A transit-amplifying progenitor with biphasic behavior contributes to epidermal renewal.

Transit-amplifying (TA) cells are progenitors that undergo an amplification phase followed by transition into an extinction phase. A long postulated epidermal TA progenitor with biphasic behavior has not yet been experimentally observed in vivo. Here, we identify such a TA population using clonal analysis of Aspm-CreER genetic cell-marking in mice, which uncovers contribution to both homeostasis and injury repair of adult skin. This TA population is more frequently dividing than a Dlx1-CreER-marked long-term self-renewing (e.g. stem cell) population. Newly developed generalized birth-death modeling of long-term lineage tracing data shows that both TA progenitors and stem cells display neutral competition, but only the stem cells display neutral drift. The quantitative evolution of a nascent TA cell and its direct descendants shows that TA progenitors indeed amplify the basal layer before transition and that the homeostatic TA population is mostly in extinction phase. This model will be broadly useful for analyzing progenitors whose behavior changes with their clone age. This work identifies a long-missing class of non-self-renewing biphasic epidermal TA progenitors and has broad implications for understanding tissue renewal mechanisms.

A case-control study: epigenetic age acceleration in psoriasis.

Psoriasis (PsO) is a chronic inflammatory skin condition, often accompanied by psoriatic arthritis (PsA) and linked to various comorbidities and increased mortality rates. This study aimed to explore the relationship between PsO and accelerated biological aging, specifically focusing on epigenetic DNA methylation clocks. Using a matched case-control design, 20 PsO cases were selected along with age, race, and sex-matched 20 controls without PsO from the Skin Disease Biorepository at Brown Dermatology, Inc, Providence, Rhode Island. Blood samples retrieved from both groups were analyzed for DNA methylation, and epigenetic ages were calculated using DNA methylation clocks, including Horvath, Hannum, Pheno, SkinBlood, and Grim ages. Generalized estimation equations were employed to test the differences in epigenetic and chronological ages between PsO cases and controls, as well as within various subgroups in comparison to their respective controls. There were no statistically significant differences in epigenetic ages between PsO cases and controls. However, notably, PsO cases with PsA demonstrated an accelerated PhenoAge, compared to their matched controls. This study represents a pioneering investigation into the potential link between PsO and epigenetic aging, shedding light on the possibility of accelerated epigenetic aging in PsA, possibly associated with heightened inflammatory burden. These findings emphasize the systemic impact of PsA on the aging process, prompting the need for deeper exploration into autoimmune pathways, inflammation, and epigenetic modifications underlying PsO pathogenesis and aging mechanisms. Larger-scale studies with diverse populations are imperative to discern PsO subgroups experiencing accelerated biological aging and decipher the intricate interplay between PsO, inflammation, and aging pathways.

A Pearl for Pretibial and Forearm Repair Following Mohs Micrographic Surgery.

Wound repair of the pretibial and forearm regions presents a challenge during dermatologic surgery as these areas are under significant tension and exhibit increased skin fragility. Various methodologies have been proposed for the closure and repair of such wounds, however, the use of the bilayered suture technique may be simpler and more effective than other techniques such as the pinch stitch, pully stitch, slip-knot stitch, pulley set-back dermal suture, horizontal mattress suture, pully stitch, and tandem pulley stitch. Our objective was to describe a novel method for the repair of pretibial and forearm wounds following Mohs micrographic surgery utilizing bilayered closure followed by tissue adhesive application.  J Drugs Dermatol. 2024;23(5):380.     doi:10.36849/JDD.7139  .

Specialties with Few Underrepresented Applicants Lack Diversity Information on Residency Websites.

INTRODUCTION: With the advent of virtual interviews and the increasing accessibility of internet resources, students increasingly rely on program websites for residency application decisions. In this cross-sectional study, we evaluated the presence of diversity or inclusion information in the least diverse US specialties' residency program websites, including dermatology, orthopedic surgery, otolaryngology, plastic surgery, and urology residency programs. METHODS: Two authors independently reviewed each Accreditation Council for Graduate Medical Education-accredited non-military US residency program website and ranked the websites' diversity and inclusion information using six pre-determined criteria based on previous studies in the literature. RESULTS: This study reveals that more than half of residency programs of each specialty met zero of the diversity and inclusion information criteria. CONCLUSIONS: Residency program websites in the least diverse specialties are lacking important information for prospective applicants that may help signal programs' commitment to inclusivity and attract a diverse candidate pool.

Racial Disparities in the Treatment of Hidradenitis Suppurativa: An Analysis of Data from the National Ambulatory Medical Care Survey.

Hidradenitis suppurativa (HS) is a painful, disfiguring, chronic inflammatory disease affecting the axillary, inframammary, and groin regions. Black Americans are disproportionately affected by HS. Structural barriers may be responsible for a lack of better prevention and management. This paper discusses possible reasons that may lead to a more severe presentation and barriers to treatment. Moseley I, Ragi SD, Handler MZ. racial disparities in the treatment of hidradenitis suppurativa: an analysis of data from the National Ambulatory Medical Care Survey. J Drugs Dermatol. 2023;22(7):692-694. doi:10.36849/JDD.6803.

Tinea versicolour in underrepresented groups: An All of Us database analysis.

Tinea versicolour, used interchangeably with pityriasis versicolour (PV), is a superficial fungal infection of the stratum corneum caused by Malassezia furfur, a fungus of the normal flora of the skin. PV occurs when conditions favour proliferation of the organism's mycelial form, such as in environments with high temperatures/humidity, in immunodeficient/immunocompromised states, and during pregnancy. PV presents as numerous well- demarcated macules with a powdery scale. Prior epidemiologic studies have indicated that underrepresented groups defined by race experience a higher burden of PV as compared to White patients. However, the burden of PV in other underrepresented groups has not previously been examined, as underrepresented groups are frequently excluded from studies evaluating the impact of dermatologic disease. The new National Institute of Health All of Us Research Program (AoU) aims to build one of the world's largest and most diverse databases to promote elucidation of health disparities, particularly in communities that have been historically excluded from biomedical research.

Pedigree Analysis of Families and Patients Affected by Retinitis Pigmentosa.

Family pedigrees allow for a more thorough understanding of human genetic disorders. They are used to help establish patterns of inheritance and to identify individuals at risk of disease. Pedigree analysis can be helpful in identifying genetic disorders that demonstrate mechanisms such autosomal dominant or recessive inheritance, X-linked inheritance, and anticipation.

Visual Function Tests.

Inherited retinal diseases (IRDs), including retinitis pigmentosa, have devastating consequences for the visual function of affected individuals. Chief among these are a gradual loss of visual field, visual acuity, and night vision (otherwise known as nyctalopia). These changes often occur slowly, over a course of decades. Objective modalities for assessing these many aspects of visual function are crucial, not only to the monitoring of disease progression but, in recent years, also to evaluating the efficacy or lack thereof of new therapeutic interventions in the setting of clinical trials. This chapter will provide descriptions of these valuable assessment modalities, alongside discussions of their advantages and limitations in the context of serving those afflicted by IRDs.

Ophthalmic Fluorescein Angiography.

Following its implementation in the 1960s, fluorescein angiography (FA) has become a widely used and reliable tool in the diagnosis of retinal and choroidal disorders. FA is an imaging modality utilized to examine the circulation of the retina and choroid. Here, we describe the process of obtaining fundus images with sodium fluorescein dye as a contrast agent. Using this methodology, ophthalmologists may examine the retinal and choroidal vasculature to diagnose a wide scope of retinal and choroidal diseases.

Protocol for Indocyanine Green Angiography.

Indocyanine green (ICG) angiography was first approved by the Food and Drug Administration for human use in the 1956. Prior to its use in chorioretinal angiograms, ICG was used to measure blood flow and track cardiac output. It was only in 1969 when two researchers, Kyuga Kogure and Earl Choromokos from the University of Miami, first used ICG to create more accurate angiograms. In the following years, researchers were able to hone the underlying science of this new form of angiography. As time passed and technology advanced, the application of ICG in clinical practice became widespread. Today ICG is used to diagnose and monitor the progression of retinal and choroidal diseases affecting millions of individuals across the globe. ICG utilizes the injection of indocyanine green dye into a patient's bloodstream to visualize abnormalities of the choroid and retina by evaluating choroidal circulation. ICG angiography is useful in the diagnosis and management of occult choroidal neovascularization in age-related macular degeneration and may be used in other inflammatory conditions with central serous chorioretinopathy. ICG angiography offers advanced imaging for improved monitoring and treatment of a wide variety of choroidal and retinal diseases.

Use of the Medmont Dark-Adapted Chromatic Perimeter for Assessing Rod Function in Retinitis Pigmentosa.

Medmont Dark-Adapted Chromatic (DAC) Perimeter enables efficient and quantifiable evaluation of rod-mediated (scotopic) vision. DAC tests rod function at multiple retinal locations, creating a topographical map of rod-mediated vision. These dynamic rod responses can be used as a functional marker to monitor disease progression and functional alterations in inherited retinal dystrophies, such as retinitis pigmentosa, Stargardt disease, cone-rod dystrophy, and choroideremia. In this chapter, we describe a protocol for the operation and analysis of the Medmont DAC in monitoring and assessing various retinal disorders.

CRISPR Off-Target Analysis Platforms.

The clustered regularly interspaced short palindromic repeats (CRISPR)-Caspase9 (Cas9) system provides a programmable technology that may be used to edit the eukaryotic genome and epigenome. CRISPR/Cas9 includes a guide RNA targeted to a gene of interest which hybridizes to a nucleotide sequence next to a protospacer-adjacent motif (PAM) which guides the Cas9 endonucleases to the target site for cleavage via double-strand breaks. A caveat of the CRISPR/Cas9 system is the creation of off-target double-strand breaks (DSBs) which may result in anomalous insertions, deletions, and translocations. Thus, assays for the sensitive detection and analysis of off-target editing are critical. Here, we describe currently available CRISPR technologies, CRISPR applications, and current analysis platforms to detect off-target effects including genome-wide, unbiased identification of DSBs enabled by sequencing (GUIDE-Seq), high-throughput genomic translocation sequencing (HTGTS), breaks labeling, enrichments on streptavidin and next-generation sequencing (BLESS), and in vitro nuclease-digested genome sequencing (Digenome-seq).