Conectar
by Artiom Gruzdev, Wendy N. Jefferson, Thomas B. Hagler, Gregory J. Scott, Manas K. Ray, Ginger W. Muse, Rani S. Sellers, Carmen J. Williams
FVB/N mice, which are commonly used for cancer studies, have accelerated onset of endometrial cancer following developmental estrogenic chemical exposure. These mice also have a polymorphism in the mitochondrial gene, mt-Atp8, leading to increased production of reactive oxygen species. We hypothesized that this polymorphism contributes to the enhanced endometrial cancer phenotype in FVB/N mice. To test this idea, we generated conplastic FVB/N-mt129S6/SvEvTac mice (FVB/N nuclear genome; 129S6/SvEvTac mitochondria: FVB/N-mt129). The impact of 129S6 versus FVB/N mitochondrial genomes on endometrial cancer development following neonatal exposure to the xenoestrogen, diethylstilbestrol, was tested by comparing the cancer phenotypes of FVB/N mice to FVB/N-mt129 mice. There was no difference in cancer incidence regardless of mitochondria source, but cancer grade was higher in the conplastic strain. Additionally, while the FVB/N genetic background is considered non-permissive for generation of pluripotent mouse embryonic stem cells, blastocysts from the conplastic background readily generated mouse embryonic stem cell clones that supported gene editing in culture and subsequently generated germline competent chimeric founder mice. FVB/N-mt129 mice are a potentially powerful resource for generating germline competent embryonic stem cells with an FVB/N nuclear genome and for studying cancer phenotypes.To generate an in-depth understanding of the perceptions and experiences of individuals with youth-onset type 2 diabetes (T2D) to inform knowledge translation initiatives and clinical care.
Interpretive descriptive qualitative study.
Individuals were eligible to participate if they received a T2D diagnosis on or before 18 years of age, resided in Manitoba, and were between 10 and 25 years of age at the time of data collection. Twenty-two individuals (13 females, 7 males, 2 prefer not to indicate gender; mean age = 19.3 years) participated in 22 semi-structured interviews (mean length: 29:01 min) remotely using Zoom video conferencing software or by telephone. Data were analysed using inductive thematic analysis.
Four themes were generated: (1) Low public knowledge, misconceptions, and stigma impact youth experiences including those of diagnosis, disclosure, treatment, and supports; (2) shared familial experiences impacts perception of the future; (3) mental and emotional wellness is critically important but requires more attention; and (4) T2D carries unanticipated positive and negative impacts for youth.
Findings illustrate the complex interrelationships between public and personal conceptions of T2D, stigma, and T2D navigation, emphasising the centrality of emotional and mental well-being to participants' T2D experiences and management. This representation of experiences and perceptions of youth onset T2D offers direction for holistic and youth-centred research and care and highlights areas where further mental health and educational resources would be beneficial.
The knowledge translation resource being developed from this study involves input from patient and public partners.
Poor chest health is the leading cause of early mortality in children with cerebral palsy (CP). It is also the most common reason to seek healthcare, accruing significant costs and reducing quality-of-life for children and families. Clinical trials examining chest health interventions in CP are characterised by inconsistent outcome measures, limiting the capacity for evidence synthesis to inform clinical application. The study aims to develop a core outcome set (COS) and related measurement instruments to assess, monitor and evaluate chest health in children with CP, both in research and routine clinical practice. The COS will reflect the views of children, young people, parent/carers, clinicians and researchers, emphasising under-represented groups in research and those at risk of poorer chest health.
A 3-phase methodology will be conducted in line with the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. (1) Candidate outcomes will be identified through a qualitative evidence synthesis and interviews with key stakeholders. Findings will be mapped to COMET-taxonomy, generating a list of candidate outcomes. (2) An international e-Delphi survey will invite stakeholders to rate the importance of each outcome, followed by a consensus meeting to ratify the COS. (3) A structured review, guided by health measurement taxonomy, will evaluate relevant instruments, with a final meeting to agree on recommended measures for each COS domain.
Ethical approval was provided by the University of Plymouth Research Ethics Committee for the qualitative interview study (ID5116), e-Delphi study and consensus meeting (ID5636). Study findings will be published open access in a peer-reviewed journal and presented at relevant national and international conferences.
COMET registration: 2590 (https://www.comet-initiative.org/Studies/Details/2590)
CRD42024562735.
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