Systemic Medications Associated With Hair Texture Changes.

BACKGROUND: In addition to hair loss, alterations in hair texture can be a worrisome side effect of certain medications yet are seldom reported and poorly characterized. OBJECTIVE: To systematically analyze the scientific literature to characterize medication-associated hair texture changes. METHODS: Relevant primary literature within PubMed and Cochrane was reviewed from 1985-2021 including 31 articles (1 randomized controlled trial with texture changes incidentally noted, 6 cohort, 1 cross-sectional, 23 case studies), comprising 2594 patients. RESULTS: Texture changes were associated primarily with antineoplastic agents (n = 97), antiepileptics (n = 56), retinoids (n = 15), immunomodulators (n = 3), and antiretroviral therapy (n = 1). Average age was 48.4 years old (41.2% female). De novo or exaggerated curling patterns were most commonly reported. Average time to texture change varied from 4.5 months (immunomodulators) to 17 months (antiretrovirals). Prognosis was seldom discussed with reversibility noted across all medication classes (n = 17/21; 3 weeks to 5 years post therapy). Irreversible changes were linked with antiretrovirals, retinoids, and antineoplastics. LIMITATIONS: Inability to define true incidence rates, ethnicity, and severity of texture changes due to the nature of available literature. CONCLUSIONS: Hair texture changes are potential side effects of antineoplastics, antiepileptics, retinoids, immunomodulators, and antiretroviral therapy. As these can have associated psychosocial impact, awareness among prescribing physicians is important.J Drugs Dermatol. 2022;21(9):989-996 doi:10.36849/JDD.6852.

Shapiro xanthogranuloma: An essential diagnosis for dermatologists and dermatopathologists to recognize to avoid misdiagnosis of a hematopoietic malignancy in infants and neonates.

The Shapiro xanthogranuloma is a histopathologic form of xanthogranuloma that shows closely packed monomorphous cells, which can extend into the subcutaneous fat; it usually lacks routine diagnostic features of xanthogranuloma. Herein we describe two cases of Shapiro xanthogranuloma occurring in a neonate and in an infant, which were initially thought to be hematologic malignancies. One patient's presentation as a "blueberry muffin baby" added to the diagnostic confusion. Pediatric dermatologists, dermatologists, and dermatopathologists need to be aware of the Shapiro xanthogranuloma and its clinicopathologic features to avoid misdiagnosis of a hematopoietic malignancy in neonates and infants.

Chromatin accessibility and histone acetylation in the regulation of competence in early development.

As development proceeds, inductive cues are interpreted by competent tissues in a spatially and temporally restricted manner. While key inductive signaling pathways within competent cells are well-described at a molecular level, the mechanisms by which tissues lose responsiveness to inductive signals are not well understood. Localized activation of Wnt signaling before zygotic gene activation in Xenopus laevis leads to dorsal development, but competence to induce dorsal genes in response to Wnts is lost by the late blastula stage. We hypothesize that loss of competence is mediated by changes in histone modifications leading to a loss of chromatin accessibility at the promoters of Wnt target genes. We use ATAC-seq to evaluate genome-wide changes in chromatin accessibility across several developmental stages. Based on overlap with p300 binding, we identify thousands of putative cis-regulatory elements at the gastrula stage, including sites that lose accessibility by the end of gastrulation and are enriched for pluripotency factor binding motifs. Dorsal Wnt target gene promoters are not accessible after the loss of competence in the early gastrula while genes involved in mesoderm and neural crest development maintain accessibility at their promoters. Inhibition of histone deacetylases increases acetylation at the promoters of dorsal Wnt target genes and extends competence for dorsal gene induction by Wnt signaling. Histone deacetylase inhibition, however, is not sufficient to extend competence for mesoderm or neural crest induction. These data suggest that chromatin state regulates the loss of competence to inductive signals in a context-dependent manner.

Single Cell Proteomics by Data-Independent Acquisition To Study Embryonic Asymmetry in Xenopus laevis.

Techniques that allow single cell analysis are gaining widespread attention, and most of these studies utilize genomics-based approaches. While nanofluidic technologies have enabled mass spectrometric analysis of single cells, these measurements have been limited to metabolomics and lipidomic studies. Single cell proteomics has the potential to improve our understanding of intercellular heterogeneity. However, this approach has faced challenges including limited sample availability, as well as a requirement of highly sensitive methods for sample collection, cleanup, and detection. We present a technique to overcome these limitations by combining a micropipette (pulled glass capillary) based sample collection strategy with offline sample preparation and nanoLC-MS/MS to analyze proteins through a bottom-up proteomic strategy. This study explores two types of proteomics data acquisition strategies namely data-dependent (DDA) and data-independent acquisition (DIA). Results from the study indicate DIA to be more sensitive enabling analysis of >1600 proteins from ∼130 µm Xenopus laevis embryonic cells containing <6 nL of cytoplasm. The method was found to be robust in obtaining reproducible protein quantifications from single cells spanning the 1-128-cell stages of development. Furthermore, we used micropipette sampling to study intercellular heterogeneity within cells in a single embryo and investigated embryonic asymmetry along both animal-vegetal and dorsal-ventral axes during early stages of development. Investigation of the animal-vegetal axis led to discovery of various asymmetrically distributed proteins along the animal-vegetal axis. We have further compared the hits found from our proteomic data sets with other studies and validated a few hits using an orthogonal imaging technique. This study forms the first report of vegetal enrichment of the germ plasm associated protein DDX4/VASA in Xenopus embyos. Overall, the method and data presented here holds promise to enable important leads in developmental biology.

Mio/dChREBP coordinately increases fat mass by regulating lipid synthesis and feeding behavior in Drosophila.

During nutrient excess, triglycerides are synthesized and stored to provide energy during times of famine. The presence of high glucose leads to the activation of carbohydrate response element binding protein (ChREBP), a transcription factor that induces the expression of a number of glycolytic and lipogenic enzymes. ChREBP is expressed in major metabolic tissues and while we have a basic understanding of ChREBP function in liver, in vivo genetic systems to study the function of ChREBP in other tissues are lacking. In this study, we characterized the role of the Drosophila homolog of ChREBP, Mlx interactor (Mio), in controlling fat accumulation in larvae and adult flies. In Mio mutants, high sugar-induced lipogenic enzyme mRNA expression is blunted and lowering Mio levels specifically in the fat body using RNA interference leads to a lean phenotype. A lean phenotype is also observed when the gene bigmax, the fly homolog of ChREBP's binding partner Mlx, is decreased in the larval fat body. Interestingly, depleting Mio in the fat body results in decreased feeding providing a potential cause of the lowered triglycerides observed in these animals. However, Mio does not seem to function as a general regulator of hunger-induced behaviors as decreasing fat body Mio levels has no effect on sleep under fed or starved conditions. Together, these data implicate a role for Mio in controlling fat accumulation in Drosophila and suggests that it may act as a nutrient sensor in the fat body to coordinate feeding behavior with nutrient availability.