Atypical cutaneous manifestations of methicillin resistant Staphylococcus aureus infections in two immunocompetent pediatric patients: Case reports and review of the literature.

Although many clinical variants of Staphylococcus aureus infection are well-recognized, atypical presentations may mimic other conditions. We describe two cases of atypical S. aureus infections in pediatric patients: a S. aureus infection presenting with a vesicopustular rash mimicking varicella zoster virus and a case of multifocal panniculitis. Both of these cases were specifically caused by methicillin-resistant S. aureus (MRSA). Additional cases of atypical S. aureus infections and presenting features from the current literature are also discussed.

Chromatin accessibility profiling reveals that human fibroblasts respond to mechanical stimulation in a cell-specific manner.

Fibroblasts in the skin are highly heterogeneous, both in vivo and in vitro. One difference between follicular (dermal papilla fibroblasts [DP]) and interfollicular fibroblasts (papillary fibroblasts [PFi]) in vitro is their ability to differentiate in response to osteogenic media (OM), or mechanical stimulation. Here, we asked whether differences in the ability of DP and PFi to respond to differentiation stimuli are due to differences in chromatin accessibility. We performed chromatin accessibility and transcriptional profiling of DP and PFi in human skin, which arise from a common progenitor during development, yet display distinct characteristics in adult tissue and in vitro. We found that cells cultured in growth media had unique chromatin accessibility profiles; however, these profiles control similar functional networks. Upon introduction of a chemical perturbation (OM) to promote differentiation, we observed a divergence not only in the accessible chromatin signatures but also in the functional networks controlled by these signatures. The biggest divergence between DP and PFi was observed when we applied 2 perturbations to cells: growth in OM and mechanical stimulation (a shock wave [OMSW]). DP readily differentiate into bone in OMSW conditions, while PFi lack differentiation capability in vitro. In the DP we found a number of uniquely accessible promoters that controlled osteogenic interaction networks associated with bone and differentiation functions. Using ATAC-seq and RNA-seq we found that the combination of 2 stimuli (OMSW) could result in significant changes in chromatin accessibility associated with osteogenic differentiation, but only within the DP (capable of osteogenic differentiation). De novo motif analysis identified enrichment of motifs bound by the TEA domain (TEAD) family of transcription factors, and inter-cell comparisons (UpSet analysis) displayed large groups of genes to be unique to single cell types and conditions. Our results suggest that these 2 stimuli (OMSW) elicit cell-specific responses by modifying chromatin accessibility of osteogenic-related gene promoters.

Mechanical stimulation of human hair follicle outer root sheath cultures activates adjacent sensory neurons.

Mechanical stimuli, such as stroking or pressing on the skin, activate mechanoreceptors transmitting information to the sensory nervous system and brain. It is well accepted that deflection of the hair fiber that occurs with a light breeze or touch directly activates the sensory neurons surrounding the hair follicle, facilitating transmission of mechanical information. Here, we hypothesized that hair follicle outer root sheath cells act as transducers of mechanical stimuli to sensory neurons surrounding the hair follicle. Using electrochemical analysis on human hair follicle preparations in vitro, we were able to show that outer root sheath cells release ATP and the neurotransmitters serotonin and histamine in response to mechanical stimulation. Using calcium imaging combined with pharmacology in a coculture of outer root sheath cells with sensory neurons, we found that the release of these three molecules from hair follicle cells leads to activation of sensory neurons.

A catena between psychiatric disorders and non-scarring alopecias-A systematic review.

For many years, clinical observations have suggested that there is an intrinsic connection between psychological state and skin diseases. Stress responses are typically mediated by several hormones, which are modulated via the hypothalamic-pituitary-adrenal axis. This typical stress response is not only one theory for psychiatry disorder pathophysiology, but it also modifies hair growth by altering the skin's inflammatory environment. Given that different forms of hair loss, such as androgenetic alopecia, alopecia areata, or telogen effluvium, and hair follicle cycling can be altered by immune cells within the follicle milieu, we hypothesized that specific forms of hair loss are correlated to psychiatric illnesses. To address this, we conducted a systematic review by searches in April and May 2021 through Ovid MEDLINE and PUBMED (ranging from 1951 to the present day), identifying 179 reports. A further 24 reports were identified through website and citation searches giving a total of 201 reports. After applying exclusion criteria, 21 papers were reviewed, and 17 were included for data analysis. It is undeniable that hair loss greatly affects Health-related Quality of Life (HrQol) and it is heavily associated with major depressive disorder and anxiety. The correlation between hair loss and mental health disorders was significant, however, due to the low number of publications with quantitative data we were not able to identify correlations between each hair loss type with each psychiatric disorder. Further studies to better connect specific hair loss diseases to specific disorders are therefore critical in bettering the way both psychiatric disease, and hair loss, are managed.

Male pattern hair loss: Can developmental origins explain the pattern?

Male pattern hair loss (MPHL), also referred to as male androgenetic alopecia (AGA) is the most common type of non-scarring progressive hair loss, with 80% of men suffering from this condition in their lifetime. In MPHL, the hair line recedes to a specific part of the scalp which cannot be accurately predicted. Hair is lost from the front, vertex, and the crown, yet temporal and occipital follicles remain. The visual effect of hair loss is due to hair follicle miniaturisation, where terminal hair follicles become dimensionally smaller. Miniaturisation is also characterised by a shortening of the growth phase of the hair cycle (anagen), and a prolongation of the dormant phase (kenogen). Together, these changes result in the production of thinner and shorter hair fibres, referred to as miniaturised or vellus hairs. It remains unclear why miniaturisation occurs in this specific pattern, with frontal follicles being susceptible while occipital follicles remain in a terminal state. One main factor we believe to be at play, which will be discussed in this viewpoint, is the developmental origin of the skin and hair follicle dermis on different regions of the scalp.

Anagen hair follicles transplanted into mature human scars remodel fibrotic tissue.

Despite the substantial impact of skin scarring on patients and the healthcare system, there is a lack of strategies to prevent scar formation, let alone methods to remodel mature scars. Here, we took a unique approach inspired by how healthy hairbearing skin undergoes physiological remodelling during the regular cycling of hair follicles. In this pilot clinical study, we tested if hair follicles transplanted into human scars can facilitate tissue regeneration and actively remodel fibrotic tissue, similar to how they remodel the healthy skin. We collected full-thickness skin biopsies and compared the morphology and transcriptional signature of fibrotic tissue before and after transplantation. We found that hair follicle tranplantation induced an increase in the epidermal thickness, interdigitation of the epidermal-dermal junction, dermal cell density, and blood vessel density. Remodelling of collagen type I fibres reduced the total collagen fraction, the proportion of thick fibres, and their alignment. Consistent with these morphological changes, we found a shift in the cytokine milieu of scars with a long-lasting inhibition of pro-fibrotic factors TGFß1, IL13, and IL-6. Our results show that anagen hair follicles can attenuate the fibrotic phenotype, providing new insights for developing regenerative approaches to remodel mature scars.

Self-administration of medications in inpatient postnatal women: an opportunity to empower self-care, improved medicines knowledge and adherence utilising clinical pharmacists and midwifery workforce and use of a midwife formulary.

OBJECTIVES: To assess the impact of self-administration of medicines (facilitated by a midwife formulary) on postnatal women's knowledge of certain post-delivery medications, awareness of the Green Bag Scheme, factors contributing to constipation, pain satisfaction, adherence, and time released to midwives plus feedback from these women and their midwives. METHODS: The study was conducted in consented postnatal women, who self-administered medications from their bedside lockers. The mode of delivery and parity were recorded. Data were compared in women who self-administered to those who did not. Midwives used our established midwife formulary to write their essential unprescribed medications. Direct interview questionnaires were used to obtain their knowledge on chosen post-delivery medicines, pain satisfaction, the Green Bag Scheme and factors contributing to constipation. Regular medicines counts were used to check adherence. Midwives' time not administering these self-administered medications was estimated. Self-reported questionnaires were used to obtain feedback from participants and midwives. Responses were analysed proportionately and where appropriate by simple statistics. RESULTS: Women (n=203) who self-administered were compared with those (n=401) who did not. Greater medicines' knowledge and better (96% vs 79%) pain satisfaction were found in self-administering women. Knowledge of each contributing factor to constipation varied. Mode of delivery and parity had no impact on these outcomes. Adherence seemed high 96% (195/203). Awareness of the Green Bag Scheme was poor (66/604). Most women, 94% (191/203) found the service helpful and 89% (178/200) would take part again. At least 224 hours were released to midwives by these self-administering women. 164/203 (81%) midwives felt the scheme was beneficial. CONCLUSIONS: Self-administering women had better pain satisfaction, medication knowledge and adherence. The need to improve engagement in the Green Bag Scheme was flagged. This service, supported by use of a midwife formulary, can release time to midwives to do other tasks including care for women with more complex issues. A business case for this service is under review.

Skin wrinkles and folds enable asymmetric stretch in the elephant trunk.

The elephant's trunk is multifunctional: It must be flexible to wrap around vegetation, but tough to knock down trees and resist attack. How can one appendage satisfy both constraints? In this combined experimental and theoretical study, we challenged African elephants to reach far-away objects with only horizontal extensions of their trunk. Surprisingly, the trunk does not extend uniformly, but instead exhibits a dorsal "joint" that stretches 15% more than the corresponding ventral section. Using material testing with the skin of a deceased elephant, we show that the asymmetry is due in part to patterns of the skin. The dorsal skin is folded and 15% more pliable than the wrinkled ventral skin. Skin folds protect the dorsal section and stretch to facilitate downward wrapping, the most common gripping style when picking up items. The elephant's skin is also sufficiently stiff to influence its mechanics: At the joint, the skin requires 13 times more energy to stretch than the corresponding length of muscle. The use of wrinkles and folds to modulate stiffness may provide a valuable concept for both biology and soft robotics.

Can plantar fibroblast implantation protect amputees from skin injury? A recipe for skin augmentation.

Skin injuries remain a persistent problem for users of lower-limb prostheses despite sustained progress in prosthesis design. One factor limiting the prevention of skin injuries is that skin on the residual limb is not suited to bear the mechanical loads of ambulation. One part of the body that is suited to this task is the sole of the foot. Here, we propose a novel strategy to actively augment skin's tolerance to load, increasing its resistance to mechanically induced injuries. We hypothesise that the load tolerance of skin can be augmented by autologous transplantation of plantar fibroblasts into the residual limb dermis. We expect that introducing plantar fibroblasts will induce the overlying keratinocytes to express plantar-specific keratins leading to a tougher epidermis. Using a computational finite element model of a weight-bearing residual limb, we estimate that skin deformation (a key driver of pressure ulcer injuries) could be halved by reprogramming skin to a plantar-like phenotype. We believe this strategy could yield new progress in pressure ulcer prevention for amputees, facilitating rehabilitation and improving quality of life for patients.

Mechanotransduction in osteogenesis.

Bone is one of the most highly adaptive tissues in the body, possessing the capability to alter its morphology and function in response to stimuli in its surrounding environment. The ability of bone to sense and convert external mechanical stimuli into a biochemical response, which ultimately alters the phenotype and function of the cell, is described as mechanotransduction. This review aims to describe the fundamental physiology and biomechanisms that occur to induce osteogenic adaptation of a cell following application of a physical stimulus. Considerable developments have been made in recent years in our understanding of how cells orchestrate this complex interplay of processes, and have become the focus of research in osteogenesis. We will discuss current areas of preclinical and clinical research exploring the harnessing of mechanotransductive properties of cells and applying them therapeutically, both in the context of fracture healing and de novo bone formation in situations such as nonunion. Cite this article: Bone Joint Res 2019;9(1):1-14.

Isolating Dermal Papilla Cells from Human Hair Follicles Using Microdissection and Enzyme Digestion.

The dermal papilla (DP) is a cluster of mesenchymal cells located at the bottom of the hair follicle. Cells within the DP interact with numerous other cell types within the follicle, including epithelial stem cells, matrix cells, and melanocytes, regulating their function. The diameter of the DP is directly proportional to the width of the hair shaft, and a decrease in both cell number and DP size is observed in hair loss conditions such as androgenetic alopecia. Conversely, microdissected ex vivo DP can instruct growth of de novo hair follicles. The study of DP cells and their role in human hair growth is often hampered by the technical challenge of DP isolation and culture. Here we describe a method used within our research group for isolating DP from human hair follicles.

Immune cell regulation of the hair cycle.

The ability to manipulate the mammalian hair cycle will lead to novel therapies and strategies to combat all forms of alopecia. Thus, in addition to the epithelial-mesenchymal interactions in the hair follicle, niche and microenvironmental signals that accompany the phases of growth, regression and rest need to be scrutinized. Immune cells are well described in skin homeostasis and wound healing and have recently been shown to play an important role in the mammalian hair cycle. In this review, we will summarize our current knowledge of the role of immune cells in hair cycle control and discuss their relevance to human hair cycling disorders. Increased attention to this aspect of the hair cycle will provide new avenues to manipulate hair regeneration in humans and provide better insight into developing better ex vivo models of hair growth.

Harnessing the Secretome of Hair Follicle Fibroblasts to Accelerate Ex Vivo Healing of Human Skin Wounds.

In skin homeostasis, dermal fibroblasts are responsible for coordinating the migration and differentiation of overlying epithelial keratinocytes. As hairy skin heals faster than nonhairy skin, we took bio-inspiration from the follicle and hypothesized that follicular fibroblasts would accelerate skin re-epithelialization after injury faster than interfollicular fibroblasts. Using both in vitro and ex vivo models of human skin wound closure, we found that hair follicle dermal papilla fibroblasts could accelerate closure of in vitro scratch wounds by 1.8-fold and epithelial growth capacity by 1.5-fold compared with controls (P < 0.05). We used a cytokine array to determine how the dermal papilla fibroblasts were eliciting this effect and identified two cytokines, sAXL and CCL19, that are released at significantly higher levels by follicular fibroblasts than by interfollicular subtypes. Using sAXL and CCL19 individually, we found that they could also increase closure of epithelial cells in a scratch wound by 1.2- and 1.5-fold, respectively, compared with controls (P < 0.05). We performed an unbiased transcriptional analysis, combined with pathway analysis, and postulate that sAXL accelerates wound closure by promoting migration and inhibiting epithelial differentiation of skin keratinocytes. Long term, we believe these results can be exploited to accelerate wound closure of human skin in vivo.

Morphology and composition play distinct and complementary roles in the tolerance of plantar skin to mechanical load.

Plantar skin on the soles of the feet has a distinct morphology and composition that is thought to enhance its tolerance to mechanical loads, although the individual contributions of morphology and composition have never been quantified. Here, we combine multiscale mechanical testing and computational models of load bearing to quantify the mechanical environment of both plantar and nonplantar skin under load. We find that morphology and composition play distinct and complementary roles in plantar skin's load tolerance. More specifically, the thick stratum corneum provides protection from stress-based injuries such as skin tears and blisters, while epidermal and dermal compositions provide protection from deformation-based injuries such as pressure ulcers. This work provides insights into the roles of skin morphology and composition more generally and will inform the design of engineered skin substitutes as well as the etiology of skin injury.

Hydrogel-Coated Microneedle Arrays for Minimally Invasive Sampling and Sensing of Specific Circulating Nucleic Acids from Skin Interstitial Fluid.

Minimally invasive technologies that can sample and detect cell-free nucleic acid biomarkers from liquid biopsies have recently emerged as clinically useful for early diagnosis of a broad range of pathologies, including cancer. Although blood has so far been the most commonly interrogated bodily fluid, skin interstitial fluid has been mostly overlooked despite containing the same broad variety of molecular biomarkers originating from cells and surrounding blood capillaries. Emerging technologies to sample this fluid in a pain-free and minimally-invasive manner often take the form of microneedle patches. Herein, we developed microneedles that are coated with an alginate-peptide nucleic acid hybrid material for sequence-specific sampling, isolation, and detection of nucleic acid biomarkers from skin interstitial fluid. Characterized by fast sampling kinetics and large sampling capacity (∼6.5 µL in 2 min), this platform technology also enables the detection of specific nucleic acid biomarkers either on the patch itself or in solution after light-triggered release from the hydrogel. Considering the emergence of cell-free nucleic acids in bodily fluids as clinically informative biomarkers, platform technologies that can detect them in an automated and minimally invasive fashion have great potential for personalized diagnosis and longitudinal monitoring of patient-specific disease progression.