Acquisition of epithelial plasticity in human chronic liver disease.

For many adult human organs, tissue regeneration during chronic disease remains a controversial subject. Regenerative processes are easily observed in animal models, and their underlying mechanisms are becoming well characterized1-4, but technical challenges and ethical aspects are limiting the validation of these results in humans. We decided to address this difficulty with respect to the liver. This organ displays the remarkable ability to regenerate after acute injury, although liver regeneration in the context of recurring injury remains to be fully demonstrated. Here we performed single-nucleus RNA sequencing (snRNA-seq) on 47 liver biopsies from patients with different stages of metabolic dysfunction-associated steatotic liver disease to establish a cellular map of the liver during disease progression. We then combined these single-cell-level data with advanced 3D imaging to reveal profound changes in the liver architecture. Hepatocytes lose their zonation and considerable reorganization of the biliary tree takes place. More importantly, our study uncovers transdifferentiation events that occur between hepatocytes and cholangiocytes without the presence of adult stem cells or developmental progenitor activation. Detailed analyses and functional validations using cholangiocyte organoids confirm the importance of the PI3K-AKT-mTOR pathway in this process, thereby connecting this acquisition of plasticity to insulin signalling. Together, our data indicate that chronic injury creates an environment that induces cellular plasticity in human organs, and understanding the underlying mechanisms of this process could open new therapeutic avenues in the management of chronic diseases.

Exploring the care coordination experiences of professionals and caregivers of youth with acquired brain injuries in rural areas.

PURPOSE: Acquired brain injuries (ABIs) can have devastating effects on children and their families. Families living in rural communities experience unique barriers to receiving and coordinating care for complex medical needs, but little research has examined those barriers for rural youth with ABIs. MATERIALS AND METHODS: This qualitative study explored the experiences of rural adults caring for children with ABIs through interviews with six caregivers, three school staff members, and three medical professionals who had treated at least one child with an ABI. RESULTS: Themes in their accounts include difficulty navigating complex situations, support from small communities, isolation and loneliness, the need for more professional education about ABI, and feelings of hope. Barriers to quality care coordination include navigating complex situations, access to transportation, and a lack of communication and education from healthcare agencies. Facilitators of rural care coordination include support from small communities and interagency communication. CONCLUSIONS: The results support the need for more comprehensive coordination among rural agencies involved in ABI care. Suggestions for care improvement include providing flexibility due to transportation barriers, capitalizing on the benefits of a small and caring community, and providing healthcare and education professionals with more education about ABI interventions.

Practitioners should implement tailored support systems that include initiatives to facilitate direct communication between rural medical agencies and schools.Expanding the role of care coordinators to bridge gaps across healthcare, education, and community services could enhance care coordination for children with acquired brain injuries in rural areas.Schools in rural areas should develop formal reintegration programs tailored to the needs of children with mild acquired brain injuries, leveraging existing sports protocols for non-sports-related injuries.Collaborative efforts between schools, medical teams, and community agencies can provide comprehensive education programs tailored to the rural context.The development of online options for follow-up appointments would be particularly beneficial in rural areas, where transportation barriers are more pronounced.

Sexual Debut in Early Adolescence and Individual, School, and Neighborhood Social Capital.

PURPOSE: Sexual debut in early adolescence is associated with poor health outcomes in adulthood. We examined the associations of social capital within families, schools, and neighborhoods with early sexual debut. METHODS: Using data from the Healthy Passages cohort, a longitudinal multilevel study of adolescents, we performed a series of cross-classified multilevel logistic regression models to examine (1) the relative contribution of schools and neighborhoods to the variance and (2) the association of markers of social cohesion/social capital in families, schools, and neighborhoods with sexual debut by 10th grade. RESULTS: There were 4,001 youth participants nested in 115 schools and 751 neighborhoods, with a high degree of cross-classification (1,340 unique combinations of school and neighborhoods). In models adjusting for individual demographics, neighborhoods contributed more to the variance (log odds U [95% confidence interval {CI}] [intra class correlation {ICC}%]) in sexual debut than schools: Uneighborhoods = 0.11 (0.02, 0.23) [3.2%] versus Uschools = 0.07 (0.01, 0.16) [2%]. Restriction of dating and family cohesion, markers of family social capital, were associated with reduced odds of sexual debut by 10th grade (odds ratio = 0.45 95% CI: 0.41-0.49 and 0.93, 95% CI: 0.86, 1.00). Neighborhood cohesion and education level were associated with early debut. Although reduced, there remained significant, unexplained variance in both the school and neighborhood level in the fully adjusted model (Uschool = 0.08 [0.01, 0.17] [2.3%], Uneighborhood = 0.08 [0.02, 0.17] [2.2%]). DISCUSSION: Markers of social capital at the family and neighborhood levels were associated with sexual debut by 10th grade. Developers of public health programs aiming to delay sexual debut should consider family-focused and neighborhood-focused interventions.

An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, encompasses steatosis and metabolic dysfunction-associated steatohepatitis (MASH), leading to cirrhosis and hepatocellular carcinoma. Preclinical MASLD research is mainly performed in rodents; however, the model that best recapitulates human disease is yet to be defined. We conducted a wide-ranging retrospective review (metabolic phenotype, liver histopathology, transcriptome benchmarked against humans) of murine models (mostly male) and ranked them using an unbiased MASLD 'human proximity score' to define their metabolic relevance and ability to induce MASH-fibrosis. Here, we show that Western diets align closely with human MASH; high cholesterol content, extended study duration and/or genetic manipulation of disease-promoting pathways are required to intensify liver damage and accelerate significant (F2+) fibrosis development. Choline-deficient models rapidly induce MASH-fibrosis while showing relatively poor translatability. Our ranking of commonly used MASLD models, based on their proximity to human MASLD, helps with the selection of appropriate in vivo models to accelerate preclinical research.

A Path Analysis of Latino Parental, Teenager and Cultural Variables in Teenagers' Sexual Attitudes, Norms, Self-Efficacy, and Sexual Intentions / Análise da trajetória dos pais latinos, variáveis culturais nas atitudes sexuais dos adolescentes, normas, auto-eficácia, e intenções sexuais / Análisis de ruta de padres latinos, adolescente y variables culturales en actitudes sexuales de los adolescentes, normas, autoeficacia e intenciones sexuales

to test a theoretical model based on the Parent-Based Expansion of the Theory of Planned Behavior examining relation between selected parental, teenager and cultural variables and Latino teenagers' intentions to engage in sexual behavior.

testar um modelo teórico com base na Expansão Parental da Teoria do Comportamento Planejado, examinando a relação entre pais selecionados, adolescentes e variáveis culturais e as intenções dos jovens latinos ao se envolverem com comportamento sexual.

poner a prueba un modelo teórico basado en " Parent-Based Expansion " y con base en la teoría del comportamiento planificado para examinar la relación entre los padres seleccionados, adolescente y variables culturales, como también en las intenciones de los adolescentes latinos a participar en el comportamiento sexual.

Relationships between parenting styles and risk behaviors in adolescent health: an integrative literature review / Relações entre modelos de pais e comportamentos de risco na saúde do adolescente: uma revisão integrativa da literatura / Relaciones entre los tipos de padres y comportamientos de riesgo en la salud del adolescentes: una revisión bibliográfica integrada

Research over the past 20 years suggests that the quality of the parent-adolescent relationship significantly affects the development of risk behaviors in adolescent health. The purpose of this paper is to present a review of studies published between 1996-2007 that address specific relationships between parenting styles and six priority adolescent risk behaviors. The review supports the substantial influence of parenting style on adolescent development. Adolescents raised in authoritative households consistently demonstrate higher protective and fewer risk behaviors than adolescents from non-authoritative families. There is also considerable evidence to show that parenting styles and behaviors related to warmth, communication and disciplinary practices predict important mediators, including academic achievement and psychosocial adjustment. Careful examination of parenting style patterns in diverse populations, particularly with respect to physical activity and unintentional injury, will be a critical next step in the development of efficacious, culturally tailored adolescent health promotion interventions.

Resultados de investigaciones realizadas durante los últimos 20 años muestran que la calidad en las relaciones entre padres e hijos ha provocado un impacto significativo en el desarrollo de comportamientos de riesgo para la salud del adolescente. El objetivo de este artículo es mostrar una revisión bibliográfica de estudios publicados entre 1996-2007, analizando relaciones específicas entre los tipos de padres y los seis principales comportamientos de riesgo en adolescentes. Adolescentes criados bajo una disciplina autoritaria muestran comportamientos más seguros y menores comportamientos de riesgo al ser comparados con adolescentes que provienen de familias poco autoritarias. El tipo paternal y comportamientos relacionados con la afectividad, comunicación familiar y disciplina predicen importantes mediadores para la formación del adolescente, incluyendo desarrollo académico y adaptación psico-social. Cuidadosas evaluaciones sobre los tipos de padres estándar en poblaciones diversas será una próxima etapa crítica para el desarrollo de intervenciones eficaces y adaptadas culturalmente para la promoción de la salud del adolescente.

Pesquisas realizadas durante os últimos 20 anos sugerem que a qualidade da relação entre pais e adolescentes tem obtido impacto significante no desenvolvimento de comportamentos de risco a saúde dos adolescentes. A finalidade deste estudo é apresentar uma revisão bibliográfica de estudos publicados entre o ano de 1996 e 2007, que analisam relações especificas entre modelos de pais e seis principais comportamentos de risco em adolescentes. Os adolescentes crescidos sob disciplina autoritária demonstraram consistentemente mais comportamentos seguros e menos comportamentos de risco comparados a adolescentes vindos de famílias não autoritárias. O modelo dos pais e comportamentos relacionados a afetividade, comunicação familiar e práticas disciplinares, predizem importantes mediadores na formação do adolescente, incluindo o desenvolvimento acadêmico e o ajuste psico-social. Avaliações cuidadosas de modelos padrões de pais em diversas populações, será uma próxima etapa crítica no desenvolvimento de intervenções eficazes e culturalmente adaptadas, na promoção de saúde a adolescentes.