Vitamin D ameliorates adipose browning in chronic kidney disease cachexia.

Patients with chronic kidney disease (CKD) are often 25(OH)D3 and 1,25(OH)2D3 insufficient. We studied whether vitamin D repletion could correct aberrant adipose tissue and muscle metabolism in a mouse model of CKD-associated cachexia. Intraperitoneal administration of 25(OH)D3 and 1,25(OH)2D3 (75 µg/kg/day and 60 ng/kg/day respectively for 6 weeks) normalized serum concentrations of 25(OH)D3 and 1,25(OH)2D3 in CKD mice. Vitamin D repletion stimulated appetite, normalized weight gain, and improved fat and lean mass content in CKD mice. Vitamin D supplementation attenuated expression of key molecules involved in adipose tissue browning and ameliorated expression of thermogenic genes in adipose tissue and skeletal muscle in CKD mice. Furthermore, repletion of vitamin D improved skeletal muscle fiber size and in vivo muscle function, normalized muscle collagen content and attenuated muscle fat infiltration as well as pathogenetic molecular pathways related to muscle mass regulation in CKD mice. RNAseq analysis was performed on the gastrocnemius muscle. Ingenuity Pathway Analysis revealed that the top 12 differentially expressed genes in CKD were correlated with impaired muscle and neuron regeneration, enhanced muscle thermogenesis and fibrosis. Importantly, vitamin D repletion normalized the expression of those 12 genes in CKD mice. Vitamin D repletion may be an effective therapeutic strategy for adipose tissue browning and muscle wasting in CKD patients.

Vitamin D repletion ameliorates adipose tissue browning and muscle wasting in infantile nephropathic cystinosis-associated cachexia.

BACKGROUND: Ctns-/- mice, a mouse model of infantile nephropathic cystinosis, exhibit hypermetabolism with adipose tissue browning and profound muscle wasting. Ctns-/- mice are 25(OH)D3 and 1,25(OH)2 D3 insufficient. We investigated whether vitamin D repletion could ameliorate adipose tissue browning and muscle wasting in Ctns-/- mice. METHODS: Twelve-month-old Ctns-/- mice and wild-type controls were treated with 25(OH)D3 and 1,25(OH)2 D3 (75 µg/kg/day and 60 ng/kg/day, respectively) or an ethylene glycol vehicle for 6 weeks. Serum chemistry and parameters of energy homeostasis were measured. We quantitated total fat mass and studied expression of molecules regulating adipose tissue browning, energy metabolism, and inflammation. We measured lean mass content, skeletal muscle fibre size, in vivo muscle function (grip strength and rotarod activity), and expression of molecules regulating muscle metabolism. We also analysed the transcriptome of skeletal muscle in Ctns-/- mice using RNAseq. RESULTS: Supplementation of 25(OH)D3 and 1,25(OH)2 D3 normalized serum concentration of 25(OH)D3 and 1,25(OH)2 D3 in Ctns-/- mice, respectively. Repletion of vitamin D partially or fully normalized food intake, weight gain, gain of fat, and lean mass, improved energy homeostasis, and attenuated perturbations of uncoupling proteins and adenosine triphosphate content in adipose tissue and muscle in Ctns-/- mice. Vitamin D repletion attenuated elevated expression of beige adipose cell biomarkers (UCP-1, CD137, Tmem26, and Tbx1) as well as aberrant expression of molecules implicated in adipose tissue browning (Cox2, Pgf2α, and NF-κB pathway) in inguinal white adipose tissue in Ctns-/- mice. Vitamin D repletion normalized skeletal muscle fibre size and improved in vivo muscle function in Ctns-/- mice. This was accompanied by correcting the increased muscle catabolic signalling (increased protein contents of IL-1ß, IL-6, and TNF-α as well as an increased gene expression of Murf-2, atrogin-1, and myostatin) and promoting the decreased muscle regeneration and myogenesis process (decreased gene expression of Igf1, Pax7, and MyoD) in skeletal muscles of Ctns-/- mice. Muscle RNAseq analysis revealed aberrant gene expression profiles associated with reduced muscle and neuron regeneration, increased energy metabolism, and fibrosis in Ctns-/- mice. Importantly, repletion of 25(OH)D3 and 1,25(OH)2 D3 normalized the top 20 differentially expressed genes in Ctns-/- mice. CONCLUSIONS: We report the novel findings that correction of 25(OH)D3 and 1,25(OH)2 D3 insufficiency reverses cachexia and may improve quality of life by restoring muscle function in an animal model of infantile nephropathic cystinosis. Mechanistically, vitamin D repletion attenuates adipose tissue browning and muscle wasting in Ctns-/- mice via multiple cellular and molecular mechanisms.

[Environmental risk factors for autism spectrum disorders in children].

OBJECTIVE: To investigate the environmental risk factors for autism spectrum disorders (ASD) in children. METHODS: In this case-control study, 81 boys with ASD, 74 boys with global developmental delay (GDD), and 163 healthy boys were enrolled. A self-designed nurturing environment questionnaire was used to record general demographic data, family social-economic status, parents' living habits and environmental exposure, maternal health status during pregnancy, birth situations, and rearing environment after birth. Multivariate logistic regression was used to identify environmental risk factors for ASD and GDD. RESULTS: Multivariate logistic regression analysis showed that six environmental risk factors such as maternal occupational toxicant exposure, diseases during pregnancy and a history of passive smoking, children's birth places, the frequency of outdoor activities in the second year after birth, and the opportunities to communicate with other age-matched children were significantly associated with the incidence of ASD (OR=20.67, 3.559, 2.422, 2.646, 23.820, and 5.081, respectively; P<0.05). Among the above six risk factors, passive smoking during pregnancy, the opportunities to communicate with their peers, and the frequency of outdoor activities in the second year after birth were also significantly associated with the incidence of GDD (P<0.05). CONCLUSIONS: Maternal occupational toxicant exposure, diseases during pregnancy, and low level of children's birth places may be the specific risk factors associated with ASD, and passive smoking during pregnancy, fewer opportunities to communicate with their peers, and fewer outdoor activities in the second year after birth are non-specific risk factors for ASD, indicating that the development of ASD may be influenced by both genes and environmental factors.

Cachexia and protein-energy wasting in children with chronic kidney disease.

Children with chronic kidney disease (CKD) are at risk for "cachexia" or "protein-energy wasting" (PEW). These terms describe a pathophysiologic process resulting in the loss of muscle, with or without loss of fat, and involving maladaptive responses, including anorexia and elevated metabolic rate. PEW has been defined specifically in relation to CKD. We review the diagnostic criteria for cachexia and PEW in CKD and consider the limitations and applicability of these criteria to children with CKD. In addition, we present an overview of the manifestations and mechanisms of cachexia and PEW. A host of pathogenetic factors are considered, including systemic inflammation, endocrine perturbations, and abnormal neuropeptide signaling, as well as poor nutritional intake. Mortality risk, which is 100- to 200-fold higher in patients with end-stage renal disease than in the general population, is strongly correlated with the components of cachexia/PEW. Further research into the causes and consequences of wasting and growth retardation is needed in order to improve the survival and quality of life for children with CKD.

Charting the developmental trajectories of attention and executive function in Chinese school-aged children.

Attention is a complex domain that has reawakened research interest in recent years. There are relatively few studies that have examined age-related changes across different attention subcomponents, such as selection, maintenance, and control, using large samples covering a wide age range. The present study assessed performance in 466 participants in order to identify the ages at which mature performance was reached across differing attention subcomponents. Furthermore, we investigated whether the nature of the attentional demands or task difficulty predicted the age at which stable levels of performance were reached. The results supported the former rather than the latter alternative.

The impact of inflammation on bone mass in children.

Bone is a dynamic tissue. Skeletal bone integrity is maintained through bone modeling and remodeling. The mechanisms underlying this bone mass regulation are complex and interrelated. An imbalance in the regulation of bone remodeling through bone resorption and bone formation results in bone loss. Chronic inflammation influences bone mass regulation. Inflammation-related bone disorders share many common mechanisms of bone loss. These mechanisms are ultimately mediated through the uncoupling of bone remodeling. Cachexia, physical inactivity, pro-inflammatory cytokines, as well as iatrogenic factors related to effects of immunosuppression are some of the common mechanisms. Recently, cytokine signaling through the central nervous system has been investigated for its potential role in bone mass dysregulation in inflammatory conditions. Growing research on the molecular mechanisms involved in inflammation-induced bone loss may lead to more selective therapeutic targeting of these pathological signaling pathways.

Neonatal screening for congenital hypothyroidism and phenylketonuria in China.

BACKGROUND: Neonatal screening is helpful to prevent serious disability and sufferings caused by congenital or inherited disease. This study was to review the status of neonatal screening for congenital hypothyroidism (CH) and phenylketonuria (PKU) in China. METHODS: We analyzed data of neonatal screening for CH and PKU in the past two decades which were obtained from the national network of neonatal screening centers collected by the National Center for Clinical Laboratory. RESULTS: Of 18.8 million newborns screened from 1985 to 2007, 9198 were identified with CH, giving a prevalence of 1/2047. In 19.0 million newborns screened in the same period, 1638 had PKU, with a prevalence of 1/11 572. An increasing number of neonates have been subjected to neonatal screening in China annually during this period. Data from Zhejiang Neonatal Screening Center showed that the recall rate of neonates suspected with CH and PKU was 95.52% in 2007. Confirmatory tests were performed and treatments were initiated in most of the neonates with CH and PKU within a month after birth. CONCLUSIONS: More governmental support at different levels is needed to make neonatal screening more efficient. The screening should be improved with a satisfactory control system including shorter time of report and a higher recall rate.

[A study on the social adjustment and its affective factors in Down syndrome children].

OBJECTIVE: To explore the social adjustment status and affected factors thereof in Down syndrome children. METHODS: The family environment, cognitive development and social adjustment were examined in 36 Down syndrome children aged 52 - 167 months, 30 mental age-matched children aged 20 - 65 months, and 40 chronological age-matched children aged 43 - 144 months with questionnaire of family influential factors, Peabody Picture Vocabulary Test (PPVT) and Infants-Junior Middle School Students' Social-Life Abilities Scale from September 2004 to July 2006. The gender and general family environment were matched among the three groups. The information about the mode of delivery, history of newborn, family structure, income of family, and parents' education could be gathered from the questionnaire (used by parents). PPVT was adopted as research tool of cognitive development. Infants-Junior Middle School Students' Social-Life Abilities Scale was adopted as research tool of social adjustment. RESULTS: There were no differences between the Down syndrome children and mental age-matched group in communication and socialization. The Down syndrome children were better than the mental age-matched group in self-help [(20.0 +/- 4.8) vs (13.3 +/- 4.7), t = 5.72, P = 0.000]; locomotion [(7.5 +/- 1.4) vs (6.4 +/- 1. 6), t = 3.10, P = 0.003]; occupation [(8.2 +/- 2.4) vs (6.2 +/- 2.0), t = 3.68, P = 0.000], and self-direction [(5.9 +/- 2.6) vs (4.6 +/- 2.0), t = 2. 28, P = 0.026]. The chronological age-matched group were much better than the Down syndrome children in all factors of social-life abilities, including self-help [(20.0 +/- 4.8) vs (26.5 +/- 4.9), t = 5.84, P = 0.000]; locomotion [(7.5 +/- 1.4) vs (11.4 +/- 3.3), t = 6.76, P = 0.000]; occupation [(8.2 +/- 2.4) vs (14.4 +/- 3.9), t = 8.55, P = 0.000]; communication [(8.3 +/- 3.6) vs (18.3 +/- 4.8), t = 10.38, P = 0.000]; socialization [(9.6 +/- 2.3) vs (17.1 +/- 4.2), t = 9.76, P = 0.000], and self-direction [(5.9 +/- 2.6) vs (13. 8 +/- 4.6), t = 9.25, P = 0.000]. There was a relationship between the raw score of PPVT and social-life abilities in these children. Even after controlling effect of age, it was still associated with self-help (r = 0.70, P = 0.000), locomotion (r = 0.74, P = 0.000), occupation (r = 0.77, P = 0.000), communication (r = 0.86, P = 0.000), socialization (r = 0.80, P = 0.000), and self-direction (r = 0.76, P = 0.000). Multiple stepwise regression showed that the main factor influencing self-help was family structure. Family structure and mother's education influenced locomotion. Family structure and newborn history influenced occupation, communication, socialization and self-direction. CONCLUSION: Down syndrome children have better social adjustment than the mental age-matched group, yet worse than the chronological age-matched group. Cognition development, family environment and newborn history differently influence the Down syndrome child, which means proper intervention can improve their social adjustment.

Study on the social adaptation of Chinese children with down syndrome.

PURPOSE: To evaluate social adjustment and related factors among Chinese children with Down syndrome (DS). PATIENTS AND METHODS: A structured interview and Peabody Picture Vocabulary Test (PPVT) were conducted with a group of 36 DS children with a mean age of 106.28 months, a group of 30 normally-developing children matched for mental age (MA) and a group of 40 normally-developing children matched for chronological age (CA). Mean scores of social adjustment were compared between the three groups, and partial correlations and stepwise multiple regression models were used to further explore related factors. RESULTS: There was no difference between the DS group and the MA group in terms of communication skills. However, the DS group scored much better than the MA group in self-dependence, locomotion, work skills, socialization and self-management. Children in the CA group achieved significantly higher scores in all aspects of social adjustment than the DS children. Partial correlations indicate a relationship between social adjustment and the PPVT raw score and also between social adjustment and age (significant r ranging between 0.24 and 0.92). A stepwise linear regression analysis showed that family structure was the main predictor of social adjustment. Newborn history was also a predictor of work skills, communication, socialization and self-management. Parental education was found to account for 8% of self-dependence. Maternal education explained 6% of the variation in locomotion. CONCLUSION: Although limited by the small sample size, these results indicate that Chinese DS children have better social adjustment skills when compared to their mental-age-matched normally-developing peers, but that the Chinese DS children showed aspects of adaptive development that differed from Western DS children. Analyses of factors related to social adjustment suggest that effective early intervention may improve social adaptability.