Emotional responses of piglets under long-term exposure to negative and positive auditory stimuli.

The stress caused by sound is inevitable. The stress caused by noise and the positive effects of music can affect the endocrine of animals and their welfare. In this study, a total of 72 hybrid piglets (Large White × Duroc × Min pig) were randomly divided into 3 groups, including music (Mozart K.448, 60-70 dB), noise (recorded mechanical noise, 80-85 dB), and control (natural background sound, <40 dB) groups. S-IgA (secretory immunoglobulin A), IL-6 (interleukin-6), IL-8 (interleukin-8), and positive emotion-related behaviors were used as indicators to discuss whether noise induced stress and inflammation in piglets or whether music could have positive effects. Six hours of auditory exposure were given daily (10:00-16:00), which lasted for 56 days. Behavioral responses of the piglets were observed, and the concentrations of salivary S-IgA and serum IL-6 and IL-8 were measured. The results showed that the concentration of S-IgA increased in the noise and control groups on the 57th day (P < 0.05); S-IgA concentration in the music group was unchanged after long-term music exposure. The concentrations of IL-6 and IL-8 showed that long-term noise exposure might lead to stress and inflammation in piglets. Tail-wagging and play behaviors of the piglets in the music group were significantly greater than those in the noise and control groups, which implied that long-term music exposure improved the emotional state of the piglets in a restricted and barren environment.

[Development and performance test of the environment scale of unintentional injury in the home for children aged 0-6 years old in urban area of China].

Objective: To develop the environment scale of unintentional injury in the home for children aged 0-6 years living in urban area of China, and test its validity and reliability. Methods: The content of the environment scale was established through the literature review, expert consultation and pilot study. A total of 1 104 children aged 0-6 years in urban area of Changsha were enrolled in this study by using a multi-stage stratified cluster random sampling method. The questionnaire was used to collect the basic information of children, the incidence of unintentional injury and the status of home environment. The reliability of the scale was tested by using Cronbach's α coefficient and split-half reliability coefficient. The content validity and construct validity were tested by using Pearson correlation analysis and factor analysis. All children were divided into two groups according to the incidence of unintentional injury in the home and the discrimination validity of the scale was tested by using t-test. Results: The scale had 54 items in 6 dimensions. The number of eligible questionnaires was 1 074, including 554 (51.6%) from boys and 519 (48.3%) from children under 3 years old. The incidence rate of unintentional injury and in-home injury was 18.34% (197 children) and 10.71% (115 children). The internal consistency reliability (Cronbach's α) coefficient for the scale was 0.87 and the split-efficacy reliability coefficient was 0.82, both meeting the standard of reliability above 0.70. The Pearson correlation coefficient between each dimension and the whole scale ranged from 0.53 to 0.84 (all P values <0.001). The common factor cumulative variance contribution rate of the scale was 58.34%. There were 54 items with factor loadings greater than 0.30. The root mean square error of approximation, comparative fit index and goodness-of-fit index were 0.07, 0.61 and 0.71, respectively. The score of scale in children with injury was significantly higher than that in children without injury (P=0.022). Conclusion: The validity and reliability of the environment scale for unintentional injury in the home for children aged 0-6 years old in the urban area of China are good.

Effects of health education intervention on negative emotion and quality of life of patients with laryngeal cancer after postoperative radiotherapy.

PURPOSE: The study aimed to explore and analyze the effects of health education intervention on patients with laryngeal cancer and evaluate negative emotions and quality of life after receiving postoperative radiotherapy. Furthermore the relationship between health education intervention methods and its correlation to complications and relapse rates require greater understanding. MATERIAL AND METHODS: Patients with aryngeal cancer receiving surgery and postoperative radiotherapy were randomly divided into observation and control groups. A quality of life questionnaire was used to evaluate patients' current life quality as well as negative emotions experienced. The collected data was evaluated using the Self-rating Anxiety Scale (SAS) as well as the Self-rating Depression Scale (SDS). At the time of discharge, patients' satisfaction on nursing and perception of health knowledge was assessed. Three and six months after discharge, patients were given follow-up visits and questionnaire surveys to evaluate their rehabilitation. This was done in relation with the Morningside Rehabilitation Stats Scale (MRSS), incidence of complications and recurrence. RESULTS: The scores of negative emotions, exhibited during the study, were lower in the observation group than in the control group. A month after discharge had a positive correlation to improved quality of life. This was highlighted in the observation group in comparison with the control group. The data collected following discharge revealed an improvement in quality of life, compared with that at the time of admission. Compared with the control group, the SAS and SDS scores in the observation group were decreased a month after discharge. Compared with the scores on admission, the SAS and SDS scores in both groups were decreased one month after discharge. The observation group had a lower incidence of complications than that of the control group. Six months after discharge, in the observation group, the MRSS score was lower than before discharge while in the control group, the MRSS score was higher than before discharge. CONCLUSIONS: Health education intervention can significantly improve the quality of life and reduce experiences relating to negative emotion in patients with laryngeal cancer. This improvement was seen following surgery and radiotherapy. Additionally effective reduction rates in the incidence of postoperative complications and recurrence were exhibited following methods of health education intervention.

HDAC8 and STAT3 repress BMF gene activity in colon cancer cells.

Histone deacetylase (HDAC) inhibitors are undergoing clinical trials as anticancer agents, but some exhibit resistance mechanisms linked to anti-apoptotic Bcl-2 functions, such as BH3-only protein silencing. HDAC inhibitors that reactivate BH3-only family members might offer an improved therapeutic approach. We show here that a novel seleno-α-keto acid triggers global histone acetylation in human colon cancer cells and activates apoptosis in a p21-independent manner. Profiling of multiple survival factors identified a critical role for the BH3-only member Bcl-2-modifying factor (Bmf). On the corresponding BMF gene promoter, loss of HDAC8 was associated with signal transducer and activator of transcription 3 (STAT3)/specificity protein 3 (Sp3) transcription factor exchange and recruitment of p300. Treatment with a p300 inhibitor or transient overexpression of exogenous HDAC8 interfered with BMF induction, whereas RNAi-mediated silencing of STAT3 activated the target gene. This is the first report to identify a direct target gene of HDAC8 repression, namely, BMF. Interestingly, the repressive role of HDAC8 could be uncoupled from HDAC1 to trigger Bmf-mediated apoptosis. These findings have implications for the development of HDAC8-selective inhibitors as therapeutic agents, beyond the reported involvement of HDAC8 in childhood malignancy.

Engagement of Toll-like receptor 2 enhances interleukin (IL)-17(+) autoreactive T cell responses via p38 mitogen-activated protein kinase signalling in dendritic cells.

Functional analysis of single Toll-like receptors (TLRs) in vivo is necessary to understand how they shape the ocular inflammation involved in uveitis. In this study we explored the role and mechanisms of TLR-2 agonists on the autoreactive T helper type 17 (Th17) response in experimental autoimmune uveitis (EAU). Treatment by peptidoglycan (PGN), a specific TLR-2 agonist, remarkably increased mRNA levels of Th17-lineage genes interleukin (IL)-17A, IL-21 and RAR-related orphan receptor (ROR)γt and promoted antigen-specific Th17 response in EAU mice. A mixture of PGN and interphotoreceptor retinoid-binding protein peptide (IRBP161-180 ) could effectively induce EAU in the absence of complete Freund's adjuvant (CFA). PGN treatment also enhanced the pathogenic activities of activated antigen-specific Th17 cells in vivo. PGN significantly increased the production of IL-1ß, IL-6 and IL-23 of dendritic cells (DCs) and enhanced their ability to promote IL-17(+) uveitogenic T cells. Enhanced immunostimulatory activities of PGN-DCs depend upon p38 activation. Inhibition of p38 mitogen-activated protein kinase (MAPK) activity dramatically decreased IL-17 gene expression and antigen-specific Th17 responses stimulated by PGN-DCs. Our findings suggest that PGN treatment dramatically promotes the IL-17(+) uveitogenic T cell responses via enhancing the immunostimulatory activities of DCs. This effect may be mediated, at least in part, by activation of the p38 signalling pathway in DCs.

The effect of mesenchymal stem cells on dynamic changes of T cell subsets in experimental autoimmune uveoretinitis.

Mesenchymal stem cells (MSCs) are being explored extensively as a promising treatment for autoimmune diseases. We have recently reported that MSCs could ameliorate experimental autoimmune uveoretinitis (EAU) in rats. In this study, we examined further the effects of MSCs on the dynamics of T cell subsets in both eye and spleen and their cytokine production during the course of EAU. We focused on when and where the MSCs had inhibitory effects on T helper type 1 (Th1) and Th17 cells and how long the inhibitory effect lasted, in order to provide more mechanistic evidence for MSCs on the treatment of uveitis. Compared to the control group, administration of MSCs decreased the production of Th1 and Th17 cytokines significantly, while the production of Th2 and regulatory T cell (T(reg)) cytokines [interleukin (IL)-10 and transforming growth factor (TGF)-ß] was elevated during the entire course of EAU. Correspondingly, the dynamic levels of IL-17 in the aqueous humour (AqH) were reduced in MSC-treated rats. Moreover, the ratio of Th17/T(reg) cells in both spleen and eye was decreased. These results provide powerful evidence that MSCs can regulate negatively both Th1 and Th17 responses and restore the balance of Th17/T(regs) in the whole course of EAU, which is important for the regression of the disease.

Lessons learned from developing a drug evidence base to support pharmacovigilance.

OBJECTIVE: This work identified challenges associated with extraction and representation of medication-related information from publicly available electronic sources. METHODS: We gained direct observational experience through creating and evaluating the Drug Evidence Base (DEB), a repository of drug indications and adverse effects (ADEs), and supplemented this through literature review. We extracted DEB content from the National Drug File Reference Terminology, from aggregated MEDLINE co-occurrence data, and from the National Library of Medicine's DailyMed. To understand better the similarities, differences and problems with the content of DEB and the SIDER Side Effect Resource, and Vanderbilt's MEDI Indication Resource, we carried out statistical evaluations and human expert reviews. RESULTS: While DEB, SIDER, and MEDI often agreed on medication indications and side effects, cross-system shortcomings limit their current utility. The drug information resources we evaluated frequently employed multiple, disparate vaguely related UMLS concepts to represent a single specific clinical drug indication or adverse effect. Thus, evaluations comparing drug-indication and drug-ADE coverage for such resources will encounter substantial numbers of false negative and false positive matches. Furthermore, our review found that many indication and ADE relationships are too complex - logically and temporally - to represent within existing systems. CONCLUSION: To enhance applicability and utility, future drug information systems deriving indications and ADEs from public resources must represent clinical concepts uniformly and as precisely as possible. Future systems must also better represent the inherent complexity of indications and ADEs.

The clinicopathological significance of BUBR1 overexpression in hepatocellular carcinoma.

BACKGROUND AND AIMS: BUBR1 is a key component of the mitotic spindle checkpoint, and its roles in human cancers are controversial and unclear. The aim of this study was to investigate the clinicopathological significance of BUBR1 expression in hepatocellular carcinoma (HCC). METHODS: The BUBR1 protein and its mRNA levels were measured in 58 HCCs, nine high-grade dysplastic nodules and their paired non-tumorous liver tissues by quantitative real-time polymerase chain reaction (qPCR) and western blot, respectively. In addition, immunochemical analysis of the BUBR1 protein was performed in 458 HCCs and 46 dysplastic nodules, and the clinicopathological significance of the BUBR1 expression was evaluated. RESULTS: The BUBR1 expression at both mRNA and protein levels was elevated in two of nine high-grade dysplastic nodules and in 37 of 58 (64%) HCCs. BUBR1 was overexpressed in 207 of 458 (45%) HCCs by immunohistochemistry. Intriguingly, high expression of the BUBR1 was correlated with larger tumour size, higher histological grade, advanced pathological stage, and poor overall and recurrence-free survival. There was a higher frequency of BUBR1 overexpression in cases with positive serum HBsAg than those with negative HBsAg. Moreover, BUBR1 overexpression was associated with P53 staining and high Ki67 labelling indices in HCC tissues. CONCLUSIONS: BUBR1 was overexpressed in about 45% HCCs, and its overexpression may be a relative lately event in HCC progression. Overexpression of BUBR1 was associated with worse prognosis and is a potential prognostic factor for patients with HCC.

Antiosteoporotic activity of icariin in ovariectomized rats.

Icariin was evaluated for its antiosteoporotic activity in an ovariectomized rat model of osteoporosis. The rats were divided into sham and OVX groups. The OVX rats were then subdivided into five groups treated with water, nylestriol (1 mg/kg body weight, weekly, orally) or icariin (ICA) (5, 25, and 125 mg/kg body weight, daily, orally) for 12 weeks. In OVX rats, the increases of body weight, serum BGP and ALP were significantly decreased by ICA treatment. In OVX rats, atrophy of uterus and descent of BMD were suppressed by treatment with ICA. In addition, ICA (125 mg/kg body weight) completely corrected the decreased serum concentration of Calcium, Phosphorus, and E(2) observed in OVX rats. ICA (125 mg/kg body weight) increased biomechanical strength significantly in comparison to the sham group. Histological results also showed its protective action through promotion of bone formation. The findings, assessed on the basis of biochemical, bone mineral density, biomechanical, and histopathological parameters, showed that ICA has a definite antiosteoporotic effect, similar to estrogen, especially effective for prevention bone fracture induced by estrogen deficiency.

WHNMR--a universal NMR application package.

A PC-based NMR off-line data processing system is developed and described in detail. With this software system, one-dimensional (1D), two-dimensional (2D), and NMR imaging (MRI) data can be processed easily, and give reliable results. By the applications of this system, a versatile software interface is set up to achieve data exchanging and integrated usage with other PC application software and aids the PC to become an effective and powerful workstation.