Thiazole-based IL-17 inhibitors discovered by scaffold morphing.

The pro-inflammatory cytokine interleukin-17A (IL-17) plays an important role in the body's defense against bacterial and fungal infections. However, overexpression of IL-17 has been associated with several diseases, including rheumatoid arthritis, asthma, psoriasis, and even cancer. The role of IL-17 in psoriasis has been confirmed by clinical use of IL-17 antibodies, e.

Introducing entrustable professional activities for postgraduate medical training in Switzerland.

Introduction: Graduate medical education is being reformed in many countries, with a focus on the principles of competency-based medical education (CBME). A main novel aspect in this context is the implementation of entrustable professional activities (EPAs). The introduction of EPAs aims to better align training curricula with clinical practice, provide individualized supervision, and enhance the quality of feedback.

Vulcanization Accelerators and Silica Coupling Agents in Polyisoprene Melts.

The achievement of sufficient dispersion of vulcanization accelerators is critical to tailoring superior cross-linked elastomers. Modern recipes rely on multicomponent formulations with silica particles covered by coupling agents. We study the molecular properties of select accelerators in polyisoprene melts and their affinity for functionalized surfaces via extensive all-atom molecular dynamics simulations.

SLC6A19 inhibition facilitates urinary neutral amino acid excretion and lowers plasma phenylalanine.

BACKGROUNDThe toxic accumulation of phenylalanine (Phe) in the brain underlies the neurological presentation of phenylketonuria (PKU). Solute carrier family 6 member 19 (SLC6A19) is the major transporter responsible for the (re)absorption of Phe in the kidney and intestine. Here, we describe the characterization of the first small molecule SLC6A19 inhibitor to enter clinical development for the treatment of PKU.

Discovery and Exploration of 1,3,4-Oxadiazole and α-Fluoroacrylate Containing IL-17 Inhibitors.

IL-17, a pro-inflammatory cytokine produced mainly by Th17 cells, is involved in the immune response to fungal and bacterial infections, whereas its aberrant production is associated with autoimmune and inflammatory diseases. IL-17 blocking antibodies like secukinumab (Cosentyx) have been developed and are used to treat conditions like psoriasis, psoriatic arthritis, and ankylosing spondylitis. Recently, the low molecular weight IL-17 inhibitor LY3509754 entered the clinic but was discontinued in Phase 1 due to adverse effects.

The Successful Use of Upadacitinib as Monotherapy for Hidradenitis Suppurativa and Ulcerative Colitis in the Setting of Refractory Disease.

Hidradenitis suppurativa (HS) and ulcerative colitis (UC) are associated chronic inflammatory conditions with complex disease courses and potential for overlapping therapeutic management. We describe a case of severe pediatric HS and UC that were poorly controlled despite several standard-of-care therapies, including infliximab and ustekinumab. Transitioning the patient to upadacitinib monotherapy resulted in clinical improvement of both her UC and HS within 3 months, and she was then able to be weaned off her other systemic therapies.

Exploring GVS as a display modality: signal amplitude and polarity, in various environments, impacts on posture, and with dual-tasking.

Galvanic Vestibular Stimulation (GVS) has been proposed as an alternative display modality to relay information without increasing demands on the visual or auditory sensory modalities of the wearer or in environments where those modalities cannot be used (e.g., covert night operations).

Risk of invasive waterfowl interaction with poultry production: Understanding potential for avian pathogen transmission via species distribution models.

Recent outbreaks of highly pathogenic avian influenza have devastated poultry production across the United States, with more than 77 million birds culled in 2022-2024 alone. Wild waterfowl, including various invasive species, host numerous pathogens, including highly pathogenic avian influenza virus (HPAIV), and have been implicated as catalysts of disease outbreaks among native fauna and domestic birds. In major poultry-producing states like Arkansas, USA, where the poultry sector is responsible for significant economic activity (>$4 billion USD in 2022), understanding the risk of invasive waterfowl interactions with domestic poultry is critical.

The effect of chemical constitution on polyisoprene dynamics.

Polyisoprene (PI) melts have been studied, with most reports focusing on systems with high 1,4-cis content. In contrast, 1,4-trans PI homopolymers or random copolymers have seldom been examined, despite a handful of investigations suggesting a distinct dynamic behavior. Herein, we employ all-atom simulations to investigate the effect of chemical architecture on the dynamics of cis and trans-PI homopolymers, as well as copolymers.

Bacteriophages: An Alternative to Combat Antibiotic Resistance?

Antibiotic resistance has become one of the largest pitfalls of modern medicine, and this has fueled the search for a safe and effective alternative. Of these alternatives, bacteriophage (phage) therapy has emerged as a potential option since it is capable of destroying pathogenic bacteria, without disrupting commensal bacterial populations. Although numerous studies have shown its efficacy in various conditions such as dysentery, sepsis, and meningitis, very little research has focused on its prospective usage to treat dermatological conditions.

Efficacy of Galvanic Vestibular Stimulation as a Display Modality Dissociated from Self-Orientation.

Objective: We propose and assess galvanic vestibular stimulation (GVS) as a novel means to provide information dissociated from self-orientation.

Background: In modern user interfaces, visual and auditory modalities dominate information transfer so much that these "processing channels" become overloaded with information. Fortunately, the brain is capable of processing separate sensory sources in parallel enabling alternative display modalities to inform operators more effectively and without increasing cognitive strain.

Comparing propofol anaesthesia guided by Bispectral Index monitoring and frontal EEG wave analysis with standard monitoring in laparoscopic surgery: protocol for the 'EEG in General Anaesthesia - More Than Only a Bispectral Index' Trial, a multicentre, double-blind, randomised controlled trial.

Introduction: The use of Bispectral Index (BIS) monitors for assessing depth of sedation has led to a reduction in both the incidence of awareness and anaesthetic consumption in total intravenous anaesthesia. However, these monitors are vulnerable to artefacts. In addition to the processed number, the raw frontal electroencephalogram (EEG) can be displayed as a curve on the same monitor.

Investigation of Radial Shaft Seal Swelling Using a Special Tribometer and Magnetic Resonance Imaging.

Compatibility between the rubber material of radial shaft seals and the lubricants to be sealed is an important requirement that customers demand of their lubricant suppliers. Among other effects that may result from incompatibility, the penetration of lubricant components into the rubber (swelling) can impair the seal's functionality due to changes in its geometry and mechanical behavior. Typically, the penetration of a lubricant into an elastomer is evaluated after an immersion test using volumetric, gravimetric, and extraction measurements.

Bleach baths for atopic dermatitis: A systematic review and meta-analysis including unpublished data, Bayesian interpretation, and GRADE.

Background: Bleach bathing is frequently recommended to treat atopic dermatitis (AD), but its efficacy and safety are uncertain.

Objective: To systematically synthesize randomized controlled trials (RCTs) addressing bleach baths for AD.

Methods: We searched MEDLINE, EMBASE, CENTRAL, and GREAT from inception to December 29, 2021, for RCTs assigning patients with AD to bleach vs no bleach baths.

The risk of metastases from squamous cell carcinoma of the skin.

Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer, accounting for 20% of all skin cancers. The risk of the disease continues to rise annually with an estimated 50-200% increase in incidence within the last three decades. Although cSCC is one of the most common skin cancers, reported having 1 million cases per year in the United States, there is inconsistency with its reported metastatic rate.

DMSO: an aid to combat pain and pruritus.

Dimethyl sulfoxide (DMSO) is a highly reactive by-product of paper production in the form of an odorless, colorless liquid that has been studied since the 1860s. Initially it was utilized as a solvent, but more recently it is being investigated for therapeutic applications. Owing to its versatility, the use of DMSO has been proposed in many different medical fields for a variety of applications, with possibly the widest use being in the field of dermatology.

Who can do this procedure? Using entrustable professional activities to determine curriculum and entrustment in anesthesiology - An international survey.

Introduction: As competency-based curricula get increasing attention in postgraduate medical education, Entrustable Professional Activities (EPAs) are gaining in popularity. The aim of this survey was to determine the use of EPAs in anesthesiology training programs across Europe and North America.

Methods: A survey was developed and distributed to anesthesiology residency training program directors in Switzerland, Germany, Austria, Netherlands, USA and Canada.

The dangers of human papillomavirus (HPV) laser plume and best safety practices.

Human papillomavirus (HPV) remains to be one of the most common viruses that afflicts the skin and mucosa. Direct contact with cutaneous lesions facilitates a majority of viral transmission. However, the development of laser therapy as treatment for HPV brought to attention the concern of infectious laser plume and the risk it poses to those inhaling it.