Physical work conditions and disparities in later life functioning: Potential pathways.

Research in the US on the social determinants of reduced physical functioning at older ages has typically not considered physical work conditions as contributors to disparities. We briefly describe a model of occupational stratification and segregation, review and synthesize the occupational health literature, and outline the physiological pathways through which physical work exposures may be tied to long-term declines in physical functioning. The literature suggests that posture, force, vibration, and repetition are the primary occupational risk factors implicated in the development of musculoskeletal disorders, through either acute injuries or longer-term wear and tear. Personal risk factors and environmental and structural work characteristics can modify this association. In the long-term, these musculoskeletal disorders can become chronic and ultimately lead to functional limitations and disabilities that interfere with one's quality of life and ability to remain independent. We then use data on occupational characteristics from the Occupational Information Network (O*NET) linked to the 2019 American Community Survey (ACS) to examine disparities among sociodemographic groups in exposure to these risk factors. Occupations with high levels of these physical demands are not limited to those traditionally thought of as manual or blue-collar jobs and include many positions in the service sector. We document a steep education gradient with less educated workers experiencing far greater physical demands at work than more educated workers. There are pronounced racial and ethnic differences in these exposures with Hispanic, Black, and Native American workers experiencing higher risks than White and Asian workers. Occupations with high exposures to these physical risk factors provide lower compensation and are less likely to provide employer-sponsored health insurance, making it more difficult for workers to address injuries or conditions that arise from their jobs. In sum, we argue that physical work exposures are likely an important pathway through which disparities in physical functioning arise.

Canopy Homolog 2 as a Novel Molecular Target in Hepatocarcinogenesis.

In the present study, the role of a novel protein involved in neurite development and endoplasmic reticulum (ER) stress, canopy homolog 2 (CNPY2), was investigated in mouse and human hepatocarcinogenesis. Firstly, a sensitive quantitative and qualitative detection of protein expression using QSTAR Elite LC-Ms/Ms was performed for the analysis of lysates of microdissected hepatocellular altered foci (AF), adenomas (HCAs), carcinomas (HCCs) and peri-tumoral livers from C57Bl/6J mice treated with diethylnitrosamine (DEN) and then maintained for 27 or 38 weeks on basal diet. Significant overexpression of 18.5 kDa CNPY2 processed form was demonstrated in AF, HCAs and HCCs, while low expression was observed in the livers of DEN-treated and control mice. Furthermore, CNPY2 elevation in AF and tumors was coordinated with accumulation of numerous cytoskeletal proteins, including cytokeratins 8 and 18, actin, non-muscle myosin and septin 9 and those involved in ER and mitochondrial stresses such as calreticulin, prohibitins 1 and 2 and YME1-like-1. Knockdown of CNPY2 in Huh7 and HepG2 human liver cancer cells resulted in significant suppression of cell survival and invasive potential, inhibition of cyclin D1, induction of p21Waf1/Cip1 and suppression of the apoptosis inhibitor Bcl2. In contrast, transfection of a mouse CNPY2 (mCNPY2-Ds-Red) vector plasmid in Huh7 and HepG2 cancer cells, with subsequent accumulation of CNPY2 in the ER, resulted in significant increase in cancer cells survival. Clinicopathological analysis in 90 HCV-positive HCC patients, revealed significant association of CNPY2 overexpression with poor overall (p = 0.041) survival. Furthermore, CNPY2 increase was associated with vessel invasion (p = 0.038), poor histological differentiation (p = 0.035) and advanced clinical stage (p = 0.016). In conclusion, CNPY2 is a promising molecular target elevated early in hepatocarcinogenesis and prognostic marker for human HCV-associated HCC. CNPY2 is involved in the processes of ER stress, cell cycle progression, proliferation, survival and invasion of liver tumor cells.