The influence of partner appearance in the assessment of a person with obesity: an experimental study.

PURPOSE: This study analyzes whether knowing that a male with obesity has a romantic relationship with a normal weight woman improves impressions about him. METHODS: An online experiment was conducted with a sample of 3024 adult participants (1828 women and 1196 men) with a mean age of 36.11 (SD = 13.49). Each participant was shown two photographs: one of a male target with obesity and one of his female partner (who had either normal weight or obesity depending on the condition). The respondents' sex was added as a fixed factor into the analyses. Physical attractiveness was rated using an item with a scale ranging from 0 to 100. Competence, warmth, and morality were measured using a 17-item adjective list. RESULTS: The target was assessed as more attractive when he had a partner with normal weight (F(1, 3009) = 4.85, p = .028, [Formula: see text] = .002), and was also given higher scores for competence (F(1, 3009) = 4.93, p = .026, [Formula: see text] = .002), warmth (F(1, 3009) = 4.32, p = .038, [Formula: see text] = .001), and morality (F(1, 3009) = 11.16, p = .001, [Formula: see text] = .004). There was a significant interaction between partner weight and the respondents' sex for physical attractiveness, as the difference between the scores in each condition was only significant for women. CONCLUSION: It is possible that women perceived that the male target who had a normal weight partner had a higher status or some hidden quality besides his physical appearance, and thus rated him as more attractive. LEVEL OF EVIDENCE: Level I, experimental study.

The effect of personal and group discrimination on the subjective well-being of people with mental illness: the role of internalized stigma and collective action intention.

The goal of this study is to test a model in which personal discrimination predicts internalized stigma, while group discrimination predicts a greater willingness to engage in collective action. Internalized stigma and collective action, in turn, are associated to positive and negative affect. A cross-sectional study with 213 people with mental illness was conducted. The model was tested using path analysis. Although the data supported the model, its fit was not sufficiently good. A respecified model, in which a direct path from collective action to internalized stigma was added, showed a good fit. Personal and group discrimination appear to impact subjective well-being through two different paths: the internalization of stigma and collective action intentions, respectively. These two paths, however, are not completely independent, as collective action predicts a lower internalization of stigma. Thus, collective action appears as an important tool to reduce internalized stigma and improve subjective well-being. Future interventions to reduce the impact of stigma should fight the internalization of stigma and promote collective action are suggested.

NYVAC immunization induces polyfunctional HIV-specific T-cell responses in chronically-infected, ART-treated HIV patients.

We report the results of the Theravac-01 phase I trial, which was conducted to evaluate the safety and immunogenicity of a poxvirus-based vector, NYVAC, expressing Gag, Pol, Nef, and Env from an HIV clade B isolate. NYVAC-B vaccine was injected intra-muscularly into ten HIV-infected patients successfully treated with antiretroviral therapy, twice on day 0 and again at week 4. Safety and immunogenicity were monitored for 48 weeks. HIV-specific T-cell responses following immunization were quantitatively analyzed using an IFN-γ ELISPOT assay and qualitatively characterized for their functional profile (including multiple cytokines secretion plus cytotoxic and proliferation capacity) by polychromatic flow cytometry. Our results indicate that the NYVAC-B vaccine is safe and highly immunogenic, as indicated by increased HIV-specific T-cell responses in virtually all vaccinees. Interestingly, both an expansion of preexisting T-cell responses, and the appearance of newly detected HIV-specific CD4(+) and CD8(+) T-cell responses were observed. Furthermore, immunization mostly induced an increase in Gag-specific T-cell responses. In conclusion, NYVAC-B immunization induces broad, vigorous, and polyfunctional HIV-specific T-cell responses, suggesting that poxvirus-based vaccine regimens may be instrumental in the therapeutic HIV vaccine field.

Mutations conferring resistance to viral DNA polymerase inhibitors in camelpox virus give different drug-susceptibility profiles in vaccinia virus.

Cidofovir or (S)-HPMPC is one of the three antiviral drugs that might be used for the treatment of orthopoxvirus infections. (S)-HPMPC and its 2,6-diaminopurine counterpart, (S)-HPMPDAP, have been described to select, in vitro, for drug resistance mutations in the viral DNA polymerase (E9L) gene of vaccinia virus (VACV). Here, to extend our knowledge of drug resistance development among orthopoxviruses, we selected, in vitro, camelpox viruses (CMLV) resistant to (S)-HPMPDAP and identified a single amino acid change, T831I, and a double mutation, A314V+A684V, within E9L. The production of recombinant CMLV and VACV carrying these amino acid substitutions (T831I, A314V, or A314V+A684V) demonstrated clearly their involvement in conferring reduced sensitivity to viral DNA polymerase inhibitors, including (S)-HPMPDAP. Both CMLV and VACV harboring the A314V change showed comparable drug-susceptibility profiles to various antivirals and similar impairments in viral growth. In contrast, the single change T831I and the double change A314V+A684V in VACV were responsible for increased levels of drug resistance and for cross-resistance to viral DNA polymerase antivirals that were not observed with their CMLV counterparts. Each amino acid change accounted for an attenuated phenotype of VACV in vivo. Modeling of E9L suggested that the T→I change at position 831 might abolish hydrogen bonds between E9L and the DNA backbone and have a direct impact on the incorporation of the acyclic nucleoside phosphonates. Our findings demonstrate that drug-resistance development in two related orthopoxvirus species may impact drug-susceptibility profiles and viral fitness differently.

Deletion of major nonessential genomic regions in the vaccinia virus Lister strain enhances attenuation without altering vaccine efficacy in mice.

The vaccinia virus (VACV) Lister strain was one of the vaccine strains that enabled smallpox eradication. Although the strain is most often harmless, there have been numerous incidents of mild to life-threatening accidents with this strain and others. In an attempt to further attenuate the Lister strain, we investigated the role of 5 genomic regions known to be deleted in the modified VACV Ankara (MVA) genome in virulence in immunodeficient mice, immunogenicity in immunocompetent mice, and vaccine efficacy in a cowpox virus challenge model. Lister mutants were constructed so as to delete each of the 5 regions or various combinations of these regions. All of the mutants replicated efficiently in tissue culture except region I mutants, which multiplied more poorly in human cells than the parental strain. Mutants with single deletions were not attenuated or only moderately so in athymic nude mice. Mutants with multiple deletions were more highly attenuated than those with single deletions. Deleting regions II, III, and V together resulted in total attenuation for nude mice and partial attenuation for SCID mice. In immunocompetent mice, the Lister deletion mutants induced VACV specific humoral responses equivalent to those of the parental strain but in some cases lower cell-mediated immune responses. All of the highly attenuated mutants protected mice from a severe cowpox virus challenge at low vaccine doses. The data suggest that several of the Lister mutants combining multiple deletions could be used in smallpox vaccination or as live virus vectors at doses equivalent to those used for the traditional vaccine while displaying increased safety.

Consequences of Perceived Personal and Group Discrimination against People with Hearing and Visual Impairments.

The main objective of this study was to examine the consequences of perceived discrimination in people with hearing and visual impairments. Using path analysis, we attempted to validate a multigroup model in which perceived personal discrimination is associated with internalization of stigma, which, in turn, is negatively related to self-esteem; conversely, perceived discrimination against the in-group contributes to enhanced group identification, which promotes the intention to engage in collective action, which, in turn, has beneficial effects on self-esteem. The sample consisted of a total of 200 Spanish-speaking participants, of whom 104 had hearing impairments and 96 had visual impairments. The results showed that the proposed multigroup model fit the data well. For both groups, internalized stigma played a mediating role in the relationship between perceived personal discrimination and self-esteem. However, the pathway from group discrimination to self-esteem was not as clearly supported by the data. The results are interpreted from a psychosocial perspective and may contribute to design interventions aimed at improving the well-being of people with hearing and visual impairments.

Differential activation profiles of Crimean-Congo hemorrhagic fever virus- and Dugbe virus-infected antigen-presenting cells.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic, tick-borne member of the family Bunyaviridae and the genus Nairovirus. To better elucidate the pathogenesis of CCHFV, we analysed the host innate immune response induced in antigen-presenting cells (APCs) infected in vitro by CCHFV. Monocyte-derived dendritic cells (DCs) and macrophages (MPs) were both shown to be permissive for CCHFV and to replicate the virus, as monitored by genomic and antigenomic strand quantification. Virus replication was, however, controlled, corroborating an efficient alpha interferon-induced response. The upregulation of CD-83 and CD-86 indicated that CCHFV induced a partial maturation of DCs, which were also shown to activate the secretion of interleukin (IL)-6 and IL-8, but no tumour necrosis factor alpha (TNF-alpha). On the other hand, in MPs, CCHFV infection elicited a high IL-6 and TNF-alpha response and a moderate chemokine response. Nevertheless, when we compared these APC responses with those seen after infection with Dugbe virus (DUGV), a mildly pathogenic virus genetically close to CCHFV, we found that, in spite of some similarities, DUGV induced a higher cytokine/chemokine response in MPs. These results suggest that CCHFV is able to inhibit the activation of inflammatory mediators selectively in infection in vitro and that these differences could be relevant in pathogenesis.

Perceived discrimination and self-esteem among family caregivers of children with autism spectrum disorders (ASD) and children with intellectual disabilities (ID) in Spain: The mediational role of affiliate stigma and social support.

BACKGROUND: People with autism spectrum disorders (ASD) and people with intellectual disabilities (ID) are stigmatized, and therefore discriminated against worldwide and, on many occasions, this stigma and discrimination are expanded to include their family caregivers. The main objective of this research was to examine the consequences of perceived discrimination on family caregivers of children with ASD and children with ID. METHODS: The sample consisted of 109 Spanish caregivers of children with ASD and 83 caregivers of children with ID. They completed four questionnaires: Multidimensional Perceived Discrimination Scale, Affiliate Stigma Scale, Social Support Questionnaire and Rosenberg Self-Esteem Scale. RESULTS: Using path analysis, we found support for a model in which personal discrimination perceived by caregivers was positively associated with affiliate stigma, which, in turn, was negatively related to caregivers' self-esteem. The model also shows the total mediational role of affiliate stigma in the association between perceived discrimination and self-esteem and the partial mediational role that social support plays in the association between perceived discrimination and caregivers' self-esteem. CONCLUSIONS: Caregivers' perceived discrimination negatively influences caregivers' self-esteem, but this relationship is mediated by both affiliate stigma (totally) and social support (partially). These results have theoretical and practical implications and may contribute to improving the quality of life of parents of children with ASD and ID that in turn would result in an improvement of the quality of life of their children.

[Financial fraud and health: a qualitative approach]. / Fraudes financieros, salud y calidad de vida: un estudio cualitativo.

During the economic crisis, developed countries have experienced financial fraud, with effects on the physical and mental health of the people affected, and on social domains. Based on the theoretical framework in literature reviews and in quantitative studies, this paper aims to obtain evidence on the effects of financial fraud on health and on the family and social environments of those affected. An intentional sample of 32 people affected by abusive and multi-currency mortgages, preferred and swap stock in Madrid was approached. In-depth interviews were conducted, and the resulting data was analysed using content analysis. Fraud-affected individuals had conditions of age, sex, educational level and occupations that possibly allowed them to accumulate economic resources throughout the course of their lives and, predictably in many cases, to take out fraudulent financial products, based on trust in the financial institutions. Financial fraud has led to the emergence of various processes of anomia and adverse health effects. The consequences on health were physical ailments (symptoms and diseases in various systems and parts of the body) and mental disorders (anxiety, depression, suicidal ideation), all affecting lifestyles, behaviour and personal and social relationships, both in affected individuals and their families. The increase in the use of medical drugs and health services serves as a final corollary to the imbalances on the affected people's health. Individuals and the Spanish society demand public health policy measures to mitigate the effects on health and the recovery of their confidence in the banking and political system.

How to cope with disabilities: Development and psychometric properties of the Coping With Disability Difficulties Scale (CDDS).

PURPOSE/OBJECTIVE: The aim of this study was to develop and test the psychometric properties of the Coping With Disability Difficulties Scale (CDDS), a scale to measure the coping strategies used by people with disabilities to face the disability-related difficulties (caused by both disability itself and by stigma) they encounter in their daily lives. METHOD/DESIGN: An initial pool of 110 items was developed based on previous literature and the results of a qualitative study using semistructured interviews. The psychometric characteristics of the CDDS were examined in 3 samples of people with disabilities (each of which included participants with physical, visual, and hearing impairments; total N = 590). RESULTS: A final scale of 17 items was obtained. The factor structure of the CDDS was tested and replicated with an adequate fit (root mean square error of approximation [RMSEA] = 0.056; goodness-of-fit index [GFI] = 0.98; comparative fit index [CFI] = 0.98) using confirmatory factor analysis. The internal consistency of the 4 factors (positive thinking, social sensitization and support, adaptation, and avoidance) was adequate to excellent (with alphas ranging from .68 to .86). CONCLUSIONS/IMPLICATIONS: To the authors' knowledge, this is the first coping scale that is specifically designed for people with disabilities, and it can be highly useful for both research and applied purposes. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Inhibition of vaccinia virus replication by two small interfering RNAs targeting B1R and G7L genes and their synergistic combination with cidofovir.

In view of the threat of the potential use of variola virus in a terrorist attack, considerable efforts have been performed to develop new antiviral strategies against orthopoxviruses. Here we report on the use of RNA interference, either alone or in combination with cidofovir, as an approach to inhibit orthopoxvirus replication. Two selected small interfering RNAs (siRNAs), named siB1R-2 and siG7L-1, and a previously reported siRNA, i.e., siD5R-2 (which targets the viral D5R mRNA), were evaluated for antiviral activity against vaccinia virus (VACV) by plaque reduction and virus yield assays. siB1R-2 and siG7L-1, administered before or after viral infection, reduced VACV replication by more than 90%. Also, these two siRNAs decreased monkeypox virus replication by 95% at a concentration of 1 nM. siB1R-2 and siG7L-1 were demonstrated to specifically silence their corresponding transcripts, i.e., B1R and G7L mRNAs, without induction of a beta interferon response. Strong synergistic effects were observed when siB1R-2, siG7L-1, or siD5R-2 was combined with cidofovir. In addition, the antiviral activities of these three siRNAs were evaluated against VACV resistant to cidofovir and other acyclic nucleoside phosphonates. siG7L-1 and siD5R-2 remained active against four of five VACV mutants, while siB1R-2 showed activity against only one of the mutants. Our results showed that siRNAs are potent inhibitory agents in vitro, not only against wild-type VACV but also against several cidofovir-resistant VACV. Furthermore, we showed that a combined therapy using siRNA and cidofovir may be useful in the treatment of poxvirus infections.

Consequences of perceived personal and group discrimination against people with physical disabilities.

OBJECTIVE: To analyze the consequences for self-esteem of perceived discrimination against people with physical disabilities, as individuals and as a group. METHOD: A structural model based on the psychosocial literature was tested in a sample of 288 Spanish participants with different degrees of physical disability. This model predicted that personal perceived discrimination would be associated with the internalization of stigma that, in turn, would be negatively associated with the self-esteem of people with physical disabilities. On the other hand, group perceived discrimination, was predicted to enhance group identification and promote intention to contribute to collective action and hence have a beneficial effect on the self-esteem of people with physical disabilities. RESULTS: The model provided a good fit to the data. The relationship between personal discrimination and the self-esteem of people with physical disabilities was completely mediated by internalized stigma. The model also showed that group perceived discrimination had only an indirect effect on self-esteem. CONCLUSION: This research makes two main contributions. From a theoretical perspective we found that perceived personal and group discrimination influence self-esteem through different paths. From an applied point of view, our results may contribute to the design of interventions to enhance the quality of life of people with physical disabilities. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Specific inhibition of orthopoxvirus replication by a small interfering RNA targeting the D5R gene.

BACKGROUND: Concerns about the potential use of smallpox in bioterrorism have stimulated interest in the development of novel antiviral treatments. Currently, there are no effective therapies against smallpox and new treatment strategies are greatly needed. METHODS: In this study, specifically designed small interfering RNAs (siRNAs), targeting five proteins essential for orthopoxvirus replication, were investigated for their ability to inhibit vaccinia virus strain Western Reserve (VACVWR) replication. RESULTS: Among these siRNAs, 100 nM siD5R-2, an siRNA targeting the D5 protein, decreased VACVWR replication up to 90% when used either prophylactically or therapeutically in human lung carcinoma A549 cells. This siRNA induced a striking concentration-dependent inhibition of VACVWR replication and a prolonged prophylactic antiviral effect that lasted for 72 h, at a concentration of 100 nM. Confocal microscopy of Alexa-siD5R-2-treated VACVWR-infected cells confirmed a decrease in viral replication. Furthermore, siD5R-2 was shown to specifically reduce the D5R mRNA and protein expression using real-time reverse transcriptase-PCR and western blotting analysis, without inducing interferon-13 in A549 cells. We also demonstrated the antiviral potency of siD5R-2 against different pathogenic orthopoxviruses, such as cowpox and monkeypox viruses, which were inhibited up to 70% at the lowest concentration (1 nM) tested. Finally, siD5R-2 showed antiviral effects in VACVWR-infected human keratinocyte and fibroblast cell cultures. CONCLUSIONS: These results suggest that siD5R-2 could be a potential candidate to treat poxvirus infections.

Specific targeting of the F13L protein by ST-246 affects orthopoxvirus production differently.

BACKGROUND: ST-246 is a potent anti-orthopoxviral molecule targeting the F13L protein of vaccinia virus, which is involved in the wrapping of viruses. The discrepancy in sensitivities of several orthopoxviruses to ST-246 has raised questions about potential differences in their replicative cycles and/or the presence of another drug target. METHODS: Density gradients were used to evaluate the differences between the viral cycles of vaccinia, cowpox and camelpox viruses. Also, to investigate if ST-246 inhibits a single target, we compared its activity to that of small interfering RNAs designed to silence the F13L gene (siF13Ls). RESULTS: We showed that the spread of vaccinia virus involved both intracellular and extracellular enveloped viruses, whereas both cowpox and camelpox viruses seemed to propagate via non-enveloped intracellular forms and cell-associated viral particles. Although ST-246 exerted a clear antiviral activity by interfering with the egress of the virus from infected cells, we observed that cowpox and camelpox viruses, in contrast to vaccinia virus, could be directed towards a lytic cycle under ST-246 treatment. We specifically knocked down the F13L transcripts of vaccinia and camelpox viruses by > 85%, reduced virus progeny by 90% and showed that siF13Ls affect camelpox and vaccinia virus propagation differently. Flow cytometry data validated that ST-246 interfered with the activity of the F13L protein, whereas siF13Ls silenced the F13L gene. CONCLUSIONS: Our observations support that vaccinia, cowpox and camelpox viruses exhibit different levels of sensitivity to ST-246 because of dissimilarities between their ways of propagation, and provide a better understanding of the mode of action of ST-246.

Perceived Discrimination and Emotional Reactions in People with Different Types of Disabilities: A Qualitative Approach.

The purpose of this study is to assess the discourse of people with disabilities regarding their perception of discrimination and stigma. Semi-structured interviews were conducted with ten adults with physical disabilities, ten with hearing impairments and seven with visual impairments. The agreement between the coders showed an excellent reliability for all three groups, with kappa coefficients between .82 and .96. Differences were assessed between the three groups regarding the types of discrimination they experienced and their most frequent emotional responses. People with physical disabilities mainly reported being stared at, undervalued, and subtly discriminated at work, whereas people with hearing impairments mainly reported encountering barriers in leisure activities, and people with visual impairments spoke of a lack of equal opportunities, mockery and/or bullying, and overprotection. Regarding their emotional reactions, people with physical disabilities mainly reported feeling anxious and depressed, whereas people with hearing impairments reported feeling helpless, and people with visual impairments reported feeling anger and self-pity. Findings are relevant to guide future research and interventions on the stigma of disability.

Activity of the anti-orthopoxvirus compound ST-246 against vaccinia, cowpox and camelpox viruses in cell monolayers and organotypic raft cultures.

BACKGROUND: The potential use of variola virus as a biological weapon has renewed efforts in the development of antiviral agents against orthopoxviruses. ST-246 [4-trifluoromethyl-N-(3,3a,4,4a,5,5a,6,6a-octahydro-1,3-di oxo-4,6-ethenocycloprop [f]isoindol-2(1 H)-yl)-benzamide] is an anti-orthopoxvirus compound active against several orthopoxviruses including vaccinia virus (VV), cowpox virus (CPV), camelpox virus (CMLV), ectromelia virus (ECTV) and variola virus in cell culture. The compound has been shown to inhibit the release of extracellular virus by targeting the F13L W protein and to protect mice from W, CPV and ECTV orthopoxvirus-induced disease. METHODS: The antiviral activity of ST-246 was assessed against extracellular and intracellular W, CPV and CMLV production in human embryonic lung (HEL) fibroblasts and primary human keratinocyte (PHK) cell monolayers, as well as in three-dimensional raft cultures. RESULTS: ST-246 inhibited preferentially the production of extracellular virus compared with intracellular virus production in HEL and PHK cells (for W) and in PHK cells (for CMLV). In organotypic epithelial raft cultures, ST-246 at 20 microg/ml inhibited extracellular W and CMLV production by 6 logs, whereas intracellular virus yield was reduced by 2 logs. In the case of CPV, both extracellular and intracellular virus production were completely inhibited by ST-246 at 20 microg/ml. Histological sections of the infected rafts, treated with increasing amounts of drug, confirmed the antiviral activity of ST-246: the epithelium was protected and there was no evidence of viral infection. Electron microscopic examination confirmed the absence of intracellular enveloped virus forms in W-, CPV- and CMLV-infected cells treated with 10 microg/ml of ST-246. CONCLUSIONS: These data indicate that ST-246 is a potent anti-orthopoxvirus compound; the mode of inhibition is dependent on the virus and cell type.

[Healthcare response to bioterrorism]. / La réponse sanitaire au risque biologique terroriste.

Bioterrorists seek to use highly virulent pathogens to cause social and economic disruption. Historical agents such as anthrax, Yersinia pestis and botulinum toxin can easily be produced, whereas others such as hemorragic fever virus require much more sophisticated infrastructure and government-scale resources. In the near future, with the spread of new biotechnologies, bioterrorists may produce new transgenic pathogens. Epidemiological surveillance and diagnostic capacities should thus be more reactive. Real-time epidemiological surveillance together with a network of high-security laboratories would enable us to cope effectively with new infectious diseases that emerge naturally or through human manipulation. Clinical and research skills should be merged in infection-control centers, bringing a new dynamic to microbiology.

Subtle and blatant perceived discrimination and well-being in lesbians and gay men in Spain: The role of social support.

BACKGROUND: The situation of lesbians and gay men (LGs) in Spain has improved significantly in recent decades. However, Spanish society still exhibits prejudice and discrimination. The current study pursues three main goals: 1) to analyse the extent to which LGs perceive blatant and subtle discrimination, 2) to explore the relationship between perceived discrimination and LGs’ psychological and subjective well-being, and 3) to analyse the possible mediational role of social support in reducing the negative influence of perceived discrimination on well-being. METHOD: The sample comprised 237 lesbians and 232 gay men. RESULTS: The results show higher perceived subtle than blatant discrimination, and that subtle discrimination affects LGs’ well-being more negatively than blatant discrimination. Results show that social support helps to alleviate the negative effects of discrimination on well-being. CONCLUSIONS: These results are important and may contribute to the design of interventions to improve the well-being of lesbians and gay men.