Understanding public perceptions toward sustainable healthcare through psychological network analysis of material preference and attitudes toward plastic medical devices.

Recent and potential future health-care users (i.e., the public) are important stakeholders in the transition toward environmentally sustainable healthcare. However, it remains unclear whether, according to the public, there is room for sustainable innovations in materials for plastic medical devices (PMD). This study explores preferences regarding conventional or bio-based PMD, and psychological mechanisms underlying these preferences. We administered two surveys among Dutch adults from a research panel. Results from the first survey (i.e., open-text survey on attitude elements; NStudy1 = 66) served as input for the second survey (i.e., Likert-scale survey on beliefs, emotions, perceived control, social norms, trust, related to current and bio-based PMD, and health and age; NStudy2 = 1001; Mage = 47.35; 54.4% female). The second survey was completed by 501 participants who, in the last two years, received care in which PMD were used, and 500 participants who did not. Cross-sectional psychological networks were estimated with data from the second study using the EBICglasso method. Results showed that participants preferred bio-based over conventional PMD, and this applied regardless of whether devices are used inside or outside of the body. Results also showed emotions play an important role, with emotions regarding bio-based PMD being strongly related to preference. Furthermore, comparing recent and potential future receivers of PMD revealed differences in preference but comparable relations between preference and other psychological variables. This study shows that receivers' perspectives should not be seen as potential barriers, but as additional motivation for transitioning toward sustainable healthcare. Recommendations for implementation are discussed.

A Network Approach to Compliance: A Complexity Science Understanding of How Rules Shape Behavior.

To understand how compliance develops both in everyday and corporate environments, it is crucial to understand how different mechanisms work together to shape individuals' (non)compliant behavior. Existing compliance studies typically focus on a subset of theories (i.e., rational choice theories, social theories, legitimacy theories, capacity theories, and opportunity theories) to understand how key variables from one or several of these theories shape individual compliance. The present study provides a first integrated understanding of compliance, rooted in complexity science, in which key elements from these theories are considered simultaneously, and their relations to compliance and each other are explored using network analysis. This approach is developed by analyzing online survey data (N = 562) about compliance with COVID-19 mitigation measures. Traditional regression analysis shows that elements from nearly all major compliance theories (except for social theories) are associated with compliance. The network analysis revealed groupings and interconnections of variables that did not track the existing compliance theories and point to a complexity overlooked in existing compliance research. These findings demonstrate a fundamentally different perspective on compliance, which moves away from traditional narrow, non-network approaches. Instead, they showcase a complexity science understanding of compliance, in which compliance is understood as a network of interacting variables derived from different theories that interact with compliance. This points to a new research agenda that is oriented on mapping compliance networks, and testing and modelling how regulatory and management interventions interact with each other and compliance within such networks. Supplementary Information: The online version contains supplementary material available at 10.1007/s10551-022-05128-8.

How compliance with behavioural measures during the initial phase of a pandemic develops over time: A longitudinal COVID-19 study.

In this longitudinal research, we adopt a complexity approach to examine the temporal dynamics of variables related to compliance with behavioural measures during the COVID-19 pandemic. Dutch participants (N = 2399) completed surveys with COVID-19-related variables five times over a period of 10 weeks (23 April-30 June 2020). With these data, we estimated within-person COVID-19 attitude networks containing a broad set of psychological variables and their relations. These networks display variables' predictive effects over time between measurements and contemporaneous effects during measurements. Results show (1) bidirectional effects between multiple variables relevant for compliance, forming potential feedback loops, and (2) a positive reinforcing structure between compliance, support for behavioural measures, involvement in the pandemic and vaccination intention. These results can explain why levels of these variables decreased throughout the course of the study. The reinforcing structure points towards potentially amplifying effects of interventions on these variables and might inform processes of polarization. We conclude that adopting a complexity approach might contribute to understanding protective behaviour in the initial phase of pandemics by combining different theoretical models and modelling bidirectional effects between variables. Future research could build upon this research by studying causality with interventions and including additional variables in the networks.

Understanding change in COVID-19 vaccination intention with network analysis of longitudinal data from Dutch adults.

Prior research into the relationship between attitudes and vaccination intention is predominantly cross-sectional and therefore does not provide insight into directions of relations. During the COVID-19 vaccines development and enrollment phase, we studied the temporal dynamics of COVID-19 vaccination intention in relation to attitudes toward COVID-19 vaccines and the pandemic, vaccination in general, social norms and trust. The data are derived from a longitudinal survey study with Dutch participants from a research panel (N = 744; six measurements between December 2020 and May 2021; age 18-84 years [M = 53.32]) and analyzed with vector-autoregression network analyses. While cross-sectional results indicated that vaccination intention was relatively strongly related to attitudes toward the vaccines, results from temporal analyses showed that vaccination intention mainly predicted other vaccination-related variables and to a lesser extent was predicted by variables. We found a weak predictive effect from social norm to vaccination intention that was not robust. This study underlines the challenge of stimulating uptake of new vaccines developed during pandemics, and the importance of examining directions of effects in research into vaccination intention.

Tailored interventions into broad attitude networks towards the COVID-19 pandemic.

This study examines how broad attitude networks are affected by tailored interventions aimed at variables selected based on their connectiveness with other variables. We first computed a broad attitude network based on a large-scale cross-sectional COVID-19 survey (N = 6,093). Over a period of approximately 10 weeks, participants were invited five times to complete this survey, with the third and fifth wave including interventions aimed at manipulating specific variables in the broad COVID-19 attitude network. Results suggest that targeted interventions that yield relatively strong effects on variables central to a broad attitude network have downstream effects on connected variables, which can be partially explained by the variables the interventions were aimed at. We conclude that broad attitude network structures can reveal important relations between variables that can help to design new interventions.

A Psychological Network Approach to Attitudes and Preventive Behaviors During Pandemics: A COVID-19 Study in the United Kingdom and the Netherlands.

Preventive behaviors are crucial to prevent the spread of the coronavirus causing COVID-19. We adopted a complex psychological systems approach to obtain a descriptive account of the network of attitudes and behaviors related to COVID-19. A survey study (N = 1,022) was conducted with subsamples from the United Kingdom (n = 502) and the Netherlands (n = 520). The results highlight the importance of people's support for, and perceived efficacy of, the measures and preventive behaviors. This also applies to the perceived norm of family and friends adopting these behaviors. The networks in both countries were largely similar but also showed notable differences. The interplay of psychological factors in the networks is also highlighted, resulting in our appeal to policy makers to take complexity and mutual dependence of psychological factors into account. Future research should study the effects of interventions aimed at these factors, including effects on the network, to make causal inferences.

Localization of BRCA1 protein in breast cancer tissue and cell lines with mutations.

BACKGROUND: The breast and ovarian cancer susceptibility gene (BRCA1) encodes a tumor suppressor. The BRCA1 protein is found primarily in cell nuclei and plays an important role in the DNA damage response and transcriptional regulation. Deficiencies in DNA repair capabilities have been associated with higher histopathological grade and worse prognosis in breast cancer. METHODS: In order to investigate the subcellular distribution of BRCA1 in tumor tissue we randomly selected 22 breast carcinomas and tested BRCA1 protein localization in frozen and contiguous formalin-fixed, paraffin embedded (FFPE) tissue, using pressure cooker antigen-retrieval and the MS110 antibody staining. To assess the impact of BRCA1 germline mutations on protein localization, we retrospectively tested 16 of the tumor specimens to determine whether they contained the common Ashkenazi Jewish founder mutations in BRCA1 (185delAG, 5382insC), and BRCA2 (6174delT). We also compared co-localization of BRCA1 and nucleolin in MCF7 cells (wild type) and a mutant BRCA1 cell line, HCC1937 (5382insC). RESULTS: In FFPE tissue, with MS110 antibody staining, we frequently found reduced BRCA1 nuclear staining in breast tumor tissue compared to normal tissue, and less BRCA1 staining with higher histological grade in the tumors. However, in the frozen sections, BRCA1 antibody staining showed punctate, intra-nuclear granules in varying numbers of tumor, lactating, and normal cells. Two mutation carriers were identified and were confirmed by gene sequencing. We have also compared co-localization of BRCA1 and nucleolin in MCF7 cells (wild type) and a mutant BRCA1 cell line, HCC1937 (5382insC) and found altered sub-nuclear and nucleolar localization patterns consistent with a functional impact of the mutation on protein localization. CONCLUSIONS: The data presented here support a role for BRCA1 in the pathogenesis of sporadic and inherited breast cancers. The use of well-characterized reagents may lead to further insights into the function of BRCA1 and possibly the further development of targeted therapeutics.

Estrogens promote cell-cell adhesion of normal and malignant mammary cells through increased desmosome formation.

The association of estrogen receptor alpha (ERα) expression with differentiated breast tumors presenting a lower metastasis risk could be explained by the estrogen modulation of cell adhesion, motility and invasiveness. Since desmosomes play a crucial role in cell-cell adhesion and may interfere in tumor progression, we studied their regulation by estrogens in human breast cancer and normal mammary cells. Estrogens increased the formation of desmosomes in normal and malignant cells. Furthermore, four desmosomal proteins (desmocollin, γ-catenin, plakophilin and desmoplakin) appeared significantly up-regulated by estrogens in three ERα-expressing cancer cell lines and this effect was reversed by a pure antiestrogen. Finally, silencing of ERα or desmoplakin expression by specific siRNA revealed that estrogen-modulated desmosomal proteins are essential for the estrogenic control of intercellular adhesion. This estrogen modulation of desmosome formation could contribute to the lower invasiveness of ERα-positive tumors and to the integrity of epithelial layers in estrogen target tissues.

Prognostic significance of TRIM24/TIF-1α gene expression in breast cancer.

In this study, we have analyzed the expression of TRIM24/TIF-1α, a negative regulator of various transcription factors (including nuclear receptors and p53) at the genomic, mRNA, and protein levels in human breast tumors. In breast cancer biopsy specimens, TRIM24/TIF-1α mRNA levels (assessed by Real-Time Quantitative PCR or microarray expression profiling) were increased as compared to normal breast tissues. At the genomic level, array comparative genomic hybridization analysis showed that the TRIM24/TIF-1α locus (7q34) exhibited both gains and losses that correlated with mRNA levels. By re-analyzing a series of 238 tumors, high levels of TRIM24/TIF-1α mRNA significantly correlated with various markers of poor prognosis (such as the molecular subtype) and were associated with worse overall survival. By using a rabbit polyclonal antibody for immunochemistry, the TRIM24/TIF-1α protein was detected in nuclei of normal luminal epithelial breast cells, but not in myoepithelial cells. Tissue microarray analysis confirmed that its expression was increased in epithelial cells from normal to breast infiltrating duct carcinoma and correlated with worse overall survival. Altogether, this work is the first study that shows that overexpression of the TRIM24/TIF-1α gene in breast cancer is associated with poor prognosis and worse survival, and it suggests that this transcription coregulator may play a role in mammary carcinogenesis and represent a novel prognostic marker.

BRCA1 protein and nucleolin colocalize in breast carcinoma tissue and cancer cell lines.

The breast and ovarian cancer susceptibility gene BRCA1 encodes a tumor suppressor. BRCA1 protein, which is involved in DNA damage response, has been thought to be found primarily in cell nuclei. In the present investigation, immunohistological studies of BRCA1 protein in frozen breast cancer tissue and MCF7 and HeLa cell lines revealed BRCA1 expression in both nucleoli and nucleoplasmic foci. Immunoelectron microscopic studies of estrogen-stimulated MCF7 cells demonstrated BRCA1 protein localization in the granular components of the nucleolus. Moreover, immunofluorescence of BRCA1 and nucleolin double-labeling showed colocalization in both nucleoli and nucleoplasmic foci in breast tumor cells and asynchronously growing MCF7 and HeLa cells. Multiparameter analysis of BRCA1 and nucleolin in relation to cell cycle position (DNA content) showed expression during G1-S and persistence of BRCA1 during G2/M. After gamma-irradiation of MCF7 cells, BRCA1 protein dispersed from nucleoli and nucleoplasmic foci to other nucleoplasmic sites, which did not colocalize with nucleolin. Small interfering RNA-mediated knockdown of BRCA1 protein resulted in decreased immunofluorescence staining, which was confirmed by Western blotting. The observed colocalization of BRCA1 and nucleolin raises new possibilities for the nucleoplasm-nucleolus pathways of these proteins and their functional significance.

Role of estrogens and their receptors in adhesion and invasiveness of breast cancer cells.

Estrogen receptors (ERs) are overexpressed in human breast cancers (BCs) and associated with differentiated tumors and with a more favorable prognosis. Paradoxically, ERs mediate the mitogenic action of estrogens in human BC cells and the efficacy of antiestrogens in adjuvant therapy of primary tumors. The exact mechanism underlying the ER protection against cancer progression to metastasis remains to be investigated. Herein, we show that ERs decrease invasiveness of BC cells. Detailed studies revealed that the unliganded and the E2-activated ERs decrease cancer cell invasion in vitro through two distinct mechanisms. In the presence of ligand, ERalpha inhibits invasion through a mechanism requiring the functional ERalpha domains involved in the transcriptional activation of target genes. Moreover, using different approaches, we found that cell-cell contacts were markedly increased by 17beta-estradiol (E2) treatment and decreased by the pure antiestrogen, ICI182,780. This cell-cell adhesion was associated with an increase of the major intercellular junctions, desmosomes. Conversely, in the absence of ligand, ERalpha also inhibits invasion through a distinct mechanism involving protein-protein interaction with the region of the first zinc finger of ERalpha. The relationship of these data with clinical studies and their potential therapeutic consequences will be discussed.

Localization of BRCA1 protein in human breast cancer cells.

There is still an ongoing debate concerning the cellular localization of BRCA1 protein in breast cancer. To address this question, we compared the localization of BRCA1 protein using several monoclonal (Ab-1) or polyclonal (C20, D20, I20) antibodies under different technical conditions on human breast cancer cell lines. We worked on the fixation and permeabilization conditions in order to preserve the morphological structures of the cells, as confirmed by transmission electron microscopy studies. As expected from the gene sequence analysis and the biochemical features, both nucleus and cytoplasmic BRCA1 protein staining were detected in cells fixed for 60 min in 4% paraformaldehyde and permeabilized with either 0.3% saponin or 0.02% Triton. In these conditions, the same results were obtained: (i) with the four antibodies tested, (ii) with several dilutions (up to tenfold) of the monoclonal antibody, and (iii) in all the tested breast cancer cell lines. In addition, we validated the functionality of these conditions by quantifying the effects of estrogens and their antagonists on the regulation of BRCA1 protein expression in the MCF7 cell line.