral ulcers, arthralgia, photosensitivity and nephritis. Herein, we report a rare comorbidity, multiple avascular necrosis (AVN), in an adolescent SLE patient and also highlight the importance of risk factors for this comorbidity with a brief literature review. A 13-year-old female patient was admitted with severe headache, visual plus auditory hallucinations, polyarthritis and a history of recurrent oral ulcers. Acneiform malar rash, arthritis, cytopenia, low complement levels and autoantibody positivity yielded SLE diagnosis. We diagnosed her as having multifocal AVN after the 4th dose of cyclophosphamide, with bilateral knee pain and swelling and typical geographical lesions on magnetic resonance imaging. Avascular necrosis is a rare comorbidity of SLE and neuropsychiatric involvement, cyclophosphamide administration and severe disease may be the possible risk factors in addition to corticosteroid use. Further multicenter studies investigating the possible risk factors of AVN with a large number of patients are needed.

Mannose-Binding Lectin 2 Gene Polymorphism in PANDAS Patients.

INTRODUCTION: Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), a subgroup of obsessive-compulsive disorder (OCD), has received much attention even though the specific underlying mechanisms remain unknown. Mannose-binding lectin (MBL) is a key factor in the innate immune response. The aim of this study was to investigate the role of MBL2 gene polymorphisms in pediatric OCD patients diagnosed as PANDAS, PANDAS-Variant and non-PANDAS. METHODS: The study included 102 pediatric OCD patients (59 [57.8% ] PANDAS, 20 [19.6% ] non-PANDAS, and 23 [22.5% ] PANDAS-Variant) and 60 healthy controls. Polymorphisms at codon 52, 54 and 57 of the MBL2 gene were investigated. RESULTS: Codon 54 polymorphism and any variant of MBL2 gene were significantly more frequent in the OCD group than in the control group (OR=2.97, 95% CI: 1.26-6.97; and OR=2.66, 95% CI: 1.32-5.38, respectively). According to regression analysis, the presence of any variant of MBL2 gene was found in 14.50-fold increased frequency in the PANDAS subgroup compared with the non-PANDAS subgroup (95% CI: 2.49-84.19). CONCLUSIONS: Our findings support an association between MBL2 genotypes and pediatric OCD, particularly PANDAS-OCD.

The prevalence of childhood psychopathology in Turkey: a cross-sectional multicenter nationwide study (EPICPAT-T).

AIM: The aim of this study was to determine the prevalence of childhood psychopathologies in Turkey. METHOD: A nation-wide, randomly selected, representative population of 5830 children (6-13 years-old) enrolled as a 2nd,3rd or 4th grade student in 30 cities were evaluated for presence of a psychiatric or mental disorder by a Sociodemographic Form, Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version (K-SADS-PL), and DSM-IV-Based Screening Scale for Disruptive Behavior Disorders in Children and Adolescents scales. Impairment criterion was assessed via a 3 point-Likert scale by the parent and the teacher independently. RESULTS: Overall prevalence of any psychopathology was 37.6% without impairment criterion, and 17.1% with impairment criterion. Attention-deficit hyperactivity disorder was the most frequent diagnosis, followed by anxiety (19.5% and 16.7% without impairment, 12.4% and 5.3% with impairment, respectively). Lower education level and presence of a physical or psychiatric problem of the parents were independent predictors of any psychopathology of the offspring. CONCLUSION: This is the largest and most comprehensive epidemiological study to determine the prevalence of psychopathologies in children and adolescents in Turkey. Our results partly higher than, and partly comparable to previous national and international studies. It also contributes to the literature by determining the independent predictors of psychopathologies in this age group.

Recantation of Sexual Abuse Disclosure Among Child Victims: Accommodation Syndrome.

BACKGROUND: Disclosing the sexual abuse may be related on many individual and/or environmental factors in all age groups. The sociocultural context is the most influential factor of the disclosing process especially for those living in patriarchal cultural values. This study compares the impacts of sexual abuse and other sociodemographic variables between recanting and non-recanting victimized groups in Adana city from Turkey. METHODS: The samples attending our department were divided into two groups: group 1 comprised victims who recanted their first abuse disclosure, and group 2 comprised victims who insisted on the veracity of their first report at further evaluations. The characteristics of the child, family, and abuser were compared between recanting victims and non-recanting victims by retrospective data. RESULTS: Each group included 27 children, for a total of 54 subjects. All adverse social reactions after the sexual abuse, including keeping secrets and a repressive family attitude, were higher among group 1 victims than group 2 victims (p < 0.0001). CONCLUSIONS: Although they are victimized by protecting family integrity, victims may show a tendency to keep secrets and to not immediately disclose an abuse event.

Prevalence of Childhood Affective disorders in Turkey: An epidemiological study.

AIM: To determine the prevalence of affective disorders in Turkey among a representative sample of Turkish population. METHODS: This study was conducted as a part of the "The Epidemiology of Childhood Psychopathology in Turkey" (EPICPAT-T) Study, which was designed by the Turkish Association of Child and Adolescent Mental Health. The inclusion criterion was being a student between the second and fourth grades in the schools assigned as study centers. The assessment tools used were the K-SADS-PL, and a sociodemographic form that was designed by the authors. Impairment was assessed via a 3 point-Likert type scale independently rated by a parent and a teacher. RESULTS: A total of 5842 participants were included in the analyses. The prevalence of affective disorders was 2.5 % without considering impairment and 1.6 % when impairment was taken into account. In our sample, the diagnosis of bipolar disorder was lacking, thus depressive disorders constituted all the cases. Among depressive disorders with impairment, major depressive disorder (MDD) (prevalence of 1.06%) was the most common, followed by dysthymia (prevalence of 0.2%), adjustment disorder with depressive features (prevalence of 0.17%), and depressive disorder-NOS (prevalence of 0.14%). There were no statistically significant gender differences for depression. Maternal psychopathology and paternal physical illness were predictors of affective disorders with pervasive impairment. CONCLUSION: MDD was the most common depressive disorder among Turkish children in this nationwide epidemiological study. This highlights the severe nature of depression and the importance of early interventions. Populations with maternal psychopathology and paternal physical illness may be the most appropriate targets for interventions to prevent and treat depression in children and adolescents.

A Simple Spectrofluorimetric Method for Iron Determination with a Chalcone-Based Schiff Base.

A chalcone-based Schiff base (5), capable of detecting iron (III) in partially aqueous media, has been designed, then synthesized by the condensation of 3-formyl-2-hydroxyquinoline and acetophenone. To determine iron (III) ion, a simple spectrofluorimetric method was developed by using the synthesized Schiff base. The developed method was validated by analyzing the certified reference material (CRM-SA-C Sandy Soil C). During the process of the determination of iron in food samples, satisfactory accuracy was obtained for spinach and rocket. Nitric acid and hydrogen fluoride were used for the digestion of the certified reference material whereas only nitric acid was used for food samples, in a closed microwave system. Measurements were carried out by using the modified standard addition method. The standard addition graph was linear until 5.0 mg/L. in determination of iron (III). Detection and quantification limits were 0.06 and 0.20 mg/L., respectively. The presented method is simple, time-saving, cost-effective and suitable for determination of iron content of soil and foods.

Synthesis and Biological Evaluation of Novel Bischalcone Derivatives as Carbonic Anhydrase Inhibitors.

Design and synthesis of a new type of bischalcones as an alternative to natural and synthetic bischalcones are reported for the first time. Key steps involved the solvent-free Claisen-Schmidt condensation of chalcones, and the successful first application of the diazotization-diazocoupling reaction in the synthesis of CNNC-linked bischalcones by simple structural modification of p-aminoacetophenone. The structures of all compounds were confirmed by means of FT-IR, (1) H and (13) C NMR, ESI/MS, and elemental analysis. In addition, the newly synthesized compounds were screened for carbonic anhydrase inhibition activities. Almost all bischalcones exhibited moderate-to-good inhibitory activities.

Vitamin D insufficiency in a boy with obsessive-compulsive disorder.

Vitamin D deficiency not only causes low bone mass but also may lead to neuropsychiatric disorders. In the present case, vitamin D supplementation reduced obsessive-compulsive disorder (OCD) symptoms associated with streptococcal infection in a 7-year-old boy. Sudden onset of symptoms, including excessive hand washing and fear of touching anything, had occurred 1 month before presentation. Although there are few studies on a possible causal relationship between vitamin D and neuropsychiatric disorders, the present report; together with previous data, suggest an etiological role of vitamin D-related immune processes.

Tibia stress fracture secondary to obsessive compulsive disorder.

Obsessive compulsive disorder (OCD) is a chronic psychiatric disorder characterized by obsessions and compulsions. Early-onset OCD is one of the most common mental illnesses of children and adolescents, with a prevalence of 1% to 3%. It is related to worse lifespan symptoms and prognosis. Therefore, the treatment of OCD in children and adolescent has gained importance. If it is not treated successfully, the compulsive behaviors may cause extreme stress for children and their parents. Although minor complications of OCD are commonly observed, major complications are considerably rare due to the nature of compulsive behaviors. Apparently, loss of vision, autocastration, rectal prolapse are examples of major complications secondary to OCD. As far as we know, it is the first case of tibia stress fracture secondary to OCD. In the present case report, we will discuss tibia stress fracture developing secondary to compulsive behavior due to OCD.

Effects of methylphenidate on appetite and growth in children diagnosed with attention deficit and hyperactivity disorder.

The purpose of this study was to determine the levels of leptin, ghrelin, and nesfatin-1 to elucidate the causes of poor appetite and growth retardation in patients receiving methylphenidate therapy for attention deficit hyperactivity disorder. The study was performed on 89 male subjects; 48 patients and 41 healthy controls, aged 7-14 years. Following treatment, patients' leptin levels increased and ghrelin levels decreased while no significant change was found in nesfatin-1 levels. Of the 48 patients, 34 developed lack of appetite. In patients who developed lack of appetite, body weight SDS, body mass index (BMI), and BMI SDS were statistically significantly reduced; moreover, height SDS was reduced, though not to a statistically significant extent. This study attempted to elucidate the mechanisms that mediate the association between methylphenidate and appetite and growth, for which no studies have yet to be published.

Vitamin D Deficiency in Obsessive-Compulsive Disorder Patients with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections: A Case Control Study.

INTRODUCTION: Previous studies have indicated that vitamin D deficiency is common in psychiatric patients, particularly in those with neuropsychiatric disorders such as autism and schizophrenia. Vitamin D is an important neurosteroid hormone and immunomodulatory agent that also has bone metabolic effects. There has been an increasing interest in immune-related neuropsychiatric symptoms that are triggered by group A beta-hemolytic streptococcal infections. In this study, we aimed to compare the serum levels of vitamin D between obsessive-compulsive disorder (OCD) patients with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) and control subjects. METHODS: Thirty-three OCD patients with PANDAS and 20 healthy controls were enrolled in the study. Serum 25-hydroxyvitamin D (25-(OH) D), calcium, phosphorus, alkaline phosphatase, and parathormone levels of the two groups were compared. Serum 25-(OH) D levels of <15 ng/mL were classified as vitamin D deficiency. The children's Yale-Brown Obsessive Compulsive Scale (YBOCS) and Clinical Global Impression (CGI) were used to assess the severity of OCD symptoms. RESULTS: There was no significant difference in serum 25-(OH) D levels between the patient and control groups. However, vitamin D deficiency was significantly more frequent in the patient group than in the control group (48.5% vs. 20.0%; p=0.038). Moreover, OCD patients with vitamin D deficiency had higher rates of comorbid ADHD than those without vitamin D deficiency (87.5% vs. 52.6%; p=0.027). While serum phosphorus levels were negatively correlated with age as well as alkaline phosphatase and ASO levels, they were positively correlated with the YBOCS total score and global severity score. Serum parathormone levels were positively correlated with the YBOCS total score, compulsion score, obsession score, and global severity score. CONCLUSION: This study supports the hypothesis that an association between vitamin D metabolism and PANDAS-related OCD exists. We suggest that biochemical parameters predicting metabolic bone diseases are more common in PANDAS patients. There is a need for prospective studies to show a clear association between PANDAS and bone metabolic turnover based on autoimmune mechanisms.