•This study examined perfectionism, work motivation, and workaholism.•The sample comprised 131 employees.•Self-oriented perfectionism (SOP) positively predicted workaholism.•Identified and ...introjected regulation mediated the SOP–workaholism relationship.•The findings suggest perfectionism and work motivation contribute to workaholism.
Even though it has been over 20years since Spence and Robbins (1992) first showed perfectionism and workaholism to be closely related, the relationship between perfectionism and workaholism is still under-researched. In particular, it has remained unclear why perfectionism is linked to workaholism. Using data from 131 employees, this study—examining self-oriented and socially prescribed perfectionism—investigated whether intrinsic–extrinsic work motivation could explain the positive relationship between perfectionism and workaholism. Whereas socially prescribed perfectionism was unrelated to workaholism, self-oriented perfectionism showed a positive correlation with workaholism. Furthermore autonomous (integrated and identified regulation) and controlled (introjected and external regulation) work motivation showed positive correlations. However, when all predictors were entered in a regression analysis, only self-oriented perfectionism, identified regulation, and introjected regulation positively predicted workaholism. In addition, a mediation analysis showed that identified and introjected regulation fully mediated the effect of self-oriented perfectionism on workaholism. The findings suggest that high levels of work motivation explain why many self-oriented perfectionists are workaholic.
This study aims to develop a learning media called Stelar for practical activities to digital manage archives and create digital letters. The learning media can be accessed by three students who act ...as leaders, secretaries and archivists. In addition, this learning media is also designed to be monitored by the teacher. Thus, the teacher can provide an assessment in the form of numbers and important notes on the work of students. The type of this research was Research and Development using the ADDIE model, namely Analyze, Design, Development, Implementation, Evaluation. Based on the results of the application of learning media to 99 students to work on administrative activities using Stelar media, an average score of 88.5% was obtained. In addition, based on filling out a learner questionnaire to determine the effectiveness of learning media, a score of 90% was obtained. Thus, it can be concluded that the Stelar instructional media can be well accepted and is suitable for use in the learning process of Office Administration students in Indonesia. Keywords: Stelar, office administration, learning media, ADDIE
Respiratory syncytial virus (RSV) infection and shingles are two viral diseases that affect older adults, and a combined vaccine to protect against both could be beneficial. RSV infection causes ...hospitalisations and significant morbidity in both children and adults and can be fatal in the elderly. The RSV fusion (F) envelope glycoprotein induces a strong RSV-neutralising antibody response and is the target of protective immunity in the first RSV vaccine for older adults, recently approved by the FDA. An initial childhood infection with the varicella zoster virus (VZV) results in chickenpox disease, but reactivation in older adults can cause shingles. This reactivation in sensory and autonomic neurons is characterized by a skin-blistering rash that can be accompanied by prolonged pain. The approved protein-in-adjuvant shingles vaccine induces VZV glycoprotein E (gE)-fspecific antibody and CD4+ T cell responses and is highly effective. Here we report the evaluation of RSV/shingles combination vaccine candidates based on non-replicating chimpanzee adenovirus (ChAd) vectors. We confirmed the cellular and humoral immunogenicity of the vaccine vectors in mice using T cell and antibody assays. We also carried out an RSV challenge study in cotton rats which demonstrated protective efficacy following a homologous prime-boost regimen with our preferred vaccine candidate.
Skeletal aging is associated with reduced proliferative potential of bone marrow (BM) multipotential stromal cells (MSCs). Recent data suggest the involvement of type 1 interferon (IFN1) signalling ...in hematopoietic stem cell (HSC) senescence. Considering that BM-HSCs and BM-MSCs share the same BM niche, we investigated IFN1 expression profile in human BM-MSCs in relation to donor age, culture-expansion and IFN1 (α and β) stimulation. Fluorescence-activated cell sorting was used to purify uncultured BM-MSCs from younger (19–41, n = 6) and older (59–89, n = 6) donors based on the CD45lowCD271+ phenotype, and hematopoietic-lineage cells (BM-HLCs, CD45+CD271−) were used as controls. Gene expression was analysed using integrated circuits arrays in sorted fractions as well as cultured/stimulated BM-MSCs and Y201/Y202 immortalised cell lines. IFN1 stimulation led to BM-MSC growth arrest and upregulation of many IFN1-stimulated genes (ISGs), with IFNβ demonstrating stronger effects. Uncultured MSCs were characterised by a moderate-level ISG expression similar to Y201 cells. Age-related changes in ISG expression were negligible in BM-MSCs compared to BM-HLCs, and intracellular reactive oxygen species (ROS) levels in BM-MSCs did not significantly correlate with donor age. Antiaging genes Klotho and SIRT6 correlated with more ISGs in BM-MSCs than in BM-HLCs. In patients with osteoarthritis (OA), BM-MSCs expressed considerably lower levels of several ISGs, indicating that their IFN1 signature is affected in a pathological condition. In summary, BM-MSCs possess homeostatic IFN1 gene expression signature in health, which is sensitive to in vitro culture and external IFN1 stimulation. IFN signalling may facilitate in vivo BM-MSC responses to DNA damage and combating senescence and aberrant immune activation.
What Wester and Reyes deftly accomplish with this collection of essays is better than a set of definitions through which to analyse twenty-first century Gothic literature: it is a road map and a ...glossary of terms for the coming century, which shows the analytical reader the cultural framework in which Gothic literature is not only being written but also received. ...where vampires, werewolves and ghosts were once to be feared, especially within a Christian context (as they represented eternal damnation or the beastly desires within), they now hold a very different power and place within culture. Though I wasn’t convinced by Reyes’ comment that it would be inevitable someone falls in love with the person that eats your husband’s brain (97), the horror of how to deal with those who once committed awful crimes but return to the community is a keen discussion on our personal morality and capacity for forgive. The fear of viruses and our own capacity to create situations in which we unwillingly infect and hurt each other was a little too close comfort in a post Covid-19 world, but Reyes’ exploration of the deep issues that have given rise to zombie apocalypse narratives in recent years shows how maybe these fears are not fantastical but sensible.
There are varying data concerning the effect of prior anti-vector immunity on the T-cell response induced by immunisation with an identical vectored vaccine containing a heterologous antigen insert. ...To determine whether prior exposure to ChAdOx1-SARS-CoV2 immunisation (Vaxzevriasup.® ) impacts magnitudes of antigen-specific T-cell responses elicited by subsequent administration of the same viral vector (encoding HBV antigens, ChAdOx1-HBV), healthy volunteers that had received Vaxzevriasup.® (n = 15) or the Pfizer or Moderna mRNA COVID-19 vaccine (n = 11) between 10 and 18 weeks prior were recruited to receive a single intramuscular injection of ChAdOx1-HBV. Anti-ChAdOx1-neutralising antibody titers were determined, and vector or insert-specific T-cell responses were measured by a gamma-interferon ELISpot and intracellular cytokine staining (ICS) assay using multiparameter flow cytometry. Participants were followed for three months after the ChAdOx1-HBV injection, which was well-tolerated, and no dropouts occurred. The baseline ChAdOx1 neutralisation titers were higher in the Vaxzevriasup.® cohort (median of 848) than in the mRNA cohort (median of 25). T-cell responses to HBV antigens, measured by ELISpot, were higher on day 28 in the mRNA group (p = 0.013) but were similar between groups on day 84 (p = 0.441). By ICS, these differences persisted at the last time point. There was no clear correlation between the baseline responses to the adenoviral hexon and the subsequent ELISpot responses. As vaccination within 3 months using the same viral vector backbone affected the insert-specific T-cell responses, a greater interval after prior adenoviral immunisation using heterologous antigens may be warranted in settings in which these cells play critical roles.
BackgroundThe use of immunotherapeutic vaccination in prostate cancer is a promising approach that likely requires the induction of functional, cytotoxic T cells . The experimental approach described ...here uses a well-studied adenovirus-poxvirus heterologous prime-boost regimen, in which the vectors encode a combination of prostate cancer antigens, with the booster dose delivered by either the intravenous or intramuscular (IM) route. This prime-boost regimen was investigated for antigen-specific CD8+ T cell induction.MethodsThe coding sequences for four antigens expressed in prostate cancer, 5T4, PSA, PAP, and STEAP1, were inserted into replication-incompetent chimpanzee adenovirus Oxford 1 (ChAdOx1) and into replication-deficient modified vaccinia Ankara (MVA). In four strains of mice, ChAdOx1 prime was delivered intramuscularly, with an MVA boost delivered by either IM or intravenous routes. Immune responses were measured in splenocytes using ELISpot, multiparameter flow cytometry, and a targeted in vivo killing assay.ResultsThe prime-boost regimen was highly immunogenic, with intravenous administration of the boost resulting in a sixfold increase in the magnitude of antigen-specific T cells induced and increased in vivo killing relative to the intramuscular boosting route. Prostate-specific antigen (PSA)-specific responses were dominant in all mouse strains studied (C57BL/6, BALBc, CD-1 and HLA-A2 transgenic).ConclusionThis quadrivalent immunotherapeutic approach using four antigens expressed in prostate cancer induced high magnitude, functional CD8+ T cells in murine models. The data suggest that comparing the intravenous versus intramuscular boosting routes is worthy of investigation in humans.
BackgroundVTP-850 is a novel antigen-specific immunotherapeutic consisting of 2 nonreplicating viral-vectored components: ChAdOx1-PCAQ, based on an adenoviral vector, and MVA-PCAQ, based on a ...modified vaccinia virus Ankara (MVA) vector. Both components encode the same 4 prostate cancer antigens: prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), six transmembrane epithelial antigen of prostate 1 (STEAP1), and 5T4, an oncofetal antigen. Preclinical studies in inbred, outbred, and HLA-A2 transgenic mice show that VTP-850 is highly immunogenic. Immune responses were measured in splenocytes using IFN-γ ELISpot assay, multiparameter flow cytometry, and targeted in vivo killing assays. VTP-850 elicited T cell responses to each of the 4 encoded antigens. Intravenous administration of MVA-PCAQ resulted in a 6-fold increase in the magnitude of antigen-specific T cells induced and increased in vivo killing relative to the intramuscular administration route.1 MethodsThis is a first-in-human multicenter Phase 1/2 trial to evaluate safety, PSA response rate and duration, and induced T cell response of VTP-850 in men with biochemical recurrence of prostate cancer after definitive local therapy. Phase 1 (15–18 participants) will follow a 3+3 design to determine the recommended phase 2 regimen (RP2R); dose level of both ChAdOx1-PCAQ and MVA-PCAQ, and route of administration of MVA-PCAQ (IM or IV). Phase 2 will consist of 2 stages. In Stage 1, 19 additional participants will be enrolled at the RP2R. If 4 or more of the 25 participants dosed at the RP2R have a PSA response (≥50% reduction in serum PSA), Stage 2 will enroll 100 additional participants. Participants will be followed for 6 months or until start of new therapy (e.g. ADT) or until development of metastatic disease. Participants who have a PSA response during the 6 months follow up will be followed for up to an additional 18 months. Patients who have undergone primary therapy for prostate cancer and have biochemical recurrence are eligible. Patients must have nonmetastatic (M0) disease by conventional imaging (e.g. CT, bone scan); serum PSA of >0.3 ng/mL (prior radical prostatectomy) or 2 ng/mL above nadir (prior external beam radiation or brachytherapy); PSA doubling time ≤12 months; and testosterone >75 ng/dL. They cannot have received ADT within 6 months prior to Day 1 and cannot have received prior chemotherapy, immunotherapy or experimental agent for prostate cancer. The trial is open in multiple centers in the USA.Trial RegistrationClinicaltrials.gov Identifier: NCT05617040ReferenceVardeu A, Davis C, McDonald I, Stahlberg G, Thapa B, Piotrowska K, Marshall M, Evans T, Wheeler V, Sebastian S, Anderson K. Intravenous administration of viral vectors expressing prostate cancer antigens enhances the magnitude and functionality of CD8+ T cell responses: description of immune response to PCAQ in mice and comparison of IM vs IV boost. J Immunother Cancer 2022;10:e005398. doi:10.1136/jitc-2022–005398 Journal of Immunotherapy of Cancer https://jitc.bmj.com/content/10/11/e005398Ethics ApprovalThe trial has been approved by Advarra Central IRB (protocol ID Pro00067777) and applicable local IRBs for open sites (at the time of writing, IRB Advarra, approval numbers SSU00203836, SSU00213065, SSU00215354, SSU00211225, SSU00220023; IRB WCG, approval number 20232112; IRB-Columbia Research, approval number AAAU4814; IRB-Fox Chase Cancer Center, approval number 23–1001).
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