Tryptophan pathway catabolites (serotonin, 5-hydroxyindolacetic acid, kynurenine) and enzymes (monoamine oxidase and indole amine 2,3 dioxygenase) in patients with septic shock: A prospective observational study versus healthy controls.

Septic shock is associated with a strong inflammatory response that induces vasodilation and vascular hyporeactivity. We investigated the role for tryptophan-pathway catabolites of proinflammatory cytokines in septic shock.We prospectively included 30 patients with very recent-onset septic shock and 30 healthy volunteers. The following were assayed once in the controls and on days 1, 2, 3, 7, and 14 in each patient: plasma free and total tryptophan, platelet and plasma serotonin, total blood serotonin, urinary serotonin, plasma and urinary 5-hydroxyindolacetic acid, plasma kynurenine, monoamine oxidase activity, and total indole amine 2,3-dioxygenase activity. Organ-system failure and mortality were recorded.Compared with the healthy controls, the patients with septic shock had 2-fold to 3-fold lower total tryptophan levels throughout the 14-day study period. Platelet serotonin was substantially lower, while monoamine oxidase activity and 5-hydroxyindolacetic acid were markedly higher in the patients than in the controls, consistent with the known conversion of tryptophan to serotonin, which is then promptly and largely degraded to 5-hydroxyindolacetic acid. Plasma kynurenine was moderately increased and indole amine 2,3-dioxygenase activity markedly increased in the patients versus the volunteers, reflecting conversion of tryptophan to kynurenine. Changes over time in tryptophan metabolites were not associated with survival in the patients but were associated with the Sequential Organ Failure Assessment score and hemodynamic variables including hypotension and norepinephrine requirements.Our results demonstrate major tryptophan pathway alterations in septic shock. Marked alterations were found compared with healthy volunteers, and tryptophan metabolite levels were associated with organ failure and hemodynamic alterations. Tryptophan metabolite levels were not associated with surviving septic shock, although this result might be ascribable to the small sample size.Trial registration: ClinicalTrials.gov; No: NCT00684736; URL: www.clinicaltrials.gov.

Differential effects of makeup on perceived age.

Makeup accentuates three youth-related visual features - skin homogeneity, facial contrast, and facial feature size. By manipulating these visual features, makeup should make faces appear younger. We tested this hypothesis in an experiment in which participants estimated the age of carefully controlled photographs of faces with and without makeup. We found that 40- and especially 50-year-old women did appear significantly younger when wearing makeup. Contrary to our hypothesis, 30-year-old women looked no different in age with or without makeup, while 20-year-old women looked older with makeup. Two further studies replicated these results, finding that makeup made middle-aged women look younger, but made young women look older. Seeking to better understand why makeup makes young women look older, we ran a final study and found evidence that people associate makeup use with adulthood. By activating associations with adulthood, makeup may provide an upward bias on age estimations of women who are not clearly adult. We propose that makeup affects social perceptions through bottom-up routes, by modifying visual cues such as facial contrast, facial feature size, and skin homogeneity, and also through top-down routes, by activating social representations and norms associated with makeup use.

Validation of digital photographic reference scales for evaluating facial aging signs.

BACKGROUND: Validated tools are essential to evaluate facial skin aging for both dermatological and cosmetic investigations. While many visual aging scales have been developed, few have been validated and none in terms of degree of distinguishability (DD). We developed and validated a series of visual scales using a novel digital interface for scoring facial skin aging in Caucasian women. MATERIALS AND METHODS: Three dermatologists independently established scales for 12 distinct aging signs from high-definition facial photographs of 400 adult women (Fitzpatrick phototypes I-IV) taken under standardized conditions. They then selected a consensus scale for each individual sign with a representative photo per grade. Scales were integrated into a digital interface allowing simultaneous viewing of all grades of each scale alongside the photograph of a test subject. Next, scales were validated by a different dermatologist, a general practitioner and a non-medical expert skin evaluator using photos of 350 women which had not been used for establishing the scales. RESULTS: Kappa estimates showed almost perfect agreement for wrinkle and skin aging scales (≥0.85) and moderate to substantial agreement for scales relating to color irregularities (telangiectasia, solar lentigines, freckles) for both inter- and intra-observer reproducibility. Intra-observer DD estimates were mostly high. Non-dermatologists performed well on reproducibility for both Kappa (from 0.6 to 0.9) and DD estimates. CONCLUSION: Our work demonstrates that the digital interface scales for 12 distinct aging features are highly suitable for use in clinical and epidemiological studies on skin aging by both dermatologists and non-dermatologists.

Facial Contrast Is a Cross-Cultural Cue for Perceiving Age.

Age is a fundamental social dimension and a youthful appearance is of importance for many individuals, perhaps because it is a relevant predictor of aspects of health, facial attractiveness and general well-being. We recently showed that facial contrast-the color and luminance difference between facial features and the surrounding skin-is age-related and a cue to age perception of Caucasian women. Specifically, aspects of facial contrast decrease with age in Caucasian women, and Caucasian female faces with higher contrast look younger (Porcheron et al., 2013). Here we investigated faces of other ethnic groups and raters of other cultures to see whether facial contrast is a cross-cultural youth-related attribute. Using large sets of full face color photographs of Chinese, Latin American and black South African women aged 20-80, we measured the luminance and color contrast between the facial features (the eyes, the lips, and the brows) and the surrounding skin. Most aspects of facial contrast that were previously found to decrease with age in Caucasian women were also found to decrease with age in the other ethnic groups. Though the overall pattern of changes with age was common to all women, there were also some differences between the groups. In a separate study, individual faces of the 4 ethnic groups were perceived younger by French and Chinese participants when the aspects of facial contrast that vary with age in the majority of faces were artificially increased, but older when they were artificially decreased. Altogether these findings indicate that facial contrast is a cross-cultural cue to youthfulness. Because cosmetics were shown to enhance facial contrast, this work provides some support for the notion that a universal function of cosmetics is to make female faces look younger.

Case-control cohort study of patients' perceptions of disability in mastocytosis.

BACKGROUND: Indolent forms of mastocytosis account for more than 90% of all cases, but the types and type and severity of symptoms and their impact on the quality of life have not been well studied. We therefore performed a case-control cohort study to examine self-reported disability and impact of symptoms on the quality of life in patients with mastocytosis. METHODOLOGY/PRINCIPAL FINDINGS: In 2004, 363 mastocytosis patients and 90 controls in France were asked to rate to their overall disability (OPA score) and the severity of 38 individual symptoms. The latter was used to calculate a composite score (AFIRMM score). Of the 363 respondents, 262 were part of an ongoing pathophysiological study so that the following data were available: World Health Organization classification, standard measures of physical and psychological disability, existence of the D816V KIT mutation, and serum tryptase level. The mean OPA and AFIRMM scores and the standard measures of disability indicated that most mastocytosis patients suffer from disabilities due to the disease. Surprisingly, the patient's measurable and perceived disabilities did not differ according to disease classification or presence or absence of the D816V KIT mutation or an elevated (> or = 20 ng/mL) serum tryptase level. Also, 32 of the 38 AFIRMM symptoms were more common in patients than controls, but there were not substantial differences according to disease classification, presence of the D816V mutation, or the serum tryptase level. CONCLUSIONS: On the basis of these results and for the purposes of treatment, we propose that mastocytosis be first classified as aggressive or indolent and that indolent mastocytosis then be categorized according to the severity of patients' perceived symptoms and their impact on the quality of life. In addition, it appears that mastocytosis patients suffer from more symptoms and greater disability than previously thought, that mastocytosis may therefore be under-diagnosed, and that the symptoms of the indolent forms of mastocytosis might be due more to systemic release of mediators than mast cell burden.

Phenotypic and genotypic characteristics of mastocytosis according to the age of onset.

Adult's mastocytosis is usually associated with persistent systemic involvement and c-kit 816 mutation, while pediatrics disease is mostly limited to the skin and often resolves spontaneously. We prospectively included 142 adult patients with histologically proven mastocytosis. We compared phenotypic and genotypic features of adults patients whose disease started during childhood (Group 1, n = 28) with those of patients whose disease started at adult's age (Group 2, n = 114). Genotypic analysis was performed on skin biopsy by sequencing of c-kit exons 17 and 8 to 13. According to WHO classification, the percentage of systemic disease was similar (75 vs. 73%) in 2 groups. C-kit 816 mutation was found in 42% and 77% of patients in groups 1 and 2, respectively (p<0.001). 816 c-kit mutation was associated with systemic mastocytosis in group 2 (87% of patients with systemic mastocytosis vs. 45% with cutaneous mastocytosis, p = 0.0001). Other c-kit activating mutations were found in 23% of patients with mastocytosis' onset before the age of 5, 0% between 6 and 15 years and 2% at adults' age (p<0.001). In conclusion, pathogenesis of mastocytosis significantly differs according to the age of disease's onset. Our data may have major therapeutic relevance when considering c-kit-targeted therapy.