Exposure to secondhand smoke in cars and e-cigarette use among 10-11 year old children in Wales: CHETS Wales 2 key findings report

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Meroterpenoids: A Comprehensive Update Insight on Structural Diversity and Biology.

Funder: This research was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Fast-track Research Funding ProgramMeroterpenoids are secondary metabolites formed due to mixed biosynthetic pathways which are produced in part from a terpenoid co-substrate. These mixed biosynthetically hybrid compounds are widely produced by bacteria, algae, plants, and animals. Notably amazing chemical diversity is generated among meroterpenoids via a combination of terpenoid scaffolds with polyketides, alkaloids, phenols, and amino acids. This review deals with the isolation, chemical diversity, and biological effects of 452 new meroterpenoids reported from natural sources from January 2016 to December 2020. Most of the meroterpenoids possess antimicrobial, cytotoxic, antioxidant, anti-inflammatory, antiviral, enzyme inhibitory, and immunosupressive effects

Electronic-cigarette use among young people in Wales: evidence from two cross-sectional surveys

Objectives To examine the prevalence of electronic(e)-cigarette use, prevalence of e-cigarette and tobacco use by age, and associations of e-cigarette use with sociodemographic characteristics, tobacco and cannabis use among young people in Wales. Design Data from two nationally-representative cross-sectional surveys undertaken in 2013–2014. Logistic regression analyses, adjusting for school-level clustering, examined sociodemographic characteristics of e-cigarette use, and associations between e-cigarette use and smoking. Setting Primary and secondary schools in Wales. Participants Primary-school children aged 10–11 (n=1601) and secondary-school students aged 11–16 (n=9055). Results Primary-school children were more likely to have used e-cigarettes (5.8%) than tobacco (1.6%). Ever use of e-cigarettes remained more prevalent than ever use of tobacco until age 14–15. Overall, 12.3% of secondary-school students (aged 11–16) reported ever using e-cigarettes, with no differences according to gender, ethnicity or family affluence. The percentage of ‘never smokers’ reporting having used e-cigarettes was 5.3% at age 10–11 to 8.0% at age 15–16. The proportion of children who had ever used an e-cigarette and reported currently smoking increased from 6.9% among 10–11 year olds to 39.2% in 15–16 year olds. Only 1.5% (n=125) of 11–16 year-olds, including 0.3% of never smokers, reported regular e-cigarette use (use at least once a month). Current weekly smokers were 100 times more likely than non-smokers to report regular e-cigarette use (relative risk ratio (RRR=121.15; 95% CI 57.56 to 254.97). Regular e-cigarette use was also more likely among those who had smoked cannabis (RRR 53.03; 95% CI 38.87 to 80.65). Conclusions Many young people (including never-smokers) have tried e-cigarettes. However, regular use is less common, and is associated with tobacco cigarette use. Longitudinal research is needed to understand age-related trajectories of e-cigarette use and to understand the temporal nature of relationships between e-cigarette and tobacco use

E-cigarette use and intentions to smoke among 10-11-year-old never-smokers in Wales

AbstractBackground E-cigarettes are seen by some as offering harm reduction potential, where used effectively as smoking cessation devices. However, there is emerging international evidence of growing use among young people, amid concerns that this may increase tobacco uptake. Few UK studies examine the prevalence of e-cigarette use in non-smoking children or associations with intentions to smoke.Methods A cross-sectional survey of year 6 (10–11-year-old) children in Wales. Approximately 1500 children completed questions on e-cigarette use, parental and peer smoking, and intentions to smoke. Logistic regression analyses among never smoking children, adjusted for school-level clustering, examined associations of smoking norms with e-cigarette use, and of e-cigarette use with intentions to smoke tobacco within the next 2 years.Results Approximately 6% of year 6 children, including 5% of never smokers, reported having used an e-cigarette. By comparison to children whose parents neither smoked nor used e-cigarettes, children were most likely to have used an e-cigarette if parents used both tobacco and e-cigarettes (OR=3.40; 95% CI 1.73 to 6.69). Having used an e-cigarette was associated with intentions to smoke (OR=3.21; 95% CI 1.66 to 6.23). While few children reported that they would smoke in 2 years’ time, children who had used an e-cigarette were less likely to report that they definitely would not smoke tobacco in 2 years’ time and were more likely to say that they might.Conclusions E-cigarettes represent a new form of childhood experimentation with nicotine. Findings are consistent with a hypothesis that children use e-cigarettes to imitate parental and peer smoking behaviours, and that e-cigarette use is associated with weaker antismoking intentions

Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders

The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins, and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Utilizing exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with YnMyr chemical proteomics in the model organisms and human cells, with the latter also being subjected further to ACBD6 peroxisomal localization studies. The affected individuals (23 males and 22 females), with ages ranging from 1 to 50 years old, typically present with a complex and progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) with significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%), and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia (76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%), microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement disorder was dystonia (94%), frequently leading to early-onset progressive postural deformities (97%), limb dystonia (55%), and cervical dystonia (31%). A jerky tremor in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing with advancing age (32%), and simple motor and vocal tics were among other frequent movement disorders. Midline brain malformations including corpus callosum abnormalities (70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and small inferior cerebellar vermis (38% each), as well as hypertrophy of the clava (24%) were common neuroimaging findings. acbd6-deficient zebrafish and Xenopus models effectively recapitulated many clinical phenotypes reported in patients including movement disorders, progressive neuromotor impairment, seizures, microcephaly, craniofacial dysmorphism, and midbrain defects accompanied by developmental delay with increased mortality over time. Unlike ACBD5, ACBD6 did not show a peroxisomal localisation and ACBD6-deficiency was not associated with altered peroxisomal parameters in patient fibroblasts. Significant differences in YnMyr-labelling were observed for 68 co- and 18 post-translationally N-myristoylated proteins in patient-derived fibroblasts. N-Myristoylation was similarly affected in acbd6-deficient zebrafish and Xenopus tropicalis models, including Fus, Marcks, and Chchd-related proteins implicated in neurological diseases. The present study provides evidence that bi-allelic pathogenic variants in ACBD6 lead to a distinct neurodevelopmental syndrome accompanied by complex and progressive cognitive and movement disorders

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly