Biosignatures of defective sebaceous gland activity in sebum-rich and sebum-poor skin areas in adult atopic dermatitis.

Atopic dermatitis (AD) is a composite disease presenting disruption of the skin permeability barrier (SPB) in the stratum corneum (SC). Recent evidence supports derangement of the sebaceous gland (SG) activity in the AD pathomechanisms. The objective of this study was to delineate profiles of both sebaceous and epidermal lipids and of aminoacids from SG-rich (SGR) and SG-poor (SGP) areas in AD. Both sebum and SC were sampled from SGR areas, while SC was sampled also from SGP areas in 54 adult patients with AD, consisting of 34 and 20 subjects, respectively with and without clinical involvement of face, and in 44 age and sex-matched controls. Skin biophysics were assessed in all sampling sites. Disruption of the SBP was found to be associated with dysregulated lipidome. Abundance of sapienate and lignocerate, representing, respectively, sebum and the SC type lipids, were decreased in sebum and SC from both SGR and SGP areas. Analogously, squalene was significantly diminished in AD, regardless the site. Extent of lipid derangement in SGR areas was correlated with the AD severity. The abundance of aminoacids in the SC from SGR areas was altered more than that determined in SGP areas. Several gender-related differences were found in both controls and AD subgroups. In conclusion, the SG activity was differently compromised in adult females and males with AD, in both SGR and SGP areas. In AD, alterations in the aminoacidome profiles were apparent in the SGR areas. Lipid signatures in association with aminoacidome and skin physical properties may serve the definition of phenotype clusters that associate with AD severity and gender.

Impact of Leave-on Skin Care Products on the Preservation of Skin Microbiome: An Exploration of Ecobiological Approach.

Purpose: Skincare products are used daily to maintain a healthy skin, although their skin microbiome impact is still poorly known. Preserving the natural resources and mechanisms of the skin ecosystem is essential, and a novel approach based on these premises, called ecobiology, has recently emerged in skincare. We evaluated the impact on the skin microbiome of three types of leave-on face skincare products: a hydrophilic solution, a micellar solution, and an oil-in-water emulsion. Patients and Methods: Samples for microbial profiling were obtained from 20 Caucasian females twenty-four hours and four days following daily application of the skincare products and compared to an untreated area. The bacterial diversity and the abundance of the skin microbiome were analyzed by 16S rRNA gene sequencing using an Illumina MiSeq platform. Results: Our results confirmed the skin microbiome diversity and the prevalence of Cutibacterium spp. and Staphylococcus spp. at sebaceous sites. The bacterial diversity and abundance were not affected by the products, and no dissimilarities versus the control nor between each product were noted at both times. Conclusion: These preliminary results demonstrate for the first time that three types of leave-on face skincare products have no impact on the human skin microbiome and can be considered to be "microbiome friendly".

Residual Sleepiness Risk in Aircrew Members with -Obstructive Sleep Apnea Syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a major problem in aviation medicine because it is responsible for sleepiness and high cardiovascular risk, which could jeopardize flight safety. Residual sleepiness after the treatment is not a rare phenomenon and its management is not homogenous in aviation medicine. Thus, we decided to perform a study to describe this management and propose guidelines with the help of the literature.METHODS: This is a retrospective study including all aircrew members with a history of OSAS who visited our aeromedical center between 2011 and 2018. Residual sleepiness assessment was particularly studied.RESULTS: Our population was composed of 138 aircrew members (mean age 50.1 ± 9.6 yr, 76.8% civilians, 80.4% pilots); 65.4% of them had a severe OSAS with a mean Epworth Sleepiness Scale (ESS) at 8.5 ± 4.7 and a mean apnea hypopnea index of 36.2 ± 19.2/h. Of our population, 59.4% performed maintenance of wakefulness tests (MWT) and 10.1% had a residual excessive sleepiness. After the evaluation, 83.1% of our population was fit to fly.DISCUSSION: An evaluation of treatment efficiency is required in aircrew members with OSAS. Furthermore, it is important to have an objective proof of the absence of sleepiness. In this case, ESS is not sufficient and further evaluation is necessary. Many tests exist, but MWT are generally performed and the definition of a normal result in aeronautics is important. This evaluation should not be reserved to solo pilots only.Monin J, Rebiere E, Guiu G, Bisconte S, Perrier E, Manen O. Residual sleepiness risk in aircrew members with obstructive sleep apnea syndrome. Aerosp Med Hum Perform. 2023; 94(2):74-78.

Prevalence of sleep disorders in a large French cohort of aircrew members and risk of in-flight sleepiness.

BACKGROUND: /objectives: Sleep disorders are a critical issue for flight safety. Previous studies have shown a high prevalence of sleep disorders and excessive sleepiness in the general population and some aircrews. The objectives of this study are to measure the prevalence of excessive daytime sleepiness and sleep disorders in aircrews, and to determine the risk factors of falling asleep during a flight. METHODS: this is a monocentric study based on questionnaires, including all professional civilian and military aircrews examined in an aeromedical center between January and May 2021. The questionnaire, created for this study, included information about socio-demographic characteristics, aeronautical experience, lifestyle, sleep habits, an Epworth sleepiness scale, and screening tests for chronic insomnia, sleep apnea syndrome and restless legs syndrome. RESULTS: 749 aircrew members were included (86.2% male, 58.9% civilian, 74.1% pilot, mean age 43.4 ± 9.6 years), 45.9% of the population had at least one sleep disorder (chronic insomnia 39.5%, sleep apnea syndrome 10.5%, restless legs syndrome 4.1%), 15.5% had an excessive daytime sleepiness, and 24.6% reported in-flight sleep while on duty. Chronic insomnia, screen use before bedtime, use of sleeping pills, inadequate recovery time after a flight, female gender and civilian status were found as risk factors of in-flight sleep in the multivariate analysis. CONCLUSION: this study emphasizes the need to improve the screening and prevention of sleep disorders in this particular population.

Travel health study in commercial aircrew members.

BACKGROUND: Aircrew members of airlines are exposed to travel risks. The objectives of our study are to assess the experience of aircrews about these risks and their knowledge about prevention means. METHODS: We conducted an observational qualitative study in commercial aircrews at the aeromedical center of Percy Military Hospital between November 2018 and June 2019. RESULTS: 200 aircrews answered the questionnaire, 54% of which were pilots, 91% work on long and/or medium-haul flights, 82.5% of airmen are concerned by their immunization status. Vaccination rate varied according to the vaccine. Two third of airmen usually go to malaria-endemic countries, 12% of respondents use antimalarial treatment in such infected countries, while 93.5% protect themselves against mosquito bites mainly with insect repellent. In case of a fever after a stay in a malaria-endemic country, only 51.5% of respondents immediately think about acute malaria. Aircrews are very motivated by their job but 58% of them feel tired probably linked to quality of sleep and effects of jet-lag, with a statistically significant difference between pilots and cabin crews (43% vs 75% [p < 0.01]). CONCLUSION: Aircrew members know a lot about travel issues. Malaria remains a major concern for aircrews, but it is necessary to maintain information about this topic throughout their career and to provide them with repellents, what many airlines actually do. Fatigue management is also important for airmen, so as they use different technics to accelerate recovery. Some airlines try to help them with a guide for aircrew fatigue management. This particular population involved in flight safety has few risky behaviors; nevertheless, alcohol misuse and drug use are screened during medical examinations and by airlines.

Prevalence of benign epileptiform variants during initial EEG examination in French military aircrew.

INTRODUCTION: In France, a systematic EEG is performed during initial examination in military aircrew applicants, which may provide an estimation of the prevalence of benign epileptiform variants in healthy adults. METHODS: We analyzed standard EEG (21 scalp electrodes, 20minutes, 400Hz sampling rate) of military aircrew applicants examined in the French Main Aeromedical Center in 2016. EEGs were analyzed using both bipolar and referential montages. The collected data were EEG abnormalities and benign epileptiform variants. The kappa inter-observer index for the detection of benign epileptiform variants was calculated. RESULTS: Our population was composed of 495 subjects (86.7% males, mean age 22.5±4.8 years), wishing to become a pilot in 69.7% of cases. None of the applicants reported any neurological disease and none was taking regular medication. EEG was considered as normal for 96.4% of them. Encountered EEG abnormalities were mainly asymmetric and sharp slow wave bursts. Drowsiness was recorded during 13.9% of these EEG. Benign epileptiform variants were present in 7.7% of our population: anterior theta activities (4%), posterior slow waves (2.8%), alpha variants (0.6%) and wicket spikes (0.2%). Hyperventilation induced EEG slowing in 14.1% of cases. During intermittent photic stimulation, physiological photic driving was observed in 15.2% of subjects. DISCUSSION: Many previous studies have been dedicated to the prevalence of benign epileptiform variants but results are often heterogeneous and based on patients in whom there was an indication for EEG. Our results thus bring data on benign epileptiform variants prevalence in a young adult population characterized by the absence of neurologic disorders. Our study demonstrates that anterior theta activities, posterior slow waves, alpha variants and wicket spikes are the most frequent benign EEG variants in such a young adult population.

Epidemiology of Airmen Treated with Immunosuppressive Drugs and Vaccination Concerns.

BACKGROUND: Immunosuppressive treatments are increasingly prescribed in a variety of diseases. This issue concerns airmen. METHODS: To assess the problem, we conducted an observational retrospective study in the aircrew population examined in 2014 at the Aeromedical Center of Percy Military Hospital. RESULTS: Airmen treated with immunosuppressive drugs accounted for 0.5% of the total population (N = 13,326). Rheumatic and digestive diseases were the main etiologies, respectively 43% and 35% of cases. One-third of airmen took such medications during at least 3 yr and three-quarters of airmen were declared fit to fly, with some limitations. DISCUSSION: Due to their working conditions, airmen are exposed to a real infectious risk, which is, however, difficult to evaluate. The risk is obviously increased by immunosuppressive drugs and may affect flight safety. Aeromedical evaluation should consider this problem. Vaccination plays a central role in the prevention of infectious risk. Based on French recommendations, we propose a vaccination schedule for these particular patients.Guiu G, Monin J, Hamm-Hornez A-P, Manen O, Perrier E. Epidemiology of airmen treated with immunosuppressive drugs and vaccination concerns. Aerosp Med Hum Perform. 2018; 89(4):377-382.

Progression of early repolarization patterns at a four year follow-up in a female flight crew population: Implications for aviation medicine.

BACKGROUND: To assess the prevalence, the appearance, and the distribution, as well as the fluctuation over time of early repolarization patterns after four years in a female population derived from the French aviation sector. METHODS: This was a retrospective longitudinal study from 1998 to 2010 of a population of female employees who received a full clinical examination and an electrocardiogram (ECG) upon their recruitment and after a period of four years. RESULTS: A total of 306 women were included (average of 25.87 ± 3.3 years of age). The prevalence of early repolarization was 9.2%. The most common appearance was J-point slurring for 64.3% (i.e. 20/28 subjects) that occurred in the inferior leads for 28.6% (i.e. 8/28 subjects). After four years, the prevalence was 7.5%, with a regression of this aspect in five of the subjects. There were no changes in the ECG in terms of the distribution and the appearance among the 23 subjects for whom the aspect persisted. Over the course of this four year period all of the subjects remained asymptomatic. CONCLUSIONS: Early repolarization in this largely physically inactive female population was common, and it fluctuated over time. At present, no particular restrictions can be placed on asymptomatic flight crew who exhibit this feature in the absence of a prior medical history for heart disease.

Prevalence of Intraventricular Conduction Disturbances in a Large French Population.

BACKGROUND: Recommendations for the interpretation of electrocardiogram have been published in 2009. The aim of this study was to define the prevalence of intraventricular conduction disturbances (ICoDs) in a large population, using these recommendations. METHODS: From 01/31/1996 to 09/22/2010, an electrocardiogram was performed at each visit for all aircrew members examined for fitness assessment in an aeromedical center. The prevalence of left bundle branch block (LBBB), right bundle branch block (RBBB), incomplete LBBB, incomplete RBBB, nonspecific intraventricular disturbance (NIVCD), left anterior fascicular block (LAFB), and left posterior fascicular block (LPFB) was measured and compared by age and gender. RESULTS: The global prevalence of ICoD was 3.09% in our population of 69,186 patients. The most frequent types of ventricular blocks were IRBBB (1.25%) and LAFB (1.10%), whereas RBBB (0.46%), LBBB (0.08%), ILBBB (0.03%), NIVCD (0.05%), and LPFB (0.13%) were rare findings. ICoDs are more frequent for males and older age groups (P < 0.001). DISCUSSION: Our results are comparable to studies concerning low cardiovascular risks populations. The association between ICoD and cardiovascular diseases needs to be studied in this population.

Spine injuries related to high-performance aircraft ejections: a 9-year retrospective study.

BACKGROUND: During an aircraft ejection, the pilot is exposed to accelerations to the point of human tolerance, which may cause spinal injuries. Many nations have reported a spinal trauma rate of about 20-30%, with plain radiography as the first-line exam. Insofar as ejection seats and diagnostic imaging have improved, the objectives of this study are to describe the spine injuries among recently ejected French aircrew, to analyze the spinal imaging used, and, if necessary, to propose a better standardized radiological procedure. METHODS: A retrospective cohort study included all aircrews of the French forces who ejected from 2000 to 2008, with an authorized access to the technical reports of the investigations. RESULTS: There were 36 ejections collected, 75% with an MK-10 seat and an arrival on dry land. All pilots were alive, but 42% of them sustained 24 spinal fractures, most of the time with a simple compression of the thoracic segment, but also 4 ligamentous or discal lesions. Computed tomography or RMI was used in 64% of cases and four fractures were missed or underestimated on X-ray. One complex fracture required surgical treatment. A return to flying duties was frequently possible within a period of 6 mo. CONCLUSIONS: New generation ejection seats remain highly traumatic for the spine. It is recommended that all ejected aircrews be assessed with computed tomography to improve the sensitivity of the screening for fractures. The risk of asymptomatic lesions makes necessary the systematic use of a stretcher for initial evacuation when possible.

Differential expression of cathepsins K, S and V between young and aged Caucasian women skin epidermis.

Cutaneous aging translates drastic structural and functional alterations in the extracellular matrix (ECM). Multiple mechanisms are involved, including changes in protease levels. We investigated the age-related protein expression and activity of cysteine cathepsins and the expression of two endogenous protein inhibitors in young and aged Caucasian women skin epidermis. Immunofluorescence studies indicate that the expression of cathepsins K, S and V, as well as cystatins A and M/E within keratinocytes is reduced in photoprotected skin of aged women. Furthermore, the overall endopeptidase activity of cysteine cathepsins in epidermis lysates decreased with age. Albeit dermal elastic fiber and laminin expression is reduced in aged skin, staining of nidogen-1, a key protein in BM assembly that is sensitive to proteolysis by cysteine, metallo- and serine proteases, has a similar pattern in both young and aged skin. Since cathepsins contribute to the hydrolysis and turnover of ECM/basement membrane components, the abnormal protein degradation and deposition during aging process may be related in part to a decline of lysosomal/endosomal cathepsin K, S and V activity.

Binding of chondroitin 4-sulfate to cathepsin S regulates its enzymatic activity.

Human cysteine cathepsin S (catS) participates in distinct physiological and pathophysiological cellular processes and is considered as a valuable therapeutic target in autoimmune diseases, cancer, atherosclerosis, and asthma. We evaluated the capacity of negatively charged glycosaminoglycans (heparin, heparan sulfate, chondroitin 4/6-sulfates, dermatan sulfate, and hyaluronic acid) to modulate the activity of catS. Chondroitin 4-sulfate (C4-S) impaired the collagenolytic activity (type IV collagen) and inhibited the peptidase activity (Z-Phe-Arg-AMC) of catS at pH 5.5, obeying a mixed-type mechanism (estimated Ki = 16.5 ± 6 µM). Addition of NaCl restored catS activity, supporting the idea that electrostatic interactions are primarly involved. Furthermore, C4-S delayed in a dose-dependent manner the maturation of procatS at pH 4.0 by interfering with the intermolecular processing pathway. Binding of C4-S to catS was demonstrated by gel-filtration chromatography, and its affinity was measured by surface plasmon resonance (equilibrium dissociation constant Kd = 210 ± 40 nM). Moreover, C4-S induced subtle conformational changes in mature catS as observed by intrinsic fluorescence spectroscopy analysis. Molecular docking predicted three specific binding sites on catS for C4-S that are different from those found in the crystal structure of the cathepsin K-C4-S complex. Overall, these results describe a novel glycosaminoglycan-mediated mechanism of catS inhibition and suggest that C4-S may modulate the collagenase activity of catS in vivo.

Hormesis-based anti-aging products: a case study of a novel cosmetic.

Application of hormesis in aging research and interventions is becoming increasingly attractive and successful. The reason for this is the realization that mild stress-induced activation of one or more stress response (SR) pathways, and its consequent stimulation of repair mechanisms, is effective in reducing the age-related accumulation of molecular damage. For example, repeated heat stress-induced synthesis of heat shock proteins has been shown to have a variety of anti-aging effects on growth and other cellular and biochemical characteristics of normal human skin fibroblasts, keratinocytes and endothelial cells undergoing aging in vitro. Therefore, searching for potential hormetins - conditions and compounds eliciting SR-mediated hormesis - is drawing attention of not only the researchers but also the industry involved in developing healthcare products, including nutriceuticals, functional foods and cosmeceuticals. Here we present the example of a skin care cosmetic as one of the first successful product developments incorporating the ideas of hormesis. This was based on the studies to analyse the molecular effects of active ingredients extracted from the roots of the Chinese herb Sanchi (Panax notoginseng) on gene expression at the level of mRNAs and proteins in human skin cells. The results showed that the ginsenosides extracted from Sanchi induced the transcription of stress genes and increased the synthesis of stress proteins, especially the heat shock protein HSP1A1 or Hsp70, in normal human keratinocytes and dermal fibroblasts. Furthermore, this extract also has significant positive effects against facial wrinkles and other symptoms of facial skin aging as tested clinically, which may be due to its hormetic mode of action by stress-induced synthesis of chaperones involved in protein repair and removal of abnormal proteins. Acceptance of such a hormesis-based product by the wider public could be instrumental in the social recognition of the concept of hormesis as the beneficial effects of mild stress of choice, and will encourage the development of novel health care products with physical, nutritional and mental hormetins.

Cleavage of nidogen-1 by cathepsin S impairs its binding to basement membrane partners.

Cathepsin S (catS), which is expressed in normal human keratinocytes and localized close to the dermal-epidermal junction (DEJ) degrades some of major basement membrane (BM) constituents. Among them, catS readily hydrolyzed in a time and dose dependent manner human nidogen-1 (nid-1) and nidogen-2, which are key proteins in the BM structure. CatS preferentially cleaved nid-1 at both acid and neutral pH. Hydrolysis of nid-1 was hampered in murine ctss(-/-) spleen lysates pretreated with inhibitors of other classes of proteases. Nid-1 was cleaved within its G2 and G3 globular domains that are both involved in interactions with other BM components. Binding assays with soluble and immobilized ligands indicated that catS altered the formation of complexes between nid-1 and other BM components. Assuming that the cleavage of nid-1 impairs its ability to crosslink with BM partners and perturbs the viscoelastic properties of BM matrix, these data indicate that catS may participate in BM proteolysis, in addition to already identified proteases.

Human skin keratinocytes, melanocytes, and fibroblasts contain distinct circadian clock machineries.

Skin acts as a barrier between the environment and internal organs and performs functions that are critical for the preservation of body homeostasis. In mammals, a complex network of circadian clocks and oscillators adapts physiology and behavior to environmental changes by generating circadian rhythms. These rhythms are induced in the central pacemaker and peripheral tissues by similar transcriptional-translational feedback loops involving clock genes. In this work, we investigated the presence of functional oscillators in the human skin by studying kinetics of clock gene expression in epidermal and dermal cells originating from the same donor and compared their characteristics. Primary cultures of fibroblasts, keratinocytes, and melanocytes were established from an abdominal biopsy and expression of clock genes following dexamethasone synchronization was assessed by qPCR. An original mathematical method was developed to analyze simultaneously up to nine clock genes. By fitting the oscillations to a common period, the phase relationships of the genes could be determined accurately. We thereby show the presence of functional circadian machinery in each cell type. These clockworks display specific periods and phase relationships between clock genes, suggesting regulatory mechanisms that are particular to each cell type. Taken together, our data demonstrate that skin has a complex circadian organization. Oscillators are present not only in fibroblasts but also in epidermal keratinocytes and melanocytes and are likely to act in coordination to drive rhythmic functions within the skin.

Role of neurotrophins on dermal fibroblast survival and differentiation.

Neurotrophins (NTs) belong to a family of growth factors that play a critical role in the control of skin homeostasis. NTs act through the low-affinity receptor p75NTR and the high-affinity receptors TrkA, TrkB, and TrkC. Here we show that dermal fibroblasts (DF) and myofibroblasts (DM) synthesize and secrete all NTs and express NT receptors. NTs induce differentiation of DF into DM, as shown by the expression of α-SMA protein. The Trk inhibitor K252a, TrkA/Fc, TrkB/Fc, or TrkC/Fc chimera prevents DF and DM proliferation. In addition, p75NTR siRNA inhibits DF proliferation, indicating that both NT receptors mediate DF proliferation induced by endogenous NTs. Autocrine NTs also induce DF migration through p75NTR and Trk, as either silencing of p75NTR or Trk/Fc chimeras prevent this effect, in absence of exogenous NTs. Finally, NGF or BDNF statistically increase the tensile strength in a dose dependent manner, as measured in a collagen gel through the GlaSbox device. Taken together, these results indicate that NTs exert a critical role on fibroblast and could be involved in tissue re-modeling and wound healing.

Ground vasovagal presyncopes and fighter pilot fitness: aeromedical concerns.

BACKGROUND: Vasovagal episodes are common events but may have consequences for flight safety, particularly in high-performance aircrafts, where the autonomic nervous system is impacted during +G(z) accelerations. However, the risk is difficult to assess in the case of ground presyncopes. CASE REPORT: A 27-yr-old fighter pilot experienced a feeling of faintness at a daily briefing. He had previously shown no medical history except for a single episode. The initial physical examination was normal. During vagal maneuvers, the pilot developed a cardiac pause and a tilt-table test was positive. Other investigations were normal.The pilot lost consciousness twice in centrifuge testing while previous tests had shown a good cardiovascular tolerance. He was declared unfit to fly fast jets but fit as a multicrew transport pilot with a waiver. DISCUSSION: The epidemiology of vasovagal reactions is difficult to estimate in aircrew. A late occurrence in the career can be explained by either a newly acquired hypervagotonia, or an old predisposition with specific triggering factors in which psychosocial aspects are important. In such circumstances three steps are necessary to assess fitness: 1) to check for other etiologies; 2) to look for vasovagal predisposition; and 3) to check psychiatric condition. The studies about the predictive value of the tilt-test must be taken into account. CONCLUSION: In the case of vasovagal presyncope in a fighter pilot, the aeromedical decision should consider the medical history of the pilot, the results of investigations, and the experience and motivation of the individual under review. Centrifuge testing may be useful in difficult situations.

A photographic scale for the evaluation of facial skin aging in Indian women.

The process of facial skin aging differs between different ethnic populations. Standardized tools to objectively evaluate facial skin aging in clinical and epidemiological studies in different ethnic populations are needed. We designed and validated a photonumeric scale for assessment of facial aging in the Indian population. A total of 149 subjects were selected from an electronic photographic database of 300 women from the Mumbai region. An expert consensus panel selected nine subjects representing a spectrum of skin damage from none to severe, on the basis of wrinkling and tissue slackening. The nine-point scale, composed of one face-on and one oblique photo of the same subject per grade, was validated by nine independent judges in 99 subjects with a repetition two weeks later. Inter-observer reliability and intra-observer reproducibility were calculated using Kappa coefficients. Validation of the scale showed a high level of inter-observer reliability between the consensus and independent panels, and intra-observer reproducibility between the two evaluations performed by the independent judges. In conclusion, this nine-point facial aging scale is a reliable tool for clinical evaluations of skin damage in Indian women, suitable for use in clinical and epidemiological studies.

Melanin transfer in human skin cells is mediated by filopodia--a model for homotypic and heterotypic lysosome-related organelle transfer.

Transfer of the melanocyte-specific and lysosome-related organelle, the melanosome, from melanocytes to keratinocytes is crucial for the protection of the skin against harmful ultraviolet radiation (UVR)--our main physiological cutaneous stressor. However, this commonplace event remains a most enigmatic process despite several early hypotheses. Recently, we and others have proposed a role for filopodia in melanin transfer, although conclusive experimental proof remained elusive. Using known filopodial markers (MyoX/Cdc42) and the filopodial disrupter, low-dose cytochalasin-B, we demonstrate here a requirement for filopodia in melanosome transfer from melanocytes to keratinocytes and also, unexpectedly, between keratinocytes. Melanin distribution throughout the skin represents the key phenotypic event in skin pigmentation. Melanocyte filopodia were also necessary for UVR-stimulated melanosome transfer, as this was also inhibited by MyoX knockdown and low-dose cytochalasin-B. Knockdown of keratinocyte MyoX protein, in its capacity as a phagocytosis effector, resulted in the inhibition of melanin uptake by keratinocytes. This indicates a central role for phagocytosis by keratinocytes of melanocyte filopodia. In summary, we propose a new model for the regulation of pigmentation in human skin cells under both constitutive and facultative (post-UVR) conditions, which we call the "filopodial-phagocytosis model." This model also provides a unique and highly accessible way to study lysosome-related organelle movement between mammalian cells.