Poor sleep quality in children with atopic dermatitis and its effects on behavior: A multicenter cross-sectional study from a low-middle-income country.

BACKGROUND: Sleep disturbance in children with atopic dermatitis (AD) frequently goes unnoticed and can be associated with behavioral challenges. The aims of this study were to determine (a) the prevalence and factors associated with sleep disturbance and behavioral problems and (b) the correlation between sleep disturbance and behavioral problems in children with AD. METHODS: This cross-sectional study involved children aged 4-12 years old with moderate to severe AD. Age and sex-matched healthy children were recruited as the comparison group. The Children's Sleep Habits Questionnaire (CSHQ) and the Strengths and Difficulties Questionnaire (SDQ) were used to assess sleep disturbance and behavioral problems, respectively. Higher scores in both questionnaires signify more disturbance. RESULTS: Seventy patients and 141 controls were recruited. Median (interquartile range) age of patients was 5 (4,8) years. Patients had later sleep time (p < 0.001), longer night awakening (p < 0.001), and shorter sleep duration (p < 0.001) compared to controls. CSHQ total scores and all its domains, except for sleep-disordered breathing were significantly higher in patients compared to controls. Patients also had significantly higher SDQ total difficulties scores in all domains, except for peer problems. Severity of AD was significantly associated with high CSHQ and SDQ scores. There was a moderate positive correlation between the total CSHQ score and total SDQ score in patients (r = 0.532). CONCLUSIONS: Children with moderate-to-severe AD had significantly more sleep disturbance and more behavioral problems than their healthy peers. Sleep disturbance had a positive correlation with behavioral problems. Severity of AD was associated with sleep disturbance and behavioral problems.

Fut9 Deficiency Causes Abnormal Neural Development in the Mouse Cerebral Cortex and Retina.

α1,3-Fucosyltransferase 9 (Fut9) is responsible for the synthesis of Lewis X [LeX, Galß1-4(Fucα1-3)GlcNAc] carbohydrate epitope, a marker for pluripotent or multipotent tissue-specific stem cells. Although Fut9-deficient mice show anxiety-related behaviors, structural and cellular abnormalities in the brain remain to be investigated. In this study, using in situ hybridization and immunohistochemical techniques in combination, we clarified the spatiotemporal expression of Fut9, together with LeX, in the brain and retina. We found that Fut9-expressing cells are positive for Ctip2, a marker of neurons residing in layer V/VI, and TLE4, a marker of corticothalamic projection neurons (CThPNs) in layer VI, of the cortex. A birthdating analysis using 5-ethynyl-2'-deoxyuridine at embryonic day (E)11.5, 5-bromo-2'-deoxyuridine at E12.5, and in utero electroporation of a GFP expression plasmid at E14.5 revealed a reduction in the percentage of neurons produced at E11.5 in layer VI/subplate of the cortex and in the ganglion cell layer of the retina in P0 Fut9-/- mice. Furthermore, this reduction in layer VI/subplate neurons persisted into adulthood, leading to a reduction in the number of Ctip2strong/Satb2- excitatory neurons in layer V/VI of the adult Fut9-/- cortex. These results suggest that Fut9 plays significant roles in the differentiation, migration, and maturation of neural precursor cells in the cortex and retina.

Antioxidant Modulation of mTOR and Sirtuin Pathways in Age-Related Neurodegenerative Diseases.

In the human body, cell division and metabolism are expected to transpire uneventfully for approximately 25 years. Then, secondary metabolism and cell damage products accumulate, and ageing phenotypes are acquired, causing the progression of disease. Among these age-related diseases, neurodegenerative diseases have attracted considerable attention because of their irreversibility, the absence of effective treatment and their relationship with social and economic pressures. Mechanistic (formerly mammalian) target of rapamycin (mTOR), sirtuin (SIRT) and insulin/insulin growth factor 1 (IGF1) signalling pathways are among the most important pathways in ageing-associated conditions, such as neurodegeneration. These longevity-related pathways are associated with a diversity of various processes, including metabolism, cognition, stress reaction and brain plasticity. In this review, we discuss the roles of sirtuin and mTOR in ageing and neurodegeneration, with an emphasis on their regulation of autophagy, apoptosis and mitochondrial energy metabolism. The intervention of neurodegeneration using potential antioxidants, including vitamins, phytochemicals, resveratrol, herbals, curcumin, coenzyme Q10 and minerals, specifically aimed at retaining mitochondrial function in the treatment of Alzheimer's disease, Parkinson's disease and Huntington's disease is highlighted.

Cellular Uptake and Bioavailability of Tocotrienol-Rich Fraction in SIRT1-Inhibited Human Diploid Fibroblasts.

Tocotrienol-rich fraction (TRF) is palm vitamin E that consists of tocopherol and tocotrienol. TRF is involved in important cellular regulation including delaying cellular senescence. A key regulator of cellular senescence, Sirtuin 1 (SIRT1) is involved in lipid metabolism. Thus, SIRT1 may regulate vitamin E transportation and bioavailability at cellular level. This study aimed to determine the role of SIRT1 on cellular uptake and bioavailability of TRF in human diploid fibroblasts (HDFs). SIRT1 gene in young HDFs was silenced by small interference RNA (siRNA) while SIRT1 activity was inhibited by sirtinol. TRF treatment was given for 24 h before or after SIRT1 inhibition. Cellular concentration of TRF isomers was determined according to the time points of before and after TRF treatment at 0, 24, 48, 72 and 96 h. Our results showed that all tocotrienol isomers were significantly taken up by HDFs after 24 h of TRF treatment and decreased 24 h after TRF treatment was terminated but remained in the cell up to 72 h. The uptake of α-tocopherol, α-tocotrienol and ß-tocotrienol was significantly higher in senescent cells as compared to young HDFs indicating higher requirement for vitamin E in senescent cells. Inhibition of SIRT1 gene increased the uptake of all tocotrienol isomers but not α-tocopherol. However, SIRT1 inhibition at protein level decreased tocotrienol concentration. In conclusion, SIRT1 may regulate the cellular uptake and bioavailability of tocotrienol isomers in human diploid fibroblast cells while a similar regulation was not shown for α-tocopherol.