Deep and Superficial Dyspareunia Questionnaire: a patient-reported outcome measure for genito-pelvic dyspareunia.

Introduction: Dyspareunia affects 8%-22% of women worldwide and an unknown number of gender-diverse people. Dyspareunia is commonly categorized into deep and superficial subtypes based on pain location and underlying etiology; however, current assessment tools inadequately differentiate between pain locations.

Aim: This study aimed to develop a patient-reported outcome measure (PROM) that independently assesses deep and superficial dyspareunia and its psychosocial correlates: the Deep and Superficial Dyspareunia Questionnaire (DSDQ).

Genome-wide analyses of Mycobacterium tuberculosis complex isolates reveal insights into circulating lineages and drug resistance mutations in The Gambia.

Tuberculosis (TB), caused by the complex (MTBC), remains a pressing global health challenge, with the West African region, including The Gambia, experiencing a substantial burden. This study explores the genetic diversity of MTBC strains circulating in The Gambia for nearly two decades (2002-2021) to enhance understanding of drug resistance dynamics and inform targeted diagnostic and treatment strategies. Using whole-genome sequencing (WGS) data from 1,803 TB isolates, we identified the predominance of lineage 4 (L4, 67.

An Industry Perspective on the Use of Novel Excipients in Lipid Nanoparticles-Nonclinical Considerations.

Nucleic acid drug delivery with lipid nanoparticle (LNP) formulations has enabled the development of novel therapeutics and vaccines. LNP formulations are composed of both naturally occurring and synthetic lipid excipients. This perspective shares current practices in the nonclinical safety assessment of novel lipid excipients contained in LNP formulations and identifies gaps in current regulatory guidance on this topic.

Does Productivity in Healthcare Matter? An Unfortunate Post-Pandemic Legacy.

In speeches this year, a bank of canada official announced that our country experienced no growth in productivity over the past two years (Rogers 2024a, 2024b). To improve this predicament, the bank says businesses should focus on adding value and being more efficient. These recommendations should be heeded by healthcare - the industry exceeds 12% of Canada's gross domestic product and is growing (CIHI 2024b).

Cullin-RING ligase BioE3 reveals molecular-glue-induced neosubstrates and rewiring of the endogenous Cereblon ubiquitome.

Background: The specificity of the ubiquitination process is mediated by the E3 ligases. Discriminating genuine substrates of E3s from mere interacting proteins is one of the major challenges in the field. We previously developed BioE3, a biotin-based approach that uses BirA-E3 fusions together with ubiquitin fused to a low-affinity AviTag to obtain a site-specific and proximity-dependent biotinylation of the substrates.

Pelvic pain & endometriosis: the development of a patient-centred e-health resource for those affected by endometriosis-associated dyspareunia.

Background: We recognized a paucity of accessible, evidence-based, empowering patient-centred resources for those with endometriosis-associated dyspareunia. Affecting more than 50% of people with endometriosis, dyspareunia can significantly impact relationships, chronic pain and the ability to have a family. We aimed to develop a patient-centred educational website for those affected by endometriosis-associated dyspareunia.

Vitamin D, C-Reactive Protein, and Increased Fall Risk: A Genetic Epidemiological Study.

: Falls are a major public health concern. Daily vitamin D supplementation is a proposed fall prevention strategy; however, safety concerns have arisen from some clinical trials showing increased fall risk when using higher vitamin D dosing methods. The relationship between vitamin D and falls may be influenced by factors, such as inflammation, which can alter the balance of essential nutrients like vitamin D and retinol, potentially affecting motor function.

Impact of On-Road U.S. Vehicle Electrification and Lightweighting on Critical Materials Demand.

The electrification of the transport sector is crucial for reducing greenhouse gas emissions and the reliance on fossil fuels. Battery electric vehicles (BEVs) depend on critical materials (CMs) for their batteries and electronic components, yet their widespread adoption may face constraints due to the limited availability of CMs. This study assesses the implications of vehicle electrification and lightweighting (material substitution) on the U.

The misclassification of depression and anxiety disorders in the multiple sclerosis prodrome: A probabilistic bias analysis.

Background: Studies suggest that depression/anxiety form part of the multiple sclerosis (MS) prodrome. However, several biases have not been addressed. We re-examined this association after correcting for: (i) misclassification of individuals not seeking healthcare, (ii) differential surveillance of depression/anxiety in the health system, and (iii) misclassified person-time from using the date of the first MS-related diagnostic claim (i.

Indirect Formation of Peptide Bonds as a Prelude to Ribosomal Transpeptidation.

The catalytic competency of the ribosome in extant protein biosynthesis is thought to arise primarily from two sources: an ability to precisely juxtapose the termini of two key substrates─3'-aminoacyl and -acyl-aminoacyl tRNAs─and an ability to ease direct transpeptidation by their desolvation and encapsulation. In the absence of ribosomal, or enzymatic, protection, however, these activated alkyl esters undergo efficient hydrolysis, while significant entropic barriers serve to hamper their intermolecular cross-aminolysis in bulk water. Given that the spontaneous emergence of a catalyst of comparable size and sophistication to the ribosome in a prebiotic RNA world would appear implausible, it is thus natural to ask how appreciable peptide formation could have occurred with such substrates in bulk water without the aid of advanced ribozymatic catalysis.

Ustilago maydis Trf2 ensures genome stability by antagonizing Blm-mediated telomere recombination: Fine-tuning DNA repair factor activity at telomeres through opposing regulations.

TRF2 is an essential and conserved double-strand telomere binding protein that stabilizes chromosome ends by suppressing DNA damage response and aberrant DNA repair. Herein we investigated the mechanisms and functions of the Trf2 ortholog in the basidiomycete fungus Ustilago maydis, which manifests strong resemblances to metazoans with regards to the telomere and DNA repair machinery. We showed that UmTrf2 binds to Blm in vitro and inhibits Blm-mediated unwinding of telomeric DNA substrates.

Understanding the impact of placental oxidative and nitrative stress in pregnancies complicated by fetal growth restriction.

Fetal growth restriction (FGR) impacts approximately 10 % of all pregnancies worldwide and is associated with major adverse effects on fetal health in both the short- and long-term [1]. FGR most commonly arises as a result of impaired placentation, occurring in up to 60 % of cases in developed countries [2]. This narrative review outlines the impact of defective placentation on the placenta, focusing on redox imbalance, how this leads to placental oxidative and nitrative stress, and the implications of these stressors on placental nutrient transfer, premature replicative senescence, and trophoblast cell death.

Engaging Canadians in Health Policy Is no Trivial Matter.

There are many challenges with stewarding a public healthcare delivery system in Canada. The system is a beast with its own momentum. The public shares sad experiences with accessing emergency departments or securing a primary care physician on a daily basis.

The Influence of Wait Time on Surgical Outcomes in Elective Lumbar Degenerative Spine Conditions: A Retrospective Multicentre Cohort Study.

Study Design: Retrospective cohort study.

Objectives: The impact of delayed access to operative treatment on patient reported outcomes (PROs) for lumbar degenerative conditions remains unclear. The goal of this study is to evaluate the association between wait times for elective lumbar spine surgery and post-operative PROs.

Impact of Bisphenol A and its alternatives on oocyte health: a scoping review.

Background: Bisphenol A (BPA) is an endocrine disrupting chemical released from plastic materials, including food packaging and dental sealants, persisting in the environment and ubiquitously contaminating ecosystems and human populations. BPA can elicit an array of damaging health effects and, alarmingly, 'BPA-free' alternatives mirror these harmful effects. Bisphenol exposure can negatively impact female fertility, damaging both the ovary and oocytes therein.

Spending on Healthcare: What Is the Right Number?

Healthcare is canada's favourite punching bag. Admittedly, Canadian healthcare has many problems and, sometimes, it feels as though the system cannot get anything right. But is all the criticism fair?

RNA-directed peptide synthesis across a nicked loop.

Ribosomal translation at the origin of life requires controlled aminoacylation to produce mono-aminoacyl esters of tRNAs. Herein, we show that transient annealing of short RNA oligo:amino acid mixed anhydrides to an acceptor strand enables the sequential transfer of aminoacyl residues to the diol of an overhang, first forming aminoacyl esters then peptidyl esters. Using N-protected aminoacyl esters prevents unwanted peptidyl ester formation in this manner.

Pilot Study to Determine the Effectiveness of a Home Health Nursing Simulation.

Demand for home care has increased due to the expansion of preventive care, people living longer with chronic conditions, and the need for healthcare services as the baby boom population ages. Nurses must be prepared to meet the needs of patients and families in the home setting. Home care nursing simulations have been utilized as a teaching-learning strategy in baccalaureate nursing education, yet less is known about their use with practicing home care nurses and associate degree nursing students.

The inclusion of children and adolescents in tuberculosis diagnostic development and evaluation-a consensus statement.

The diagnosis of paediatric tuberculosis remains a challenge due to the non-specificity of symptoms and the paucibacillary nature of tuberculosis in children. However, in the development of new tuberculosis diagnostics, the unique needs of children and adolescents are rarely considered in the design process, with delays in evaluation and approval. No clear guidance is available on when and how to include children and adolescents in tuberculosis diagnostic development and evaluation.