Clarifying the relationship between ostracism and relational devaluation.

We examine how three perspectives on relational devaluation relate to needs threat following ostracism. In two experiments with 179 first-year psychology students, distress was greatest when participants were ostracized without any prior throws, and distress decreased linearly with increasing prior inclusion. In Experiment 3, using 76 first-year psychology students, we manipulated expectations of exclusion and found expectations predicted distress following ostracism, suggesting ostracism's distress can be influenced by norm-based expectations of inclusion, and that progressive relational devaluation is not a necessary condition for ostracism's distress.

The effect of sampling methods on the apparent constituents of ink from the squid Sepioteuthis australis.

Results of experiments conducted on ink recovered from the squid Sepioteuthis australis indicate that there is no epinephrine or protein naturally present in the ink as it would be ejected in vivo. Protein content was effectively zero when ink was syringed from the duct end of the ink sac of freshly killed animals. By contrast, there were proteins in samples collected from dead specimens where ink was collected by a stripping method. From these samples, a single large molecular weight protein was identified as having tyrosinase activity. Digestion of syringed ink did not yield signs of melanin-bound proteins. Analysis of supernatants after centrifugation of squid ink consistently revealed the presence of DOPA, dopamine, and taurine, whereas epinephrine and nor-epinephrine were recorded from what was believed to be contaminated ink. Histological investigations of the ink sac revealed a compartmentalised glandular structure distal to the duct end. Closer observation of the glandular tissue showed that compartments increased in size as they matured and moved further into the lumen. It was concluded that the presence of epinephrine and tyrosinase (or a related protein) in the ink of S. australis could be attributed to rupturing of basal glandular compartments or contamination from other sources during the extraction process.

Pharmacokinetics of fexofenadine following LPS administration to rats.

The function and expression of drug transporters, including P-glycoprotein (P-gp) and organic-anion transporting polypeptides (Oatps), have been investigated but it is not well established how variables such as disease processes affect them. Fexofenadine is a substrate of these transporters and it was previously shown that its clearance is reduced in the rat isolated perfused liver following treatment with E.coli lipopolysaccharide (LPS). However, whether this translates to altered fexofenadine pharmacokinetics in vivo is yet to be established. E.coli LPS at 5 mg/kg or sterile saline (control) was injected intraperitoneally in rats. Oral or intravenous (IV) fexofenadine (10 mg/kg) was administered 24 h later and plasma and urine samples collected for pharmacokinetic analysis. LPS treatment did not significantly change the pharmacokinetics of IV fexofenadine, although there was a good correlation between weight loss and clearance suggesting reduced clearance in more severely affected animals. However, AUC(0-∞) of oral fexofenadine was a significantly higher in LPS-treated animals (13.9 ± 9.76 min · µg/ml) compared to controls (5.53 ± 1.12 min · µg/ml). In conclusion, LPS treatment increased the bioavailability of fexofenadine but did not affect other pharmacokinetic parameters. This is consistent with a reduction in hepatic Oatp and/or P-gp for a high extraction ratio drug such as fexofenadine.

A social comparison theory meta-analysis 60+ years on.

These meta-analyses of 60+ years of social comparison research focused on 2 issues: the choice of a comparison target (selection) and the effects of comparisons on self-evaluations, affect, and so forth (reaction). Selection studies offering 2 options (up or down) showed a strong preference (and no evidence of publication bias) for upward choices when there was no threat; there was no evidence for downward comparison as a dominant choice even when threatened. Selections became less differentiable when a lateral choice was also provided. For reaction studies, contrast was, by far, the dominant response to social comparison, with ability estimates most strongly affected. Moderator analyses, tests and adjustments for publication bias showed that contrast is stronger when the comparison involves varying participants' standing for ability (effect estimates, -0.75 to -0.65) and affect (-0.83 to -0.65). Novel personal attributes were subject to strong contrast for ability (-0.5 to -0.6) and affect (-0.6 to -0.7). Dissimilarity priming was associated with contrast (-0.44 to -0.27; no publication bias), consistent with Mussweiler (2003). Similarity priming provided modest support for Collins (1996) and Mussweiler (2003), with very weak assimilation effects, depending on the publication bias estimator. Studies including control groups indicated effects in response to upward and downward targets were comparable in size and contrastive. Limitations of the literature (e.g., small number of studies including no-comparison control conditions), unresolved issues, and why people choose to compare upward when the most likely result is self-deflating contrast are discussed. (PsycINFO Database Record

Inhibition of indoleamine 2,3-dioxygenase activity by fatty acids and prostaglandins: A structure function analysis.

Indoleamine 2,3-dioxygenase-1 (IDO-1) catalyses the first and rate-limiting step in the metabolism of L-tryptophan. Degradation of L-Trp leads to the production of several immunosuppressive metabolites, including N-formyl kynurenine and kynurenine (Kyn). Apart from a normal physiological role, IDO-1 has also been identified to play a crucial role in immune suppression and tumour induced tolerance. Indeed, many primary tumours express high levels of IDO-1 compared to normal cells of the same stroma. IDO-1 is accepted as being an inducible negative regulator of T cell viability, proliferation and activation. As such, IDO-1 has become a target of intense interest for pharmacological inhibition, for the treatment of cancer. We have previously demonstrated that AA and the prostaglandin metabolite, PGD2, repressed the IFNγ mediated activity of IDO-1 in THP-1 cells and human monocytes. In this study, we characterise the structure-function relationship of fatty acids and eicosanoids towards inhibition of IDO-1 activity in THP-1 cells and human monocytes. Using a commercial library of fatty acids, 55% of fatty acids inhibited IDO-1 activity. The activity of individual FAs was affected by chain length, number of double bonds and bond configuration. Interrogation of an AA derived eicosanoid library identified 13 PGs with significant inhibitory activity. A structure-function analysis revealed that the γ position of the cyclopentenone ring, double bond in the α-ß position of the cyclopentenone ring, the presence of multiple OH groups in the side arm and the addition of an ethanolamide group, significantly increased the inhibitory activity of the PGs. Based on this data we have identified the structure of two possible compounds that may be even more potent pharmacological repressors of IDO-1.

Physical factors affecting chloroquine binding to melanin.

Chloroquine is an antimalarial drug but is also prescribed for conditions such as rheumatoid arthritis. Long-term users risk toxic side effects, including retinopathy, thought to be caused by chloroquine accumulation on ocular melanin. Although the binding potential of chloroquine to melanin has been investigated previously, our study is the first to demonstrate clear links between chloroquine adsorption by melanin and system factors including temperature, pH, melanin type, and particle size. In the current work, two Sepia melanins were compared with bovine eye as a representative mammalian melanin. Increasing the surface anionic character due to a pH change from 4.7 to 7.4 increased each melanin's affinity for chloroquine. Although the chloroquine isotherms exhibited an apparently strong interaction with each melanin, isosteric heat analysis indicated a competitive interaction. Buffer solution cations competed effectively at low surface coverage; chloroquine adsorption occurs via buffer cation displacement and is promoted by temperature-influenced secondary structure swelling.

Persistent disability associated with ankle sprains: a prospective examination of an athletic population.

The purpose of this study was to examine a young athletic population to update the data regarding epidemiology and disability associated with ankle injuries. At the United States Military Academy, all cadets presenting with ankle injuries during a 2-month period were included in this prospective observational study. The initial evaluation included an extensive questionnaire, physical examination, and radiographs. Ankle sprain treatment included a supervised rehabilitation program. Subjects were reevaluated at 6 weeks and 6 months with subjective assessment, physical examination, and functional testing. The mean age for all subjects was 20 years (range, 17-24 years). There were 104 ankle injuries accounting for 23% of all injuries seen. There were 96 sprains, 7 fractures, and 1 contusion. Of the 96 sprains, 4 were predominately medial injuries, 76 were lateral, and 16 were syndesmosis sprains. Ninety-five percent had returned to sports activities by 6 weeks; however, 55% of these subjects reported loss of function or presence of intermittent pain, and 23% had a decrement of >20% in the lateral hop test when compared with the uninjured side. At 6 months, all subjects had returned to full activity; however, 40% reported residual symptoms and 2.5% had a decrement of >20% on the lateral hop test. Neither previous injury nor ligament laxity was predictive of chronic symptomatology. Furthermore, chronic dysfunction could not be predicted by the grade of sprain (grade I vs. II). The factor most predictive of residual symptoms was a syndesmosis sprain, regardless of grade. Syndesmosis sprains were most prevalent in collision sports. This study demonstrates that even though our knowledge and understanding of ankle sprains and rehabilitation of these injuries have progressed in the last 20 years, chronic ankle dysfunction continues to be a prevalent problem. The early return to sports occurs after almost every ankle sprain; however, dysfunction persists in 40% of patients for as long as 6 months after injury. Syndesmosis sprains are more common than previously thought, and this confirms that syndesmosis sprains are associated with prolonged disability.

Chloroquine and hydroxychloroquine binding to melanin: Some possible consequences for pathologies.

For many years chloroquine was used as a prophylactic agent against malaria, and more recently as a mild immunosuppressive. However, due to lengthy treatment periods, adverse effects have become apparent, which included retinopathy. The structurally related hydroxychloroquine is less toxic, thought to be owing to a lower tissue accumulation in melanin rich areas. This study primarily focused on quantifying melanin binding between chloroquine and hydroxychloroquine at physiological pH to investigate the potential link between binding and reported toxicity. In addition, for the first time this study quantified the actual extent of adsorption of chloroquine and hydroxychloroquine to melanin and examined the desorption profile of both drugs from melanin to demonstrate the affinity between the pigment and the solutes. The results suggest that there is a difference between the adsorption affinities of chloroquine and hydroxychloroquine, potentially explaining the differences in bioaccumulation in retinal tissue. In addition, both solutes displayed a strong physical attraction to the absorbent.

Pancultural nostalgia: prototypical conceptions across cultures.

Nostalgia is a frequently experienced complex emotion, understood by laypersons in the United Kingdom and United States of America to (a) refer prototypically to fond, self-relevant, social memories and (b) be more pleasant (e.g., happy, warm) than unpleasant (e.g., sad, regretful). This research examined whether people across cultures conceive of nostalgia in the same way. Students in 18 countries across 5 continents (N = 1,704) rated the prototypicality of 35 features of nostalgia. The samples showed high levels of agreement on the rank-order of features. In all countries, participants rated previously identified central (vs. peripheral) features as more prototypical of nostalgia, and showed greater interindividual agreement regarding central (vs. peripheral) features. Cluster analyses revealed subtle variation among groups of countries with respect to the strength of these pancultural patterns. All except African countries manifested the same factor structure of nostalgia features. Additional exemplars generated by participants in an open-ended format did not entail elaboration of the existing set of 35 features. Findings identified key points of cross-cultural agreement regarding conceptions of nostalgia, supporting the notion that nostalgia is a pancultural emotion.