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.

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.

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.

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.

A bald statement - Current approaches to manipulate miniaturisation focus only on promoting hair growth.

Hair plays a large part in communication and society with its role changing through time and across cultures. Most people do not leave the house before combing their hair or shaving their beard and for many hair loss or irregular hair growth can have a significant impact on their psychological health. Somewhat unsurprisingly, according to GMR Data, today's global hair care industry is worth an estimated $87 Billion, with hair loss estimated at $2.8 Billion. Considering that no current hair loss-related products can completely reverse hair loss, it is reasonable to believe this market could expand significantly with the discovery of a comprehensive therapy. As such, a great deal of research focuses on overcoming hair loss, and in particular, a common form of hair loss known as androgenetic alopecia (AGA) or male pattern baldness. In AGA, hair follicles miniaturise in a large step change from a terminal to a vellus state. Within this viewpoint article, we discuss how influx and efflux of cells into and out from the dermal papilla (DP) can modulate DP size during the hair cycle. As DP size is positively correlated with the size of the hair fibre produced by a follicle, we argue here that therapies for treating AGA should be developed which can alter DP size, rather than just promote hair growth. We also discuss current therapeutics for AGA and emphasise the importance of using the right model systems to analyse miniaturisation.

Does clinical testing support the current guidance definition of prolonged contact for nickel allergy?

BACKGROUND: The European Chemical Agency (ECHA) definition of prolonged contact was introduced in 2014 and has not been evaluated clinically. OBJECTIVES: To assess whether nickel-sensitized individuals react on patch testing with high nickel-releasing metal discs for short and repetitive periods. MATERIALS AND METHODS: We patch tested 45 nickel-sensitized individuals double-blind with 2 different types of high nickel-releasing discs for 10, 30 and 60 minutes on 3 occasions over a period of 2 weeks, and for 1 longer period. Discs were tested for nickel release. RESULTS: Nickel release from both discs significantly exceeded the 0.5 µg Ni/cm2 /week limit of the EU REACH nickel restriction. However, only 1 individual tested had a largely dose-dependent allergic reaction. CONCLUSIONS: The majority of nickel-allergic subjects did not react to nickel discs after 2 hours or after repetitive exposures of up to 30 minutes on 3 occasions over a period of 2 weeks. The length of time needed to cause nickel allergic contact dermatitis in most nickel-allergic individuals is longer than the ECHA guidance definition. Longer test times are needed to define the time required to cause dermatitis in most nickel-allergic individuals. As a limitation, the test conditions did not adequately assess real-life factors such as friction, which is relevant for some uses of nickel.

Methods for the isolation and 3D culture of dermal papilla cells from human hair follicles.

The dermal papilla is a cluster of mesenchymal cells located at the base of the hair follicle which have a number of important roles in the regulation of hair growth. As a consequence, in vitro models of these cells are widely used to study the molecular mechanisms which underlie hair follicle induction, growth and maintenance. While dermal papilla from rodent hair follicles can be digested prior to cell isolation, the unique extracellular matrix composition found in human dermal papilla renders enzymes such as trypsin and collagenase insufficient for digestion of the dermal papilla into a single cell suspension. As such, to grow human dermal papilla cells in vitro, the papilla has to first be isolated via a micro-dissection approach from the follicle. In this article we describe the micro-dissection and culture methods, which we use within our laboratory, for the study of human dermal papilla cells.

FGF5 is a crucial regulator of hair length in humans.

Mechanisms that regulate the growth of eyelashes have remained obscure. We ascertained two families from Pakistan who presented with familial trichomegaly, or extreme eyelash growth. Using a combination of whole exome sequencing and homozygosity mapping, we identified distinct pathogenic mutations within fibroblast growth factor 5 (FGF5) that underlie the disorder. Subsequent sequencing of this gene in several additional trichomegaly families identified an additional mutation in FGF5. We further demonstrated that hair fibers from forearms of these patients were significantly longer than hairs from control individuals, with an increased proportion in the growth phase, anagen. Using hair follicle organ cultures, we show that FGF5 induces regression of the human hair follicle. We have identified FGF5 as a crucial regulator of hair growth in humans for the first time, to our knowledge, and uncovered a therapeutic target to selectively regulate eyelash growth.

Occupational skin disease among Australian healthcare workers: a retrospective analysis from an occupational dermatology clinic, 1993-2014.

BACKGROUND: Healthcare workers (HCWs) are at risk of developing occupational skin disease (OSD). OBJECTIVES: To ascertain the causes of OSD in Australian HCWs in a tertiary referral clinic. METHODS: A retrospective review was performed of patients assessed at the Occupational Dermatology Clinic in Melbourne from 1993 to 2014. RESULTS: Of 685 HCWs assessed in the clinic over a period of 22 years, 555 (81.0%) were diagnosed with OSD. The most common diagnosis was irritant contact dermatitis (ICD) (79.1%), followed by allergic contact dermatitis (ACD) (49.7%). Natural rubber latex allergy was also relatively frequent (13.0%). The major substances causing ACD were rubber glove chemicals (thiuram mix and tetraethylthiuram disulfide), preservatives (formaldehyde, formaldehyde releasers, and isothiazolinones), excipients in hand cleansers, which are hard-to-avoid weak allergens, and antiseptics. ACD caused by commercial hand cleansers occurred more frequently than ACD caused by alcohol-based hand rubs (ABHRs). Occupational ICD was mostly caused by water/wet work and hand cleansers, and environmental irritants such as heat and sweating. CONCLUSIONS: Understanding the causes of OSD in HCWs is important in order to develop strategies for prevention. We suggest that skin care advice should be incorporated into hand hygiene education. The use of ABHRs should be encouraged, weak allergens in skin cleansers should be substituted, and accelerator-free gloves should be recommended for HCWs with OSD.

Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth.

De novo organ regeneration has been observed in several lower organisms, as well as rodents; however, demonstrating these regenerative properties in human cells and tissues has been challenging. In the hair follicle, rodent hair follicle-derived dermal cells can interact with local epithelia and induce de novo hair follicles in a variety of hairless recipient skin sites. However, multiple attempts to recapitulate this process in humans using human dermal papilla cells in human skin have failed, suggesting that human dermal papilla cells lose key inductive properties upon culture. Here, we performed global gene expression analysis of human dermal papilla cells in culture and discovered very rapid and profound molecular signature changes linking their transition from a 3D to a 2D environment with early loss of their hair-inducing capacity. We demonstrate that the intact dermal papilla transcriptional signature can be partially restored by growth of papilla cells in 3D spheroid cultures. This signature change translates to a partial restoration of inductive capability, and we show that human dermal papilla cells, when grown as spheroids, are capable of inducing de novo hair follicles in human skin.

Allergic contact dermatitis to substitute hair dyes in a patient allergic to para-phenylenediamine: Pure henna, black tea and indigo powder.

We report a case of a 50-year-old lady with allergic contact dermatitis to para-phenylenediamine, who in her quest to find a substitute hair dye, subsequently reacted to a number of plant-based hair dyes, including pure henna, black tea and indigo powder respectively. While these substances all contain tannins, testing to possible constituents tannic acid and gallic acid was negative.

Interrogating the integument: the role of the epidermis in hair induction.

Hair follicle development is driven by interactions between the epithelium and underlying mesenchyme. These reciprocal interactions are essential for development, as a lack of response from either the mesenchyme or epithelium results in arrested growth. A large body of research has focused on the role of mesenchymal cells during hair follicle development and their inductive properties for hair neogenesis. In this commentary, the role of the epidermis during hair follicle induction will be 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.

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.

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.

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.