This review analyzes strategies to prevent or reduce the transmission of diseases caused by pathogenic variants in mitochondrial DNA (mtDNA). Among these, we will focus on prenatal screening, preimplantation genetic testing, gene-editing techniques, other molecular tools, and selected heterologous mitochondrial replacement techniques (MRTs), explaining their status and the uncertainties surrounding their clinical application. After this analysis and review, we recognise the limitations of the efficacy of prenatal and preimplantation genetic testing for mitochondrial DNA pathogenic variants, the legal constraints on gene editing, and the status of mitochondrial replacement techniques. MRTs are a safe and possibly more effective alternative for preventing diseases caused by mitochondrial DNA pathogenic variants.
Meta-analyses have consistently shown that ICT-supported writing interventions are effective, yet existing syntheses often provide limited insight into their instructional design. To address this gap, the present meta-analysis adopts a component-based instructional design perspective to examine which instructional features embedded in ICT-supported writing interventions are associated with improvements in students’ writing quality. We estimated the overall effect on writing quality (1) and tested whether design principles, their operationalization into specific instructional activities (2), feedback and scaffolding features (3), and the delivering agent (teacher, ICT, or both) (4) moderated effects. Following PRISMA guidelines, studies were identified through ERIC, PsycINFO, Web of Science, and Scopus, yielding 42 empirical studies, focusing on typically developing students. ICT-supported interventions showed a large overall positive effect on writing quality (g = 1.264, 95
This study aimed to identify the Greatest of All Time (GOAT) athlete in running events held at the Olympic Games and World Athletics championships. The achievements of 1294 men and 824 women who won at least one medal in any sprint, hurdles, or distance event at major global championships since 1896, or set a World Record (WR) since 1912, were collated. A scoring system was used to award points, with Olympic gold medals and WRs ranked joint highest. Fewer points were awarded for Olympic silver and bronze medals and for medals in World Championships (outdoor, indoor, and cross-country). Bonus points were awarded for WR longevity and the setting of WRs during Olympic finals. Athletes were also ranked by event and within historical eras. As of March 2026, Usain Bolt (Jamaica) was ranked as the male GOAT, and the highest-scoring woman was Faith Kipyegon (Kenya). Both athletes notably won “doubles” during their careers (over 100/200 m and 1500 m/5000 m, respectively) and set WRs over both distances. Marathon, steeplechase, and hurdle specialists usually competed in one event only. In an earlier era, Paavo Nurmi (Finland) had the highest combined Olympic Games/WR score across a range of distances. Athletes who successfully competed over physiologically and tactically similar events (“doubles”), such as Bolt and Kipyegon, had a greater opportunity to become the GOAT. An increase in global competition since 1972 meant greater opportunities for winning medals, especially for women. This study provides a foundation on which future performances could be evaluated.
Forest fires pose a significant threat to rural areas, affecting ecosystems, property, infrastructure, and human lives. Effective post-fire management strategies are crucial for short-term ecosystem and community recovery. This study evaluated the effectiveness of three post-fire interventions in reducing soil erosion and runoff within a temperate Atlantic–transition climate, focusing on a shrubland hillslope near organic vineyards in Corullón, NW Spain, after a moderate-severity fire. The research aimed to (i) compare the effects of plowing, straw mulching, and no intervention (control) on post-fire soil recovery, and (ii) assess the cost-effectiveness and environmental impacts of these treatments. Ten experimental plots were randomly assigned to plowing (n = 4), straw mulching (n = 4), or control (n = 2). Seventeen rainfall events were monitored between 15 days and six months post-fire. Results showed no significant differences in erosion or runoff reduction among treatments. Natural vegetation recovery, assessed visually, was rapid across all plots, with erosion and runoff stabilizing within two months. These findings suggest that, under the specific conditions of this temperate climate and moderate fire severity, early intervention techniques may not be necessary. The study concludes that natural regeneration can be a viable and cost-effective post-fire management strategy in regions with favorable environmental conditions for soil recovery, potentially reducing the need for intensive interventions.
Abstract Background Chronic kidney disease (CKD) markedly accelerates atherosclerosis, driving the excess cardiovascular morbidity and mortality in these patients. While rodent models have been indispensable for mechanistic studies, their small vessel size limits the use of non-invasive vascular imaging to monitor disease progression. Therefore, large-animal models are needed to bridge experimental insights with clinical applicability. We aimed to establish a novel minipig model of CKD to characterize the temporal changes of CKD-driven atherosclerosis. Six female Yucatan minipigs overexpressing a human gain-of-function PCSK9 mutant were randomized to CKD (n = 3) or control (n = 3) groups. CKD was induced by selective clamping of the left renal artery branches combined with contralateral nephrectomy using a minimally invasive laparoscopic approach. All animals were fed with a high-fat, high-cholesterol diet and followed for 15 months. Longitudinal assessments included vascular and renal ultrasound, computed tomography, plasma iohexol clearance for glomerular filtration rate (GFR) determination, and biochemical profiling of ions, cytokines, chemokines, and lipids, including advanced lipoprotein, lipidomic and fatty acid analyses. Between-groups differences were evaluated using effect sizes with 95% confidence intervals. Results CKD pigs exhibited a significant reduction in GFR and increased blood creatinine. They exhibited accelerated atherogenesis, reflected by enhanced progressive adventitial vasa vasorum neovascularization in both carotid and iliac arteries, a higher burden of arterial calcifications in abdominal aorta and iliac arteries and postmortem larger atherosclerotic plaques and calcified areas in coronary arteries. CKD also altered the systemic inflammation profile (elevated IL-1ra, IL-2, IL-4, IL-8, and IL-10), promoted a proatherogenic lipoprotein phenotype with triglyceride-enriched VLDL, LDL, and IDL particles, increased VLDL particle number, and reduced LDL particle size. Lipidomic analyses revealed increased circulating and renal palmitic acid and distinct lesion-specific fatty acid signatures. Fatty streaks were enriched in palmitic acid and 10,16-dihydroxy-palmitic acid, and mature carotid plaques accumulated polyunsaturated fatty acids. Conclusions This minimally invasive CKD model in gentically modified minipigs accelerates atherosclerosis and induces a unique lipidomic remodelling, providing a valuable translational platform to study kidney-vascular interactions and to test therapeutic interventions targeting CKD-driven atherosclerosis.
