"My wellbeing-their wellbeing "- An eHealth intervention for managing obesity in early care and education: Protocol for the Go NAPSACC Cares cluster randomized control trial.

BACKGROUND: To fully leverage the potential of the early care and education (ECE) setting for childhood obesity prevention, initiatives must not intervene solely at the organizational level, but rather they should also address the health needs of the ECE workers. Workers suffer disproportionately high rates of obesity, and have reported low confidence in modeling and promoting healthy eating and activity behaviors. However, information regarding the effectiveness of improving ECE workers' health behaviors or whether such improvements elicit meaningful change in the ECE environment and/or the children in their care is limited. METHOD: The proposed study will integrate a staff wellness intervention into a nationally recognized, ECE obesity prevention initiative (Go NAPSACC). Go NAPSACC+ Staff Wellness program will be assessed using a clustered randomized controlled trial including 84 ECE centers, 168 workers, and 672 2-5-year-old children. Centers will be randomly assigned to 1) standard "Go NAPSACC" or 2) Go NAPSACC+ Staff Wellness. Outcome measures will assess impact on dietary intake and PA behaviors of 2-5-year-old children at 6 months (primary aim) and 12 months. Secondarily, we will compare the impact of the intervention on centers' implementation of healthy weight practices and the effect on ECE workers' diet quality and PA at 6- and 12 months. DISCUSSION: This trial expects to increase our understanding of how ECE worker's personal health behaviors impact the health behaviors of the children in their care and the ECE environment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05656807, registered on 19 December 2022. Protocol version 1.0, 22 March 2023.

Aberrant regulation of epigenetic modifiers contributes to the pathogenesis in patients with selenoprotein N-related myopathies.

Congenital myopathies are early onset, slowly progressive neuromuscular disorders of variable severity. They are genetically and phenotypically heterogeneous and caused by pathogenic variants in several genes. Multi-minicore Disease, one of the more common congenital myopathies, is frequently caused by recessive variants in either SELENON, encoding the endoplasmic reticulum glycoprotein selenoprotein N or RYR1, encoding a protein involved in calcium homeostasis and excitation-contraction coupling. The mechanism by which recessive SELENON variants cause Multiminicore disease (MmD) is unclear. Here, we extensively investigated muscle physiological, biochemical and epigenetic modifications, including DNA methylation, histone modification, and noncoding RNA expression, to understand the pathomechanism of MmD. We identified biochemical changes that are common in patients harboring recessive RYR1 and SELENON variants, including depletion of transcripts encoding proteins involved in skeletal muscle calcium homeostasis, increased levels of Class II histone deacetylases (HDACs) and DNA methyltransferases. CpG methylation analysis of genomic DNA of patients with RYR1 and SELENON variants identified >3,500 common aberrantly methylated genes, many of which are involved in calcium signaling. These results provide the proof of concept for the potential use of drugs targeting HDACs and DNA methyltransferases to treat patients with specific forms of congenital myopathies.

An exploration of the word 'palliative' in the 19th century: searching the BMJ archives for clues.

BACKGROUND: Palliative care went through a significant evolution in the 20th century, but the 19th century has been seen my some scholars as the real turning point toward the more modern concept of hospices and palliative care. METHODS: To investigate some examples of earlier uses of the word 'palliative', a literature search was conducted within the earliest available BMJ archive sections, the years 1840 to 1842. This provided a glimpse into how the word was used in the medical literature in Victorian times, mid-nineteenth century. RESULTS: Search results brought up a number of case reports, and the word was employed to describe medicines ('use of palliatives') as well as passive, non-active treatment approaches, probably best described as a watch-and-wait strategy. Of note is that the first recorded use of the word in the archives is by a surgeon. CONCLUSIONS: Some doctors associated the word palliative with there not being any prospect for cure and only for the relief of symptoms and greater comfort of the patient. There were, however, early reflections on whether palliative treatments may in some cases increase the length of patients' lives.