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This study examined the relationships between racial knowledge and emotions as predictors of anti-racist behaviors. We analyzed responses of 135 White MSW students from a cross-sectional survey conducted in May 2018. Regression was used to analyze the relationships between colorblind attitudes, empathy, guilt, shame, and anti-racist behaviors. Results indicated that colorblind attitudes and White shame, after controlling for other factors, were correlated with fewer anti-racist behaviors; empathy and having taken an ethnic studies course were related to more anti-racist behaviors. These results provide evidence that racial emotions affect anti-racist behaviors, above and beyond what is accounted for by knowledge about racism. The results encourage educators preparing students for anti-racist practice to develop interventions that target racial emotions among White students.

BACKGROUND. Passive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19. Evidence from controlled clinical trials is inconclusive. METHODS. We conducted a randomized, open-label, controlled clinical trial at 27 hospitals in Spain. Patients had to be admitted for COVID-19 pneumonia within 7 days from symptom onset and not on mechanical ventilation or high-flow oxygen devices. Patients were randomized 1:1 to treatment with CP in addition to standard of care (SOC) or to the control arm receiving only SOC. The primary endpoint was the proportion of patients in categories 5 (noninvasive ventilation or high-flow oxygen), 6 (invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), or 7 (death) at 14 days. Primary analysis was performed in the intention-to-treat population. RESULTS. Between April 4, 2020, and February 5, 2021, 350 patients were randomly assigned to either CP (n = 179) or SOC (n = 171). At 14 days, proportion of patients in categories 5, 6, or 7 was 11.7% in the CP group versus 16.4% in the control group (P = 0.205). The difference was greater at 28 days, with 8.4% of patients in categories 5-7 in the CP group versus 17.0% in the control group (P = 0.021). The difference in overall survival did not reach statistical significance (HR 0.46, 95% CI 0.19-1.14, log-rank P = 0.087). CONCLUSION. CP showed a significant benefit in preventing progression to noninvasive ventilation or high-flow oxygen, invasive mechanical ventilation or ECMO, or death at 28 days. The effect on the predefined primary endpoint at 14 days and the effect on overall survival were not statistically significant. TRIAL REGISTRATION. Clinicaltrials.gov, NCT04345523. FUNDING. Government of Spain, Instituto de Salud Carlos III., Introduction The pressing need for treatments for the COVID-19 pandemic obliged the medical community and authorities to embrace the use of convalescent plasma (CP) as a potentially effective and easily [...]

Objective: This study provides a nuanced understanding of social work students' beliefs, emotions, and experiences around race and racism, which is needed to inform the development of antiracist pedagogies. Method: We administered an online surveyed to 532 California MSW students. All students completed a colorblindness scale; students of color completed scales on discrimination and stereotype threat, and white students completed scales on emotional responses to racial issues and antiracist behaviors. Analyses included both parametric and nonparametric statistics. Results: Controlling for sociodemographic factors, exposure to ethnic studies classes was associated with lower levels of colorblindness. Students of color (Black, Latinx, Asian, and multiracial) reported frequent experiences with discrimination and stereotype threat within MSW education, with Black students reporting the highest levels. Among white students, elevated emotional responses such as guilt and shame about racial issues were associated with increased antiracist behaviors. Conclusions: Colorblindness, which can be a barrier to antiracist practice, can be reduced by student exposure to ethnic studies courses. The development of antiracist pedagogies will require targeted strategies that consider the perspectives, emotions, and experiences that students of different racial and ethnic identities bring to MSW education. Concerted efforts are needed to address discrimination and anti-Blackness in social work education programs. [ABSTRACT FROM AUTHOR]

This study examined the relationships between racial knowledge and emotions as predictors of anti-racist behaviors. We analyzed responses of 135 White MSW students from a cross-sectional survey conducted in May 2018. Regression was used to analyze the relationships between colorblind attitudes, empathy, guilt, shame, and anti-racist behaviors. Results indicated that colorblind attitudes and White shame, after controlling for other factors, were correlated with fewer anti-racist behaviors; empathy and having taken an ethnic studies course were related to more anti-racist behaviors. These results provide evidence that racial emotions affect anti-racist behaviors, above and beyond what is accounted for by knowledge about racism. The results encourage educators preparing students for anti-racist practice to develop interventions that target racial emotions among White students. [ABSTRACT FROM AUTHOR]

Abstract Background Emissions from refineries include a wide range of substances, such as chrome, lead, nickel, zinc, arsenic, cadmium, benzene, dioxins and furans, all of which are recognized by the International Agency for Research on Cancer (IARC) as carcinogens. Various studies have shown an association between non-Hodgkin lymphoma (NHL) and residence in the vicinity of industrial areas; however, evidence of specific association between refineries and residence in the vicinity has been suggested but not yet established. The aim of this study is to investigate potential links between environmental exposure to emissions from refineries and non-Hodgkin lymphoma mortality in Spain. The spatial distribution of NHL in Spain has an unusual pattern with regions some showing higher risk than others. Methods We designed an analysis of matched geographical areas to examine non-Hodgkin lymphoma mortality in the vicinity of the 10 refineries sited in Spain over the period 1997-2006. Population exposure to refineries was estimated on the basis of distance from town of residence to the facility in a 10 km buffer. We defined 10 km radius areas to perform the matching, accounting for population density, level of industrialization and socio-demographic factors of the area using principal components analysis. For the matched towns we evaluated the risk of NHL mortality associated with residence in the vicinity of the refineries and with different regions using mixed Poisson models. Then we study the residuals to assess a possible risk trend with distance. Results Relative risks (RRs) associated with exposure showed similar values for women and for men, 1.09 (0.97-1.24) and 1.12 (0.99-1.27). RRs for two regions were statistically significant: Canary Islands showed an excess of risk of 1.35 (1.05-1.72) for women and 1.50 (1.18-1.92) for men, whilst Galicia showed an excess of risk of 1.35 (1.04-1.75) for men, but not significant excess for women. Conclusions The results suggest a possible increased risk of NHL mortality among populations residing in the vicinity of refineries; however, a potential distance trend has not been shown. Regional effects in the Canary Islands and Galicia are significantly greater than the regional average.

The aim of this review is to assess how existing literature conceptualizes LGBTQ+ Latinx youth's mental health. Studies were included if they met the following criteria: (a) assessed populations who identified as LGBTQ+ in addition to a racial/ethnic minority identity from Latin America; (b) mean sample age was between 12 and 18; (c) assessed mental health as a dependent variable; (d) reported either quantitative, qualitative, or mixed-method results; (e) written in English; and (f) collected data from participants in the USA. Twenty-three studies were included for review. A thematic synthesis produced four themes: context/setting, persecution, sense of self, and support. [ABSTRACT FROM AUTHOR]

Background: Night shift work, exposure to light at night (ALAN) and circadian disruption may increase the risk of hormone-dependent cancers. Objectives: We evaluated the association of exposure to ALAN during sleeping time with breast and prostate cancer in a population based multicase-control study (MCC-Spain), among subjects who had never worked at night. We evaluated chronotype, a characteristic that may relate to adaptation to light at night. Methods: We enrolled 1,219 breast cancer cases, 1,385 female controls, 623 prostate cancer cases, and 879 male controls from 11 Spanish regions in 2008-2013. Indoor ALAN information was obtained through questionnaires. Outdoor ALAN was analyzed using images from the International Space Station (ISS) available for Barcelona and Madrid for 2012-2013, including data of remotely sensed upward light intensity and blue light spectrum information for each geocoded longest residence of each MCC-Spain subject. Results: Among Barcelona and Madrid participants with information on both indoor and outdoor ALAN, exposure to outdoor ALAN in the blue light spectrum was associated with breast cancer [adjusted odds ratio (OR) for highest vs. lowest tertile, OR = 1.47; 95% CI: 1.00, 2.17] and prostate cancer (OR = 2.05; 95% CI: 1.38, 3.03). In contrast, those exposed to the highest versus lowest intensity of outdoor ALAN were more likely to be controls than cases, particularly for prostate cancer. Compared with those who reported sleeping in total darkness, men who slept in 'quite illuminated' bedrooms had a higher risk of prostate cancer (OR = 2.79; 95% CI: 1.55, 5.04), whereas women had a slightly lower risk of breast cancer (OR = 0.77; 95% CI: 0.39, 1.51). Conclusion: Both prostate and breast cancer were associated with high estimated exposure to outdoor ALAN in the blue-enriched light spectrum. https://doi.org/10.1289/EHP1837, Introduction The increase of artificial light at night (ALAN) in cities has altered the natural light levels in the nocturnal environment and extended human activities into the usually dark hours [...]

CCR5 plays immune functions and is the coreceptor for R5 HIV-1 strains. It exists in diverse conformations and oligomerization states. We interrogated the significance of the CCR5 structural diversity on HIV-1 infection. We show that envelope glycoproteins (gp120s) from different HIV-1 strains exhibit divergent binding levels to CCR5 on cell lines and primary cells, but not to CD4 or the CD4i monoclonal antibody E51. This owed to differential binding of the gp120s to different CCR5 populations, which exist in varying quantities at the cell surface and are differentially expressed between different cell types. Some, but not all, of these populations are antigenically distinct conformations of the coreceptor. The different binding levels of gp120s also correspond to differences in their capacity to bind CCR5 dimers/oligomers. Mutating the CCR5 dimerization interface changed conformation of the CCR5 homodimers and modulated differentially the binding of distinct gp120s. Env-pseudotyped viruses also use particular CCR5 conformations for entry, which may differ between different viruses and represent a subset of those binding gp120s. In particular, even if gp120s can bind both CCR5 monomers and oligomers, impairment of CCR5 oligomerization improved viral entry, suggesting that HIV-1 prefers monomers for entry. From a functional standpoint, we illustrate that the nature of the CCR5 molecules to which gp120/HIV-1 binds shapes sensitivity to inhibition by CCR5 ligands and cellular tropism. Differences exist in the CCR5 populations between T-cells and macrophages, and this is associated with differential capacity to bind gp120s and to support viral entry. In macrophages, CCR5 structural plasticity is critical for entry of blood-derived R5 isolates, which, in contrast to prototypical M-tropic strains from brain tissues, cannot benefit from enhanced affinity for CD4. Collectively, our results support a role for CCR5 heterogeneity in diversifying the phenotypic properties of HIV-1 isolates and provide new clues for development of CCR5-targeting drugs. [ABSTRACT FROM AUTHOR]

Background: Maraviroc (MVC) is an allosteric CCR5 inhibitor used against HIV-1 infection. While MVC-resistant viruses have been identified in patients, it still remains incompletely known how they adjust their CD4 and CCR5 binding properties to resist MVC inhibition while preserving their replicative capacity. It is thought that they maintain high efficiency of receptor binding. To date however, information about the binding affinities to receptors for inhibitor-resistant HIV-1 remains limited. Results: Here, we show by means of viral envelope (gp120) binding experiments and virus-cell fusion kinetics that a MVC-resistant virus (MVC-Res) that had emerged as a dominant viral quasispecies in a patient displays reduced affinities for CD4 and CCR5 either free or bound to MVC, as compared to its MVC-sensitive counterpart isolated before MVC therapy. An alanine insertion within the GPG motif (G310_P311insA) of the MVC-resistant gp120 V3 loop is responsible for the decreased CCR5 binding affinity, while impaired binding to CD4 is due to sequence changes outside V3. Molecular dynamics simulations of gp120 binding to CCR5 further emphasize that the Ala insertion alters the structure of the V3 tip and weakens interaction with CCR5 ECL2. Paradoxically, infection experiments on cells expressing high levels of CCR5 also showed that Ala allows MVC-Res to use CCR5 efficiently, thereby improving viral fusion and replication efficiencies. Actually, although we found that the V3 loop of MVC-Res is required for high levels of MVC resistance, other regions outside V3 are sufficient to confer a moderate level of resistance. These sequence changes outside V3, however, come with a replication cost, which is compensated for by the Ala insertion in V3. Conclusion: These results indicate that changes in the V3 loop of MVC-resistant viruses can augment the efficiency of CCR5-dependent steps of viral entry other than gp120 binding, thereby compensating for their decreased affinity for entry receptors and improving their fusion and replication efficiencies. This study thus sheds light on unsuspected mechanisms whereby MVC-resistant HIV-1 could emerge and grow in treated patients. [ABSTRACT FROM AUTHOR]

Spatial aggregation of different industrial facilities leads to simultaneous release of pollutant emissions. Our objective is to study cancer mortality risk associated with residence in the vicinity of pollutant factories. We used data on industries for year 2007 (3458 facilities). For the 8,098 Spanish towns, we defined a factor with 4 levels based on the number of factories in a radius of 2.5 km from the centroid of each town (industrial factor).We also used data of land cover use to approximate the percentage of municipal land used for industrial activities in each Spanish town (land-used variable). For both variables we fitted Poisson models with random terms to account for spatial variation. We estimated risk trends related with increasing number of factories or percentage of land used for industrial activities. We studied 33 cancer causes. For the industrial factor, 11 causes showed trend associated with increasing factor level. For the land use variable, 8 causes showed statistically significant risks. Almost all tumours related to the digestive system and the respiratory system showed increased risks. Thus mortality by these tumours could be associated to residence in towns nearby industrial areas with positive trend linked to increasing levels of industrial activity. [ABSTRACT FROM AUTHOR]

Maraviroc is a nonpeptidic small molecule human immunodeficiency virus type 1 (HIV-1) entry inhibitor that has just entered the therapeutic arsenal for the treatment of patients. We recently demonstrated that maraviroc binding to the HIV-1 coreceptor, CC chemokine receptor 5 (CCR5), prevents it from binding the chemokine CCL3 and the viral envelope glycoprotein gpl2O by an allosteric mechanism. However, incomplete knowledge of ligand-binding sites and the lack of CCR5 crystal structures have hampered an in-depth molecular understanding of how the inhibitor works. Here, we addressed these issues by combining site-directed mutagenesis (SDM) with homology modeling and docking. Six crystal structures of G-protein-coupled receptors were compared for their suitability for CCR5 modeling. All CCR5 models had equally good geometry, but that built from the recently reported dimeric structure of the other HIV-1 coreceptor CXCR4 bound to the peptide CVX15 (Protein Data Bank code 30E0) best agreed with the SDM data and discriminated CCR5 from non-CCR5 binders in a virtual screening approach. SDM and automated docking predicted that maraviroc inserts deeply in CCR5 transmembrane cavity where it can occupy three different binding sites, whereas CCL3 and gpl2O lie on distinct yet overlapped regions of the CCR5 extracellular loop 2. Data suggesting that the transmembrane cavity remains accessible for maraviroc in CCL3-bound and gpl2O-bound CCR5 help explain our previous observation that the inhibitor enhances dissociation of preformed ligand-CCR5 complexes. Finally, we identified residues in the predicted CCR5 dimer interface that are mandatory for gpl2O binding, suggesting that receptor dimerization might represent a target for new CCR5 entry inhibitors. [ABSTRACT FROM AUTHOR]

CC chemokine receptor 5 (CCR5) is a G-protein-coupled receptor for the chemokines CCL3, -4, and -5 and a coreceptor for entry of R5-tropic strains of human immunodeficiency virus type 1 (HIV-1) into CD4+ T-cells. We investigated the mechanisms whereby nonpeptidic, low molecular weight CCR5 ligands block HIV-1 entry and infection. Displacement binding assays and dissociation kinetics demonstrated that two of these molecules, i.e. TAK779 and maraviroc (MVC), inhibit CCL3 and the HIV-1 envelope glycoprotein gp120 binding to CCR5 by a noncompetitive and allosteric mechanism, supporting the view that they bind to regions of CCR5 distinct from the gp120- and CCL3-binding sites. We observed that TAK779 and MVC are full and weak inverse agonists for CCR5, respectively, indicating that they stabilize distinct CCR5 conformations with impaired abilities to activate G-proteins. Dissociation of [125I]CCL3 from CCR5 was accelerated by TAK779, to a lesser extent by MVC, and by GTP analogs, suggesting that inverse agonism contributes to allosteric inhibition of the chemokine binding to CCR5. TAK779 and MVC also promote dissociation of [35S]gp120 from CCR5 with an efficiency that correlates with their ability to act as inverse agonists. Displacement experiments revealed that affinities of MVC and TAK779 for the [35S]gp120-binding receptors are in the same range (IC50 ∼6.4 versus 22 nm), although we found that MVC is 100-fold more potent than TAK779 for inhibiting HIV infection. This suggests that allosteric CCR5 inhibitors not only act by blocking gp120 binding but also alter distinct steps of CCR5 usage in the course of HIV infection. [ABSTRACT FROM AUTHOR]

The literature differentiates between two domains of machismo: traditional machismo and caballerismo. Research has largely focused on measuring machismo among English speakers. We evaluated whether Estrada’s (2011) 2-factor model of machismo was invariant across language (English vs. a direct Spanish translation). A series of multigroup confirmatory factor analyses were conducted between respondents who completed the survey in English (n = 428) and Spanish (n = 102). Analyses suggested the hypothesized 2-factor model did not fit across language groups. While the traditional 2-factor structure emerged in the English language data, exploratory factor analysis indicated a 3-factor structure of machismo among Spanish-speaking respondents. One of the new factors (inherent machismo), among Spanish-speaking respondents, was associated with internalized heterosexism, suggesting that the new factor structure may capture the belief that masculine men are superior. These findings suggest there is a need for the development of culturally appropriate Spanish language assessment. [ABSTRACT FROM AUTHOR]

An abstract of the article "Allosteric Regulation by Non Peptidic, Low Molecular Weight Compounds of CCR5 Coupling to G-Poteins and Iteraction Wth GP 120- Consequences on Inhibition of R5 HIV-1 Infection," by Patricia Rueda, Javier Garcia-Perez, Isabelle Staropoli, Esther Kellenberger, Jose Alcami, Fernando Arenzana-Seisdedos and Bernard Lagane is presented.

The requirement of human immunodeficiency virus (HIV)-induced CCR5 activation for infection by R5 HIV type 1 (HIV-1) strains remains controversial. Ectopic CCR5 expression in CD4[sup +]-transformed cells or pharmacological inhibition of G[sub α]i proteins coupled to CCR5 left unsolved whether CCR5-dependent cell activation is necessary for the HIV life cycle. In this study, we investigated the role played by HIV-induced CCR5dependent cell signaling during infection of primary CD4-expressing leukocytes. Using lentiviral vectors, we restored CCR5 expression in T lymphocytes and macrophages from individuals carrying the homozygous 32-bp deletion of the CCR5 gene (ccr5 Δ32/Δ32). Expression of wild-type (wt) CCR5 in ccr5 Δ32/Δ32 cells permitted infection by R5 HIV isolates. We assessed the capacity of a CCR5 derivative carrying a mutated DRY motif (CCR5-R126N) in the second intracellular loop to work as an HIV-1 coreceptor. The R126N mutation is known to disable G protein coupling and agonist-induced signal transduction through CCR5 and other G proteincoupled receptors. Despite its inability to promote either intracellular calcium mobilization or cell chemotaxis, the inactive CCR5-R126N mutant provided full coreceptor function to several R5 HIV-1 isolates in primary cells as efficiently as wt CCR5. We conclude that in a primary, CCR5-reconstituted CD4[sup +] cell environment, G protein signaling is dispensable for R5 HIV-1 isolates to actively infect primary CD4[sup +] T lymphocytes or macrophages. [ABSTRACT FROM AUTHOR]

HIV-1 infects CD4 T lymphocytes (CD4TL) through binding the chemokine receptors CCR5 or CXCR4. CXCR4-using viruses are considered more pathogenic, linked to accelerated depletion of CD4TL and progression to AIDS. However, counterexamples to this paradigm are common, suggesting heterogeneity in the virulence of CXCR4-using viruses. Here, we investigated the role of the CXCR4 chemokine CXCL12 as a driving force behind virus virulence. In vitro, CXCL12 prevents HIV-1 from binding CXCR4 and entering CD4TL, but its role in HIV-1 transmission and propagation remains speculative. Through analysis of thirty envelope glycoproteins (Envs) from patients at different stages of infection, mostly treatment-naïve, we first interrogated whether sensitivity of viruses to inhibition by CXCL12 varies over time in infection. Results show that Envs resistant (RES) to CXCL12 are frequent in patients experiencing low CD4TL levels, most often late in infection, only rarely at the time of primary infection. Sensitivity assays to soluble CD4 or broadly neutralizing antibodies further showed that RES Envs adopt a more closed conformation with distinct antigenicity, compared to CXCL12-sensitive (SENS) Envs. At the level of the host cell, our results suggest that resistance is not due to improved fusion or binding to CD4, but owes to viruses using particular CXCR4 molecules weakly accessible to CXCL12. We finally asked whether the low CD4TL levels in patients are related to increased pathogenicity of RES viruses. Resistance actually provides viruses with an enhanced capacity to enter naive CD4TL when surrounded by CXCL12, which mirrors their situation in lymphoid organs, and to deplete bystander activated effector memory cells. Therefore, RES viruses seem more likely to deregulate CD4TL homeostasis. This work improves our understanding of the pathophysiology and the transmission of HIV-1 and suggests that RES viruses' receptors could represent new therapeutic targets to help prevent CD4TL depletion in HIV+ patients on cART., Competing Interests: The authors have declared that no competing interests exist.

CCR5 plays immune functions and is the coreceptor for R5 HIV-1 strains. It exists in diverse conformations and oligomerization states. We interrogated the significance of the CCR5 structural diversity on HIV-1 infection. We show that envelope glycoproteins (gp120s) from different HIV-1 strains exhibit divergent binding levels to CCR5 on cell lines and primary cells, but not to CD4 or the CD4i monoclonal antibody E51. This owed to differential binding of the gp120s to different CCR5 populations, which exist in varying quantities at the cell surface and are differentially expressed between different cell types. Some, but not all, of these populations are antigenically distinct conformations of the coreceptor. The different binding levels of gp120s also correspond to differences in their capacity to bind CCR5 dimers/oligomers. Mutating the CCR5 dimerization interface changed conformation of the CCR5 homodimers and modulated differentially the binding of distinct gp120s. Env-pseudotyped viruses also use particular CCR5 conformations for entry, which may differ between different viruses and represent a subset of those binding gp120s. In particular, even if gp120s can bind both CCR5 monomers and oligomers, impairment of CCR5 oligomerization improved viral entry, suggesting that HIV-1 prefers monomers for entry. From a functional standpoint, we illustrate that the nature of the CCR5 molecules to which gp120/HIV-1 binds shapes sensitivity to inhibition by CCR5 ligands and cellular tropism. Differences exist in the CCR5 populations between T-cells and macrophages, and this is associated with differential capacity to bind gp120s and to support viral entry. In macrophages, CCR5 structural plasticity is critical for entry of blood-derived R5 isolates, which, in contrast to prototypical M-tropic strains from brain tissues, cannot benefit from enhanced affinity for CD4. Collectively, our results support a role for CCR5 heterogeneity in diversifying the phenotypic properties of HIV-1 isolates and provide new clues for development of CCR5-targeting drugs., Competing Interests: The authors have declared that no competing interests exist.