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Background: Previous studies on the association between pain and cognitive decline or impairment have yielded mixed results, while studies from low- and middle-income countries (LMICs) or specifically on mild cognitive impairment (MCI) are scarce. Thus, we investigated the association between pain and MCI in LMICs and quantified the extent to which perceived stress, sleep/energy problems, and mobility limitations explain the pain/MCI relationship. Methods: Data analysis of cross-sectional data from six LMICs from the Study on Global Ageing and Adult Health (SAGE) were performed. MCI was based on the National Institute on Aging-Alzheimer's Association criteria. "Overall in the last 30 days, how much of bodily aches or pain did you have?" was the question utilized to assess pain. Associations were examined by multivariable logistic regression analysis and meta-analysis. Results: Data on 32,715 individuals aged 50 years and over were analysed [mean (SD) age 62.1 (15.6) years; 51.7% females]. In the overall sample, compared to no pain, mild, moderate, and severe/extreme pain were dose-dependently associated with 1.36 (95% CI = 1.18–1.55), 2.15 (95% CI = 1.77–2.62), and 3.01 (95% CI = 2.36–3.85) times higher odds for MCI, respectively. Mediation analysis showed that perceived stress, sleep/energy problems, and mobility limitations explained 10.4%, 30.6%, and 51.5% of the association between severe/extreme pain and MCI. Conclusions: Among middle-aged to older adults from six LMICs, pain was associated with MCI dose-dependently, and sleep problems and mobility limitations were identified as potential mediators. These findings raise the possibility of pain as a modifiable risk factor for developing MCI. [ABSTRACT FROM AUTHOR]

Vaccines are among the most cost-effective public health interventions for preventing infection-induced morbidity and mortality, yet much remains to be learned regarding the mechanisms by which vaccines protect. Systems immunology combines traditional immunology with modern 'omic profiling techniques and computational modeling to promote rapid and transformative advances in vaccinology and vaccine discovery. The NIH/NIAID Human Immunology Project Consortium (HIPC) has leveraged systems immunology approaches to identify molecular signatures associated with the immunogenicity of many vaccines. However, comparative analyses have been limited by the distributed nature of some data, potential batch effects across studies, and the absence of multiple relevant studies from non-HIPC groups in ImmPort. To support comparative analyses across different vaccines, we have created the Immune Signatures Data Resource, a compendium of standardized systems vaccinology datasets. This data resource is available through ImmuneSpace, along with code to reproduce the processing and batch normalization starting from the underlying study data in ImmPort and the Gene Expression Omnibus (GEO). The current release comprises 1405 participants from 53 cohorts profiling the response to 24 different vaccines. This novel systems vaccinology data release represents a valuable resource for comparative and meta-analyses that will accelerate our understanding of mechanisms underlying vaccine responses. Measurement(s) Transcriptomics • Hemagglutination Inhibition Assay • IgG IgM IgA Total Measurement • Virus-neutralizing Antibody • ELISA Technology Type(s) Microarray • RNA sequencing • Hemagglutination Inhibition Assay • ELISA • Microneutralization Assay • serum neutralization of viral infectivity assay Sample Characteristic - Organism Homo sapiens [ABSTRACT FROM AUTHOR]

Gaining a better understanding of the immune cell subsets and molecular factors associated with protective or pathological immunity against severe acute respiratory syndrome coronavirus (SARS-CoV)-2 could aid the development of vaccines and therapeutics for coronavirus disease 2019 (COVID-19). Single-cell technologies, such as flow cytometry, mass cytometry, single-cell transcriptomics and single-cell multi-omic profiling, offer considerable promise in dissecting the heterogeneity of immune responses among individual cells and uncovering the molecular mechanisms of COVID-19 pathogenesis. Single-cell immune-profiling studies reported to date have identified innate and adaptive immune cell subsets that correlate with COVID-19 disease severity, as well as immunological factors and pathways of potential relevance to the development of vaccines and treatments for COVID-19. For facilitation of integrative studies and meta-analyses into the immunology of SARS-CoV-2 infection, we provide standardized, download-ready versions of 21 published single-cell sequencing datasets (over 3.2 million cells in total) as well as an interactive visualization portal for data exploration. This Review provides an overview of existing studies using single-cell technologies to provide insights over the immune responses and molecular mechanisms at work in COVID-19. [ABSTRACT FROM AUTHOR]

Through the formation of concentration gradients, morphogens drive graded responses to extracellular signals, thereby fine-tuning cell behaviors in complex tissues. Here we show that the chemokine CXCL13 forms both soluble and immobilized gradients. Specifically, CXCL13+ follicular reticular cells form a small-world network of guidance structures, with computer simulations and optimization analysis predicting that immobilized gradients created by this network promote B cell trafficking. Consistent with this prediction, imaging analysis show that CXCL13 binds to extracellular matrix components in situ, constraining its diffusion. CXCL13 solubilization requires the protease cathepsin B that cleaves CXCL13 into a stable product. Mice lacking cathepsin B display aberrant follicular architecture, a phenotype associated with effective B cell homing to but not within lymph nodes. Our data thus suggest that reticular cells of the B cell zone generate microenvironments that shape both immobilized and soluble CXCL13 gradients. Morphogens such as chemokines form gradients to direct graded responses and modulate cell behaviors. Here the authors show, using imaging and computer simulation, that the chemokine CXCL13 originated from follicular reticular cells in the lymph nodes forms both soluble and immobilized gradients to regulate B cell recruitment and migration. [ABSTRACT FROM AUTHOR]

Problem gambling is known to be associated with significant stigma, but there is limited research on the negative stereotypes that underpin this judgement. Understanding the stereotypes that contribute to the stigmatisation of problem gambling may help to identify new approaches to reducing gambling stigma. Using data collected during 100 in-depth qualitative interviews with gamblers in Victoria, Australia, we explored factors which underpin negative stereotypes about people with gambling problems, the influence of negative stereotypes on behaviours and attitudes and differences in attitudes to different gambling products. Participants perceived that people with gambling problems were lacked responsibility and control, as were 'lazy', 'stupid' and 'greedy.' Electronic gambling machine (EGM) gamblers were particularly stigmatised. Negative stereotypes focusing on personal responsibility led to feelings of guilt and shame in people with gambling problems, as well as increased social isolation, and also impacted on moderate-risk gamblers, who contrasted their own behaviour with a stereotyped idea of a person with a gambling problem. Participants linked stereotyped portrayals of problem gambling to discussions of the gambling industry, which they perceived focused on control and responsibility, and the media, which they perceived emphasised extreme negative consequences from gambling. This study suggests that negative stereotypes focusing on personal responsibility for gambling problems are a factor leading to the stigmatisation of people with gambling problems. [ABSTRACT FROM AUTHOR]

In 2014, 12 European countries are operating Intellectual Property (IP) Box regimes that provide substantially reduced rates of corporate tax for income derived from important forms of intellectual property. We describe the key features of the policies and incorporate them into forward-looking measures of the cost of capital and the effective average tax rate. We show that the treatment of expenses relating to IP income is particularly important in determining the effective tax burden. A key finding is that regimes that allow expenses to be deducted at the ordinary corporate income tax rate, as opposed to the lower IP Box tax rate, may result in negative effective average tax rates and can thereby provide a subsidy to unprofitable projects. We discuss the ways in which IP Boxes are likely to affect firms' decisions and relate this to possible policy aims. While some regimes attempt to link the tax benefit to real activities, others have designed a policy targeted at the income streams associated with intellectual property. A key concern is the role that IP Boxes may play in increased tax competition between European countries. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "The "Walk of Shame": a Qualitative Study of the Influences of Negative Stereotyping of Problem Gambling on Gambling Attitudes and Behaviors" which appeared on the July 5, 2017 issue.