Intention to Vaccinate Against the Novel 2019 Coronavirus Disease: The Role of Health Locus of Control and Religiosity.

The urgency to develop a vaccine against the 2019 coronavirus (COVID-19) has waxed stronger in speed, scale, and scope. However, wisdom dictates that we take a vantage position and start to examine the demographic predictors of COVID-19 vaccine hesitancy. The objective of this study was to examine the role of health locus of control (HLOC) in the relationship between religiosity and COVID-19 vaccination intention. In a cross-sectional survey (N = 501), we found a significantly negative association between religiosity and COVID-19 vaccination intention. This relationship was partially mediated by external HLOC. Collaborative efforts with religious institutions may influence COVID-19 vaccine uptake.

Psychological Pathways Linking Public Trust During the Coronavirus Pandemic to Mental and Physical Well-being.

The well-being of the public during the 2019 coronavirus (COVID-19) pandemic is deeply rooted in institutional trust in the government's risk communication effort. The objective of this study was to examine the psychological pathway through which public trust in the government is associated with mental and physical well-being. We collected cross-sectional data from 501 participants aged ≥18 years using an online panel. Public trust in the government was assessed as our exposure variable. We screened for psychological distress by combining the Patient Health Questionnaire and the General Anxiety Disorder scale. Physical well-being was examined using self-rated health. We further assessed the roles of risk perceptions. The author conducted a one-way analysis of variance (ANOVA), Pearson's correlations, multivariable regressions, and mediation analyses (using the Preachers and Hayes' approach). Participants were 55.29% female, 67.86% Caucasian/white with a mean age of 32.44 ± 11.94 years. Public trust in the government regarding COVID-19 was negatively correlated with psychological distress (r = -0.20; p < 0.001) and positively associated with physical well-being (r = 0.13; p < 0.001). After adjusting for sociodemographic and socioeconomic factors, public trust remained negatively associated with psychological distress (ß = -0.19; 95% confidence intervals, [CI] -0.30, -0.09) and positively associated with physical well-being (ß = 0.26; 95% CI [0.16, -0.37]). Perceived self-efficacy to practice COVID-19 protective behavior partially mediated the relationship between public trust and psychological distress (13.07%); and physical well-being (28.02%). Perceived self-efficacy to protect self against COVID-19 infection can serve as a psychological pathway through which public trust may be associated with mental and physical health.

Exposure to coronavirus news on mainstream media: The role of risk perceptions and depression.

OBJECTIVE: The mainstream media tend to rely on news content that will increase risk perceptions of pandemic outbreaks to stimulate public response and persuade people to comply with preventive behaviours. The objective of this study was to examine associations between exposure to coronavirus disease (COVID-19) news, risk perceptions, and depressive symptoms. METHODS: Cross-sectional data were collected from 501 participants who were ≥18 years. Exposure to COVID-19 news was assessed as our exposure variable. We screened for depression (outcome variable) with the Patient Health Questionnaire and examined the roles of risk perceptions. Multiple linear regressions and mediation analysis with 1000 bootstrap resamples were conducted. RESULTS: Participants were 55.29% female, 67.86% White with mean age 32.44 ± 11.94 years. After controlling for sociodemographic and socio-economic factors, news exposure was positively associated with depressive symptoms ß = .11; 95% confidence interval (95%CI) = 0.02-0.20. Mediation analysis showed that perceived vulnerability to COVID-19 mediated 34.4% of this relationship (ß = .04; 95%CI = 0.01-0.06). CONCLUSION: Perceived vulnerability to COVID-19 can serve as a pathway through which exposure to COVID-19 news on mainstream media may be associated with depressive symptoms. Based on our findings, we offered recommendations for media-health partnership, practice, and research.

Gallium disrupts iron metabolism of mycobacteria residing within human macrophages.

Mycobacterium tuberculosis and M. avium complex (MAC) enter and multiply within monocytes and macrophages in phagosomes. In vitro growth studies using standard culture media indicate that siderophore-mediated iron (Fe) acquisition plays a critical role in the growth and metabolism of both M. tuberculosis and MAC. However, the applicability of such studies to conditions within the macrophage phagosome is unclear, due in part to the absence of experimental means to inhibit such a process. Based on the ability of gallium (Ga(3+)) to concentrate within mononuclear phagocytes and on evidence that Ga disrupts cellular Fe-dependent metabolic pathways by substituting for Fe(3+) and failing to undergo redox cycling, we hypothesized that Ga could disrupt Fe acquisition and Fe-dependent metabolic pathways of mycobacteria. We find that Ga(NO(3))(3) and Ga-transferrin produce an Fe-reversible concentration-dependent growth inhibition of M. tuberculosis strains and MAC grown extracellularly and within human macrophages. Ga is bactericidal for M. tuberculosis growing extracellularly and within macrophages. Finally, we provide evidence that exogenously added Fe is acquired by intraphagosomal M. tuberculosis and that Ga inhibits this Fe acquisition. Thus, Ga(NO(3))(3) disruption of mycobacterial Fe metabolism may serve as an experimental means to study the mechanism of Fe acquisition by intracellular mycobacteria and the role of Fe in intracellular survival. Furthermore, given the inability of biological systems to discriminate between Ga and Fe, this approach could have broad applicability to the study of Fe metabolism of other intracellular pathogens.

Iron acquisition from Pseudomonas aeruginosa siderophores by human phagocytes: an additional mechanism of host defense through iron sequestration?

Chelation of iron to iron-binding proteins is a strategy of host defense. Some pathogens counter this via the secretion of low-molecular-weight iron-chelating agents (siderophores). Human phagocytes possess a high-capacity mechanism for iron acquisition from low-molecular-weight iron chelates. Efficient acquisition and sequestration of iron bound to bacterial siderophores by host phagocytes could provide a secondary mechanism to limit microbial access to iron. In the present work we report that human neutrophils, macrophages, and myeloid cell lines can acquire iron from the two Pseudomonas aeruginosa siderophores. Analogous to iron acquisition from other low-molecular-weight chelates, iron acquisition from the siderophores is ATP independent, induced by multivalent cationic metals, and unaffected by inhibitors of endocytosis and pinocytosis. In vivo, this process could serve as an additional mechanism of host defense to limit iron availability to invading siderophore-producing microbes.

Despite structural similarities between gp91phox and FRE1, flavocytochrome b558 does not mediate iron uptake by myeloid cells.

Superoxide (O2-) generated by the phagocyte reduced nicotinamide adenine dinucleotide phosphate oxidase is dependent on electron transfer by flavocytochrome b558 (flavocytochrome b), a transmembrane heterodimer that forms the redox center of the oxidase at the plasma or phagosomal membrane. The larger of its two subunits, gp91phox, is homologous to the yeast iron reductase subunit FRE1, and these two proteins share many structural and functional characteristics. Because FRE1 is required for iron uptake in yeast, we hypothesized that flavocytochrome b might serve a similar function in human phagocytes and thus provide a mechanism for the transferrin-independent iron acquisition observed in myeloid cells. To determine whether flavocytochrome b was required for iron uptake, we compared iron acquisition by polymorphonuclear neutrophils (PMNs) or Epstein-Barr virus (EBV)-transformed B lymphocytes derived from individuals with X-linked chronic granulomatous disease (CGD) with iron acquisition by normal cells. Our results indicate that all cells acquired iron to the same extent and that uptake could be significantly enhanced in the presence of the trivalent metal gallium. The gallium enhancement of iron uptake observed in PMNs or in EBV-transformed B lymphocytes derived from healthy individuals was mirrored by those derived from individuals deficient in flavocytochrome b. Furthermore, both normal and CGD-derived EBV-transformed B lymphocytes had similar iron reductase activity, suggesting that flavocytochrome b is not a biologically significant iron reductase. In contrast to previously suggested hypotheses, these results show conclusively that flavocytochrome b is not necessary for cellular iron acquisition, despite structural and functional similarities between yeast iron reductases and flavocytochrome b.

Polyvalent cationic metals induce the rate of transferrin-independent iron acquisition by HL-60 cells.

The trivalent metals iron, aluminum, and gallium greatly increase the rate of iron acquisition from low molecular weight chelates by human myeloid cells. The present study explores the mechanism responsible. Gallium-induced iron acquisition was shown to lead to stable cellular association of iron, the magnitude of which varied with the chelate to which the iron was bound. The majority of this iron initially associated with the plasma membrane. Cellular depletion of ATP did not affect the response to gallium nor did it require the continued presence of extracellular gallium. However, continued cell association of gallium was needed as subsequent cellular exposure to metal chelators resulted in a rapid loss of the "induced" phenotype. Other trivalent metals (lanthanum and gadolinium) and tetravalent metals (tin and zirconium) but not divalent metals also induced iron acquisition. Neither enhanced iron reduction nor protein kinase C or tyrosine kinases appeared involved in gallium-mediated induction of iron acquisition. Exposure of HL-60 cells to polyvalent cationic metals results in a dramatic and sustained increase in the rate of iron acquisition from low molecular weight chelating agents. This could be important for the rapid clearance of iron by phagocytes from the extracellular environment at sites of local tissue damage.

Acquisition of iron bound to low molecular weight chelates by human monocyte-derived macrophages.

The iron content of tissue macrophages increases under conditions of elevated extracellular iron. Studies of macrophage iron acquisition have generally focused on iron uptake from transferrin via receptor-mediated endocytosis. However, in vivo macrophages are also exposed to extracellular low m.w. iron chelates, particularly under conditions of iron overload. Therefore, we examined the mechanism of iron acquisition from low m.w. chelates by human monocyte-derived macrophages. Iron acquisition was influenced by the nature of the iron chelate: Fe-ascorbate > Fe-citrate > Fe-nitrilotriacetate (NTA) = Fe-ADP > Fe-glycyl-L-histidyl-L-lysine > Fe-diethylenetriamine pentaacetic acid >> Fe-EDTA = Fe-deferoxamine. With the exception of Fe-EDTA and Fe-deferoxamine, iron acquisition was greater than that with diferric transferrin. As assessed by using iron acquisition from NTA as a model, the process is temperature dependent, but pH independent (pH 5 to 8), and is influenced by the medium in which the cells are suspended. Acquisition is not affected by NaF, 2-deoxy-D-glucose, NaCN, or monocyte-derived macrophage exposure to trypsin, pronase, phenylarsine oxide, dihydrocytochalasin B, filipin, nystatin, or digitonin. The rate of iron acquisition from NTA is induced by iron pre-exposure as well as aluminum. In contrast, NTA chelates of other transition metals (Cd, Cu, Ga, Mn, and Zn) inhibited iron uptake by 20 to 80%. Unlike results obtained with Ga-NTA, Ga(NO3)3 increased iron uptake from NTA. Data obtained with neutrophils, and undifferentiated U937 and HL-60 cells were similar, which suggests that myeloid cells share this pathway for iron acquisition. Iron acquisition via this mechanism may allow macrophages and other leukocytes to clear local states of iron overload in vivo.

Iron sequestration by macrophages decreases the potential for extracellular hydroxyl radical formation.

Alveolar macrophages (AM) from smokers contain a much higher quantity of intracellular iron than AM from nonsmokers. Since some forms of iron will catalyze the formation of hydroxyl radical (.OH) from superoxide and hydrogen peroxide, the ability of AM derived from smokers and nonsmokers to generate .OH was assessed. No detectable .OH was produced by AM from either source, suggesting that iron sequestration by AM may limit the potential for .OH-mediated lung injury. Consistent with this hypothesis, the ability of bronchoalveolar lavage fluid (BAL) from smokers and nonsmokers to act as an .OH catalyst decreased after exposure to AM. We found that, like AM, human monocyte-derived macrophages (MDM) have the ability to acquire large quantities of iron from small low molecular weight iron chelates as well as decrease the ability of BAL to act as a .OH catalyst. When MDM or AM were exposed to the iron chelates or BAL they were then able to generate .OH after phorbol myristate acetate stimulation. However, when acutely iron-loaded or BAL-exposed MDM were placed in culture, their ability to produce .OH decreased with time to the level of non-iron-exposed controls. This process correlated with iron translocation from the plasma membrane to the cytosol as well as a 3-9-fold increase in cellular ferritin. No increase in antioxidant enzyme levels or induction of the heat shock response was observed. Iron sequestration by macrophages may protect nearby cells from exposure to potentially cytotoxic iron-catalyzed oxidants such as .OH.

Modified acetylenic steroids as potent mechanism-based inhibitors of cytochrome P-450SCC.

Synthesized 20-(4-tetrahydropyranyl-1-butynyloxy)-5-pregnen-3 alpha,20 beta- diol [steroid I] and 20-(3-tetrahydropyranyl-1-propargyloxy)-5-pregnen- 3 alpha,20 beta-diol [steroid III] have been found to inactivate purified adrenocortical cytochrome P-450SCC. When incubated with the enzyme under turnover conditions, steroid I inactivated cytochrome P-450SCC by about 85% in 40 min. This is in contrast to the free triol analog, steroid II which inactivated the enzyme by only 45% within the same incubation period. A comparison of steroid III with its free triol analog, steroid IV, also showed that the diol is a more effective inactivator of the enzyme than the triol. The partition ratio was calculated by two different methods. Each of the steroids I-IV bound to the enzyme with spectrophotometric dissociation constant (Ks) in the micromolar range, producing Type II low spin spectra changes during titration of the enzyme. In addition, it was found that the binding of each of the compounds to the enzyme occurred without inactivation of the enzyme and that the inactivation under turnover condition, is not as a result of conversion to the denatured P-420 species. This demonstrated that steroids I and III could correctly be designated as mechanism-based (suicide) inhibitors. The kinetic studies demonstrated that steroids with the tetrahydropyranyl substituent are more potent inhibitors of cytochrome P-450SCC as shown by an initial turnover rate of 0.06 min-1, an inactivation rate constant of 0.05 min-1, and a partition ratio of about 1.0 for steroid I. Based on our finding, possible mechanisms of inactivation of cytochrome P-450SCC by these acetylenic steroids are proposed.