Remedial Dosing Recommendations for Sirolimus Delayed or Missed Dosages Caused by Poor Medication Compliance in Pediatric Tuberous Sclerosis Complex Patients.

BACKGROUND: Delayed or missed dosages caused by poor medication compliance significantly affected the treatment of diseases in children. AIMS: The present study aimed to investigate the influence of delayed or missed dosages on sirolimus pharmacokinetics (PK) in pediatric tuberous sclerosis complex (TSC) patients and to recommend remedial dosages for nonadherent patients. METHODS: A published sirolimus population PK model in pediatric TSC patients was used to assess the influence of different nonadherence scenarios and recommend optimally remedial dosages based on Monte Carlo simulation. Thirteen nonadherent scenarios were simulated in this study, including delayed 2h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 16 h, 18 h, 20 h, 22 h, 23.5 h, and missed one dosage. Remedial dosing strategies contained 10-200% of scheduled dosages. The optimal remedial dosage was that with the maximum probability of returning the individual therapeutic range. RESULTS: For delayed or missed sirolimus dosages in pediatric TSC patients, when the delayed time was 0-8 h, 8-10 h, 10-18 h, 18-22.7 h, 22.7-24 h, 70%, 60%, 40%, 30%, 20% scheduled dosages were recommended to take immediately. When one dosage was missed, 120% of scheduled dosages were recommended at the next dose. CONCLUSION: It was the first time to recommend remedial dosages for delayed or missed sirolimus therapy caused by poor medication compliance in pediatric TSC patients based on Monte Carlo simulation. Meanwhile, the present study provided a potential solution for delayed or missed dosages in clinical practice.

Systematic review and meta-analysis of the effects of exercise on depression in adolescents.

BACKGROUND: Depression is widespread among adolescents and seriously endangers their quality of life and academic performance. Developing strategies for adolescent depression has important public health implications. No systematic review on the effectiveness of physical exercise for adolescents aged 12-18 years with depression or depressive symptoms has previously been conducted. This study aims to systematically evaluate the effect of physical exercise on adolescent depression in the hope of developing optimum physical exercise programs. METHODS: Nine major databases at home and abroad were searched to retrieve randomized controlled trials (RCTs) on exercise interventions among adolescents with depression or depressive symptoms. The retrieval period started from the founding date of each database to May 1, 2021. The methodological quality of the included articles was evaluated using the modified PEDro scale. A meta-analysis, subgroup analysis, sensitivity analysis, and publication bias tests were then conducted. RESULTS: Fifteen articles, involving 19 comparisons, with a sample size of 1331, were included. Physical exercise significantly reduced adolescent depression (standardized mean difference [SMD] = - 0.64, 95% CI - 0.89, - 0.39, p < 0.01), with a moderate effect size, in both adolescents with depression (SMD = -0.57, 95% CI - 0.90, - 0.23, p < 0.01) and adolescents with depressive symptoms (SMD = - 0.67, 95% CI - 1.00, - 0.33, p < 0.01). In subgroups of different depression categories (depression or depressive symptoms), aerobic exercise was the main form of exercise for the treatment of adolescents with depression. For adolescents with depression, interventions lasting 6 weeks, 30 min/time, and 4 times/week had optimum results. The effects of aerobic exercise and resistance + aerobic exercise in the subgroup of adolescents with depressive symptoms were significant, while the effect of physical and mental exercise (yoga) was not significant. For adolescents with depressive symptoms, aerobic exercise lasting 8 weeks, 75-120 min/time, and 3 times/week had optimum results. Physical exercise with moderate intensity is a better choice for adolescents with depression and depressive symptoms. CONCLUSIONS: Physical exercise has a positive effect on the improvement of depression in adolescents. The protocol for this study was registered with INPLASY (202170013). DOI number is 10.37766/inplasy2021.7.0013. Registration Date:2021.7.06.

Improved anaerobic digestion efficiency of high-solid sewage sludge by enhanced direct interspecies electron transfer with activated carbon mediator.

High-solid anaerobic digestion (AD) faces the problems of easy acidification and low methane production efficiency. In this study, activated carbon (AC)-enhanced direct interspecies electron transfer (DIET) was investigated to overcome such problems. Results showed the conversion of volatile fatty acids (VFAs) into methane rate was increased with AC addition, which led improved methane production efficiency. The methane yields from the early AD stage improved by 124.0-146.3% with AC addition. The T80 shortened by 8-9 days with AC addition. The relative abundances of Geobacter, Syntrophomonas and Methanosaeta that associated with DIET improved for 63.65%, 256.3% and 4.35% by AC addition, which reflected the enhanced DIET with AC addition. The redox activity of AC might be responsible for the enhanced DIET. This study would advance the understanding of DIET and provide a potential solution to the problems existed in high-solid AD.

Effects of China-made recombinant human growth hormone on the treatment of growth hormone deficiency.

OBJECTIVE: To evaluate the therapeutic effect of China-made recombinant human growth hormone (r-hGH) in children with growth hormone deficiency (GHD) and to investigate the utilities of various biochemical parameters in GHD diagnosis and treatment. METHODS: Our study comprises of 30 normal children and 71 GHD children treated with China-made r-hGH substitution therapy 0.1 IU x kg(-1) x d(-1) for 6 months. Serum insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), bone turnover markers (Ost, ICTP), and anti-growth hormone antibody (GHAb) were detected before and after r-hGH treatment. RESULTS: After the first 3 and 6 months of treatment, growth velocities of GHD children were significantly increased (13.1 +/- 3.7 and 12.6 +/- 3.6 cm/year) compared with pretreatment values (2.9 +/- 0.8 cm/year, P < 0.01). GHD Children had obviously reduced serum levels of IGF-1, IGFBP-3, and bone turnover markers (Ost, ICTP) compared with normal controls (P < 0.01), and these biochemical parameters improved significantly after treatment (P < 0.01). Growth hormone antibodies were positive in 17 of 45 cases after treatment by binding capacity detection. The binding percentage of growth hormone antibody which was increased more than 30% after the treatment showed a negative correlation with growth velocity (P < 0.01). CONCLUSIONS: (1) The growth stimulating effect and safety were confirmed in using China-made r-hGH in the treatment of GHD children for 6 months. (2) The measurements of serum IGF-1 and IGFBP-3 may serve as useful parameters in the diagnosis of GHD. (3) Serum Ost and ICTP are useful laboratory criteria for evaluating the effect of r-hGH therapy in the early stage. (4) It is necessary to monitor serum levels of GHAb during r-hGH therapy.

[Oral glucose tolerance and insulin release test in 52 cases of obese and overweight children].

OBJECTIVE: To assess the state of glucose metabolism and beta-cell function in obese and overweight children. METHODS: Levels of glucose and insulin were detected during oral glucose tolerance test in 52 obese and overweight children aged 11.3 +/- 1.8 years with body mass index (BMI) 30.2 +/- 19.2 kg/m(2). Insulin resistance index (IR = FIN x FPG/22.5), insulin sensitivity index (IS = 1/FIN x FPG) and ratio of insulin increment to glucose increment at 30' (I(30)-I(0)/G(30)-G(0)) post oral glucose were measured. (FIN = fasting insulin. FPG = fasting plasma glucose). The IR, IS and the ratio post oral glucose were compared among groups with varying BMI and between groups of impaired glucose tolerance (IGT) and control. Serum triglyceride determination and B ultrasonography of liver were performed. RESULTS: (1) one patient with type 2 diabetes (1.9%) and 5 patients with IGT (9.6%) were found. (2) IR (> or = 2.8) was observed in 76.9% of the cases. (3) The IR, IS and their ratio showed no difference between the compared groups. (4) IR and IS did not show significant difference but there was significant difference in ratio between the IGT and control group. (5) Increased serum triglyceride and fatty liver were noted in 36.5% and 53.3% of the cases, respectively. CONCLUSION: The results indicated that insulin resistance and reduced insulin sensitivity in obese and overweight children are common, and these changes seemed not to correlated with the varying degree of BMI. Beta-cells function was obviously impaired in obese children with IGT and disorder of lipid metabolism exists in many obese and overweight children revealed.

[Construction of eukaryotic expression vector of murine SLC gene and characterization of its chemotactic function].

AIM: To construct the eukaryotic expression vector of murine SLC gene and study the chemotactic function of murine SLC in-vitro and in-vivo. METHODS: Murine SLC gene was cloned by RT-PCR from the thymus tissue of a C57BL/6 mouse. Eukaryotic expression vector of SLC gene-pcDNA3.1 mSLC was constructed and transfected into B16F10 cells by gene gun. Culture supernatant was collected 48 hours after the transfection and chemotactic function of expression product to lymphocytes was detected by a chemotaxis chamber. SLC expression was detected by RT-PCR. Lymphocytic infiltration was observed in SLC gene transfected murine abdominal skin. RESULTS: The gene cloned from the C57BL/6 mouse thymus tissue was SLC gene Scya21b. Transfected cells expressed SLC mRNA, and culture supernatant of those cells had a potent chemotactic function to lymphocytes. Histological examination of transfected skin showed obvious lymphocytic infiltration. CONCLUSION: The SLC gene was cloned from the mouse thymus tissue and could be expressed in B16F10 cells. The expression product in-vitro and in-vivo had a remarkable chemotactic function to lymphocytes.