Malassezia-associated skin diseases in the pediatric population.

Malassezia are yeast species that commonly colonize healthy skin. However, they have been associated with or implicated in the pathogenesis of numerous skin disorders, particularly in the setting of pediatric populations. In this review, we will focus on several Malassezia-associated skin conditions manifesting in infants, children, and adolescents: pityriasis versicolor, Malassezia folliculitis, infantile and adolescent seborrheic dermatitis, head and neck dermatitis, and neonatal cephalic pustulosis. We examine the literature and provide an overview of these conditions, including clinical presentation in diverse skin colors, diagnosis, risk factors, and treatment and management. Additionally, we summarize and highlight some of the proposed theories on the role of Malassezia spp. in the pathogenesis of these skin conditions.

One-Pot Synthesis of a Linear [4]Catenate Using Orthogonal Metal Templation and Ring-Closing Metathesis.

The efficient synthesis of well-defined, linear oligocatenanes possessing multiple mechanical bonds remains a formidable challenge in the field of mechanically interlocked molecules. Here, a one-pot synthetic strategy is described to prepare a linear [4]catenate using orthogonal metal templation between a macrocycle precursor, composed of terpyridine and phenanthroline ligands spaced by flexible glycol linkers, and a closed phenanthroline-based molecular ring. Implementation of two simultaneous ring-closing metathesis reactions after metal complexation resulted in the formation of three mechanical bonds. The linear [4]catenate product was isolated in 55% yield as a mixture of topological diastereomers. The intermediate metal complexes and corresponding interlocked products (with and without metals) were characterized by nuclear magnetic resonance, mass spectrometry, gel permeation chromatography, and UV-vis absorption spectroscopy. We envision that this general synthetic strategy may pave the way for the synthesis of higher order linear oligocatenates/catenanes with precise molecular weights and four or more interlocking molecular rings.

More yeast, more problems?: reevaluating the role of Malassezia in seborrheic dermatitis.

Seborrheic dermatitis (SD) is an inflammatory skin disorder and eczema subtype increasingly recognized to be associated with significant physical, psychosocial, and financial burden. The full spectrum of SD, including dandruff localized to the scalp, is estimated to affect half of the world's population. Despite such high prevalence, the exact etiopathogenesis of SD remains unclear. Historically, many researchers have theorized a central, causative role of Malassezia spp. based on prior studies including the proliferation of Malassezia yeast on lesional skin of some SD patients and empiric clinical response to antifungal therapy. However, upon closer examination, many of these findings have not been reproducible nor consistent. Emerging data from novel, targeted anti-inflammatory therapeutics, as well as evidence from genome-wide association studies and murine models, should prompt a reevaluation of the popular yeast-centered hypothesis. Here, through focused review of the literature, including laboratory studies, clinical trials, and expert consensus, we examine and synthesize the data arguing for and against a primary role for Malassezia in SD. We propose an expansion of SD pathogenesis and suggest reframing our view of SD to be based primarily on dysregulation of the host immune system and skin epidermal barrier, like other eczemas.

The Global Prevalence of Seborrheic Dermatitis: A Systematic Review and Meta-Analysis.

Importance: Seborrheic dermatitis is a prevalent chronic inflammatory skin disease, yet its global prevalence, pathogenesis, and epidemiology remain inadequately defined. Objective: To provide a detailed estimation of the global prevalence of seborrheic dermatitis, analyze demographic variations, and explore differences in various settings. Data Sources: Embase, PubMed, Scopus, and Cochrane Database of Systematic Reviews were searched from inception through October 2023. Study Selection: Original investigations on seborrheic dermatitis prevalence were included after duplicate screening of titles, abstracts, and full articles, including only studies with clinician-diagnosed cases. Data Extraction and Synthesis: Following PRISMA guidelines, data were extracted and quality was assessed independently by multiple reviewers. A random-effects model using restricted maximum likelihood was used for meta-analysis and subgroup analyses. Main Outcome and Measure: The primary outcome was the pooled estimate of global seborrheic dermatitis prevalence. Results: From 1574 identified articles, 121 studies were included, encompassing 1 260 163 individuals and revealing a pooled global seborrheic dermatitis prevalence of 4.38% (95% CI, 3.58%-5.17%), with significant heterogeneity (I2 = 99.94%). Subgroup analyses showed variations by age, with a higher prevalence in adults (5.64% [95% CI, 4.01%-7.27%]) compared to children (3.70% [95% CI, 2.69%-4.80%]) and neonates (0.23% [95% CI, 0.04%-0.43%]). Geographic analyses indicated variability, with the highest prevalence in South Africa (8.82% [95% CI, 3.00%-14.64%]) and the lowest in India (2.62% [95% CI, 1.33%-3.92%]). Conclusions and Relevance: This comprehensive meta-analysis provides a detailed estimation of the global prevalence of seborrheic dermatitis, highlighting significant variability across different demographics and settings.

Topologically Controlled Syntheses of Unimolecular Oligo[n]catenanes.

Catenanes are a well-known class of mechanically interlocked molecules that possess chain-like architectures and have been investigated for decades as molecular machines and switches. However, the synthesis of higher-order catenanes with multiple, linearly interlocked molecular rings has been greatly impeded by the generation of unwanted oligomeric byproducts and figure-of-eight topologies that compete with productive ring closings. Here, we report two general strategies for the synthesis of oligo[n]catenanes that rely on a molecular "zip-tie" strategy, where the "zip-tie" is a central core macrocycle precursor bearing two phenanthroline (phen) ligands to make odd-numbered oligo[n]catenanes, or a preformed asymmetric iron(II) complex consisting of two macrocycle precursors bearing phen and terpyridine ligands to make even-numbered oligo[n]catenanes. In either case, preformed macrocycles or [2]catenanes are threaded onto the central "zip-tie" core using metal templation prior to ring-closing metathesis (RCM) reactions that generate several mechanical bonds in one pot. Using these synthetic strategies, a family of well-defined linear oligo[n]catenanes were synthesized, where n = 2, 3, 4, 5, or 6 interlocked molecular rings, and n = 6 represents the highest number of linearly interlocked rings reported to date for any isolated unimolecular oligo[n]catenane.

An updated meta-analysis of genome scans for hypertension and blood pressure in the NHLBI Family Blood Pressure Program (FBPP).

A meta-analysis of the results from a multicenter genome-wide linkage study for hypertension and blood pressure (BP) based on an initial sample of 6,245 individuals was published in 2003. We report here a combined linkage analysis of hypertension and BP using the complete Family Blood Pressure Program (FBPP) dataset, which includes a total of 12,028 genotyped individuals. Genome-wide linkage analyses for hypertension and BP were first performed in each of the studied ethnic group within each network and the results were combined with a meta-analysis using a modified Fisher's method of combining P values. Our meta-analysis of genome scans for the latest FBPP dataset reveals suggestive linkage for hypertension and BP at several regions on the human genome. Strong evidence for linkage at two of these regions, 2p14 and 3p14.1, have also been published in previous meta-analyses, making them good candidate locations for susceptibility variants.