Supernatants from lymphocytes stimulated with Bacillus Calmette-Guerin can modify the antigenicity of tumours and stimulate allogeneic T-cell responses

BACKGROUND: Reduced expression of class 1 human leucocyte antigens (HLA1) is often a mechanism by which tumours evade surveillance by the host immune system. This is often associated with an immune function that is unable to mount appropriate responses against disease, which can result in a state that favours carcinogenesis. METHODS: In the current study, we have explored the effects of Bacillus Calmette-Guerin (BCG) on the cytokine output of leucocytes, which is a key determinant in generating antitumour action, and have also assessed the effect of these cytokine cocktails on HLA1 expression in solid tumour cell lines. RESULTS: BCG potently activated a broad range of leucocytes, and also enhanced the production of cytokines that were Th(1)-predominant. Supernatants from BCG-treated leucocytes significantly increased the expression of HLA1 on the surface of cancer cell lines, which correlated with increased cytolytic T-cell activity. We also showed that the increased HLA1 expression was associated with activation of intracellular signalling pathways, which was triggered by the increases in the Th(1)-cytokines interferon-γ and tumour necrosis factor-α, as counteracting their effects negated the enhancement. CONCLUSION: These studies reaffirm the role of BCG as a putative immunotherapy through their cytokine-modifying effects on leucocytes and their capacity to enhance tumour visibility

Development of policies and practices of social responsibility in Portuguese companies: implications of the SA8000 standard

Series: Management and Industrial EngineeringThis study aims to explore the implications of the SA8000 standard in the implementation of Corporate Social Responsibility (CSR) policies and practices in Portuguese companies. Although this is not a recent issue, it is a subject that has motivated a growing interest on the part of the business and academic community. CSR should be seen as a new business management model, which includes universal human values as well as ethical decisions that ensure the satisfaction of the interests and needs of all stakeholders and the community in general. Regarding the empirical aspect of this research, a qualitative approach was followed through the application of a semi-structured interview to certified and not certified companies by SA8000 standard, in order to understand possible disparities with regard to the implementation of CSR policies and practices. Although the certification is the guarantee of the commitment of the companies with the CSR, the truth is that this is seen by the companies as a form of differentiation in the market. In general terms, it can be concluded that the policies and practices of CSR do not differ in relation to certification, which means that all companies have the possibility of making a difference by being socially responsible.Delfina Gomes acknowledges that this study was conducted at the Research Center in Political Science (UID/CPO/0758/2019), University of Minho/University of Évora, and was supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Education and Science through national funds

Considering the Case for Biodiversity Cycles: Reexamining the Evidence for Periodicity in the Fossil Record

Medvedev and Melott (2007) have suggested that periodicity in fossil biodiversity may be induced by cosmic rays which vary as the Solar System oscillates normal to the galactic disk. We re-examine the evidence for a 62 million year (Myr) periodicity in biodiversity throughout the Phanerozoic history of animal life reported by Rohde & Mueller (2005), as well as related questions of periodicity in origination and extinction. We find that the signal is robust against variations in methods of analysis, and is based on fluctuations in the Paleozoic and a substantial part of the Mesozoic. Examination of origination and extinction is somewhat ambiguous, with results depending upon procedure. Origination and extinction intensity as defined by RM may be affected by an artifact at 27 Myr in the duration of stratigraphic intervals. Nevertheless, when a procedure free of this artifact is implemented, the 27 Myr periodicity appears in origination, suggesting that the artifact may ultimately be based on a signal in the data. A 62 Myr feature appears in extinction, when this same procedure is used. We conclude that evidence for a periodicity at 62 Myr is robust, and evidence for periodicity at approximately 27 Myr is also present, albeit more ambiguous.Comment: Minor modifications to reflect final published versio

Electronic Health Literacy Across the Lifespan: Measurement Invariance Study

Background: Electronic health (eHealth) information is ingrained in the healthcare experience to engage patients across the lifespan. Both eHealth accessibility and optimization are influenced by lifespan development, as older adults experience greater challenges accessing and using eHealth tools as compared to their younger counterparts. The eHealth Literacy Scale (eHEALS) is the most popular measure used to assess patient confidence locating, understanding, evaluating, and acting upon online health information. Currently, however, the factor structure of the eHEALS across discrete age groups is not well understood, which limits its usefulness as a measure of eHealth literacy across the lifespan. Objective: The purpose of this study was to examine the structure of eHEALS scores and the degree of measurement invariance among US adults representing the following generations: Millennials (18-35-year-olds), Generation X (36-51-year-olds), Baby Boomers (52-70-year-olds), and the Silent Generation (71-84-year-olds). Methods: Millennials (N=281, mean 26.64 years, SD 5.14), Generation X (N=164, mean 42.97 years, SD 5.01), and Baby Boomers/Silent Generation (N=384, mean 62.80 years, SD 6.66) members completed the eHEALS. The 3-factor (root mean square error of approximation, RMSEA=.06, comparative fit index, CFI=.99, Tucker-Lewis index, TLI=.98) and 4-factor (RMSEA=.06, CFI=.99, TLI=.98) models showed the best global fit, as compared to the 1- and 2-factor models. However, the 4-factor model did not have statistically significant factor loadings on the 4th factor, which led to the acceptance of the 3-factor eHEALS model. The 3-factor model included eHealth Information Awareness, Search, and Engagement. Pattern invariance for this 3-factor structure was supported with acceptable model fit (RMSEA=.07, Δχ2=P>.05, ΔCFI=0). Compared to Millennials and members of Generation X, those in the Baby Boomer and Silent Generations reported less confidence in their awareness of eHealth resources (P<.001), information seeking skills (P=.003), and ability to evaluate and act on health information found on the Internet (P<.001). Results: Young (18-48-year olds, N=411) and old (49-84-year olds, N=419) adults completed the survey. A 3-factor model had the best fit (RMSEA=.06, CFI=.99, TLI=.98), as compared to the 1-factor, 2-factor, and 4-factor models. These 3-factors included eHealth Information Awareness (2 items), Information Seeking (2 items), and Information and Evaluation (4 items). Pattern invariance was supported with the acceptable model fit (RMSEA=.06, Δχ2=P>.05, ΔCFI=0). Compared with younger adults, older adults had less confidence in eHealth resource awareness (P<.001), information seeking skills (P<.01), and ability to evaluate and act upon online health information (P<.001). Conclusions: The eHEALS can be used to assess, monitor uniquely, and evaluate Internet users’ awareness of eHealth resources, information seeking skills, and engagement abilities. Configural and pattern invariance was observed across all generation groups in the 3-factor eHEALS model. To meet gold the standards for factor interpretation (ie, 3 items or indicators per factor), future research is needed to create and assess additional eHEALS items. Future research is also necessary to identify and test items for a fourth factor, one that captures the social nature of eHealth

A sense of embodiment is reflected in people's signature size

BACKGROUND: The size of a person's signature may reveal implicit information about how the self is perceived although this has not been closely examined. METHODS/RESULTS: We conducted three experiments to test whether increases in signature size can be induced. Specifically, the aim of these experiments was to test whether changes in signature size reflect a person's current implicit sense of embodiment. Experiment 1 showed that an implicit affect task (positive subliminal evaluative conditioning) led to increases in signature size relative to an affectively neutral task, showing that implicit affective cues alter signature size. Experiments 2 and 3 demonstrated increases in signature size following experiential self-focus on sensory and affective stimuli relative to both conceptual self-focus and external (non-self-focus) in both healthy participants and patients with anorexia nervosa, a disorder associated with self-evaluation and a sense of disembodiment. In all three experiments, increases in signature size were unrelated to changes in self-reported mood and larger than manipulation unrelated variations. CONCLUSIONS: Together, these findings suggest that a person's sense of embodiment is reflected in their signature size

Effectiveness of guided self-help in decreasing expressed emotion in family caregivers of people diagnosed with depression in Thailand: a randomised controlled trial

Background: High expressed emotion (EE) can extend the duration of illness and precipitate relapse; however, little evidence-based information is available to assist family caregivers of individuals with depression. In the present exploratory study, we examined the effectiveness of a cognitive behaviour therapy (CBT) based guided self-help (GSH) manual in decreasing EE in caregivers of people with depression, in Thailand. Method: A parallel group randomised controlled trial was conducted, following CONSORT guidelines, with 54 caregivers who were allocated equally to GSH or control group (standard outpatient department support). In addition, both groups were contacted weekly by telephone. EE was assessed, using the Family Questionnaire (FQ), at baseline, post-test (Week 8) and follow-up (Week 12). Results: FQ scores at baseline indicated that both groups had similar, though moderately high level of EE. However, between baseline and post-test EE scores decreased markedly in the intervention group, but in contrast, they increased slightly in the control group. Between post-test and follow-up, little change took place in the EE scores of either group. Overall, the intervention group recipients of GSH showed a significant decrease in EE whereas the control group recipients of standard outpatient department support reported a slight increase in EE. Conclusion: These findings provide preliminary evidence that GSH is beneficial in reducing EE in caregivers, which is advantageous to family members with depression and caregivers. The approach may be used as an adjunct to the limited outpatient department support given to caregivers by mental health professionals and, perhaps, to caregivers who do not attend these departments

Seeking legitimacy through CSR: Institutional Pressures and Corporate Responses of Multinationals in Sri Lanka

Arguably, the corporate social responsibility (CSR) practices of multinational enterprises (MNEs) are influenced by a wide range of both internal and external factors. Perhaps most critical among the exogenous forces operating on MNEs are those exerted by state and other key institutional actors in host countries. Crucially, academic research conducted to date offers little data about how MNEs use their CSR activities to strategically manage their relationship with those actors in order to gain legitimisation advantages in host countries. This paper addresses that gap by exploring interactions between external institutional pressures and firm-level CSR activities, which take the form of community initiatives, to examine how MNEs develop their legitimacy-seeking policies and practices. In focusing on a developing country, Sri Lanka, this paper provides valuable insights into how MNEs instrumentally utilise community initiatives in a country where relationship-building with governmental and other powerful non-governmental actors can be vitally important for the long-term viability of the business. Drawing on neo-institutional theory and CSR literature, this paper examines and contributes to the embryonic but emerging debate about the instrumental and political implications of CSR. The evidence presented and discussed here reveals the extent to which, and the reasons why, MNEs engage in complex legitimacy-seeking relationships with Sri Lankan institutions

The C-Terminal Domain of the Arabinosyltransferase Mycobacterium tuberculosis EmbC Is a Lectin-Like Carbohydrate Binding Module

The D-arabinan-containing polymers arabinogalactan (AG) and lipoarabinomannan (LAM) are essential components of the unique cell envelope of the pathogen Mycobacterium tuberculosis. Biosynthesis of AG and LAM involves a series of membrane-embedded arabinofuranosyl (Araf) transferases whose structures are largely uncharacterised, despite the fact that several of them are pharmacological targets of ethambutol, a frontline drug in tuberculosis therapy. Herein, we present the crystal structure of the C-terminal hydrophilic domain of the ethambutol-sensitive Araf transferase M. tuberculosis EmbC, which is essential for LAM synthesis. The structure of the C-terminal domain of EmbC (EmbCCT) encompasses two sub-domains of different folds, of which subdomain II shows distinct similarity to lectin-like carbohydrate-binding modules (CBM). Co-crystallisation with a cell wall-derived di-arabinoside acceptor analogue and structural comparison with ligand-bound CBMs suggest that EmbCCT contains two separate carbohydrate binding sites, associated with subdomains I and II, respectively. Single-residue substitution of conserved tryptophan residues (Trp868, Trp985) at these respective sites inhibited EmbC-catalysed extension of LAM. The same substitutions differentially abrogated binding of di- and penta-arabinofuranoside acceptor analogues to EmbCCT, linking the loss of activity to compromised acceptor substrate binding, indicating the presence of two separate carbohydrate binding sites, and demonstrating that subdomain II indeed functions as a carbohydrate-binding module. This work provides the first step towards unravelling the structure and function of a GT-C-type glycosyltransferase that is essential in M. tuberculosis. Author Summary Top Tuberculosis (TB), an infectious disease caused by the bacillus Mycobacterium tuberculosis, burdens large swaths of the world population. Treatment of active TB typically requires administration of an antibiotic cocktail over several months that includes the drug ethambutol. This front line compound inhibits a set of arabinosyltransferase enzymes, called EmbA, EmbB and EmbC, which are critical for the synthesis of arabinan, a vital polysaccharide in the pathogen's unique cell envelope. How precisely ethambutol inhibits arabinosyltransferase activity is not clear, in part because structural information of its pharmacological targets has been elusive. Here, we report the high-resolution structure of the C-terminal domain of the ethambutol-target EmbC, a 390-amino acid fragment responsible for acceptor substrate recognition. Combining the X-ray crystallographic analysis with structural comparisons, site-directed mutagenesis, activity and ligand binding assays, we identified two regions in the C-terminal domain of EmbC that are capable of binding acceptor substrate mimics and are critical for activity of the full-length enzyme. Our results begin to define structure-function relationships in a family of structurally uncharacterised membrane-embedded glycosyltransferases, which are an important target for tuberculosis therapy