BackgroundStigma is associated with health conditions that drive disease burden in low- and middle-income countries (LMICs), including HIV, tuberculosis, mental health problems, epilepsy, and substance use disorders. However, the literature discussing the relationship between stigma and health outcomes is largely fragmented within disease-specific siloes, thus limiting the identification of common moderators or mechanisms through which stigma potentiates adverse health outcomes as well as the development of broadly relevant stigma mitigation interventions.MethodsWe conducted a scoping review to provide a critical overview of the breadth of research on stigma for each of the five aforementioned conditions in LMICs, including their methodological strengths and limitations.ResultsAcross the range of diseases and disorders studied, stigma is associated with poor health outcomes, including help- and treatment-seeking behaviors. Common methodological limitations include a lack of prospective studies, non-representative samples resulting in limited generalizability, and a dearth of data on mediators and moderators of the relationship between stigma and health outcomes.ConclusionsImplementing effective stigma mitigation interventions at scale necessitates transdisciplinary longitudinal studies that examine how stigma potentiates the risk for adverse outcomes for high-burden health conditions in community-based samples in LMICs.

Endotoxemia is associated by dysregulated apoptosis of immune and non-immune cells. We investigated whether simvastatin has anti-apoptotic effects, and induces hepatocytes and lymphocytes survival signaling in endotoxin-induced liver and spleen injuries. Wistar rats were divided into the groups pretreated with simvastatin (20 or 40 mg/kg, orally) prior to a non-lethal dose of lipopolysaccharide (LPS), the LPS group, and the control. The severity of tissue inflammatory injuries was expressed as hepatic damage scores (HDS) and spleen damage scores (SDS), respectively. The apoptotic cell was detected by TUNEL (Terminal deoxynucleotidyl transferase dUTP Nick End Labeling) and immunohistochemical staining (expression of cleaved caspase-3, and anti-apoptotic Bcl-xL, survivin and NF-κB/p65). Simvastatin dose-dependently abolished HDS and SDS induced by LPS (p < 0.01), respectively. Simvastatin 40 mg/kg significantly decreased apoptotic index and caspase-3 cleavage in hepatocytes and lymphocytes (p < 0.01 vs. LPS group, respectively), while Bcl-XL markedly increased accordingly with simvastatin doses. In the simvastatin, groups were determined markedly increased cytoplasmic expression of survivin associated with nuclear positivity of NF-κB, in both hepatocytes and lymphocytes (p < 0.01 vs. LPS group). Cell-protective effects of simvastatin against LPS seemed to be mediated by up-regulation of survivin, which leads to reduced caspase-3 activation and inhibition of hepatocytes and lymphocytes apoptosis.

ABSTRACT Introduction: In January 2018 the European Commission published a Proposal for a Regulation on Health Technology Assessment (HTA): ‘Proposal for a Regulation on health technology assessment and amending Directive 2011/24/EU’. A number of stakeholders, including some Member States, welcomed this initiative as it was considered to improve collaboration, reduce duplication and improve efficiency. There were however a number of concerns including its legal basis, the establishment of a single managing authority, the preservation of national jurisdiction over HTA decision-making and the voluntary/mandatory uptake of joint assessments by Member States. Areas covered: This paper presents the consolidated views and considerations on the original Proposal as set by the European Commission of a number of policy makers, payers, experts from pricing and reimbursement authorities and academics from across Europe. Expert commentary: The Proposal has since been extensively discussed at Council and while good progress has been achieved, there are still divergent positions. The European Parliament gave a number of recommendations for amendments. If the Proposal is approved, it is important that a balanced, improved outcome is achieved for all stakeholders. If not approved, the extensive contribution and progress attained should be sustained and preserved, and the best alternative solutions found.

Alzheimer's disease represents the most common age-related neurodegenerative disorder and a leading cause of progressive cognitive impairment. Predicting cognitive decline is challenging but would be invaluable in an increasingly aging population which also experiences a rising cardiovascular risk. In order to examine whether plasma measurements of one of the established biomarkers of heart failure, brain natriuretic peptide (BNP), reflect a decline in cognitive function, associated with Alzheimer's disease neurodegeneration, BNP levels were analysed, by using a novel assay called a SOMAscan, in 1. cognitively healthy, control subjects; 2. subjects with mild cognitive impairment, and 3. subjects with Alzheimer's disease. The results of our study show that the levels of the BNP were significantly different between the three types of diagnoses (p < 0.05), whereby subjects with mild cognitive impairment had the lowest mean BNP value, and healthy subjects had the highest BNP value. Importantly, our results show that the levels of the BNP are influenced by the presence of at least one APOE4 allele in the healthy (p < 0.05) and in the Alzheimer's disease groups of subjects (p < 0.1). As the levels of the BNP appear to be independent of the APOE4 genotype in subjects with mild cognitive impairment, the results of our study support inclusion of measurements of plasma levels of the BNP in the list of the core Alzheimer's disease biomarkers for identification of the mild cognitive impairment group of patients. In addition, the results of our study warrant further investigations into molecular links between Alzheimer's disease-type cognitive decline and cardiovascular disorders.

Bimetallic Co-Re/TiO2 catalysts were developed for efficient citral hydrogenation. Bimetallic catalysts were prepared by co-impregnation (CI), successive-impregnation (SI), and surface redox method (SR). The arrangement between the Co and Re species on these systems was fully characterized using several techniques (TEM-energy-dispersive X-ray spectroscopy, H2 temperature-programmed reduction, temperature-programmed desorption, XRD, CO FTIR spectroscopy, model reaction of cyclohexane dehydrogenation), and their catalytic performances were evaluated for the selective hydrogenation of citral towards unsaturated alcohols. The Re and Co species are completely isolated in the CI sample, presenting a very limited Co-Re interaction. In SI samples, the metals coexist in a Janus-type structure with a concentration of Re around Co. Decoration/core-shell structures are observed for SR samples resulting from the redox exchange between the metallic surface of the parent Co/TiO2 catalyst and the Re7+ species of the modifier precursor salt. The contact degree between the two metals gradually increases as follows: Isolated structure (CI)<Janus-type structure(SI)<decoration/core-shell structure (SR). The unchanging structure of all SI samples independent of the Re loading leads to similar electron transfer, and the increase in Re content results in agglomeration of Re, thus decreasing the catalytic activity. Density-of-state (DOS) calculations prove that the high valence of Re is a disadvantage for the hydrogenation reaction. For SR samples, the increase of Re loading contributes to the electron transfer from Re to Co that is consistent with a change of structure from decoration to core-shell. The lack of directly accessible Co atoms for SR catalysts with fully coated structure decreases the efficiency of Re reduction. The presence of Co-Re interaction resulting from the close contact between metals plays a dominant role in the hydrogenation of citral. Nevertheless, an excessively high contact degree is unnecessary for citral hydrogenation once Co-Re interaction has formed.

Ionizing radiation is a recognized genotoxic agent, however, little is known about the role of the functional form of DNA in these processes. Post translational modifications on histone proteins control the organization of chromatin and hence control transcriptional responses that ultimately affect the phenotype. The purpose of this study was to investigate effects on chromatin caused by ionizing radiation in fish. Direct exposure of zebrafish (Danio rerio) embryos to gamma radiation (10.9 mGy/h for 3h) induced hyper-enrichment of H3K4me3 at the genes hnf4a, gmnn and vegfab. A similar relative hyper-enrichment was seen at the hnf4a loci of irradiated Atlantic salmon (Salmo salar) embryos (30 mGy/h for 10 days). At the selected genes in ovaries of adult zebrafish irradiated during gametogenesis (8.7 and 53 mGy/h for 27 days), a reduced enrichment of H3K4me3 was observed, which was correlated with reduced levels of histone H3 was observed. F1 embryos of the exposed parents showed hyper-methylation of H3K4me3, H3K9me3 and H3K27me3 on the same three loci, while these differences were almost negligible in F2 embryos. Our results from three selected loci suggest that ionizing radiation can affect chromatin structure and organization, and that these changes can be detected in F1 offspring, but not in subsequent generations.

This research examined the distribution features of red beds and 1,100 Danxia landform sites across China, while probing the relationship between these spatial patterns and geological elements. This study is based on geological and tectonic maps of China. ArcGIS software was used to process the adjacent index, then perform a spatial analysis of Danxia landforms and red beds, and a coupling analysis of Danxia landforms and red beds with tectonics. Based on a point pattern analysis of Danxia landforms, the adjacent index is 0.31, and the coefficient of variation verified by Thiessen polygon reaches 449%. These figures reflect the clustered distribution pattern of the Danxia landforms. Across the country, Danxia landforms are concentrated into three areas, namely, the Southeast China region, the Sichuan Basin region and the Qilian-Liupan region. The exposure of red beds covers 9.16 × 105 km2, which accounts for 9.5% of the total land area of China. With this research background, the geological elements of tectonics and their effects on the distribution, number, and spatial pattern of Danxia landforms and red beds were analyzed.

PurposeMarketing accountability is currently receiving increased attention from scholars and practitioners alike, with its usage mostly being linked to the improved position of marketing within the firm and to better firm performance. The purpose of this study is to assess whether a supplier’s marketing accountability also has an unobserved signaling effect on customer perceived value.Design/methodology/approachBased on a survey of advertising agency-client dyads, the authors develop and test a multilevel model that assesses the relationship between the supplier’s marketing accountability and perceived value of the client.FindingsEmpirical results indicate that marketing accountability of the agency is positively related to client-firm perceived value, that is marketing accountability also has a positive signaling effect on customers’ value perceptions.Originality/valueThis study provides novel insights on how perceptions of customer value are created in business relationships. More specifically, it highlights that marketing accountability of a supplier positively contributes to shaping clients’ value perceptions. Implications for marketing theory and practice, focused on the need for building, improving and sustaining marketing accountability within the firm and its relevance for value, are discussed and future research directions are identified.

The aim of this study is to explore the outcome of Teucrium polium (TP) medicinal plant consumption on the early stage of fetal development. We used the chicken embryo at 3 days of incubation as a model to evaluate the effect of TP plant extract during embryogenesis. In addition, quantitative polymerase chain reaction (qPCR) was applied to explore the expression of six genes related to cell proliferation, apoptosis, sur-vival, angiogenesis, and migration. Our data revealed that TP exposure inhibits angiogenesis of the chicken embryo and its chorioallantoic membrane. In addition, we found that TP extract significantly harms the normal development of the embryos since around 95% of TP-exposed embryos died after 1-3 days of treatment. Macroscopic examination did not show any anomalies in these embryos. However, qPCR analysis of activation transcription factor-3, B-cell lymphoma-2, caspase 8, inhibin subunit beta A, vascular endothelial growth factor-C, and Cadherin-6 type-2 genes revealed that these genes are considerably deregulated in heart and brain tissues from TP-exposed embryos in comparison with their matched tissues from unexposed ones. Our study implies that TP plant can have very toxic effects on the early stage of the embryo. Therefore, it is important to alert expectant women to avoid the use of this medicinal plant during pregnancy.

ABSTRACT Diaspora actors demonstrate their ability to play a role in a variety of political and social processes in their homelands, including transitional justice. Transnational diaspora memorialization initiatives have become embedded and sustained within different contexts. This paper examines how the causal mechanism of coordination affects memorialization initiatives. It compares memorialization efforts in two localities in Bosnia and Herzegovina with different levels of coordination between diaspora, returnees, and local institutional actors. Centralized coordination with the help of a homeland institution enriches existing memory narratives and aims to forward transitional justice. Memorialization and commemorative practices initiated by diaspora without homeland institutional backing can lead to coordination among a more diverse set of actors, ultimately fostering new, alternative, and more inclusive memory narratives.