The polygenic architecture of hidradenitis suppurativa reveals signaling mechanisms that implicate epithelial remodeling.

We sought to identify clinically relevant regulators of hair follicle inflammation by conducting a human genetic study of hidradenitis suppurativa (HS), a prevalent, understudied, inflammatory disease with limited effective treatments. We performed a GWAS with 6,300 cases and identified 12 independent risk loci. Epigenetic and transcriptomic analyses of HS risk variants defined cell-specific gene regulatory programs.

Vignetting and peripheral double images with intraocular lenses.

Intraocular lenses (IOLs) are widely used, yet raytrace evaluations show that vignetting at very large angles limits the visual field of the focused image, though this is not specifically noticed by patients. A rare patient observation of peripheral double images in both eyes was modeled to demonstrate that a second image can be formed more peripherally by light missing the IOL, with simulated images illustrating the effect. Bothersome "dark shadows" that are reported by a small percentage of IOL patients, called negative dysphotopsia, have a similar cause, but are never reported as double images.

Genome-wide association meta-regression identifies stem cell lineage orchestration as a key driver of acne risk.

Over 85% of the population experience acne at some point in their lives, with its severity spanning a quantitative spectrum, from mild, transient outbreaks to more persistent, severe forms of the condition. Moderate to severe disease poses a substantial global burden arising from both the physical and psychological impacts of this highly visible condition. The analytical approach taken in this study aimed to address the impact of variation in the dichotomisation of acne case control status, driven by ascertainment and study design, on effect size estimates across independent genetic association studies of acne.

Carbon emission analysis of aortic valve replacement: the environmental footprint of transcatheter vs. surgical procedures.

Background And Aims: The impact of climate change is increasingly recognized as a major public health determinant. A life cycle assessment to determine the carbon emissions associated with open surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) in the operating room (OR), and the cath lab (CATH) was performed.

Methods: Total carbon footprint from SAVR (n = 10) and TAVR (n = 10 OR-TAVR, n = 10 CATH-TAVR) from March to September 2023 was calculated.

Clinical Factors Associated With Ventricular Dysrhythmia in Emergency Department Patients With Severe QTc Prolongation After Drug Overdose.

Background: Management of severe prolongation of the corrected QT interval (QTc) following acute drug overdose presents a challenge to clinicians, as resulting ventricular dysrhythmias are rare but life-threatening. This study aimed to identify which patients with severe QTc prolongation on presentation to the emergency department (ED) after overdose will develop ventricular dysrhythmias, death, cardiac arrest, the need for rhythm control, or extracorporeal membrane oxygenation utilization.

Methods: Secondary analysis of Toxicology Investigators Consortium Core Registry data from 2013 to 2023.

A key region of Tau that is able to drive assembly and modulate inhibition by Hydromethylthionine.

Tau (dGAE) forms paired helical filaments in vitro that resemble those deposited in Alzheimer's disease brain tissue. We have previously shown that hydromethylthionine (HMT) has the ability to inhibit dGAE self-assembly at sub-stoichiometric ratios. Here, we examined two regions of tau within the core filament-forming region that possess high self-assembly propensity sequences and have explored their ability to form filaments and whether their self-assembly can be inhibited by HMT.

Inherited deficiency of DIAPH1 identifies a DNA double strand break repair pathway regulated by γ-actin.

DNA double strand break repair (DSBR) represents a fundamental process required to maintain genome stability and prevent the onset of disease. Whilst cell cycle phase and the chromatin context largely dictate which repair pathway is utilised to restore damaged DNA, it has been recently shown that nuclear actin filaments play a major role in clustering DNA breaks to facilitate DSBR by homologous recombination (HR). However, the mechanism with which nuclear actin and the different actin nucleating factors regulate HR is unclear.

The role of lipid metabolism in acne risk: integrating blood metabolite and genetic insights.

Background: Acne vulgaris is a chronic inflammatory skin condition that significantly impacts an individual's quality of life, affecting social interactions, self-esteem and body image. It primarily targets the pilosebaceous unit, where inflammation occurs. Lipid metabolism is crucial in maintaining the skin barrier and modulating inflammatory responses, with specific fatty acids, such as ω-3 and sphingomyelin acid, playing key roles.

Cholesterol Pathway Gene Variants and Reduced Keratinocyte Cholesterol Support a Final Common Druggable Pathway in Hyperproliferative Inflammatory Skin Diseases.

Hyperproliferative inflammatory skin disease (HISD) is frequently seen in rare monogenic diseases of cholesterol metabolism and responds to topical cholesterol/statin. We hypothesized that aberrant cholesterol metabolism within keratinocytes could be important in HISD more generally, driven by either immunological or lipid pathway genetic variation. Whereas other epidermal lipids have been well-characterized in HISDs, cholesterol and its metabolites have not.

GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets.

Psoriasis is a common, debilitating immune-mediated skin disease. Genetic studies have identified biological mechanisms of psoriasis risk, including those targeted by effective therapies. However, the genetic liability to psoriasis is not fully explained by variation at robustly identified risk loci.

IL-1 signaling enrichment in inflammatory skin disease loci with higher-risk allele frequencies in African ancestry.

Inflammatory skin diseases (ISDs) exhibit varying prevalence across different ancestry background and geographical regions. Genetic research for complex ISDs has predominantly centered on European Ancestry (EurA) populations and genetic effects on immune cell responses but generally failed to consider contributions from other cell types in skin. Here, we utilized 273 genetic signals from seven different ISDs: acne, alopecia areata (AA), atopic dermatitis (AD), psoriasis, systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and vitiligo, to demonstrate enriched IL1 signaling in keratinocytes, particularly in signals with higher risk allele frequencies in the African ancestry.

Epistasis of ERAP1 With 4 Major Histocompatibility Complex Class I Alleles in Frontal Fibrosing Alopecia: A Genome-Wide Association Study Meta-Analysis.

Importance: Frontal fibrosing alopecia (FFA) is an inflammatory and scarring form of hair loss of increasing prevalence that most commonly affects women. An improved understanding of the genetic basis of FFA will support the identification of pathogenic mechanisms and therapeutic targets.

Objective: To identify novel genomic loci at which common genetic variation affects FFA susceptibility and assess nonadditive effects on genetic risk between susceptibility loci.

Design concepts for advanced-technology intraocular lenses [Invited].

An intraocular lens (IOL) replaces the natural crystalline lens during cataract surgery, and although the vast majority of implants have simple optics, "advanced technology" IOLs have multifocal and extended depth of focus (EDOF) properties. Optical concepts are evaluated here, with image contrast, focal range, and unwanted visual phenomena being the primary concerns. Visual phenomena with earlier bifocal diffractive lenses led to alternative diffractive designs (trifocals, etc.

 (Boraginaceae), a distinctive new taxon of series .

In the process of studying the species and its varieties, we discovered a unique taxon of the genus that resembles but differs in having a mostly densely white-strigose stem vestiture (sometimes with spreading trichomes) and tuberculate to muricate nutlets with often whitish tubercles that are, in comparison with typical , larger, with a wider base and more pointed apex, and more densely spaced. We believe this form to be different enough to describe as a new species, . This new species occurs in southwestern North America: in California and Arizona of the United States and in northern Baja California, Mexico.

Shifting perceptions of informal operators in the service and value chains: A retrospective of 40 years of observation and advocacy for informal recyclers and waste service providers, through the eyes of five global participant-researchers.

This article offers a reflective retrospective of the literature and practice on the sector. The authors have joined to share our experience and knowledge on the interface between the formal solid waste sector and informal recyclers and operators. Together, we discuss where this discourse has come from, where it is now, and where we, as practitioners, think it is going.

Developments in the epidemiology of calcium channel blocker poisoning and implications for management.

Purpose Of Review: The aim of this study was to outline recent developments in calcium channel blocker (CCB) poisoning. The dihydropyridine CCB amlodipine is commonly prescribed in the United States, and amlodipine poisoning is increasing in frequency, presenting new challenges for clinicians because current paradigms of CCB poisoning management arose from literature on non-dihydropyridine agents.

Recent Findings: Amlodipine is now the most common CCB involved in poisoning.

Evolving trends of pharmaceutical poisonings associated with QRS complex prolongation.

Introduction: Tricyclic antidepressants often cause drug-induced QRS complex prolongation in overdose but are now less commonly prescribed. We sought to determine, among a contemporary cohort of patients, the pharmaceuticals independently associated with QRS complex prolongation in acute overdose.

Methods: We performed secondary analysis of data from the Toxicology Investigators Consortium (ToxIC) Core Registry.