Developmental milestones for productivity occupations in children and youth: An integrative review.

BACKGROUND: Limited research exists on developmental milestones for productivity occupations throughout the paediatric lifespan, and negative connotations of work for children and youth may have contributed to a paucity of literature on the topic. OBJECTIVE: To ascertain what is currently known about the timing and types of engagement in productivity occupations in children and youth aged 4-19. METHODS: Literature referencing productive occupations in children and youth aged 4-19 was searched for this integrative review. Search terms were established based on paediatric age and occupational therapy descriptors, and terminology associated with productivity. Sixty-seven peer-reviewed articles were analyzed according to the constant comparative method. RESULTS: Six core productive occupations emerged as avenues for productive engagement: paid work, school-related activities, caring for self and others, household chores, volunteering, and agricultural chores. A timeline was constructed to display common milestones for engagement in these occupations throughout the paediatric lifespan. Paediatric engagement was found to be influenced by personal (age, gender, child and youth perceptions, and safety considerations), and environmental (familial factors, parental perceptions, societal influences, and safety considerations) factors. CONCLUSIONS: Approaches to paediatric practice must account for the full spectrum of productive occupations children and youth engage in beyond the school context.

Melanoma Development and Progression Are Associated with Rad6 Upregulation and ß -Catenin Relocation to the Cell Membrane.

We have previously demonstrated that Rad6 and ß -catenin enhance each other's expression through a positive feedback loop to promote breast cancer development/progression. While ß -catenin has been implicated in melanoma pathogenesis, Rad6 function has not been investigated. Here, we examined the relationship between Rad6 and ß -catenin in melanoma development and progression. Eighty-eight cutaneous tumors, 30 nevi, 29 primary melanoma, and 29 metastatic melanomas, were immunostained with anti- ß -catenin and anti-Rad6 antibodies. Strong expression of Rad6 was observed in only 27% of nevi as compared to 100% of primary and 96% of metastatic melanomas. ß -Catenin was strongly expressed in 97% of primary and 93% of metastatic melanomas, and unlike Rad6, in 93% of nevi. None of the tumors expressed nuclear ß -catenin. ß -Catenin was exclusively localized on the cell membrane of 55% of primary, 62% of metastatic melanomas, and only 10% of nevi. Cytoplasmic ß -catenin was detected in 90% of nevi, 17% of primary, and 8% of metastatic melanoma, whereas 28% of primary and 30% of metastatic melanomas exhibited ß -catenin at both locations. These data suggest that melanoma development and progression are associated with Rad6 upregulation and membranous redistribution of ß -catenin and that ß -catenin and Rad6 play independent roles in melanoma development.

Rad6 is a Potential Early Marker of Melanoma Development.

Melanoma is the leading cause of death from skin cancer in industrialized countries. Several melanoma-related biomarkers and signaling pathways have been identified; however, their relevance to melanoma development/progression or to clinical outcome remains to be established. Aberrant activation of Wnt/ß-catenin pathway is implicated in various cancers including melanoma. We have previously demonstrated Rad6, an ubiquitin-conjugating enzyme, as an important mediator of ß-catenin stability in breast cancer cells. Similar to breast cancer, ß-catenin-activating mutations are rare in melanomas, and since ß-catenin signaling is implicated in melanoma, we examined the relationship between ß-catenin levels/activity and expression of ß-catenin transcriptional targets Rad6 and microphthalmia-associated transcription factor-M (Mitf-M) in melanoma cell models, and expression of Rad6, ß-catenin, and Melan-A in nevi and cutaneous melanoma tissue specimens. Our data show that Rad6 is only weakly expressed in normal human melanocytes but is overexpressed in melanoma lines. Unlike Mitf-M, Rad6 overexpression in melanoma lines is positively associated with high molecular weight ß-catenin protein levels and ß-catenin transcriptional activity. Double-immunofluorescence staining of Rad6 and Melan-A in melanoma tissue microarray showed that histological diagnosis of melanoma is significantly associated with Rad6/Melan-A dual positivity in the melanoma group compared to the nevi group (P=.0029). In contrast to strong ß-catenin expression in normal and tumor areas of superficial spreading malignant melanoma (SSMM), Rad6 expression is undetectable in normal areas and Rad6 expression increases coincide with increased Melan-A in the transformed regions of SSMM. These data suggest a role for Rad6 in melanoma pathogenesis and that Rad6 expression status may serve as an early marker for melanoma development.