ression and academic performance remained even in within-family analyses of monozygotic twin pairs.The proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are involved in the corneal inflammatory response and wound healing following corneal injuries. However, the mechanism by which proinflammatory cytokines modulate corneal epithelial wound healing remains unclear. In this study, we found that IL-1β or TNF-α was transiently elevated during corneal epithelial wound healing in mice. After corneal epithelial debridement, persistent treatment with IL-1β or TNF-α restrained the level of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and boosted the level of cell cycle inhibitor p16Ink4a , resulting in impaired corneal epithelial repair. When p16Ink4a was deleted, the p-STAT3 level in corneal epithelium was enhanced and corneal epithelial wound healing was clearly accelerated. In diabetic mice, IL-1β, TNF-α, and p16Ink4a appeared a sustained and strong expression in the corneal epithelium, and p16Ink4a knockdown partially reverted the defective diabetic corneal epithelial repair. Furthermore, immunoprecipitation proved that p16Ink4a interacted with p-STAT3 and thus possibly suppressed the STAT3 activity. Our findings revealed a novel mechanism that the proinflammatory cytokines modulate corneal epithelial wound healing via the p16Ink4a -STAT3 signaling.Purpose In migraine or primary headache in children, parents play a fundamental role in pain management. BAY 2402234 For this narrative review, PubMed, Google Scholar, and Psych Info were searched using the terms "parent headache", "mother/father headache", "parental impact headache", "alexithymia parents headache", "catastrophizing parent headache", "family headache", "children parent headache", and "quality of life family headache". Articles were chosen for inclusion based on their relevance in to the topic. Overview Several parental and psychological characteristics can influence in children and adolescent headache, such as parental attitudes as oppressive or overprotective; punitive parenting styles; familial psychological symptoms, especially anxiety and depression; catastrophizing about their child's pain or excessive worry about their child's headache; inability to express emotions; and feelings that may lead to somatization problems. Discussion Parents' attitudes and behaviors toward their child's headache have a strong relation with the severity of headache attacks. Mothers seem to have more influence than fathers on children's pain and emotional regulation. We suggest that the presence of caregiver-child transmission of maladaptive coping strategies, arising from difficulties expressing emotion, may lead to incorrect management of headache pain, further facilitating headache chronification.Background Irritability is frequently comorbid with ADHD. Although irritability alone has been linked to deleterious mental health and adaptive issues, the joint developmental course of ADHD and irritability symptoms during childhood as well as its association with later mental health and suicidal outcomes is not fully understood. We aimed to describe the developmental trajectories of childhood ADHD and irritability symptoms and to quantify their association with adolescent mental health and suicidal outcomes. Methods The Quebec Longitudinal Study of Child Development (QLSCD) included 1407 participants from the general population followed up from age 5 months to 17 years. We used a multitrajectory approach to identify developmental trajectories of childhood (6-12 years) ADHD and irritability symptoms. Outcome measures were adolescent (13-17 years) mental health (psychiatric symptoms/functional impairment) and suicidal outcomes. Results We identified distinct developmental profiles combined absent or very low ADHD and absent or very low irritability (940 [66.8%]; reference group), moderately high irritability and low ADHD (158 [11.2%]), moderately high ADHD and low irritability (198 [14.1%]), and combined high ADHD and high irritability (111 [7.9%]). Multivariate modeling showed that, compared to children in the reference group, those in the combined high ADHD and high irritability profile showed higher levels of ADHD continuity (d ranges = 0.40-0.50), externalizing (d ranges = 0.25-0.59), internalizing (d ranges = 0.20-0.29), and functional impairments (d ranges = 0.17-0.48) and suicidal behaviors (odds ratio (OR) = 2.12, confidence interval (CI) = 1.47-3.06) in adolescence. Conclusions The presence of persistently high levels of irritability along with ADHD symptoms during childhood significantly predicts adolescent ADHD continuity, externalizing, internalizing, and suicidal outcomes. Systematic consideration of irritability when assessing and treating ADHD may improve long-term mental health outcomes.Background Observational studies have shown that high levels of serum uric acid (UA) were associated with atrial fibrillation (AF). However, the causal effect of urate on the risk of AF is still unknown. To clarify the potential causal association between UA and AF, we performed a Mendelian randomization (MR) analysis using genetic instrumental variables (IVs). Materials and methods From the Korean GWAS dataset of 633 patients with AF (mean age 50.6 ± 7.8 years, 80.9% male, Yonsei AF Ablation cohort) who underwent radiofrequency catheter ablation and the data from 3533 controls (from the Korea Genome Epidemiology Study), we selected 9 SNPs, with a P value less than .05, associated with an increased UA serum level. Additionally, we calculated the weighted genetic risk score (wGRS) using the selected 9 SNPs, to use it as an instrumental variable. A Mendelian randomization analysis was calculated by a 2-stage estimator method. Results The conventional association between the serum UA and AF was significant (P = .001) after adjusting for potential confounding factors. The SNP rs1165196 on SLC17A1 (F-statistics = 208.34, 0.18 mg/mL per allele change, P less then .001) and wGRS (F-statistics = 222.26, 0.20 mg/mL per 1SD change, P less then .001) were significantly associated with an increase in the UA level. The MR analysis was causally associated with rs1165196 (estimated odds ratio (OR), 0.21, 95% confidence interval (CI), 0.06-0.75, P = .017), but not wGRS (estimated OR, 1.07, 95% CI, 0.57-2.01, P = .832). Conclusion The serum UA level was independently associated with the AF risk.