Germline variant screening with targeted next generation sequencing in prostate cancer: phenotype-genotype correlation.

BACKGROUND: Next generation sequencing provides new information about the molecular pathogenesis of cancer. We used a targeted NGS-based multiple gene panel comprising prostate cancer (PCa) predisposing genes to assess the prevalence of germline mutations in PCa patients. METHODS: In a cohort of twenty-one PCa patients with a family history of cancer, a targeted multigene panel consisting of 39 genes associated with hereditary cancer was created and analyzed using the next generation sequencing method. The novel and pathogenic mutations detected were confirmed by Sanger sequencing method. Thereafter, the data obtained were evaluated using different genomic variant classifiers and databases. RESULTS: With an incidence of less than 5% in different populations (MAF<0.05); a total of 81 variants were identified, including 41 missense, 16 synonymous, 3 splice-site, 11 intronic, 5 in-del and 5 novels. According to the ACMG criteria, 5 (6.2%) of these variants are pathogenic/likely pathogenic; 5 (6.2%) of them were classified as novel variants. In addition, variants having very low-frequency and unknown clinical significance (VUS) in the databases were detected.

Visualizing the Nonhomogeneous Structure of RAD51 Filaments Using Nanofluidic Channels.

RAD51 is the key component of the homologous recombination pathway in eukaryotic cells and performs its task by forming filaments on DNA. In this study we investigate the physical properties of RAD51 filaments formed on DNA using nanofluidic channels and fluorescence microscopy. Contrary to the bacterial ortholog RecA, RAD51 forms inhomogeneous filaments on long DNA in vitro, consisting of several protein patches. We demonstrate that a permanent "kink" in the filament is formed where two patches meet if the stretch of naked DNA between the patches is short. The kinks are readily seen in the present microscopy approach but would be hard to identify using conventional single DNA molecule techniques where the DNA is more stretched. We also demonstrate that protein patches separated by longer stretches of bare DNA roll up on each other and this is visualized as transiently overlapping filaments. RAD51 filaments can be formed at several different conditions, varying the cation (Mg(2+) or Ca(2+)), the DNA substrate (single-stranded or double-stranded), and the RAD51 concentration during filament nucleation, and we compare the properties of the different filaments formed. The results provide important information regarding the physical properties of RAD51 filaments but also demonstrate that nanofluidic channels are perfectly suited to study protein-DNA complexes.

Evaluation of Retinal Nerve Fiber Layer, Ganglion Cell Thickness, and Macular Thickness in Children With Comorbid Specific Learning Disorder and Attention-Deficit Hyperactivity Disorder.

PURPOSE: To investigate the changes in ocular optical coherence tomography (OCT) findings in the comorbidity of attention-deficit hyperactivity disorder (ADHD) and specific learning disorder (SLD). METHODS: This study included 40 individuals diagnosed as having ADHD along with comorbid SLD, 40 individuals diagnosed as having only ADHD, and 40 individuals with no psychiatric disorders. OCT assessments were performed on eyes of the participants to obtain retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) thickness, and macular thickness measurements. RESULTS: In total, 240 eyes were evaluated. The right and left eyes were not significantly different in terms of RNFL, GCL, and macular thickness within groups (P > .05). RNFL thickness was measured and compared across four quadrants (superior, inferior, temporal, and nasal). Although these values were not significantly different between the groups (P > .05), RNFL was observed to be thinner in children with comorbid ADHD and SLD in all quadrants. Similarly, GCL and macular thickness measurements were also not different between the groups (P > .05). CONCLUSIONS: Considering that retinal nerve fibers can be seen as an extension of the brain in the embryologic context, the results showed that OCT findings alone are not sufficient to detect the changes in ADHD and SLD comorbidity. The authors suggest that OCT is more useful in the etiology and follow-up of neurodegenerative diseases rather than neurodevelopmental disorders. [J Pediatr Ophthalmol Strabismus. 2024;61(2):128-136.].

Social media addiction, escapism and coping strategies are associated with the problematic internet use of adolescents in Türkiye: a multi-center study.

Introduction: The literature highlighted that problematic internet use can have detrimental consequences on individuals' well-being. Social media addiction, escapism and coping skills are closely related to problematic internet use. However, no study has currently examined the relationship between problematic internet use and social media use, escapism and coping skills. Method: This multicenter cross-sectional designed study evaluated the relationships between problematic internet use and social media addiction, escapism, and coping skills in 508 adolescents (319 female) aged 14-18 years. In order to collect data, sociodemographic data form, Internet Addiction Scale, Social Media Addiction Scale, Escapism Scale and Kidcope Adolescent Version have been used. First, adolescents who scored ≥50 on the Internet Addiction Test were classified as the problematic internet use group; adolescents who scored <50 were classified as the control group. Then, the relationships between problematic internet use and social media addiction, escapism and coping skills were evaluated. Results: The results showed that problematic internet use was associated with duration of social media use, impairment in social media-related functionality, preferring virtual life, and virtual pleasure, escapism, avoidant and negative coping strategies. Conclusion: These findings may provide an empirical basis for problematic internet use prevention and intervention in adolescence.

Serum Occludin and Zonulin Levels in Children With Attention-Deficit/Hyperactivity Disorder and Healthy Controls.

OBJECTIVE: To evaluate zonulin and occludin levels, potentially associated with immunological pathways in the gut-brain axis, in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: We examined the association between serum levels of zonulin and occluding, and behavioral/emotional problems in children with ADHD. 40 medication-naïve children meeting Diagnostic and statistical (DSM-5) criteria for ADHD (11 females; mean (SD) age 9.4 (1.6) years) and 39 healthy comparisons (12 females; mean (SD) age 9.3 (1.9) years) were studied. Serum zonulin and occludin levels were measured by (ELISA). RESULTS: We found higher mean (SD) serum zonulin levels [37.1 (28.2) vs 8.1 (4.5) ng/mL; P<0.001) and occludin levels [2.4 (1.6) vs 0.6 (0.4) ng/mL; P<0.001] in the ADHD group compared to control group. Serum zonulin levels had a positive correlation with weight (r=0.452; P=0.003) and BMI (r=0.401; P=0.01) among children with ADHD. Serum zonulin and occludin levels also had a positive correlation with Conners parent rating scale scores (r=0.58; P<0.001), and Strengths and difficulties questionnaire scores (r=0.49; P<0.001). Multiple linear regression analysis revealed that age, sex, weight, conduct problems and oppositional sub-scores were significant predictors of increased serum zonulin levels. CONCLUSION: These data confirm an association between ADHD, and serum zonulin and occludin levels. Pathophysiological and clinical significance of these findings needs to be elucidated.

An evaluation of parental attitudes and attachment in children with primary monosymptomatic nocturnal enuresis: A case-control study.

INTRODUCTION: Enuresis is a common childhood disorder associated with the lack of bladder control that would be expected based on the child's age or developmental stage. Enuresis affects the lives of both children and their parents due to the burden it entails in daily life. OBJECTIVE: In this study, we aimed to evaluate the dimensions of attachment between children with enuresis and their mothers, as well as the relationship with parental attitudes. METHODS: This study included 70 children were diagnosed with primary monosymptomatic nocturnal enuresis (PMNE) based on the guidelines of the International Children's Continence Society (ICCS) along with 70 children with not enuresis and any psychiatric disorders. We asked the mothers of all participants to complete the Parental Attitude Research Instrument, and the children to complete The Experiences in Close Relationships Scale Revised - Middle Childhood. RESULTS: Both groups in our study were well balanced in terms of gender, age, and sociodemographic data. Children with enuresis were found to score higher on the anxiety and avoidance dimensions of the attachment scale with statistical significance (p < 0.01). Also, on the scale completed by the mothers of children with enuresis, the subtests indicating overprotective parenting and strict discipline presented significant differences (p < 0.01). DISCUSSION: Data obtained in our study demonstrate that enuresis can have a negative effect on the mother-child attachment and parental attitudes. The use of harsh language or punishment by the mother in response to the failure of the child to achieve nocturnal dryness may affect the attachment between the mother and the child, and cause the child to experience negative emotions such as shame, anxiety, embarrassment, frustration, and loneliness. CONCLUSION: We think that it would be useful to evaluate the mother-child attachment and the crisis experienced by the family after each wetting incidence in combination with parental attitudes and behaviors in the treatment of enuresis cases.

Functional Impairments and Related Factors in Adolescents with Attention Deficit Hyperactivity Disorder During the COVID-19 Normalization Stage.

Background: Attention deficit hyperactivity disorder is a disorder associated with significant functional impairments that can have important consequences for the individual and the society. Those with attention deficit hyperactivity disorder were reported to be more vulnerable in the face of difficulties and experience more psychological problems during the coronavirus disease 2019 pandemic. It was shown that the psychological problems experienced during the pandemic could persist during the normalization stage. We aimed to assess functional impairment in adolescents with attention deficit hyperactivity disorder and the related factors during the normalization stage which involved the initiation of fully face-to-face schooling practices. Methods: This is a cross-sectional study including attention deficit hyperactivity disorder (n = 52) and a healthy control group (n = 52). Functional impairment was assessed using the Weiss functional impairment rating scale self and parent forms. We also examined the factors associated with functional impairment (internalizing-externalizing problems, parenting strategies, and perceived expressed emotion). Results: Adolescents with attention deficit hyperactivity disorder had higher functional impairment scores on Weiss functional impairment rating scale self and parent in all sub-domains and total. Weiss functional impairment rating scale self and parent total mean score had a positive correlation with negative parenting and externalizing-internalizing scores and a negative correlation with the positive parenting score. Weiss functional impairment rating scale-self total mean score was positively correlated with negative parenting and externalizing-internalizing scores and perceived expressed emotion scores. Conclusion: Our results suggest that the effects of the pandemic on children's functioning may persist in the normalization stage. For a comprehensive evaluation and effective intervention, it is important that comorbid symptoms, parenting strategies, and the perceived family climate are evaluated from the perspectives of both the parent and the adolescent.

Psychometric Properties of the Turkish Version of the Children's Saving Inventory in a Clinical Sample.

OBJECTIVE: The Children's Saving Inventory (CSI) is a measurement tool developed to assess hoarding behavior in children. This study aims to investigate the psychometric properties of the Turkish version of the CSI in a clinical sample of children and adolescents. MATERIALS AND METHODS: The study sample consisted of 52 children and adolescents diagnosed with obsessive-compulsive disorder in the 8-17 age group and their families. As a structured diagnostic interview, the Development and Well-Being Assessment (DAWBA) was applied to all participants included in the research. Hoarding disorder (HD) diagnosis was made clinically by considering the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria. The Children's Yale-Brown Obsessive- Compulsive Scale Symptom Checklist (CY-BOCS) was administered by an experienced clinician. The parents and children filled out the Obsessive-Compulsive Inventory-Child Version (OCI-CV) and CSI scales independently. RESULTS: The 20-item CSI Turkish version demonstrated good internal consistency. This 4-factor structure of the scale was confirmed by confirmatory factor analysis. Children's Saving Inventory showed convergent and discriminant validity with the OCI-CV and CY-BOCS subscales, and the higher CSI total scores in children and adolescents diagnosed with HD confirmed the construct validity. CONCLUSION: These findings support the use of the CSI Turkish version as a valid and reliable scale to investigate the hoarding behavior of children and adolescents in a clinical sample. In addition, the CSI Turkish version is currently the only validated instrument to evaluate hoarding behavior in children and adolescents, as rated by parents in Türkiye.