OpenASO: RNA Rescue - designing splice-modulating antisense oligonucleotides through community science.

Splice-modulating antisense oligonucleotides (ASOs) are precision RNA-based drugs that are becoming an established modality to treat human disease. Previously, we reported the discovery of ASOs that target a novel, putative intronic RNA structure to rescue splicing of multiple pathogenic variants of exon 16 that cause hemophilia A. However, the conventional approach to discovering splice-modulating ASOs is both laborious and expensive.

Daily Duration of Eating for Children and Adolescents: A Systematic Review and Meta-Analysis.

Time-limited eating is a dietary intervention whereby eating is limited to a specific window of time during the day. The usual eating windows of adults, and how these can be manipulated for dietary interventions, is well documented. However, there is a paucity of data on eating windows of young people, the manipulation of which may be a useful intervention for reducing obesity.

Minimization of the E. coli ribosome, aided and optimized by community science.

The ribosome is a ribonucleoprotein complex found in all domains of life. Its role is to catalyze protein synthesis, the messenger RNA (mRNA)-templated formation of amide bonds between α-amino acid monomers. Amide bond formation occurs within a highly conserved region of the large ribosomal subunit known as the peptidyl transferase center (PTC).

The heterogeneity and complexity of skin surface lipids in human skin health and disease.

The outermost epidermal layer of the skin, the stratum corneum, is not simply a barrier that safeguards skin integrity from external insults and invaders, it is also a delicately integrated interface composed of firm, essentially dead corneocytes and a distinctive lipid matrix. Together, the stratum corneum lipid matrix and sebum lipids derived from sebaceous glands give rise to a remarkably complex but quite unique blend of skin surface lipids that demonstrates tremendous heterogeneity and provides the skin with its indispensable protective coating. The stratum corneum lipid matrix is composed primarily of three major lipid classes: ceramides, non-esterified fatty acids and cholesterol, whereas sebum is a waxy mixture predominantly composed of acylglycerols, wax esters, non-esterified fatty acids, squalene, cholesterol and cholesterol esters.

Community science designed ribosomes with beneficial phenotypes.

Functional design of ribosomes with mutant ribosomal RNA (rRNA) can expand opportunities for understanding molecular translation, building cells from the bottom-up, and engineering ribosomes with altered capabilities. However, such efforts are hampered by cell viability constraints, an enormous combinatorial sequence space, and limitations on large-scale, 3D design of RNA structures and functions. To address these challenges, we develop an integrated community science and experimental screening approach for rational design of ribosomes.

Medication following bariatric surgery for type 2 diabetes mellitus (BY-PLUS) study: rationale and design of a randomised controlled study.

Introduction: Bariatric surgery is an effective method of controlling glycaemia in patients with type 2 diabetes mellitus (T2DM) and obesity. Long-term studies suggest that although glycaemic control remains good, only 20%-40% of patients will maintain remission according to the American Diabetes Association criteria.

Purpose: This trial aims to examine the safety and efficacy of combining Roux-en-Y gastric bypass or sleeve gastrectomy with goal-directed medical therapy to improve long-term glycaemic control of T2DM.

Vehicles for Drug Delivery and Cosmetic Moisturizers: Review and Comparison.

Many dermatological conditions, such as eczema and psoriasis, are treated with topical therapeutic products. Instead of applying the active drug directly onto the skin, it is combined with a vehicle to aid in its delivery across the stratum corneum (SC) and into deeper regions of the skin, namely the epidermis and dermis. Absorption into the systemic circulation is minimized.

Incursions of sea lamprey, Petromyzon marinus, and striped bass, Morone saxatilis, in Labrador waters: Episodic events or evidence of a northward range expansion?

We describe observations of sea lamprey (Petromyzon marinus) and striped bass (Morone saxatilis) incursions into Labrador, Canada. While P. marinus have been periodically observed in similar latitudes, their numbers have conspicuously increased in estuarine environments in 2020.

Pain Control Following Photorefractive Keratectomy: A Prospective Clinical Trial Comparing Codeine Versus Oxycodone for the Management of Postoperative Pain.

Purpose: To compare the efficacy of oral codeine plus acetaminophen versus oxycodone plus acetaminophen for severe pain control following photorefractive keratectomy (PRK).

Methods: This single-center trial randomized 200 patients to receive codeine 30 mg/acetaminophen 325 mg (codeine group) or oxycodone 5 mg/acetaminophen 325 mg (oxycodone group)every 4 hours as needed for severe pain for 4 days following PRK. Patients recorded postoperative pain, tablet consumption, and tetracaine use.

Recruitment of adults with moderate eczema for a randomised trial: Comparison of traditional versus modern methods.

Background: Clinical trial recruitment is challenging for investigators who often overestimate the pool of qualified, willing subjects. Moreover, there is a paucity of literature, particularly in dermatology, regarding recruitment and the comparative success of advertising strategies.

Methods: Both 'traditional' (physician referral, newspaper and radio advertisements, letterbox drops, posters/flyers, word-of-mouth) and 'modern' (patient recruitment services, social media, Google advertisements, websites, email) recruitment methods were used to enrol 100 patients (>18 years) diagnosed with moderate eczema for a randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of a topical eczema treatment over 4 weeks.

Dexamethasone-Eluting Contact Lens for the Prevention of Postphotorefractive Keratectomy Scar in a New Zealand White Rabbit Model.

Purpose: To evaluate the safety and efficacy of an experimental dexamethasone-eluting contact lens (DCL) for the prevention of postphotorefractive keratectomy (PRK) corneal haze in a New Zealand White (NZW) rabbit model.

Methods: Both eyes of 29 NZW rabbits underwent PRK. The rabbits were randomized to one of the 5 study arms for 4 weeks: tarsorrhaphy only, tarsorrhaphy and bandage contact lens (BCL) replaced weekly, tarsorrhaphy and BCL for 1 week plus topical 0.

A daily regimen of a ceramide-dominant moisturizing cream and cleanser restores the skin permeability barrier in adults with moderate eczema: A randomized trial.

The dysfunctional skin barrier in eczema patients may be attributed to decreased levels of ceramides in the stratum corneum. The aim of this study was to determine whether a two-part system consisting of a ceramide-dominant physiological lipid-based moisturizing cream and cleanser could ameliorate the signs and symptoms of moderate eczema in adults over 28 days compared to placebo. Assessments were conducted at baseline and every 7 days thereafter.

De novo 3D models of SARS-CoV-2 RNA elements from consensus experimental secondary structures.

The rapid spread of COVID-19 is motivating development of antivirals targeting conserved SARS-CoV-2 molecular machinery. The SARS-CoV-2 genome includes conserved RNA elements that offer potential small-molecule drug targets, but most of their 3D structures have not been experimentally characterized. Here, we provide a compilation of chemical mapping data from our and other labs, secondary structure models, and 3D model ensembles based on Rosetta's FARFAR2 algorithm for SARS-CoV-2 RNA regions including the individual stems SL1-8 in the extended 5' UTR; the reverse complement of the 5' UTR SL1-4; the frameshift stimulating element (FSE); and the extended pseudoknot, hypervariable region, and s2m of the 3' UTR.

Evidence of an Unusual Poly(A) RNA Signature Detected by High-Throughput Chemical Mapping.

Homopolymeric adenosine RNA plays numerous roles in both cells and noncellular genetic material. We report herein an unusual poly(A) signature in chemical mapping data generated by the Eterna Massive Open Laboratory. Poly(A) sequences of length seven or more show unexpected results in the selective 2'-hydroxyl acylation read out by primer extension (SHAPE) and dimethyl sulfate (DMS) chemical probing.

Optimising opioid substitution therapy in the prison environment.

Purpose: The purpose of this paper is to examine the current provision of opioid substitution therapy (OST) during and immediately following release from detention in prisons in England and Wales.

Design/methodology/approach: A group of experts was convened to comment on current practices and to make recommendations for improving OST management in prison. Current practices were previously assessed using an online survey and a focus group with experience of OST in prison (Webster, 2017).

Retrospective Analysis of the Post-Operative Changes in Higher-Order Aberrations: A Comparison of the WaveLight EX500 to the VISX S4 Laser in Refractive Surgery.

Introduction: In an attempt to maximize treatment outcomes, refractive surgery techniques are being directed toward customized ablations to correct not only lower-order aberrations but also higher-order aberrations specific to the individual eye. Measurement of the entirety of ocular aberrations is the most definitive means to establish the true effect of refractive surgery on image quality and visual performance. Whether or not there is a statistically significant difference in induced higher-order corneal aberrations between the VISX Star S4 (Abbott Medical Optics, Santa Ana, California) and the WaveLight EX500 (Alcon, Fort Worth, Texas) lasers was examined.

Dose Uniformity of Topical Corticosteroids: A Simulated Trial of Fluorometholone Acetate 0.1% and Loteprednol Etabonate Gel 0.5.

Purpose: The purpose of the study was to determine the concentrations of Flarex and Lotemax when shaken and not shaken. Many patients fail to shake or inappropriately shake suspensions of corticosteroids before instillation as directed. This study was designed to help determine what concentration of corticosteroid these patients are receiving.

Cognitive and Psychomotor Entrustable Professional Activities: Can Simulators Help Assess Competency in Trainees?

Background: An entrustable professional activity describes a professional task that postgraduate residents must master during their training. The use of simulation to assess performance of entrustable professional activities requires further investigation.

Questions/purposes: (1) Is simulation-based assessment of resident performance of entrustable professional activities reliable? (2) Is there evidence of important differences between Postgraduate Year (PGY)-1 and PGY-4 residents when performing simulated entrustable professional activities?

Methods: Three entrustable professional activities were chosen from a list of competencies: management of the patient for total knee arthroplasty (TKA); management of the patient with an intertrochanteric hip fracture; and management of the patient with an ankle fracture.

Comparison of pachymetry measurements between the Alcon Wavelight EX500 and Sonogage Corneo-Gage plus platforms.

Purpose: To compare the agreement of intraoperative central corneal thickness (CCT) measurements of the Wavelight EX500 (Alcon Laboratories, Fort Worth, TX) that uses optical low coherence reflectometry to the Corneo-Gage Plus ultrasound pachymetry device (Sonogage, Cleveland, OH).

Methods: In this retrospective study, 50 eyes of 26 patients undergoing LASIK were evaluated. Following LASIK flap creation, each eye was measured by both optical low coherence reflectometry and ultrasound pachymetry immediately prior to flap lifting and then again after flap lifting.

An antiaging skin care system containing alpha hydroxy acids and vitamins improves the biomechanical parameters of facial skin.

Background: The demand for antiaging products has dramatically increased in recent years, driven by an aging population seeking to maintain the appearance of youth. This study investigates the effects of an antiaging skin care system containing alpha hydroxy acids (AHAs) in conjunction with vitamins B3, C, and E on the biomechanical parameters of facial skin.

Methods: Fifty two volunteers followed an antiaging skin care regimen comprising of cleanser, eye cream, day moisturizer, and night moisturizer for 21 days.