The effect of social exchange relationships on work engagement: An empirical study of medical teams in a Private Hospital in China

After the implementation of the medical reform, private hospitals are rapidly developing in China. As late comers they face many challenges including fierce competition from other private hospitals and from public ones. This study proposes to improve their competitiveness by cultivating the work engagement level of medical teams. Based on the literature review on Social Exchange Theory, it is advanced that Leader-member Exchange (LMX) and Team-member Exchange (TMX) can positively influence work engagement while self-efficacy is the mechanism for the above relationships based on Social Cognition Theory. In addition, by reviewing related studies on interactional justice differentiation, this research takes it as a moderator to explore this effect on the above direct and indirect relations. On the basis of the literature review, theoretical analysis and logical deduction, eleven hypotheses are proposed. This study designs a questionnaire based on mature scales and conducts a survey in the case hospital through two stages of data collection, after which 370 valid questionnaires were received. Methods such as factor analysis, hierarchical regression analysis and moderated mediating model analysis are used to test the hypotheses. The results of data analysis partially support the research model.Com a implementação da reforma do sistema de saúde na China tem-se assistido a um rápido crescimento do número de hospitais privados que, no entanto, se veem confrontados com inúmeras dificuldades entre as quais a concorrência de outros hospitais privados e públicos. No sentido de ajudar a melhorar a competitividade destas unidades de saúde, esta tese procura estudar o nível de compromisso com o trabalho das equipas médicas. Através da revisão da literatura sobre a teoria das trocas sociais propõe-se que a troca membro-líder e a troca membro-grupo podem influenciar positivamente o compromisso com o trabalho entendendo-se a auto eficácia como um mecanismo mediador. O estudo considera ainda a diferenciação da justiça interativa como uma variável moderadora que permite explorar os efeitos diretos e indiretos no modelo proposto. Da revisão da literatura e da subsequente análise teórica extraíram-se onze hipóteses que refletem as relações e efeitos enunciados. A recolha de dados foi feita a partir de um questionário utilizando escalas já anteriormente validadas o qual foi administrado em duas fases no hospital privado objeto do estudo tendo-se obtido 370 respostas válidas. Análise fatorial e regressão hierárquica foram os métodos utilizados para testar as hipóteses. Os resultados obtidos suportam parcialmente o modelo teórico proposto

Circulating Cell-Free DNA

Circulating cell-free DNA (cfDNA) refers to extracellular DNA present in body fluid that may be derived from both normal and diseased cells. The concentration, integrity, genetic, and epigenetic alternations in the cfDNA may suggest pathological conditions of the body, such as inflammation, autoimmune diseases, stress, or even malignancies. cfDNA from patients with malignancies contains variants as those in the tumor tissue cells, thus allowing noninvasive assessment of tumor in real time. The clinical detection of cfDNA is one major application of liquid biopsy and has great application value in the early diagnosis of clinical tumors, real-time progression monitoring, curative effect observation and evaluation, prognosis assessment, and metastasis risk analysis. This chapter summarizes the origin of cell-free DNA and its important clinical applications as a noninvasive biomarker

Anti-tat Hutat2:Fc mediated protection against tat-induced neurotoxicity and HIV-1 replication in human monocyte-derived macrophages

Background: HIV-1 Tat is essential for HIV replication and is also a well-known neurotoxic factor causing HIV-associated neurocognitive disorder (HAND). Currently, combined antiretroviral therapy targeting HIV reverse transcriptase or protease cannot prevent the production of early viral proteins, especially Tat, once HIV infection has been established. HIV-infected macrophages and glial cells in the brain still release Tat into the extracellular space where it can exert direct and indirect neurotoxicity. Therefore, stable production of anti-Tat antibodies in the brain would neutralize HIV-1 Tat and thus provide an effective approach to protect neurons. Methods: We constructed a humanized anti-Tat Hutat2:Fc fusion protein with the goal of antagonizing HIV-1 Tat and delivered the gene into cell lines and primary human monocyte-derived macrophages (hMDM) by an HIV-based lentiviral vector. The function of the anti-Tat Hutat2:Fc fusion protein and the potential side effects of lentiviral vector-mediated gene transfer were evaluated in vitro. Results: Our study demonstrated that HIV-1-based lentiviral vector-mediated gene transduction resulted in a high-level, stable expression of anti-HIV-1 Tat Hutat2:Fc in human neuronal and monocytic cell lines, as well as in primary hMDM. Hutat2:Fc was detectable in both cells and supernatants and continued to accumulate to high levels within the supernatant. Hutat2:Fc protected mouse cortical neurons against HIV-1 Tat86-induced neurotoxicity. In addition, both secreted Hutat2:Fc and transduced hMDM led to reducing HIV-1BaL viral replication in human macrophages. Moreover, lentiviral vector-based gene introduction did not result in any significant changes in cytomorphology and cell viability. Although the expression of IL8, STAT1, and IDO1 genes was up-regulated in transduced hMDM, such alternation in gene expression did not affect the neuroprotective effect of Hutat2:Fc. Conclusions: Our study demonstrated that lentivirus-mediated gene transfer could efficiently deliver the Hutat2:Fc gene into primary hMDM and does not lead to any significant changes in hMDM immune-activation. The neuroprotective and HIV-1 suppressive effects produced by Hutat2:Fc were comparable to that of a full-length anti-Tat antibody. This study provides the foundation and insights for future research on the potential use of Hutat2:Fc as a novel gene therapy approach for HAND through utilizing monocytes/macrophages, which naturally cross the blood-brain barrier, for gene delivery. Electronic supplementary material The online version of this article (doi:10.1186/s12974-014-0195-2) contains supplementary material, which is available to authorized users

Phylogenetic analysis of porcine parvoviruses from swine samples in China

<p>Abstract</p> <p>Background</p> <p>Porcine parvovirus (PPV) usually causes reproductive failure in sows. The objective of the present study was to analyze the phylogenetic distribution and perform molecular characterization of PPVs isolated in China, as well as to identify two field strains, LZ and JY. The data used in this study contained the available sequences for NS1 and VP2 from GenBank, as well as the two aforementioned Chinese strains.</p> <p>Results</p> <p>Phylogenetic analysis shows that the PPV sequences are divided into four groups. The early Chinese PPV isolates are Group I viruses, and nearly all of the later Chinese PPV isolates are Group II viruses. LZ belongs to group II, whereas the JY strain is a Group III virus. This is the first report on the isolation of a Group III virus in China. The detection of selective pressures on the PPV genome shows that the NS1 and VP2 genes are under purifying selection and positive selection, respectively. Moreover, the amino acids in the VP2 capsid are highly variable because of the positive selection.</p> <p>Conclusions</p> <p>Our study provides new molecular data on PPV strains in China, and emphasizes the importance of etiological studies of PPV in pigs.</p

Ganoderma triterpenes Protect Against Hyperhomocysteinemia Induced Endothelial-Mesenchymal Transition via TGF-β Signaling Inhibition

Endothelial dysfunction is one of the most important pathological status in hyperhomocysteinemia (HHcy) related cardiovascular diseases. Whereas, the underlying mechanisms have not been fully elucidated yet, concomitant with the absence of effective treatment. The purpose of this study was to explore the main mechanisms involved in HHcy-induced endothelial injury and identify the protective effect of Ganoderma triterpenes (GT). Bovine aortic endothelial cells (BAECs) were applied as in vitro experimental model. The small molecular inhibitors were used to explore the signalings involved in HHcy-induced endothelial injury. The experimental results provided initial evidence that HHcy led to endothelial-mesenchymal transition (EndMT). Meanwhile, TGF-β/Smad, PI3K/AKT and MAPK pathways were activated in this process, which was demonstrated by pretreatment with TGF-β RI kinase inhibitor VI SB431542, PI3K inhibitor LY294002, p38 inhibitor SB203580, and ERK inhibitor PD98059. Furthermore, it was found that GT restrained the process of HHcy-induced EndMT via reducing oxidative stress and suppressing fore mentioned pathways with further inhibiting the activity of Snail. These results implicate that there is an untapped potential for GT as a novel therapeutic candidate for HHcy-induced EndMT through alleviating oxidative stress and canonical TGF-β/Smad and non-Smad dependent signaling pathways

Activation of p38 MAPK pathway in the skull abnormalities of Apert syndrome Fgfr2+P253R mice

<p>Abstract</p> <p>Background</p> <p>Apert syndrome is characterized by craniosynostosis and limb abnormalities and is primarily caused by FGFR2 +/P253R and +/S252W mutations. The former mutation is present in approximately one third whereas the latter mutation is present in two-thirds of the patients with this condition. We previously reported an inbred transgenic mouse model with the Fgfr2 +/S252W mutation on the C57BL/6J background for Apert syndrome. Here we present a mouse model for the Fgfr2+/P253R mutation.</p> <p>Results</p> <p>We generated inbred <it>Fgfr2</it>^{+/<it>P253R </it>}mice on the same C56BL/6J genetic background and analyzed their skeletal abnormalities. 3D micro-CT scans of the skulls of the <it>Fgfr2</it>^{+/<it>P253R </it>}mice revealed that the skull length was shortened with the length of the anterior cranial base significantly shorter than that of the <it>Fgfr2</it>^{+/<it>S252W </it>}mice at P0. The <it>Fgfr2</it>^{+/<it>P253R </it>}mice presented with synostosis of the coronal suture and proximate fronts with disorganized cellularity in sagittal and lambdoid sutures. Abnormal osteogenesis and proliferation were observed at the developing coronal suture and long bones of the <it>Fgfr2</it>^{+/<it>P253R </it>}mice as in the <it>Fgfr2</it>^{+/<it>S252W </it>}mice. Activation of mitogen-activated protein kinases (MAPK) was observed in the <it>Fgfr2</it>^{+/<it>P253R </it>}neurocranium with an increase in phosphorylated p38 as well as ERK1/2, whereas phosphorylated AKT and PKCα were not obviously changed as compared to those of wild-type controls. There were localized phenotypic and molecular variations among individual embryos with different mutations and among those with the same mutation.</p> <p>Conclusions</p> <p>Our <it>in vivo </it>studies demonstrated that the Fgfr2 +/P253R mutation resulted in mice with cranial features that resemble those of the <it>Fgfr2</it>^{+/<it>S252W </it>}mice and human Apert syndrome. Activated p38 in addition to the ERK1/2 signaling pathways may mediate the mutant neurocranial phenotype. Though Apert syndrome is traditionally thought to be a consistent phenotype, our results suggest localized and regional variations in the phenotypes that characterize Apert syndrome.</p

In-vitro and in-vivo phenotype of type Asia 1 foot-and-mouth disease viruses utilizing two non-RGD receptor recognition sites

<p>Abstract</p> <p>Background</p> <p>Foot-and-mouth disease virus (FMDV) uses a highly conserved Arg-Gly-Asp (RGD) triplet for attachment to host cells and this motif is believed to be essential for virus viability. Previous sequence analyses of the 1D-encoding region of an FMDV field isolate (Asia1/JS/CHA/05) and its two derivatives indicated that two viruses, which contained an Arg-Asp-Asp (RDD) or an Arg-Ser-Asp (RSD) triplet instead of the RGD integrin recognition motif, were generated serendipitously upon short-term evolution of field isolate in different biological environments. To examine the influence of single amino acid substitutions in the receptor binding site of the RDD-containing FMD viral genome on virus viability and the ability of non-RGD FMDVs to cause disease in susceptible animals, we constructed an RDD-containing FMDV full-length cDNA clone and derived mutant molecules with RGD or RSD receptor recognition motifs. Following transfection of BSR cells with the full-length genome plasmids, the genetically engineered viruses were examined for their infectious potential in cell culture and susceptible animals.</p> <p>Results</p> <p>Amino acid sequence analysis of the 1D-coding region of different derivatives derived from the Asia1/JS/CHA/05 field isolate revealed that the RDD mutants became dominant or achieved population equilibrium with coexistence of the RGD and RSD subpopulations at an early phase of type Asia1 FMDV quasispecies evolution. Furthermore, the RDD and RSD sequences remained genetically stable for at least 20 passages. Using reverse genetics, the RDD-, RSD-, and RGD-containing FMD viruses were rescued from full-length cDNA clones, and single amino acid substitution in RDD-containing FMD viral genome did not affect virus viability. The genetically engineered viruses replicated stably in BHK-21 cells and had similar growth properties to the parental virus. The RDD parental virus and two non-RGD recombinant viruses were virulent to pigs and bovines that developed typical clinical disease and viremia.</p> <p>Conclusions</p> <p>FMDV quasispecies evolving in a different biological environment gained the capability of selecting different receptor recognition site. The RDD-containing FMD viral genome can accommodate substitutions in the receptor binding site without additional changes in the capsid. The viruses expressing non-RGD receptor binding sites can replicate stably in vitro and produce typical FMD clinical disease in susceptible animals.</p

Human Hepatocytes with Drug Metabolic Function Induced from Fibroblasts by Lineage Reprogramming

SummaryObtaining fully functional cell types is a major challenge for drug discovery and regenerative medicine. Currently, a fundamental solution to this key problem is still lacking. Here, we show that functional human induced hepatocytes (hiHeps) can be generated from fibroblasts by overexpressing the hepatic fate conversion factors HNF1A, HNF4A, and HNF6 along with the maturation factors ATF5, PROX1, and CEBPA. hiHeps express a spectrum of phase I and II drug-metabolizing enzymes and phase III drug transporters. Importantly, the metabolic activities of CYP3A4, CYP1A2, CYP2B6, CYP2C9, and CYP2C19 are comparable between hiHeps and freshly isolated primary human hepatocytes. Transplanted hiHeps repopulate up to 30% of the livers of Tet-uPA/Rag2−/−/γc−/− mice and secrete more than 300 μg/ml human ALBUMIN in vivo. Our data demonstrate that human hepatocytes with drug metabolic function can be generated by lineage reprogramming, thus providing a cell resource for pharmaceutical applications

The p400 ATPase regulates nucleosome stability and chromatin ubiquitination during DNA repair

p400 unwinds chromatin from nucleosomes flanking double-strand breaks to facilitate recruitment of the DNA repair components brca1 and 53BP1