Rare Disease Policy in High-Income Countries: An Overview of Achievements, Challenges, and Solutions.

Objectives: To provide an overview of policy initiatives in high-income countries aimed at supporting the development and accessibility of treatments for rare diseases.

Methods: We examine how legislative, research, and pricing policies in high-income countries address barriers that have historically hindered innovation and access to rare disease treatments. By analysing examples from the EU, UK, US, Canada, Japan, and Australia, the article identifies ongoing initiatives, outlines current challenges, and explores proposed solutions to foster a sustainable, innovative, and accessible rare disease treatment ecosystem.

Non-atherosclerotic coronary causes of myocardial infarction in women.

Ischemic heart disease is the most common cardiovascular cause of death in women worldwide. Obstructive coronary atherosclerosis is the primary cause of myocardial infarction (MI), however, non-atherosclerotic mechanisms of MI, such as spontaneous coronary artery dissection, vasospasm, microvascular dysfunction, embolization, inflammation, coronary anomalies, infectious and infiltrative causes are increasingly being recognized. Emerging data suggest that women are two to five times more likely to have an MI in the absence of coronary atherosclerosis compared to men, but they continue to remain underdiagnosed and undertreated, partly due to underdiagnosis and limited understanding of these mechanisms.

Cadmium-cardiolipin disruption of respirasome assembly and redox balance through mitochondrial membrane rigidification.

The environmental pollutant cadmium (Cd) poses a threat to human health through consumption of contaminated foodstuffs culminating in chronic nephrotoxicity. Mitochondrial dysfunction and excessive reactive oxygen species (ROS) are key to Cd cellular toxicity. Cd-lipid interactions have been less considered.

HS inhibition of xanthine dehydrogenase to xanthine oxidase conversion reduces uric acid levels and improves myoblast functions.

Hydrogen sulfide (HS) is an important gasotransmitter that regulates a wide range of pathophysiological processes. Higher uric acid levels are associated with an increased risk of metabolic diseases. The causal mechanism linking HS signalling and uric acid metabolism in skeletal muscles has not yet been elucidated.

A conserved chaperone protein is required for the formation of a non-canonical type VI secretion system spike tip complex.

Type VI secretion systems (T6SS) are dynamic protein nanomachines found in Gram-negative bacteria that deliver toxic effector proteins into target cells in a contact-dependent manner. Prior to secretion, many T6SS effector proteins require chaperones and/or accessory proteins for proper loading onto the structural components of the T6SS apparatus. However, despite their established importance, the precise molecular function of several T6SS accessory protein families remains unclear.

Cup-Cage Reconstruction for Pelvic Discontinuity: Encouraging Long-Term Survival.

Background: Pelvic discontinuity (PD) poses a difficult challenge in revision total hip arthroplasty (rTHA). There is a paucity of evidence assessing five- to ten-year outcomes of cup cages for PD. This study aimed to review the survivorship and outcomes of cup-cage constructs for PD.

Latest clinical frontiers related to autism diagnostic strategies.

The diagnosis of autism is currently based on the developmental history, direct observation of behavior, and reported symptoms, supplemented by rating scales/interviews/structured observational evaluations-which is influenced by the clinician's knowledge and experience-with no established diagnostic biomarkers. A growing body of research has been conducted over the past decades to improve diagnostic accuracy. Here, we provide an overview of the current diagnostic assessment process as well as of recent and ongoing developments to support diagnosis in terms of genetic evaluation, telemedicine, digital technologies, use of machine learning/artificial intelligence, and research on candidate diagnostic biomarkers.

Sequence variants in HECTD1 result in a variable neurodevelopmental disorder.

Dysregulation of genes encoding the homologous to E6AP C-terminus (HECT) E3 ubiquitin ligases has been linked to cancer and structural birth defects. One member of this family, the HECT-domain-containing protein 1 (HECTD1), mediates developmental pathways, including cell signaling, gene expression, and embryogenesis. Through GeneMatcher, we identified 14 unrelated individuals with 15 different variants in HECTD1 (10 missense, 3 frameshift, 1 nonsense, and 1 splicing variant) with neurodevelopmental disorders (NDDs), including autism, attention-deficit/hyperactivity disorder, and epilepsy.

Impact of different foot orthoses on gait biomechanics in individuals with chronic metatarsalgia.

Background: Foot orthoses (FOs) are commonly prescribed to reduce pain and improve function in individuals with musculoskeletal disorders, including those with chronic metatarsalgia (CM). Reducing the mechanical overload under the metatarsal heads during locomotion is the central point of the treatment for CM. Medially wedged FOs (MWFOs) with a metatarsal pad could further reduce pressure loading under the metatarsal heads and modify foot and ankle biomechanics compared to standard FOs (SFOs).

AP39, a novel mitochondria-targeted hydrogen sulfide donor, promotes cutaneous wound healing in an in vivo murine model of acute frostbite injury.

Frostbite injury refers to cold tissue injury which typically affects the peripheral areas of the body, and is associated with limb loss and high rates of morbidity. Historically, treatment options have been limited to supportive care, leading to suboptimal outcomes for affected patients. The pathophysiology of frostbite injury has been understood in recent years to share similarity with that of cold ischemia-reperfusion injury as seen in solid organ transplantation, of which mitochondria play an important contributing role.

Assessing the potential acoustic impact of floating offshore wind farms in the Central Mediterranean Sea.

The Strait of Sicily, a vital marine passage with diverse fauna, is seeing a steep rise in the planning of offshore wind farm projects. This study assesses the acoustic impact of these wind farms on local marine species. Underwater propagation was modeled for three proposed floating wind farms using JASCO's Marine Operations Noise Model (MONM), which integrates a parabolic equation method for frequencies from 10 to 800 Hz and a beam-tracing model for 1 to 25 kHz.

SEEG guided mapping of primary motor cortex in children with epilepsy.

Background: Direct cortical electrical stimulation remains the gold standard for delineation of the primary motor cortex in patients with drug-resistant epilepsy (DRE) undergoing epilepsy surgery evaluation OBJECTIVE: This study aimed to explore the efficacy and safety of functional motor mapping through Stereo-EEG (SEEG) electrode contacts in children with DRE at our institute.

Methods: We performed a retrospective analysis of children who underwent SEEG evaluation and functional cortical mapping via bipolar electrical stimulation at our institution between July 2020 and June 2024. Detailed clinical, radiological and neurophysiological variable were extracted; qualitative and quantitative variables were summarized using appropriate descriptive statistics.

Administering the Lidcombe Program to children who stutter with concomitant disorders: Insights from an exploratory retrospective chart review study.

Purpose: Children who stutter (CWS) in clinical settings may present with concomitant disorders (CDs), which can complexify the delivery of the Lidcombe Program (LP). However, there is limited evidence on how CDs influence treatment outcomes in CWS, leaving clinicians with little guidance regarding best practices with these children. This exploratory study, conducted in partnership with a rehabilitation center's clinical team, aims to understand which CDs and suspected CDs speech-language pathologists document when treating CWS with the LP and their relationship to treatment characteristics and outcomes.

An investigation of the mechanism of adjacent segment disease in a porcine spine model.

Background: Fusion changes the biomechanics of the spine leading to the potential development of adjacent segment disease. Despite many studies on adjacent segment disease, it is largely unknown how spinal fixation affects the mechanical properties of the adjacent disc. The purpose of this study was to assess whether axial compression causes mechanical disruption to the annulus when the caudal spinal level is immobilized or injured.

Electronic structures of atomic silicon dimer wires as a function of length.

Bare silicon dimers on hydrogen-terminated Si(100) have two dangling bonds. These are atomically localized regions of high state density near to and within the bulk silicon band gap. We studied bare silicon dimers as monomeric units.

Plasma phosphorylated tau217 strongly associates with memory deficits in the Alzheimer's disease spectrum.

Plasma phosphorylated tau biomarkers open unprecedented opportunities for identifying carriers of Alzheimer's disease pathophysiology in early disease stages using minimally invasive techniques. Plasma p-tau biomarkers are believed to reflect tau phosphorylation and secretion. However, it remains unclear to what extent the magnitude of plasma p-tau abnormalities reflects neuronal network disturbance in the form of cognitive impairment.

Efficacy, immunogenicity, and safety of an investigational maternal respiratory syncytial virus prefusion F protein-based vaccine.

Background: In this phase 3 trial of an investigational maternal respiratory syncytial virus prefusion F protein-based vaccine (RSVPreF3-Mat), a higher rate of preterm birth was observed in the vaccine (6.8%) versus the placebo group (4.9%).

Constructing TheKeep.Ca With Thrivers of Cancer in Manitoba, Canada, in Support of Enhancing Patient Engagement: Protocol for a Pragmatic Multimethods Study.

Background: TheKeep.Ca was built to facilitate engagement with those experiencing cancer in Manitoba, Canada. Constructed between 2020 and 2024 with a group of patient advisors, the website includes information on engagement activities including research participation, the patient advisor role, and how those experiencing cancer can access these Manitoba activities.

Scaling Up Kangaroo Mother Care Through a Facility Delivery Model in Rural Districts of Pakistan: Protocol for a Mixed Methods Study.

Background: The neonatal mortality rate in Pakistan is the third highest in Asia, with 8.6 million preterm babies. These newborns require warmth, nutrition, and infection protection, typically provided by incubators.

Assessment of viable Enterobacteriaceae and Enterococcus spp. across the agro-ecosystem of an antibiotic-free swine farm.

Agricultural practices, specifically the use of antibiotics and other biocides, have repercussions on human, animal and plant health. The aim of this study was to evaluate the levels of Enterobacteriaceae and Enterococcus, as antibiotic resistant marker bacteria, in various matrices across the agro-ecosystem of an antibiotic-free swine farm in Quebec (Canada), namely pig feed, feces, manure, agricultural soil, water and sediment from a crossing stream, and soil from nearby forests. Samples were collected in fall 2022, spring and fall 2023 and spring 2024.

Nanoparticle encapsulation enables systemic IGF-Trap delivery to inhibit intra-cerebral glioma growth.

Background: Glioblastoma is an aggressive brain cancer with a 5-year survival rate of 5-10%. Current therapeutic options are limited, due in part to drug exclusion by the blood-brain barrier, restricting access of targeted drugs to the tumor. The receptor for the type 1 insulin-like growth factor (IGF-1R) was identified as a therapeutic target in glioblastoma.