mGluR5 antagonism inhibits cocaine reinforcement and relapse by elevation of extracellular glutamate in the nucleus accumbens via a CB1 receptor mechanism.

Metabotropic glutamate receptor 5 (mGluR5) antagonism inhibits cocaine self-administration and reinstatement of drug-seeking behavior. However, the cellular and molecular mechanisms underlying this action are poorly understood. Here we report a presynaptic glutamate/cannabinoid mechanism that may underlie this action. Systemic or intra-nucleus accumbens (NAc) administration of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) dose-dependently reduced cocaine (and sucrose) self-administration and cocaine-induced reinstatement of drug-seeking behavior. The reduction in cocaine-taking and cocaine-seeking was associated with a reduction in cocaine-enhanced extracellular glutamate, but not cocaine-enhanced extracellular dopamine (DA) in the NAc. MPEP alone, when administered systemically or locally into the NAc, elevated extracellular glutamate, but not DA. Similarly, the cannabinoid CB1 receptor antagonist, rimonabant, elevated NAc glutamate, not DA. mGluR5s were found mainly in striatal medium-spiny neurons, not in astrocytes, and MPEP-enhanced extracellular glutamate was blocked by a NAc CB1 receptor antagonist or N-type Ca++ channel blocker, suggesting that a retrograde endocannabinoid-signaling mechanism underlies MPEP-induced glutamate release. This interpretation was further supported by our findings that genetic deletion of CB1 receptors in CB1-knockout mice blocked both MPEP-enhanced extracellular glutamate and MPEP-induced reductions in cocaine self-administration. Together, these results indicate that the therapeutic anti-cocaine effects of mGluR5 antagonists are mediated by elevation of extracellular glutamate in the NAc via an endocannabinoid-CB1 receptor disinhibition mechanism

Nurses\u27 Workplace Social Capital and the Influence of Transformational Leadership: A Theoretical Perspective

Workplace social capital is the relational network, created by respectful interactions among members of a workforce, can contribute to the formation of a wholesome psychological work environment in an organization. Nurses\u27 workplace social capital is a derivative of the workplace social capital, formed because of the complex interactions among the nursing and between the other healthcare professionals. Transformational leadership is a style of leadership that addresses the emotional wellbeing of its workforce and inspires shared group ethics, norms, and goals. The philosophy of transformational leadership is grounded on the premise of workforce as human beings with specific needs. Transformational leadership has been confirmed as a strong predictor of nurses\u27 workplace social capital. Meanwhile, it is of an academic and/or healthcare industry operational value to scholarly assess and discern the theoretical influence of transformational leadership on nurses\u27 workplace social capital. In this paper, we have attempted to explore the associations between transformational leadership and nurses\u27 workplace social capital from a theoretical perspective. We have discussed the importance of each sub-dimension of transformational leadership (modeling the way, inspiring a shared vision, challenging the process, enabling others to act and encouraging the heart) in building up the social capital relational network. Finally, we have proposed a graphic framework of our analysis to facilitate understanding of the associations between the transformational leadership and nurses\u27 workplace social capital, in formation of a healthy work environment which is the foundation for efficiency and productivity of the workforce

Clinical and Virological Characteristics of Chronic Hepatitis B Patients with Hepatic Steatosis

Abstract Objective: This study aimed to explore clinical and virological characteristics of chronic hepatitis B (CHB) patients with hepatic steatosis in order to provide a theoretical basis for the prevention and control of hepatic steatosis. Methods: A total of 360 CHB inpatients were recruited from Affiliated Dongnan Hospital of Xiamen University and divided into hepatic steatosis group and non-hepatic steatosis group. The body mass index (BMI), waist-to-hip ratio (WHR), fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), hepatitis B e antigen (HBeAg), hepatitis B virus DNA (HBV DNA) and hepatic histological changes were detected and compared between the two groups. The association of these factors with hepatic steatosis was evaluated in CHB patients. Results: BMI, FPG, TG, TC, GGT, AST and HBV DNA showed statistically significant differences between two groups (P<0.01). The patients with hepatic steatosis had markedly higher BMI, FBG, TG and TC than those without steatosis did. No significant differences were found in ALT and HBeAg between two groups (P>0.05). In male patients, there was marked difference in the WHR between two groups (P < 0.01), which was not found in female patients (P > 0.05). The severity of hepatic steatosis increased in patients with hepatic steatosis, compared to those without steatosis (P < 0. 01), but the severities of inflammation and fibrosis in the non-hepatic steatosis group were dramatically higher than those in the hepatic steatosis group (P < 0. 01). Conclusions: BMI, WHR, FBG, TG and TC appeared to be influencing factors of CHB combined with hepatic steatosis. Hepatic steatosis in CHB patients was closely related to changes in anthropometric indices and metabolic factors but not HBV. It is necessary to improve these factors to effectively prevent hepatic steatosis in CHB patients

Assessing Nurses' Workplace Social Capital : A Study Protocol for Culturally Appropriate Instrument Development

Workplace social capital positively influences the quality but reduces the cost of healthcare services. Academic research suffers from limited and inadequate culturally sensitive nurses' workplace social capital instruments. Here we report on the design and protocol of a culturally focused instrument development study in China. The overarching objective of our dual phase study is to develop and validate a questionnaire measuring nurses' workplace social capital tailored toward Chinese cultural values and norms. In the first phase of INSTRUMENT DEVELOPMENT, the qualitative phase, we will conduct interviews with purposefully sampled nurses from five geographically diverse regions capturing 16 provinces in China to formulate the initial version of the Nurses' Workplace Social Capital Questionnaire (NWSCQ). Data collection will be stopped at the saturation point and content analysis will be performed for interview data in parallel. The initial version of the NWSCQ will be evaluated and confirmed by two-rounds of expert consultation (target N = 20) and pre-tested among 70 nurses. During the second phase of INSTRUMENT VALIDATION or the quantitative phase, we will validate the psychometric properties of the NWSCQ. The validity and reliability of the questionnaire will be examined and validated through three cross-sectional surveys among nurses (target N = 1154) randomly selected from 12 tertiary hospitals. We have reported our study protocol with the intention of sharing our experience with researchers in other countries who are striving to advance the phenomenon of culturally sensitive and social normatively appropriate nurses' workplace social capital. Findings from our study should advance the development of culturally appropriate and valid instrument of nurses' workplace social capital, another important step toward recognition and incorporation of cultural diversity in the daily operation of healthcare industry.Peer reviewe

Lot-to-lot consistency study of an Escherichia coli -produced bivalent human papillomavirus vaccine in adult women: a randomized trial.

An Escherichia. coli -produced HPV-16/18 bivalent vaccine has been proved to be well-tolerated and highly efficacious against diseases associated with vaccine HPV types. As a part of the multi-center, randomized, double-blind phase III clinical trial, this lot-to-lot consistency study aimed to assess the safety and immunogenicity consistency of this novel HPV vaccine, which is also one of the objectives of the phase III trial. A total of 3689 healthy women aged 18-45 years were enrolled and randomly assigned 1:1:1 to three lots of the HPV vaccine groups. The primary outcomes were the IgG antibody level at 1 month after the last dose (month 7). In the immunogenicity per-protocol set (PPS), almost all of the participants seroconverted at month 7 and remained seropositive at month 42. For each paired comparison of the three lot groups, the two-sides of 90% CIs of GMC ratios for both IgG and neutralizing antibodies for HPV-16 and HPV-18 at month 7 were within the equivalence interval [0.5, 2]. Lot consistency was also demonstrated at month 42. The majority of recorded solicited reactions were mild or moderate. The incidences of solicited reactions of Lot 2 and Lot 3 were slightly higher than Lot 1. However, the incidences of solicited reactions of ≥ grade 3 and solicited reactions by symptoms were all similar among the three lot groups. None of the SAEs was considered related to vaccination by the investigator. In conclusion, this study demonstrates lot-to-lot consistency of the 3 consecutive lots of the E. coli -produced HPV-16/18 bivalent vaccine

SUMOylation of DEC1 Protein Regulates Its Transcriptional Activity and Enhances Its Stability

Differentiated embryo-chondrocyte expressed gene 1 (DEC1, also known as sharp2, stra13, or BHLHB2) is a mammalian basic helix-loop-helix protein that is involved in many aspects of gene regulation through acting as a transcription factor. Changes in DEC1 expression levels have been implicated in the development of cancers. Using COS-7 cell, we showed that DEC1 can be modified by the small ubiquitin-like modifiers, SUMO1, 2 and 3. Two major SUMOylation sites (K159 and K279) were identified in the C-terminal domain of DEC1. Substitution of either K159 or K279 with arginine reduced DEC1 SUMOylation, but substitution of both K159 and K279 abolished SUMOylation, and more protein appeared to be retained in the cytoplasm compared to wild-type DEC1. The expression of DEC1 was up-regulated after serum starvation as previously reported, but at the same time, serum starvation also led to more SUMOylation of DEC1. In MCF-7 cells SUMOylation also stabilized DEC1 through inhibiting its ubiquitination. Moreover, SUMOylation of DEC1 promoted its repression of CLOCK/BMAL1-mediated transcriptional activity through recruitment of histone deacetylase1. These findings suggested that posttranslational modification of DEC1 in the form of SUMOylation may serve as a key factor that regulates the function of DEC1 in vivo