Inhibition of endocan attenuates monocrotaline-induced connective tissue disease related pulmonary arterial hypertension

Connective tissue disease related pulmonary arterial hypertension (CTD-PAH) is characterized by vascular remodeling, endothelial dysfunction and inflammation. Endocan is a novel endothelial dysfunction marker. The aim of the present study was to investigate the role of endocan in CTD-PAH. Monocrotaline (MCT)-induced PAH rats were used as the CTD-PAH model. Short hairpin RNA packed in a lentiviral vector used to inhibit endocan expression was intratracheally instilled in rats prior to the MCT injection. Endocan was found to be increased in the serum and lung of MCT-induced PAH rats. Short hairpin RNA mediated knockdown of endocan significantly decreased right ventricular systolic pressure, attenuated pulmonary remodeling and inflammatory responses in the lung. In the in vitro study, tumor necrosis factor-α (TNF-α) exposure caused increased endocan expression in the primary cultured rat pulmonary microvascular endothelial cells (RPMECs). Endocan knockdown inhibited the permeability increase and adhesion molecules secretion in RPMECs induced by TNF-α. In addition, TNF-α induced MAPK activation was blocked when endocan gene was knocked down. These data demonstrate that endocan may play an important role in the development of CTD-PAH. This study provides novel evidence to better understand the pathogenesis of CTD-PAH, which may be beneficial for the treatment of this disease.     

Rasch analysis of a Spanish language-screening parent survey

The purpose of this study was to evaluate and refine items from a parent survey designed to screen the language skills of Spanish-speaking preschoolers. This investigation applied Rasch modeling to systematically evaluate and identify items that demonstrated favorable qualities.A set of 124 parent survey items was administered to 107 Spanish-speaking parents of preschool age children. Parents completed survey items intended to provide a global measure of preschool language abilities. Rasch analyses of the survey items were conducted using WINSTEPS.Results indicated that 59 items, all vocabulary items, fit the Rasch model. Sufficient unidimensionality was obtained, with the model accounting for 58% of the variance. Item difficulty estimates ranged from −7.43 to 4.12, with a shortage of items at both the lower ability level and at the higher ability level. Analyses of pruned and remaining items identified the type of items that may be most useful for a refined item bank. These results will inform the development of new items for a Spanish language-screening parent survey for preschool age children.     

Homozygous familial hypercholesterolemia in China: Genetic and clinical characteristics from a real-world,multi-center,cohort study

BackgroundThere is a lack of large-scale data on the clinical and genotype characteristics of homozygous familial hypercholesterolemia (HoFH) patients in Asia.ObjectiveTo define the characteristics of phenotypic and genetic HoFH probands from mainland China.MethodsWe collected data from patients with suspected HoFH from ten clinical hospitals across mainland China from 2003 to 2019. Clinical data and DNA testing were obtained in all patients. The Kaplan-Meier method was used to generate survival curves, and the groups were compared with the log-rank test.ResultsA total of 108 unrelated probands with suspected HoFH (mean age 14.9 years) were included. The three most common variants were W483X (c.1448 G>A), A627T (c.1879 G>A), H583Y (c.1747 C>T). The majority (64.8%) were compound heterozygotes (n = 70), 23 (21.3%) were true HoFH patients. True HoFH showed higher LDL-C levels compared to compound HoFH (16.8±3.6 mmol/L vs. 15.0±3.1 mmol/L, P = 0.022). During follow-up, only 21.2% patients exhibited an LDL-C reduction of more than 50%. Kaplan-Meier analysis showed that the true HoFH probands had significantly worse survival rates compared to other genotype probands (13-year survival; 20.3% vs. 76.7%, respectively; P = 0.016). In addition, true HoFH shows that 2.8-fold (P = 0.022) increase any death and 3.0-fold (P = 0.023) increase cardiovascular death risk in relative to other FH.ConclusionsThis report shows that HoFH has devastating consequences, and that patients are often only diagnosed after they have been exposed to severely elevated LDL-C for years. Systematic screening and early intensive treatment are an absolute requirement for these young individuals with HoFH.     

Is neonatal jaundice associated with autism spectrum disorder,attention deficit hyperactivity disorder,and other psychological development? A nationwide prospective study

Neonatal jaundice may cause the lifelong sequelae of central nerve system developmental disorders. However, the results are inconsistent. 2016 newborns with neonatal jaundice and 8064 age-/gender-matched (1:4) controls were enrolled during 1999–2000. Participants of autistic spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and other developmental disorders that occurred during the follow-up were identified. Newborns with neonatal jaundice had increased risks of developing ASD (hazard ratio [HR]: 1.75, 95% confidence interval [CI]: 1.05–2.90), any developmental delay (HR: 1.27, 95% CI: 1.02–1.58), and developmental speech or language disorder (HR: 1.41, 95% CI: 1.11–1.79). Newborn exposure to hyperbilirubinemia was related to the increased risk of developing ASD, any developmental delay, and developmental speech or language disorder in later life.     

The role of the disc in the healing of displaced subcondylar fracture in the growing period: an experimental study in rats

The purpose of this study was to evaluate the role of the disc in the healing of condylar fractures in the growing period. 40 growing and adult male Wistar rats were randomized into 4 equal groups: growing rats suffering condylar fracture with disc damage; growing rats suffering condylar fracture without disc damage; adult rats suffering condylar fracture with disc damage; adult rats suffering condylar fracture without disc damage. 3 months after the operation all animals were killed and the outcomes were compared using mandible deviation measure, body weight evaluation and histological observation. In growing rats, when the disc was undamaged maintaining its relation to the condyle head, even though the condylar fractured fragment was displaced, the condyle healed and recovered almost to normality in 3 months. In the same condyle fracture form, once the disc was damaged and lost the normal relation with the condyle head, the outcome was unfavourable. The occurrence of damage to the disc and its attachment to the condyle head are important factors in the healing of condyle fractures in the growing period.