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.

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.

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.

Long-term follow-up of leucoderma patients treated with transplants of autologous cultured melanocytes, ultrathin epidermal sheets and basal cell layer suspension.

BACKGROUND: In vitiligo and piebaldism the lack of melanin in the epidermis is due to the fact that melanocytes are missing. The patients suffer psychologically and the white areas have lost the part of the skin barrier protection normally provided by the melanocytes. Medical treatments are ineffective in many of the patients, and surgical methods have therefore been developed. OBJECTIVES: It is important to investigate the long-term results and factors that might influence the outcome of melanocyte transplantations in order to form a basis for guidance in the selection of patients who will benefit most from the treatments. METHODS: A follow-up of 132 patients who had been treated by transplantation on 176 occasions in total, 1-7 years previously, was carried out by questionnaires and clinical examinations. We investigated the responses in five types of leucoderma to three different transplantation methods: autologous cultured melanocytes, ultrathin epidermal sheets and basal layer cell suspension. RESULTS: Stable types of leucoderma, i.e. segmental vitiligo and piebaldism, responded in most cases with 100% repigmentation, regardless of the surgical method used. For these types of leucoderma surgery seems to be the method of choice. The largest group, vitiligo vulgaris, was thoroughly scrutinized and three statistical models were used to analyse the data. The ultrathin epidermal sheet method gave somewhat better overall results, but was the method that gave the worst outcome in knee and elbow areas, emphasizing the importance of the right choice of method depending on the anatomical location to be treated. Irrespective of the method, fingers and elbows were the most difficult areas to repigment. The trunk and the arms and legs (not including elbows and knees) responded best. Patients with increasing and/or extensive vitiligo vulgaris more often showed incomplete repigmentation. They also had a lower chance of retaining their repigmentation compared with those with less extensive vitiligo. Patients in whom untreated white lesions had increased in recent years tended to respond less well to transplantation compared with patients with unchanged or decreased lesions. Within the vitiligo vulgaris group, patients with short disease duration or with small total vitiligo area responded best to transplantation. The subgroup of vitiligo vulgaris patients with hypothyroidism tend to respond less well to the transplantation and they were generally older at vitiligo onset. This information is of great importance for the selection of patients and when informing about the chances of improvement after transplantation. Slight hyperpigmentation was common, especially when ultrathin epidermal sheets had been used. No scars or indurations were seen in treated areas. CONCLUSIONS: Transplantations are the methods of choice in stable types of leucoderma. Progressive, widespread vitiligo vulgaris should never be selected for transplantation.

Lateralization of olfactory cognitive functions: effects of rhinal side of stimulation.

This study investigated differences in olfactory cognitive functions, in 40 healthy young right-handed participants, with respect to side of rhinal stimulation. The targeted functions were: perceived familiarity, episodic recognition memory, free identification and repetition priming in identification. The results showed that odors presented to the right nostril were rated as more familiar than odors presented to the left nostril and also showed significant effects of repetition priming in identification. However, no differences were found between nostrils in episodic recognition memory or free identification. These latter results indicate a rather extensive inter-hemispheric interaction in higher-order cognitive functions.

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.

The transcription factors SOX9 and SOX10 are vitiligo autoantigens in autoimmune polyendocrine syndrome type I.

Vitiligo is common in the hereditary disorder autoimmune polyendocrine syndrome type I (APS I). Patients with APS I are known to have high titer autoantibodies directed against various tissue-specific antigens. Using sera from APS I patients for immunoscreening of a cDNA library from human scalp, we identified the transcription factors SOX9 and SOX10 as novel autoantigens related to this syndrome. Immunoreactivity against SOX9 was found in 14 (15%) and against SOX10 in 20 (22%) of the 91 APS I sera studied. All patients reacting with SOX9 displayed reactivity against SOX10, suggesting shared epitopes. Among the 19 patients with vitiligo, 12 (63%) were positive for SOX10 (p < 0.0001). Furthermore, three of 93 sera from patients with vitiligo unrelated to APS I showed strong reactivity against SOX10, which may indicate a more general role of SOX10 as an autoantigen in vitiligo.

Evidence of odor priming: edibility judgements are primed differently between the hemispheres.

In olfaction, there is only weak evidence of repetition priming. Repetition priming was therefore investigated in two experiments using birhinal presentation of odors at study and monorhinal at test. Experiment 1 demonstrated repetition priming for repeated judgements of edibility in terms of response latency, but not in terms of correctness. No differences were found between the hemispheres (nostrils). Experiment 2 utilized a slightly different design, in which identity of odors was studied and judgement of edibility was tested. This time, only the right hemisphere (RH) was associated with priming. This persistence of RH priming should be seen in the light of a general tendency for superiority of the left hemisphere for correctly judging edibility. It is concluded that the olfactory system benefits from previous exposure/processing just as do vision, audition and touch. In line with previous research in vision, it is suggested that RH priming may be more associated with perceptual priming and left-hemisphere (LH) priming with conceptual priming.

Psychometrics of odor quality discrimination: method for threshold determination.

There is no natural physical continuum for odor quality along which an odor quality discrimination (OQD) threshold can be measured. In an attempt to overcome this problem, the substitution-reciprocity (SURE) method defines a framework for the measurement of an OQD threshold. More specifically, it (i) defines a threshold concept for OQD, including the quantification of qualitative change of the stimulus, and (ii) suggests how to avoid perceived intensity as an unwanted cue for discrimination. In doing this, the psychometric properties of odor quality in the case of eugenol and citral are investigated using both discrimination (experiment 1) and scaling (experiment 2). Based on discriminatory responses, a change of approximately one-third in stimulus content was needed to reach the OQD threshold for eugenol and citral.

Quantification of odor quality.

The relationship between odor quality and molecular properties is arguably the most important issue in olfaction. Despite sophistication in the chemical characterization of molecules, accompanying perceptual characterization has had little quantitative usefulness, relying mostly on enumerative description. As a result of weak interest in the topic outside industry and little agreement regarding how to measure quality, the field of olfactory psychophysics has failed to develop a substantial database for odor quality and has offered little help to other researchers, e.g. neurobiologists, in choice of stimuli, interpretation of outcome or testable hypotheses. This review scrutinizes how psychophysicists and others have measured quality and offers criteria for useful techniques. Most measures have had a subjective component that makes them anachronistic with modern methodology in experimental behavioral science, indeterminate regarding the extent of individual differences, unusable with infrahumans and of unproved ability to discern small differences. Techniques based upon performance, rather than on the more common reporting of mental content, offer firmer possibilities for growth. These techniques inevitably tap the discriminative basis of perception. The nonsubjective techniques have high sensitivity, can have counterparts in infrahuman research, are suitable to examine individual differences and yield non-negotiable answers with potential archival value. Discriminative techniques have their limitations, too-principally excess sensitivity that abridges their use to comparisons between similar-smelling stimuli. Research has begun to extend that range and may overcome the limitation. Application of discriminative methods may have the side-effect of shifting focus in structure-activity research from searches for molecular least common denominators that underlie often vague similarity to the search for molecular properties of importance in discrimination of small differences.

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.

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.

Leucoderma treated by transplantation of a basal cell layer enriched suspension.

The aim of this study was to test the usefulness of a melanocyte-enriched cell suspension for the treatment of leucoderma. After removal of a superficial (4-30 cm2) skin sample, the cells were mechanically separated in a trypsin-EDTA solution, centrifuged and washed in a melanocyte medium. The melanocyte-enriched epidermal cell suspension devoid of stratum corneum and stratum granulosum was then applied to the dermabraded depigmented skin. The 26 patients treated had piebaldism (three), vitiligo vulgaris (17), segmental vitiligo (three), halo naevi (one), naevus depigmentosus (one) and chemical leucoderma (one). In patients with widespread piebaldism we found that by diluting the cell suspension the recipient area could be increased to up to 10 times the size of the donor area with the same good results as without or with less dilution. In patients with vitiligo areas of between 50 and 90 cm2, the recipient areas were increased three- to fivefold in the donor area. Patients with piebaldism, segmental vitiligo and halo naevi healed completely, as did most patients with vitiligo. In naevus depigmentosus no effect was seen. Our new method for treatment of leucoderma has the advantage that cell culture is not needed and that it is more suitable than epidermal sheet grafts when several small areas are to be treated.

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.

Improvement of vitiligo after oral treatment with vitamin B12 and folic acid and the importance of sun exposure.

The aim of this 2-year study was to test the hypothesis that folic acid, vitamin B12 and sun exposure could be helpful in treating vitiligo. One hundred patients with vitiligo were treated with oral folic acid and vitamin B12 after being informed that sun exposure might enhance repigmentation. They were requested to keep a record of sun exposure in summer and UVB irradiation in winter. The minimal treatment time suggested was 3-6 months but should be longer if improvement was achieved. Clear repigmentation occurred in 52 patients, including 37 who exposed their skin to summer sun and 6 who used UVB lamps in winter. Repigmentation was most evident on sun-exposed areas, where 38% of the patients had previously noted repigmentation during summer months. Total repigmentation was seen in 6 patients. The spread of vitiligo stopped in 64% of the patients after treatment. Folic acid and vitamin B12 supplementation combined with sun exposure can induce repigmentation better than either the vitamins or sun exposure alone. Treatment should continue as long as the white areas continue to repigment. Further studies are needed to determine ideal minimal dosages of vitamins and UV exposure, as well as treatment time.

Epidermal sheet grafts for repigmentation of vitiligo and piebaldism, with a review of surgical techniques.

Thin epidermal sheets, obtained by a high-speed air-driven dermatome, were used to repigment white areas in 19 patients with vitiligo and one boy with piebaldism. In the depigmented skin to be treated the epidermis was removed by a rotating diamond fraise under topical and/or local anaesthesia injections. The method was used on most parts of the body, including the eyelids and genitalia. The maximum total area treated on each occasion was 190 cm2. Excellent results could be obtained if the vitiligo had been stable and had not increased anywhere during the last 2 years. Lack of immobilization could explain a poor result in some areas. The donor area on the buttocks healed quickly without depigmentation. In the transplanted area milia were observed in the first 6 months. No scarring was seen. The technique has a niche in the treatment of depigmented skin, especially in larger areas.