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Abstract Background Pancreatic ductal adenocarcinoma (PDAC) presents with a high mortality rate. Two important features of PDAC contribute to this poor outcome. The first is metastasis which occurs in ~ 80% of PDAC patients. The second is cachexia, which compromises treatment tolerance for patients and reduces their quality of life. Although various mouse models of PDAC exist, recapitulating both metastatic and cachectic features have been challenging. Methods Here, we optimize an orthotopic mouse model of PDAC by altering several conditions, including the subcloning of parental murine PDAC cells, implantation site, number of transplanted cells, and age of recipient mice. We perform spatial profiling to compare primary and metastatic immune microenvironments and RNA sequencing to gain insight into the mechanisms of muscle wasting in PDAC-induced cachexia, comparing non-metastatic to metastatic conditions. Results These modifications extend the time course of the disease and concurrently increase the rate of metastasis to approximately 70%. Furthermore, reliable cachexia endpoints are achieved in both PDAC mice with and without metastases, which is reminiscent of patients. We also find that cachectic muscles from PDAC mice with metastasis exhibit a similar transcriptional profile to muscles derived from mice and patients without metastasis. Conclusion Together, this model is likely to be advantageous in both advancing our understanding of the mechanism of PDAC cachexia, as well as in the evaluation of novel therapeutics.

Heads of public schools are low-paid key players in nation-building and are generally known to have low financial literacy. As such, some of them are known to have been over-borrowing from government and private financial institutions and are caught in a debt trap. Under such conditions, public school heads may not be satisfied with their jobs. Financial literacy, lifestyle, indebtedness, and job satisfaction may have also affected their job performance. The researchers surveyed 176 of the 323 school heads of the Schools Division of Sarangani and found them to have a high level of financial literacy, contrary to conventional belief. They were also proven to lead simple and modest lifestyles. Ironically, the respondents were found to have a high degree of indebtedness. Despite their situation, the school heads were found to be highly satisfied with their jobs and were performing very satisfactorily. The researchers concluded that financial literacy, lifestyle, and indebtedness do not matter to job performance; but job satisfaction does. The results of the study provide valuable insights into the complex interplay between financial literacy, lifestyle, indebtedness, job satisfaction, and job performance among public school heads. By identifying areas for improvement and potential avenues for intervention, the findings contribute to ongoing efforts aimed at enhancing the effectiveness and well-being of educators in the Philippines and beyond. [ABSTRACT FROM AUTHOR]

An abstract of the article "Setting Up and Oversight of Local Clinical Trial Site Laboratories with Limited Resources: A Case Study of South Africa's FACTS 001 Study" by Sarah S. Cohen, Ishana Naidoo, Romeo Martin and colleagues is presented.