Genetic and Functional Analyses of Cutibacterium Acnes Isolates Reveal the Association of a Linear Plasmid with Skin Inflammation.

Cutibacterium acnes is a commensal bacterium on the skin that is generally well-tolerated, but different strain types have been hypothesized to contribute to the disease acne vulgaris. To understand how some strain types might contribute to skin inflammation, we generated a repository of C. acnes isolates from skin swabs of healthy subjects and subjects with acne and assessed their strain-level identity and capacity to stimulate cytokine release.

Antimicrobial production by perifollicular dermal preadipocytes is essential to the pathophysiology of acne.

Innate immune defense against deep tissue infection by is orchestrated by fibroblasts that become antimicrobial when triggered to differentiate into adipocytes. However, the role of this process in noninfectious human diseases is unknown. To investigate the potential role of adipogenesis by dermal fibroblasts in acne, a disorder triggered by , single-cell RNA sequencing was performed on human acne lesions and mouse skin challenged by .

Antimicrobials from a feline commensal bacterium inhibit skin infection by drug-resistant .

Methicillin-resistant (MRSP) is an important emerging zoonotic pathogen that causes severe skin infections. To combat infections from drug-resistant bacteria, the transplantation of commensal antimicrobial bacteria as a therapeutic has shown clinical promise. We screened a collection of diverse staphylococcus species from domestic dogs and cats for antimicrobial activity against MRSP.

Mechanisms for control of skin immune function by the microbiome.

The skin represents the largest area for direct contact between microbes and host immunocytes and is a site for constant communication between the host and this diverse and essential microbial community. Coagulase-negative staphylococci are an abundant bacterial genus on the human skin and are regulated through various mechanisms that include the epidermal barrier environment and innate and adaptive immune systems within the epidermis and dermis. In turn, some species and strains of these bacteria produce beneficial products that augment host immunity by exerting specifically targeted antimicrobial, anti-inflammatory, or anti-neoplastic activity while also promoting broad innate and adaptive immune responses.

Skin Cancer Incidence in Organ Transplant Recipients Referred for Benign Skin Conditions.

Background: Solid organ transplant recipients (SOTRs) are at ∼100-fold increased risk for developing skin cancers compared with the general population, with increased morbidity and mortality. These patients are closely followed by dermatology; however, it is unclear how referral reasons from nondermatologic providers affect care in these patients.

Objective: This study examines the reason SOTRs are referred to dermatologic care by nondermatologic providers as a potential predictor of nonmelanoma skin cancer (NMSC) outcomes.

Use of Autologous Bacteriotherapy to Treat Staphylococcus aureus in Patients With Atopic Dermatitis: A Randomized Double-blind Clinical Trial.

Importance: Atopic dermatitis (AD) can be negatively affected by Staphylococcus aureus. The skin microbiome of AD is deficient in coagulase-negative Staphylococcus (CoNS) that can kill S aureus.

Objective: To evaluate if the antimicrobial-producing CoNS (CoNS-AM+) of a patient with AD can be autologously reintroduced to the same patient to inhibit survival of S aureus and improve clinical outcomes.

Development of a human skin commensal microbe for bacteriotherapy of atopic dermatitis and use in a phase 1 randomized clinical trial.

Staphylococcus aureus colonizes patients with atopic dermatitis (AD) and exacerbates disease by promoting inflammation. The present study investigated the safety and mechanisms of action of Staphylococcus hominis A9 (ShA9), a bacterium isolated from healthy human skin, as a topical therapy for AD. ShA9 killed S.

Staphylococcus epidermidis protease EcpA can be a deleterious component of the skin microbiome in atopic dermatitis.

Background: Staphylococcus aureus and Staphylococcus epidermidis are the most abundant bacteria found on the skin of patients with atopic dermatitis (AD). S aureus is known to exacerbate AD, whereas S epidermidis has been considered a beneficial commensal organism.

Objective: In this study, we hypothesized that S epidermidis could promote skin damage in AD by the production of a protease that damages the epidermal barrier.

Innate Immune Dysfunction in Rosacea Promotes Photosensitivity and Vascular Adhesion Molecule Expression.

Rosacea is a chronic skin disease characterized by photosensitivity, abnormal dermal vascular behavior, inflammation, and enhanced expression of the antimicrobial peptide LL-37. We observed that dermal endothelial cells in rosacea had an increased expression of VCAM1 and hypothesized that LL-37 could be responsible for this response. The digestion of double-stranded RNA from keratinocytes exposed to UVB blocked the capacity of these cells to induce adhesion molecules on dermal microvascular endothelial cells.

Lymphomatoid papulosis in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma: case report and literature review.

Background: Chronic lymphocytic leukemia (CLL) is a B cell lymphoproliferative disorder that characteristically presents in older individuals. Small lymphocytic lymphoma (SLL) occurs when CLL cells infiltrate lymph nodes and other tissues but spare peripheral blood and bone marrow. Lymphomatoid papulosis (LyP) is an indolent cutaneous CD30+ lymphoproliferative disorder characterized by papules and nodules that develop and spontaneously regress over weeks to months.

Cutaneous Squamous Cell Carcinomas in Solid Organ Transplant Recipients Compared With Immunocompetent Patients.

Importance: Solid organ transplant recipients (SOTRs) have a 100-fold increased risk of squamous cell carcinoma (SCC), and they may develop more aggressive SCCs compared with immunocompetent individuals.

Objective: To compare outcomes associated with aggressive behavior of SCC in SOTRs and high-risk immunocompetent patients.

Design, Setting, And Participants: A retrospective cohort study of 58 SOTRs and 40 immunocompetent patients evaluated at the Yale Transplant Dermatology Clinic in New Haven, Connecticut, who had at least 1 SCC confirmed histopathologically between January 1, 2008, and December 31, 2015.

Sirolimus-Associated Pruritus: Case Report and Review.

Sirolimus is an immunosuppressant drug used to prevent organ rejection in transplant patients. We describe a man with sirolimus-associated pruritus and review the features of this adverse event in other individuals receiving this drug. The patient was a 67-year-old heart transplant recipient receiving sirolimus as part of his immunosuppressive regimen.

A novel FOXO1-mediated dedifferentiation blocking role for DKK3 in adrenocortical carcinogenesis.

Background: Dysregulated WNT signaling dominates adrenocortical malignancies. This study investigates whether silencing of the WNT negative regulator DKK3 (Dickkopf-related protein 3), an implicated adrenocortical differentiation marker and an established tumor suppressor in multiple cancers, allows dedifferentiation of the adrenal cortex.

Methods: We analyzed the expression and regulation of DKK3 in human adrenocortical carcinoma (ACC) by qRT-PCR, immunofluorescence, promoter methylation assay, and copy number analysis.

Incidence of and Risk Factors for Skin Cancer in Organ Transplant Recipients in the United States.

Importance: Skin cancer is the most common malignancy occurring after organ transplantation. Although previous research has reported an increased risk of skin cancer in solid organ transplant recipients (OTRs), no study has estimated the posttransplant population-based incidence in the United States.

Objective: To determine the incidence and evaluate the risk factors for posttransplant skin cancer, including squamous cell carcinoma (SCC), melanoma (MM), and Merkel cell carcinoma (MCC) in a cohort of US OTRs receiving a primary organ transplant in 2003 or 2008.

Impaired consciousness in epilepsy investigated by a prospective responsiveness in epilepsy scale (RES).

Purpose: Impaired consciousness in epileptic seizures has a major negative impact on patient quality of life. Prior work on epileptic unconsciousness has mainly used retrospective and nonstandardized methods. Our goal was to validate and to obtain initial data using a standardized prospective testing battery.