The evolutionary psychological approach links evolved mechanisms of disease-avoidance to prejudices against individuals perceived as a threat to health. Perceived vulnerability to disease works as an ...adaptive strategy which explains why individuals perceived as a source of contagion are avoided. The self-report Perceived Vulnerability to Disease Questionnaire, PVDQ, is one of the most widely used to measure subjective vulnerability to disease, however, neither test–retest reliability has been studied nor has factor structure been confirmed so far in this questionnaire. In the present study, a sample of 878 participants completed the PVDQ. Subsamples also completed different scales measuring hypochondria, health fears, beliefs and attitudes, personality traits, locus of control and obsessions, in order to obtain concurrent and discriminant validity. Item relationships, Exploratory and Confirmatory Factor Analyses, reliability and validity analyses were all obtained. Our results highlight two strong, valid, and stable factors: Perceived Infectability and Germ Aversion. However, the Germ Aversion factor only showed adequate confirmatory factorial indices and high temporal stability when items 11 and 13 were removed, but failed to obtain acceptable internal consistency. Gender differences have also been studied in the present work. Implications and directions for future research in the improvement of PVDQ are discussed.
•Our study confirms two factors in PVDQ: Perceived Infectability and Germ Aversion.•Construct validity and temporal stability of the two factors are presented.•Gender differences in both factors are shown.•Explanations, directions and future research of Germ Aversion limitations are proposed.
NMR conformational analysis of a hydroxyethylamine peptide isostere developed as an aspartic protease inhibitor shows that it is a flexible architecture. Cyclization to form pyrrolidines, ...piperidines, or morpholines results in a preorganization of the whole system in solution. The resulting conformation is similar to the conformation of the inhibitor in the active site of BACE-1. This entropic gain results in increased affinity for the enzyme when compared with the acyclic system. For morpholines 27 and 29, the combination of steric and electronic factors is exploited to orient substituents toward S1, S1′, and S2′ pockets both in the solution and in the bound states. These highly preorganized molecules proved to be the most potent compounds of the series. Additionally, the morpholines, unlike the pyrrolidine and piperidine analogues, have been found to be brain penetrant BACE-1 inhibitors.
Current research on the influence of environmental and physicochemical factors in shaping the soil bacterial structure has seldom been approached from a pedological perspective. We studied the ...bacterial communities of eight soils selected along a pedogenic gradient at the local scale in a Mediterranean calcareous mountain (Sierra de María, SE Spain). The results showed that the relative abundance of Acidobacteria, Canditate division WPS-1, and Armatimonadetes decreased whereas that of Actinobacteria, Bacteroidetes, and Proteobacteria increased from the less-developed soils (Leptosol) to more-developed soils (Luvisol). This bacterial distribution pattern was also positively correlated with soil-quality parameters such as organic C, water-stable aggregates, porosity, moisture, and acidity. In addition, at a lower taxonomic level, the abundance of Acidobacteria Gp4, Armatimonadetes_gp4, Solirubrobacter, Microvirga, Terrimonas, and Nocardioides paralleled soil development and quality. Therefore, our work indicates that the composition of bacterial populations changes with pedogenesis, which could be considered a factor influencing the communities according to the environmental and physicochemical conditions during the soil formation.
Purpose To determine the association between the number of flares systemic lupus erythematosus (SLE) patients experience and damage accrual, independently of other known risk factors. Methods SLE ...patients (34 centres, nine Latin American countries) with a recent diagnosis (≤2 years) and ≥3 evaluations were studied. Disease activity was ascertained with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and damage with the SLICC/ACR Damage Index (SDI). Flare was defined as an increase ≥4 points in the SLEDAI between two study visits. An ambidirectional case- crossover design was used to determine the association between the number of flares and damage accrual. Results 901 patients were eligible for the study; 500 of them (55.5%) experienced at least one flare, being the mean number of flares 0.9 (SD: 1.0). 574 intervals from 251 patients were included in the case-crossover design since they have case and control intervals, whereas, the remaining patients did not. Their mean age at diagnosis was 27.9 years (SD: 11.1), 213 (84.9%) were women. The mean baseline SDI and SLEDAI were 1.3 (1.3) and 13.6 (8.1), respectively. Other features were comparable to those of the entire sample. After adjusting for possible confounding variables, the number of flares, regardless of their severity, was associated with damage accrual (SDI) OR 2.05, 95% CI 1.43 to 2.94, p<0.001 (OR 2.62, 95% CI 1.31 to 5.24, p=0.006 for severe and OR 1.91, 95% CI 1.28 to 2.83, p=0.001for mild-moderate). Conclusions The number of flares patients experience, regardless of their severity, increases the risk of damage accrual, independently of other known risk factors.
Economies across the globe were brought to their knees due to lockdowns and social restriction measures to contain the spread of the SARS-CoV-2, despite the quick switch to remote working. This ...downfall may be partially explained by the “water cooler effect”, which holds that higher levels of social interaction lead to higher productivity due to a boost in people’s mood. Somewhat paradoxically, however, there are reports of increased productivity in the remote working scenario. Here we address quantitatively this issue using a variety of experimental findings of social psychology that address the interplay between mood, social interaction and productivity to set forth an agent-based model for a workplace composed of extrovert and introvert agent stereotypes that differ solely on their propensities to initiate a social interaction. We find that the effects of curtailing social interactions depend on the proportion of the stereotypes in the working group: while the social restriction measures always have a negative impact on the productivity of groups composed predominantly of introverts, they may actually improve the productivity of groups composed predominantly of extroverts. Our results offer a proof of concept that the paradox of productivity during quarantine can be explained by taking into account the distinct effects of the social distancing measures on extroverts and introverts.
Graphic abstract
Objective
To determine the influence of socioeconomic factors on disease activity in a Latin American (LA) early rheumatoid arthritis (RA) multinational inception cohort at baseline.
Methods
Clinical ...evaluation, ethnicity, socioeconomic status (SES), 4‐variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR), Health Assessment Questionnaire (HAQ) disability index (DI), and erosions were recorded in 1,093 patients with early RA (<1 year from onset). Multivariate analyses evaluated influences of sex, age, marital status, education, medical coverage, SES, and ethnicity on HAQ DI, DAS28‐ESR, and presence of erosions.
Results
Ethnicities included 43% Mestizo, 31% Caucasian, 19% African LA, 4% Amerindian, and 3% other. Fifty‐eight percent were of low/low‐middle SES, 42% had <8 years of education, 21% had no medical coverage, median disease duration was 6 months (25th, 75th percentiles 4, 9 months), median HAQ DI score was 1.25 (25th, 75th percentiles 0.63, 2.00), median DAS28‐ESR score was 6.2 (25th, 75th percentiles 4.9, 7.2), and 25% had erosions. Women and Mestizos, African LA, and Amerindians had earlier onset than men or Caucasians (P < 0.01). When adjusted by country, the analysis of covariance model showed that low/low‐middle SES, female sex, partial coverage, and older age were associated with worse HAQ DI scores; only low/low‐middle SES was associated with higher DAS28 scores. Statistically significant differences were found in HAQ DI and DAS28 scores between countries. When excluding country, low/low‐middle SES, female sex, and no coverage were associated with worse HAQ DI and DAS28 scores, whereas separated/divorced/widowed status was associated with worse HAQ DI scores and age was associated with worse DAS28 scores. Logistic regression showed that older age, no coverage, and the Amerindian and other ethnic groups were associated with erosions.
Conclusion
We compared early RA patients from the main LA ethnic groups. Our findings suggest that low/low‐middle SES is important in determining disease activity. A more genetic‐related background for erosions is possible.
As part of our ongoing efforts to identify novel ligands for the metabotropic glutamate 2 and 3 (mGlu2/3) receptors, we have incorporated substitution at the C3 and C4 positions of the ...(1S,2R,5R,6R)-2-amino-bicyclo3.1.0hexane-2,6-dicarboxylic acid scaffold to generate mGlu2/3 antagonists. Exploration of this structure–activity relationship (SAR) led to the identification of (1S,2R,3S,4S,5R,6R)-2-amino-3-(3,4-difluorophenyl)sulfanylmethyl-4-hydroxy-bicyclo3.1.0hexane-2,6-dicarboxylic acid hydrochloride (LY3020371·HCl, 19f), a potent, selective, and maximally efficacious mGlu2/3 antagonist. Further characterization of compound 19f binding to the human metabotropic 2 glutamate (hmGlu2) site was established by cocrystallization of this molecule with the amino terminal domain (ATD) of the hmGlu2 receptor protein. The resulting cocrystal structure revealed the specific ligand–protein interactions, which likely explain the high affinity of 19f for this site and support its functional mGlu2 antagonist pharmacology. Further characterization of 19f in vivo demonstrated an antidepressant-like signature in the mouse forced-swim test (mFST) assay when brain levels of this compound exceeded the cellular mGlu2 IC50 value.
A concise high-yielding route to synthetically useful 1,2-diaryl (and 1-alkyl-2-aryl) ethyl and propylamines in high enantiomeric purity is described. The key step of this route is the completely ...stereoselective addition of lithium (R)-ortho-(p-toluenesulfinyl)benzylic carbanions to (S)-N-p-toluenesulfinylimines, which takes place in very high or quantitative yields. N-Desulfinylation and C-desulfinylation of the resulting adducts can be achieved with no loss of optical purity employing conventional methods (TFA and Raney-Ni, respectively).
Reactions of enantiopure 2-p-tolylsulfinylcyclopent-2-en-1-one with cyclic nitrones afforded pyrrolo or azepine-fused cyclopentadisoxazolidines in high yields under mild conditions. Comparison of ...these results with those obtained with cyclopent-2-en-1-one as the dipolarophile shows that the sulfinyl group increases the reactivity of the enonic system and efficiently controls the π-facial and endo/exo selectivities of the cycloadditions, which are also dependent on the easy cycloreversion of the resulting compounds. Results obtained in reactions with other dipoles (benzonitrile oxides and those resulting from allenoate and PPh
3
) are also reported.
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