Evaluation of the Project P.A.T.H.S. in Mainland China: Findings Based on Student Diaries

Objectives: Based on 859 student diaries, the present study evaluated a positive youth development program entitled “Tin Ka Ping (TKP) Positive Adolescent Training through Holistic Social programs (P.A.T.H.S.) ” project implemented in mainland China during the 2015–2016 academic year. Method: To understand the perceived effectiveness of the students, the study analyzed quantitative as well as qualitative data derived from the student diaries. Results: The students held very positive views toward the program and the implementers. The narratives of the students also showed that they perceived improvement in the intrapersonal, interpersonal, familial, and societal domains after joining the program. Conclusion: In conjunction with the subjective outcome evaluation findings, the present findings suggest that the “TKP P.A.T.H.S.” project is able to promote holistic development of secondary school students in mainland China

Placenta-Derived Fetal Specific mRNA Is More Readily Detectable in Maternal Plasma than in Whole Blood

BACKGROUND:Placental mRNA was detected in maternal whole blood, raising the possibility of using maternal blood for noninvasive prenatal diagnosis. We investigated fetal mRNA detection in maternal whole blood and determined if it offered advantages over maternal plasma analysis. METHODOLOGY:The concentrations of placental expressed genes, CSH1, KISS1, PLAC4 and PLAC1 in plasma and whole blood from healthy pregnant and non-pregnant individuals were compared by real-time quantitative reverse-transcriptase polymerase chain reaction analysis. Their fetal specificity was investigated by comparing the transcript concentrations in pre- and post-delivery samples and through SNP genotyping by matrix-assisted laser-desorption and ionization time-of-flight mass spectrometry. The gene expression profiles of pregnant and non-pregnant whole blood were investigated by microarray analysis. Upregulated genes in pregnant whole blood were selected for further quantitative analysis. PRINCIPAL FINDINGS:The concentrations of the four transcripts were significantly higher in third trimester maternal whole blood than corresponding plasma without significant correlations. KISS1, PLAC4 and PLAC1 were detected in non-pregnant whole blood but not plasma. The transcripts remained detectable in some postpartum whole blood samples. The PLAC4 mRNA in maternal plasma showed fetal genotype while that in corresponding whole blood indicated both fetal and maternal contributions. Microarray analysis revealed upregulation of genes involved in neutrophil functions in pregnant whole blood including DEFA4, CEACAM8, OLFM4, ORM1, MMP8 and MPO. Though possibly pregnancy-related, they were not pregnancy-specific as suggested by the lack of post-delivery reduction in concentrations. CONCLUSIONS:Maternal plasma is preferred over maternal whole blood for placenta-derived fetal RNA detection. Most studied 'placental' mRNA molecules in maternal whole blood were of maternal origin and might be derived from processes such as 'illegitimate transcription'

The relationship of self-efficacy to catastrophizing and depressive symptoms in community-dwelling older adults with chronic pain: A moderated mediation model

Self-efficacy has been consistently found to be a protective factor against psychological distress and disorders in the literature. However, little research is done on the moderating effect of self-efficacy on depressive symptoms in the context of chronic pain. This cross-sectional study aimed to examine if pain self-efficacy attenuated the direct relationship between pain intensity and depressive symptoms, as well as their indirect relationship through reducing the extent of catastrophizing when feeling pain (moderated mediation). 664 community-dwelling Chinese older adults aged 60–95 years who reported chronic pain for at least three months were recruited from social centers. They completed a battery of questionnaires on chronic pain, pain self-efficacy, catastrophizing, and depressive symptoms in individual face-to-face interviews. Controlling for age, gender, education, self-rated health, number of chronic diseases, pain disability, and pain self-efficacy, pain catastrophizing was found to partially mediate the connection between pain intensity and depressive symptoms. Furthermore, the relationship between pain intensity and depressive symptoms was moderated by pain self-efficacy. Self-efficacy was also found to moderate the relationship between pain intensity and catastrophizing and the moderated mediation effect was confirmed using bootstrap analysis. The results suggested that with increasing levels of self-efficacy, pain intensity’s direct effect on depressive symptoms and its indirect effect on depressive symptoms via catastrophizing were both reduced in a dose-dependent manner. Our findings suggest that pain self-efficacy is a significant protective factor that contributes to psychological resilience in chronic pain patients by attenuating the relationship of pain intensity to both catastrophizing and depressive symptoms

Silencing of microRNA-21 in vivo ameliorates autoimmune splenomegaly in lupus mice

MicroRNAs (miRNAs) have been implicated in B cell lineage commitment, regulation of T cell differentiation, TCR signalling, regulation of IFN signalling, and numerous other immunological processes. However, their function in autoimmunity, and specifically in systemic lupus erythematosus (SLE), remains poorly understood. B6.Sle123 is a spontaneous genetic mouse model of SLE characterized by autoantibody production, lymphosplenomegaly, and glomerulonephritis. We identified several differentially regulated miRNAs in B and T lymphocytes of B6.Sle123 mice. We found that miR-21 expression in lupus B and T cells is up-regulated and that in vivo silencing of miR-21 using a tiny seed-targeting LNA reversed splenomegaly, one of the cardinal manifestations of autoimmunity in B6.Sle123 mice, and de-repressed PDCD4 expression in vivo and in vitro. In addition, treatment with anti-miR-21 altered CD4/CD8 T cell ratios and reduced Fas receptor-expressing lymphocyte populations. Our study shows that tiny LNAs can be used to efficiently antagonize endogenous miRNAs in peripheral lymphocytes in vivo and in primary lymphocytes cultured ex vivo and can alter the course of a spontaneous genetic disease in mice

Justifying top management pay in a transitional economy

We investigate some aspects of top management pay in China\u27s listed firms. We find positive pay and performance sensitivities and elasticities for top executives. In terms of magnitude, these sensitivities are similar to those reported in U.S. firms during the 1970s. However, the pay and performance relation is slightly weaker for firms located in less developed provinces. We also find that the pay disparities between top managers and employees are positively related to a firm\u27s performance. Thus, it appears that any deviation away from a manager-worker compensation norm has to be justified by superior firm performance. In additional analyses, we find that managers\u27 perquisites are not related to performance

Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study

Objectives To validate the clinical efficacy and practical feasibility of massively parallel maternal plasma DNA sequencing to screen for fetal trisomy 21 among high risk pregnancies clinically indicated for amniocentesis or chorionic villus sampling

Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin

Pathological processes involved in the initiation of rheumatoid synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of rheumatoid arthritis ( RA) by assessing a panel of T cell, macrophage, and stromal cell related cytokines and chemokines in the synovial fluid of patients with early synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute crystal arthritis, established RA and osteoarthritis. Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines measured using a multiplex based system. Patients with early inflammatory arthritis who subsequently developed RA had a distinct but transient synovial fluid cytokine profile. The levels of a range of T cell, macrophage and stromal cell related cytokines ( e. g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast growth factor and epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent synovitis exhibited elevated levels of interferon-gamma at initiation. Early synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid cytokine profile. The cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA

Noninvasive Prenatal Diagnosis of Fetal Trisomy 21 by Allelic Ratio Analysis Using Targeted Massively Parallel Sequencing of Maternal Plasma DNA

BACKGROUND: Plasma DNA obtained from a pregnant woman contains a mixture of maternal and fetal DNA. The fetal DNA proportion in maternal plasma is relatively consistent as determined using polymorphic genetic markers across different chromosomes in euploid pregnancies. For aneuploid pregnancies, the observed fetal DNA proportion measured using polymorphic genetic markers for the aneuploid chromosome would be perturbed. In this study, we investigated the feasibility of analyzing single nucleotide polymorphisms using targeted massively parallel sequencing to detect such perturbations in mothers carrying trisomy 21 fetuses. METHODOLOGY/PRINCIPAL FINDINGS: DNA was extracted from plasma samples collected from fourteen pregnant women carrying singleton fetuses. Hybridization-based targeted sequencing was used to enrich 2 906 single nucleotide polymorphism loci on chr7, chr13, chr18 and chr21. Plasma DNA libraries with and without target enrichment were analyzed by massively parallel sequencing. Genomic DNA samples of both the mother and fetus for each case were genotyped by single nucleotide polymorphism microarray analysis. For the targeted regions, the mean sequencing depth of the enriched samples was 225-fold higher than that of the non-enriched samples. From the targeted sequencing data, the ratio between fetus-specific and shared alleles increased by approximately 2-fold on chr21 in the paternally-derived trisomy 21 case. In comparison, the ratio is decreased by approximately 11% on chr21 in the maternally-derived trisomy 21 cases but with much overlap with the ratio of the euploid cases. Computer simulation revealed the relationship between the fetal DNA proportion, the number of informative alleles and the depth of sequencing. CONCLUSIONS/SIGNIFICANCE: Targeted massively parallel sequencing of single nucleotide polymorphism loci in maternal plasma DNA is a potential approach for trisomy 21 detection. However, the method appears to be less robust than approaches using non-polymorphism-based counting of sequence tags in plasma

Transgenic Mice Over-Expressing ET-1 in the Endothelial Cells Develop Systemic Hypertension with Altered Vascular Reactivity

Endothelin-1 (ET-1) is a potent vasoconstrictor involved in the regulation of vascular tone and implicated in hypertension. However, the role of small blood vessels endothelial ET-1 in hypertension remains unclear. The present study investigated the effect of chronic over-expression of endothelial ET-1 on arterial blood pressure and vascular reactivity using transgenic mice approach. Transgenic mice (TET-1) with endothelial ET-1 over-expression showed increased in ET-1 level in the endothelial cells of small pulmonary blood vessels. Although TET-1 mice appeared normal, they developed mild hypertension which was normalized by the ETA receptor (BQ123) but not by ETB receptor (BQ788) antagonist. Tail-cuff measurements showed a significant elevation of systolic and mean blood pressure in conscious TET-1 mice. The mice also exhibited left ventricular hypertrophy and left axis deviation in electrocardiogram, suggesting an increased peripheral resistance. The ionic concentrations in the urine and serum were normal in 8-week old TET-1 mice, indicating that the systemic hypertension was independent of renal function, although, higher serum urea levels suggested the occurrence of kidney dysfunction. The vascular reactivity of the aorta and the mesenteric artery was altered in the TET-1 mice indicating that chronic endothelial ET-1 up-regulation leads to vascular tone imbalance in both conduit and resistance arteries. These findings provide evidence for the role of spatial expression of ET-1 in the endothelium contributing to mild hypertension was mediated by ETA receptors. The results also suggest that chronic endothelial ET-1 over-expression affects both cardiac and vascular functions, which, at least in part, causes blood pressure elevation