Evaluation of a Firearm Safe Storage Device Distribution Program at a Break the Cycle of Violence Summit.

This study assesses the feasibility and acceptability of a Firearm Safe Storage Device Distribution Program. The distribution took place at the Break the Cycle of Violence Summit hosted by the Johns Hopkins Medicine, the Break the Cycle Hospital Violence Intervention Program, and the Johns Hopkins Bloomberg School of Public Health Center for Gun Violence Solutions. The findings will guide future efforts to distribute safe storage devices in clinical settings.

Genotype-environment-driven dysbiosis in the skin microbiome of ichthyosis.

Monogenic skin disorders such as ichthyosis introduce multiple sources of disturbance to the skin, including the direct biochemical consequences of the genotype, the phenotypic changes in skin physiology, and an altered skin microbiome. The association between changes in the skin microbiome and the disease's genotypic and phenotypic effects are of both ecological and clinical interest but are historically obscured by 1) the limited resolution of metagenomic profiles, and 2) additional sources of variation such as age and topical/oral treatments. Here we characterize the skin microbiome from seven ichthyosis genotypes, at species, strain, and metabolic pathway levels.

The Genomic and Phenotypic Landscape of Ichthyosis: An Analysis of 1000 Kindreds.

Importance: Ichthyoses are clinically and genetically heterogeneous disorders characterized by scaly skin. Despite decades of investigation identifying pathogenic variants in more than 50 genes, clear genotype-phenotype associations have been difficult to establish.

Objective: To expand the genotypic and phenotypic spectra of ichthyosis and delineate genotype-phenotype associations.

Factor Xa: Thrombokinase from Paul Morawitz to J Haskell Milstone.

In 1904 Paul Morawitz postulated that an enzyme, which he named thrombokinase, would be the primary activator of prothrombin. Fifty years passed before J Haskell Milstone isolated, purified and functionally characterized the enzyme we now call Factor Xa. This essay summarizes Milstone's work on thrombokinase, and finds context for why his efforts succeeded while others struggled.

Use of telemedicine for ichthyosis: Patient advocacy group as conduit to expert physician advice.

Background/objectives: Patients with rare diseases are challenged when it comes to finding physicians with expertise in their condition. The Foundation for Ichthyosis and Related Skin Types (FIRST) Tele-Ichthyosis program has provided telemedicine for patients and their families with keratinizing disorders since 2009. This study aims to characterize a decade of experience with the program.

Association of the Severity of Alopecia With the Severity of Ichthyosis.

This study assesses the association between the severity of alopecia and ichthyosis disease severity and characterizes the severity of alopecia by genotype.

Mutations in PERP Cause Dominant and Recessive Keratoderma.

Investigation of genetic determinants of Mendelian skin disorders has substantially advanced understanding of epidermal biology. Here we show that mutations in PERP, encoding a crucial component of desmosomes, cause both dominant and recessive human keratoderma. Heterozygosity for a C-terminal truncation, which produces a protein that appears to be unstably incorporated into desmosomes, causes Olmsted syndrome with severe periorificial and palmoplantar keratoderma in multiple unrelated kindreds.

More than keratitis, ichthyosis, and deafness: Multisystem effects of lethal GJB2 mutations.

Background: Infant death in keratitis-ichthyosis-deafness (KID) syndrome is recognized; its association with specific genotypes and pathophysiology is inadequately understood.

Objective: We sought to discover characteristics that account for poor outcomes in lethal KID syndrome.

Methods: We collected 4 new cases and 9 previously reported, genotyped cases of lethal KID syndrome.

CARD14-associated papulosquamous eruption: A spectrum including features of psoriasis and pityriasis rubra pilaris.

Background: Heterozygous mutations in caspase recruitment domain family member 14 gene (CARD14) have been shown to be associated with psoriasis and familial pityriasis rubra pilaris (PRP). Many subjects with CARD14 mutations display features of both disorders, which can result in diagnostic uncertainty. In addition, these eruptions are often recalcitrant to conventional psoriasis therapies such as methotrexate, oral retinoids, and tumor necrosis factor-α inhibitors.

Establishing and Validating an Ichthyosis Severity Index.

We designed and validated a Visual Index for Ichthyosis Severity for scale and erythema that provides (1) written descriptions of the features characteristic of each level of severity, (2) visual standards for four body sites, and (3) two distinct standards to account for different types of scale. We tested the Visual Index for Ichthyosis Severity for reliability and reproducibility using two different settings: one that utilized scoring of 60 test photographs by 10 dermatologists, and one with in-person evaluations on 85 subjects by 12 dermatologists at the Foundation for Ichthyosis and Related Skin Types conference. The validation process revealed high reliability and reproducibility for both scale and erythema.

Expanding the Genotypic Spectrum of Bathing Suit Ichthyosis.

Importance: Bathing suit ichthyosis (BSI) is a rare congenital disorder of keratinization characterized by restriction of scale to sites of relatively higher temperature such as the trunk, with cooler areas remaining unaffected. Fewer than 40 cases have been reported in the literature. Bathing suit ichthyosis is caused by recessive, temperature-sensitive mutations in the transglutaminase-1 gene (TGM1).

Palmoplantar Keratoderma in Costello Syndrome Responsive to Acitretin.

Costello syndrome (CS) is a multisystem congenital disorder characterized by coarse facial features, cardiac defects, intellectual disability, and predisposition to malignancies. Dermatologic findings can include cutaneous papillomas, skin redundancy, acanthosis nigricans, and keratosis pilaris. Palmoplantar keratoderma (PPK) is present in approximately 76% of patients with CS, with disabling functional consequences in severe cases.

The X-Ray Crystal Structure of the Keratin 1-Keratin 10 Helix 2B Heterodimer Reveals Molecular Surface Properties and Biochemical Insights into Human Skin Disease.

Keratins 1 (K1) and 10 (K10) are the primary keratins expressed in differentiated epidermis. Mutations in K1/K10 are associated with human skin diseases. We determined the crystal structure of the complex between the distal (2B) helices of K1 and K10 to better understand how human keratin structure correlates with function.

Recurrent Coxsackievirus Infection in a Patient with Lamellar Ichthyosis.

We describe a case of coxsackievirus (CV) A6 infection in a patient with lamellar ichthyosis followed by subsequent CV A8 infection within the same year. Atypical cutaneous features characterized the infection. This observation, combined with the rapidity with which reinfection occurred, suggests that the natural history of CV infection may be altered in patients with underlying ichthyoses.

Connexin channels in congenital skin disorders.

Gap junctions and hemichannels comprised of connexins influence epidermal proliferation and differentiation. Significant advances in our understanding of the functional role of connexins in the skin have been made by studying the diseases caused by connexin mutations. Eleven clinically defined cutaneous disorders with an overlapping spectrum of phenotypes are caused by mutations in five different connexin genes, highlighting that disease presentation must be deciphered with an understanding of how connexin functions are affected.

The Protein Acyl Transferase ZDHHC21 Modulates α1 Adrenergic Receptor Function and Regulates Hemodynamics.

Objective: Palmitoylation, the reversible addition of the lipid palmitate to a cysteine, can alter protein localization, stability, and function. The ZDHHC family of protein acyl transferases catalyzes palmitoylation of numerous proteins. The role of ZDHHC enzymes in intact tissue and in vivo is largely unknown.