Perception of unfamiliar caregivers during sickness - Using the new Caregiver Perception Task (CgPT) during experimental endotoxemia.

Social withdrawal is a well-established part of sickness behavior, but in some contexts sick animals might gain from keeping close instead of keeping away. For instance, sick individuals are more willing to be near known individuals who can provide care and safety (close others) compared to when healthy. Yet, interactions with some strangers might also be beneficial (i.e., healthcare professionals), but it is not known how sickness interplay with social behavior towards such individuals. Here, we assessed if sickness affects perception of caregivers, and developed a new task, the Caregiver Perception Task (CgPT). Twenty-six participants performed the CgPT, once after an injection of lipopolysaccharide (LPS, 0.8 ng/kg body weight, n = 24), and once after an injection of saline (n = 25), one hour and forty-five minutes post-injection. During the task, participants watched short video clips of three types of caregivers: a healthcare professional taking care of a sick individual, a healthcare professional not taking care of a sick individual, and a non-healthcare professional taking care of their sick adult child or partner. After each video clip, the likability, trustworthiness, professionalism, and willingness to interact with and receive care from the caregiver were rated on visual analogue scales. Results showed that participants injected with saline rated healthcare professionals who did not take care of a sick individual less positively on all aspects compared to healthcare professionals who took care of a sick individual. Moreover, compared to saline, LPS increased the participants' willingness to receive care from healthcare professionals and non-healthcare professionals providing care, but not from healthcare professionals not providing care. Thus, our results indicate that sick individuals may approach unknown individuals with potential to provide care and support.

The walking sick: Perception of experimental sickness from biological motion.

Identification of sick conspecifics allows for avoidance of infectious threats, and is therefore an important behavioral defense against diseases. Here, we investigated if humans can identify sick individuals solely from biological motion and posture (using point-light displays). Additionally, we sought to determine which movements and sickness parameters would predict such detection. We collected video clips and derived point-light displays (one stride presented in a loop) of sick walkers (injected with lipopolysaccharide at 2.0 ng/kg body weight) and the same walkers when healthy (injected with saline). We then presented these displays to two groups, one group classified each walker as sick or healthy (study 1, n = 106), and the other group scored the walkers' health on a visual analogue scale (study 2, n = 106). The raters were able to identify sick individuals above chance, and rated sick walkers as having worse health, both from observing video clips and point-light displays. Furthermore, both sickness detection and worse apparent health were predicted by inflammation-induced increase in rigidity and slower walking, but not other cues. Altogether, these findings indicate that biological motion can serve as a sickness cue, possibly allowing humans to identify sick conspecifics from a distance, and thereby allowing for disease avoidance.

Biological motion during inflammation in humans.

Biological motion is a powerful perceptual cue that can reveal important information about the inner state of an individual. Activation of inflammatory processes likely leads to changes in gait, posture, and mobility patterns, but the specific characteristics of inflammation-related biological motion have not been characterized. The aim of this study was to determine the effect of inflammation on gait and motion in humans. Systemic inflammation was induced in 19 healthy volunteers with an intravenous injection of lipopolysaccharide (2 ng/kg body weight). Biological motion parameters (walking speed, stride length and time, arm, leg, head, and shoulder angles) were assessed during a walking paradigm and the timed-up-and-go test. Cytokine concentrations, body temperature, and sickness symptoms were measured. During inflammation, compared to placebo, participants exhibited shorter, slower, and wider strides, less arm extension, less knee flexion, and a more downward-tilting head while walking. They were also slower and took a shorter first step in the timed-up-and-go test. Higher interleukin-6 concentrations, stronger sickness symptoms, and lower body temperature predicted the inflammation-related alterations in biological motion. These findings show that biological motion contains clear information about the inflammatory status of an individual, and may be used by peers or artificial intelligence to recognize that someone is sick or contagious.

Transcriptional changes in organoculture of full-thickness human skin following topical application of all-trans retinoic acid.

In this study, we developed an organoculture of human skin to investigate the effect of topical applied all-trans retinoic acid using a gene array approach. We could by using this approach confirm previous studies on genes activated by RA in keratinocyte monocultures and also provide new insights on genes that are relevant to RA-activation in human skin. The results in the present study show this model represent a valuable pre-clinical model for studying the effects of retinoids in skin.

Guidelines for the management of vitiligo: the European Dermatology Forum consensus.

The aetiopathogenic mechanisms of vitiligo are still poorly understood, and this has held back progress in diagnosis and treatment. Up until now, treatment guidelines have existed at national levels, but no common European viewpoint has emerged. This guideline for the treatment of segmental and nonsegmental vitiligo has been developed by the members of the Vitiligo European Task Force and other colleagues. It summarizes evidence-based and expert-based recommendations (S1 level).

The melanogenesis and mechanisms of skin-lightening agents--existing and new approaches.

Skin-lightening products are commercially available for cosmetic purposes to obtain lighter skin complexion. Clinically, they are also used for treatment of hyperpigmentary disorders such as melasma, café au lait spot and solar lentigo. All of these target naturally melanin production, and many of the commonly used agents are known as competitive inhibitors of tyrosinase, one of the key enzymes in melanogenesis. In this review, we present an overview of commonly used skin-whitening ingredients that are commercialized, but we also hypothesize on other mechanisms that could be important targets to control skin pigmentation such as for example regulation of the adrenergic and glutaminergic signalling and also control of tetrahydrobiopterins in the human skin.

A serotonin-like immunoreactivity is present in human cutaneous melanocytes.

Immunohistochemistry was applied in the investigation of the possible existence of serotonin in human skin. It was found that epidermal melanocytes express a serotonin-like immunoreactivity. The immunoreactivity was associated with both the cytoplasm and the cellular membrane, though the latter was only found in certain cells. The serotonin anti-serum labeled the same cells as NKI-beteb, which is known as a reliable marker of melanocytes. Blocking experiments showed that both serotonin and NKI-beteb have different epitopes in the melanocytes. In in vitro studies, serotonin-like immunoreactivity appeared in approximately 90% of cultured human melanocytes, and was found both in the cytoplasm and also in the nuclei. Thus, we believe the melanocytes to be the origin of serotonin (or a serotonin-like molecule) in the skin.

An integrated model of intensity and quality of odor mixtures.

Several models of how odors mix to form new percepts have been presented during the last decades. Almost all these models have concerned the perceived intensity of mixtures rather than the perceived quality of mixtures. In 1994 Olsson suggested an integrated model for how perceived intensity and quality of the mixture can be predicted from the perceived intensities of the single substances. A generalized version of this model is proposed here. The model can be viewed as an extension of vector summation. The current study reviews support for this model. In doing that, assumptions of the model are defined and tested against data. It is shown how odor interaction, when the process is seen from the view of the observer, reduces to a set of simple rules that are consistent across levels of intensity and combinations of odorants.

Odor-intensity interaction in binary mixtures.

Four principles underlying odor summation in mixtures were examined on the bases of 10 Ss' magnitude estimates of 41 mixtures and their components (pyridine and DMDS). Thus, the overall intensity summation for mixtures are compared to self-addition reflected by the power function for single substances: Hypoaddition is a characteristic of both. Compromise is found for 25% of the mixtures, but it is not inherent in the power function. No level dependency is found for mixtures, although it is in accordance with the power function. Asymmetrical summation exists for mixtures and is inconsistent with the power function. Therefore, the idea of a congruence in odor-intensity summation processes is rejected. The results also constitute a successful cross-validation of the angle alpha (99 degrees vs. 102 degrees) of the perceptual vector model reported by B. Berglund et al. (1973).

Magnitude estimation of perceived odor intensity: empirical and theoretical properties.

Four subjects judged the odor intensities of 7 pyridine concentrations and a blank. Computer simulations of a judgment model were compared with the empirical data. The model generates data patterns that closely mimic empirical findings. The following patterns were confirmed: (a) A power function relates magnitude estimates and concentration with an exponent in the range of 0.7 to 1.0 (b) The exponent fluctuates so that the level constant is negatively correlated with the exponent. (c) The standard deviation of the responses is a negatively accelerated function of the mean. (d) The skewness of the responses is relatively high for low concentrations and declines toward zero with increasing concentration. (e) The correlation between responses to successive stimuli is highest when successive concentrations are similar.

Differential uptake of chloroquine by human keratinocytes and melanocytes in culture.

The antimalarial drug chloroquine has a high affinity for melanin and accumulates in melanin-rich compartments such as those of the eye. Chloroquine is also deposited in cutaneous tissue, but whether the drug distribution is restricted to melanin-producing cells of the skin is not known. In the present study, the uptake of chloroquine by normal human epidermal keratinocytes was compared with that by melanocytes. Selectively cultivated cells were incubated at drug concentrations ranging between 0 and 10000 ng/ml for periods of up to 48 h. Chloroquine was quantified in cells and medium using high performance liquid chromatography and fluorometric detection. In both types of cells there was a rapid uptake of chloroquine within the first 2 h, followed by a slower uptake for 2-6 h until a steady-state condition was reached. Dose dependency was linear, with no sign of saturation, and approximately ten times higher drug concentrations were attained in melanocytes as compared with keratinocytes. No formation of desethylchloroquine, the major systemic metabolite, was detected in either cell type. The observed affinity of chloroquine for normal epidermal melanocytes in vitro suggests that the density and melanogenic activity of skin pigment cells may influence the cutaneous drug disposition of chloroquine.

The influence of di(2-ethylhexyl)phthalate on protein turnover in rat liver.

Treatment of rats with the plasticizer di(2-ethylhexyl)phthalate increases liver weight and leads to proliferation of mitochondria and peroxisomes. Using in vivo labelling with [3H]leucine, an increased rate of incorporation into the total protein of mitochondria and microsomes was observed. The half-lives of proteins in subcellular fractions were determined using [35S]methionine labelling. The half-lives for the total protein of mitochondria, microsomes, and supernatant were increased from 6 to 25 days, from 3.5 to 5.5 days and from 2.5 to 5 days upon treatment with phthalate esters. Experiments with [14C]guanidino-L-arginine indicated that some reutilization of [35S]methionine occurred, but this did not influence the results substantially. It appears that phthalate esters increase protein synthesis and decrease protein breakdown, the former effect being of greater importance.

Naevus anaemicus with teleangiectatic vessels.

We describe a 20-year-old man with naevus anaemicus on the chest where, after dermabrasion of the epidermis, enlarged teleangiectatic dark-red vessels were seen within the previously pale area. They were clearly different from those seen on dermabrasion at this site in normal skin and in patients with vitiligo where the area is lighter red with only small punctual bleedings from arterial capillaries. The naevus anaemicus and a port-wine stain (naevus flammeus) in the same location is a phenomenon of vascular twin spotting, which was revealed when the epidermis was removed. The area was transplanted with thin epidermal grafts and healed within 2 weeks. One year later the naevus looked the same as before grafting. Much thicker grafts than those used by us will be needed, but they are not cosmetically acceptable.

Perceptual and processing differences between physical and dichorhinic odor mixtures.

Perceptual integration of sensory input from our two nostrils has received little attention in comparison to lateralized inputs for vision and hearing. Here, we investigated whether a binary odor mixture of eugenol and l-carvone (smells of cloves and caraway) would be perceived differently if presented as a mixture in one nostril (physical mixture), vs. the same two odorants in separate nostrils (dichorhinic mixture). In parallel, we investigated whether the different types of presentation resulted in differences in olfactory event-related potentials (OERP). Psychophysical ratings showed that the dichorhinic mixtures were perceived as more intense than the physical mixtures. A tendency for shift in perceived quality was also observed. In line with these perceptual changes, the OERP showed a shift in latencies and amplitudes for early (more "sensory") peaks P1 and N1 whereas no significant differences were observed for the later (more "cognitive") peak P2. The results altogether suggest that the peripheral level is a site of interaction between odorants. Both psychophysical ratings and, for the first time, electrophysiological measurements converge on this conclusion.

An interaction model for odor quality and intensity.

The perceived intensity and quality of binary odor mixtures are studied in relation to how their components are perceived when presented separately. Subjects judged the perceived intensity and quality of 6 concentrations of pyridine, 6 concentrations of n-butanol, and their 36 possible combinations. The results show that the perceived intensity of the mixture can be predicted from the perceived intensity of its components presented separately (RA and RB) by the Euclidian arithmetic model. The maximum probability of identifying a mixture as a "mixture" is reached when RA and RB are equally strong. An interaction model for mixtures that relates perceived intensity and quality is presented and tested. The test reveals that both the perceived intensity of a mixture and the probability that it will be identified as the one or the other component can, by a simple interaction model, be successfully predicted from RA and RB.

Implicit testing of odor memory: instances of positive and negative repetition priming.

The study provides a test and evaluation of a new repetition priming procedure designed to solve problems in investigating olfactory-specific priming. Although the results did not reveal any overall priming effect, a post-hoc analysis showed that incorrectly identified odors were more quickly processed than control odors, whereas correctly identified odors were processed more slowly These results are discussed and interpreted as instances of positive and negative repetition priming respectively.

Transplantation of melanocytes in vitiligo.

We report the results of a study on 100 patients (aged 12-68) with vitiligo, who were treated by transplantation of cultured autologous melanocytes to the depigmented areas, after removal of the epidermis at the recipient site by dermabrasion. The melanocytes were cultured from a 2 x 3 cm2 superficial shave biopsy taken from pigmented buttock skin. After 2-3 weeks in culture, 700-1000 cells per mm2 were applied on 60-500 cm2 dermabraded areas, and occluded for 1 week. The repigmented portion of the total treated area amounted to 95-100% in 40 patients, 65-94% in 32, 20-64% in 22, and 0-19% in six. It was more difficult to achieve complete pigmentation on the fingers, elbows and knees. In the first few months following the procedure, the treated areas were often hypo- or hyperpigmented, but after 6-8 months they had acquired the same colour as the surrounding skin. No scarring or other side-effects occurred. The donor site had repigmented after 3-6 months in all but two patients, who also showed poor pigmentation in the transplanted areas. At follow-up after 1 and 2 years in 50 and 10 patients, respectively, the repigmented areas remained unchanged. The method is time-consuming, but the results obtained indicate that the procedure can be valuable in motivated patients, when the extent of vitiligo does not exceed 30% of the total body area, and when the areas to be treated are not actively extending.

Repigmentation of vitiligo by transplantation of cultured autologous melanocytes.

Autologous cultured melanocytes were transplanted to superficially dermabraded vitiligo areas in ten patients. Good cosmetic results were obtained in nine patients with stable vitiligo, but in one patient with new, increasing areas of vitiligo no pigmentation was seen 3 months after transplantation.

Odor-intensity interaction in binary and ternary mixtures.

Eight subjects scaled the overall perceived odor intensity of binary and ternary mixtures of the odorous substances pyridine, acetone, and ethyl acrylate. The results concerning basic principles of additivity for binary mixtures comply with those of earlier studies. For the ternary mixtures, the degree of arithmetic additivity in odor intensity seemed lower when a third component was added to a binary mixture than when the second component was added to a single odor, but this did not reach statistical significance. In general, the degree of arithmetic additivity inherent in the power function for single substances was found to be of the same size as the degree of additivity for binary as well as ternary mixtures. However, for binary mixtures, the additivity of the mixtures was found to approximate that of the substance with the lower exponent. In addition, the degree of additivity of the binary mixture was monotonically related to the average arithmetic additivity of the power functions for the two components.