The Most Frequent Lenses To See Recent Program Planning For Adult: 1999-2003

The purpose of this study is to provide information regarding which theoretical framework has been frequently involved into healthy debate in the field of program planning for adults during the past decade. Also, which research methodologies have been used during that period needs to be answered for future study. By using the ERIC database, 14 articles and 11 proceeding papers were analyzed. The findings indicated that political negotiation approach has viewed as the most popular research issue. Integrative approach has also been frequently studied in recent years. However, the linear essence of the traditional model continues to play a dominant role for many practitioners. Until today, qualitative methods are mainstreams in this field. Also, in order to link practice and theory, both qualitative and quantitative studies are recently contributing to develop a theoretical framework and provide empirical evidences in various settings

Induction of Multiple Immune Regulatory Pathways with Differential Impact in HCV/HIV Coinfection

Persistent viral infections including HCV, HBV, and HIV are associated with increased immune regulatory pathways including the extrinsic FoxP3+CD4+ regulatory T cells (Tregs) and intrinsic inhibitory pathways such as programed death-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) with potentially reversible suppression of antiviral effector T cells (1–12). Immunological consequences of viral coinfections relative to these immune regulatory pathways and their interplay are not well-defined. In this study, we examined the frequency, phenotype, and effector function of circulating T cell subsets in patients with chronic HCV and/or HIV infection, hypothesizing that HCV/HIV coinfection will result in greater immune dysregulation with pathogenetic consequences (13, 14). We show that multiple T cell inhibitory pathways are induced in HCV/HIV coinfection including FoxP3+ Tregs, PD-1, and CTLA-4 in inverse association with overall CD4 T cell frequency but not with liver function or HCV RNA titers. The inverse association between CD4 T cell frequency and their FoxP3, PD-1, or CTLA-4 expression remained significant in all subjects combined regardless of HCV and/or HIV infection, suggesting a global homeostatic mechanism to maintain immune regulation relative to CD4 T cell frequency. PD-1 blockade rescued T cell responses to HIV but not HCV without significant impact by CTLA-4 blockade in vitro. Collectively, these findings highlight complex immune interactions in viral coinfections and differential regulatory pathways influencing virus-specific T cells that are relevant in immunotherapeutic development

Asymmetric distributions of H2O and SiO masers towards V627 Cas

We performed simultaneous observations of the H2O 6(1,6) - 5(2,3) (22.235080 GHz) and SiO v= 1, 2, J = 1 - 0, SiO v = 1, J = 2 - 1, 3 - 2 (43.122080, 42.820587, 86.243442, and 129.363359 GHz) masers towards the suspected D-type symbiotic star, V627 Cas, using the Korean VLBI Network. Here, we present astrometrically registered maps of the H2O and SiO v = 1, 2, J = 1 - 0, SiO v = 1, J = 2 - 1 masers for five epochs from January 2016 to June 2018. Distributions of the SiO maser spots do not show clear ring-like structures, and those of the H2O maser are biased towards the north-north-west to west with respect to the SiO maser features according to observational epochs. These asymmetric distributions of H2O and SiO masers are discussed based on two scenarios of a bipolar outflow and the presence of the hot companion, a white dwarf, in V627 Cas. We carried out ring fitting of SiO v = 1, and v = 2 masers and estimated the expected position of the cool red giant. The ring radii of the SiO v = 1 maser are slightly larger than those of the SiO v = 2 maser, as previously known. Our assumption for the physical size of the SiO maser ring of V627 Cas to be the typical size of a SiO maser ring radius (\sim4 au) of red giants yields the distance of V627 Cas to be \sim1 kpc.Comment: 7 pages, 4 figures, 1 table, Published in MNRA

Synergistic Reversal of Intrahepatic HCV-Specific CD8 T Cell Exhaustion by Combined PD-1/CTLA-4 Blockade

Viral persistence is associated with hierarchical antiviral CD8 T cell exhaustion with increased programmed death-1 (PD-1) expression. In HCV persistence, HCV-specific CD8 T cells from the liver (the site of viral replication) display increased PD-1 expression and a profound functional impairment that is not reversed by PD-1 blockade alone. Here, we report that the inhibitory receptor cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is preferentially upregulated in PD-1+ T cells from the liver but not blood of chronically HCV-infected patients. PD-1/CTLA-4 co-expression in intrahepatic T cells was associated with a profound HCV-specific effector dysfunction that was synergistically reversed by combined PD-1/CTLA-4 blockade in vitro, but not by blocking PD-1 or CTLA-4 alone. A similar effect was observed in circulating HCV-specific CD8 T cells with increased PD-1/CTLA-4 co-expression during acute hepatitis C. The functional response to combined blockade was directly associated with CTLA-4 expression, lost with CD28-depletion and CD4-independent (including CD4+FoxP3+ Tregs). We conclude that PD-1 and CTLA-4 pathways both contribute to virus-specific T cell exhaustion at the site of viral replication by a redundant mechanism that requires combined PD-1/CTLA-4 blockade to reverse. These findings provide new insights into the mechanisms of virus-specific T cell dysfunction, and suggest that the synergistic effect by combined inhibitory receptor blockade might have a therapeutic application against chronic viral infection in vivo, provided that it does not induce autoimmunity

The Nearby Evolved Stars Survey II: Constructing a volume-limited sample and first results from the James Clerk Maxwell Telescope

The Nearby Evolved Stars Survey (NESS) is a volume-complete sample of ∼850 Galactic evolved stars within 3 kpc at (sub-)mm wavelengths, observed in the CO J = (2–1) and (3–2) rotational lines, and the sub-mm continuum, using the James Clark Maxwell Telescope and Atacama Pathfinder Experiment. NESS consists of five tiers, based on distances and dust-production rate (DPR). We define a new metric for estimating the distances to evolved stars and compare its results to Gaia EDR3. Replicating other studies, the most-evolved, highly enshrouded objects in the Galactic Plane dominate the dust returned by our sources, and we initially estimate a total DPR of 4.7 × 10−5 M⊙ yr−1 from our sample. Our sub-mm fluxes are systematically higher and spectral indices are typically shallower than dust models typically predict. The 450/850 μm spectral indices are consistent with the blackbody Rayleigh–Jeans regime, suggesting a large fraction of evolved stars have unexpectedly large envelopes of cold dust

Cytokine-Modulated Natural Killer Cells Differentially Regulate the Activity of the Hepatitis C Virus

HCV genotype 2a strain JFH-1 replicates and produces viral particles efficiently in human hepatocellular carcinoma (huh) 7.5 cells, which provide a stable in vitro cell infection system for the hepatitis C virus (HCVcc system). Natural killer (NK) cells are large lymphoid cells that recognize and kill virus-infected cells. In this study, we investigated the interaction between NK cells and the HCVcc system. IL-10 is a typical immune regulatory cytokine that is produced mostly by NK cells and macrophages. IL-21 is one of the main cytokines that stimulate the activation of NK cells. First, we used anti-IL-10 to neutralize IL-10 in a coculture of NK cells and HCVcc. Anti-IL-10 treatment increased the maturation of NK cells by enhancing the frequency of the CD56+dim population in NK-92 cells. However, with anti-IL-10 treatment of NK cells in coculture with J6/JFH-1-huh 7.5 cells, there was a significant decrease in the expression of STAT1 and STAT5 proteins in NK-92 cells and an increase in the HCV Core and NS3 proteins. In addition, rIL-21 treatment increased the frequency of the CD56+dim population in NK-92 cells, Also, there was a dramatic increase in the expression of STAT1 and STAT5 proteins in rIL-21 pre-stimulated NK cells and a decrease in the expression of HCV Core protein in coculture with J6/JFH-1-huh 7.5 cells. In summary, we found that the functional activation of NK cells can be modulated by anti-IL-10 or rIL-21, which controls the expression of HCV proteins as well as HCV RNA replication

Programmed Cell Death 1 (PD-1) and Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA-4) in Viral Hepatitis

Virus-specific cluster of differentiation 8 (CD8+) cytotoxic T cells (CTL) recognize viral antigens presented on major histocompatibility complex (MHC) class I chains on infected hepatocytes, with help from CD4+ T cells. However, this CTL response is frequently weak or undetectable in patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Programmed cell death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are receptors in the CD28 family of costimulatory molecules, providing inhibitory signals to T cells. The overexpressions of PD-1 and CTLA-4 in patients with viral infection have been shown to associate with functional impairment of virus-specific T cells. In acute viral hepatitis, PD-1 and CTLA-4 are up-regulated during the symptomatic phase, and then down-regulated after recovery. These findings suggest that PD-1 and CTLA-4 have protective effects as inhibitory molecules to suppress cytotoxic T cells which induce harmful destruction of viral infected hepatocytes in self-limited viral hepatitis. In chronic viral hepatitis, the extended upregulations of PD-1 and CTLA-4 are associated with T cell exhaustion and persistent viral infection, suggesting positive correlations between expression of immune inhibitory factors and the chronicity of viral disease. In this review, we summarize recent literature relating to PD-1, CTLA-4, and other inhibitory receptors in antigen-specific T cell exhaustion in viral hepatitis, including hepatitis A, B, C, and others