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Many occupational therapy students navigate the transition to the Level II fieldwork experience effortlessly, while others require support due to a lack of perceived self-efficacy. This perception dramatically impacts fieldwork performance and challenges academic fieldwork coordinators to support students struggling to believe in their own capabilities. This study utilized a quantitative quasi-experimental research design with a purposive sample of 16 occupational therapy assistant students to determine if an educational intervention increased perceived self-efficacy and overall confidence. Data collected from the Student Confidence Questionnaire (SCQ) pre, and post-intervention provided insight into the students’ report of perceived self-efficacy and overall confidence during the Level II fieldwork experience. This questionnaire assessed the domains of professional competence, communication, adaptability, innovation, risk-taking, supervision, and clinical practice (Derdall et al., 2002). The educational module included an introduction to the key concepts of self-efficacy, self-assessment, and reflection, seven weekly reflective practice journal assignments centered around domains of the SCQ, and feedback using a reflective practice rubric to scaffold the development of self-efficacy. A statistically significant increase occurred in self-efficacy and overall confidence after the intervention across all seven domains of the post-test SCQ. The results indicated that the educational module created an influential impression on the development of self-efficacy and overall confidence during the Level II fieldwork experience. Level II fieldwork performance was not measured. Considering that many students struggle with perceived self-efficacy this educational intervention provides a potential solution to support fieldwork students challenged by a lack of belief in their own capabilities.

The dual-entry nature of occupational therapy has been a point of discussion for many years with explorations into the profession's support for the different degree programs and definitions of entry-level practice being the primary foci in the literature. There has been no comparison of the expectations of occupational therapy educators and practitioners of entry-level doctorate and master's students upon graduation despite differences in curricula and emphasis on advanced skills. This study utilized a descriptive quantitative survey to ask current educators and practitioners (n=124) to indicate their level of expectations of the two types of graduates for sixteen different clinical and professional skills and the level of expected mentorship upon graduation. Practitioners held the two groups of new graduates to the same expectations in all categories and anticipated they would need the same level of mentorship upon graduation. Despite equal expectations in all categories, there were six categories where at least 30% of participants indicated they held higher expectations of entry-level doctorate new graduates. These categories aligned with the doctoral capstone areas of foci. These results can set the foundation for further studies examining the congruence between expectations and new graduate readiness for the field and inform current curricula to prepare students to meet the professional expectations of their supervisors and colleagues.

In spite of extensive successes, cancer recurrence after radiation treatment (RT) remains one of the significant challenges in the cure of localized prostate cancer (PCa). This study focuses on elucidating a novel adaptive response to RT that could contribute to cancer recurrence. Here, we used PC3 cell line, an adenocarcinoma from a bone metastasis and radio-resistant clone 695 cell line, which survived after total radiation dose of 66 Gy (2 Gy × 33) and subsequently regrew in nude mice after exposure to fractionated radiation at 10 Gy (2 Gy × 5). Clone 695 cells not only showed an increase in surviving fraction post-radiation but also an increase in hydrogen peroxide (H2O2) production when compared to PC3 cells. At the single cell level, confocal microscope images coupled with IMARIS rendering software demonstrate an increase in mitochondrial mass and membrane potential in clone 695 cells. Utilizing the Seahorse XF96 instrument to investigate mitochondrial respiration, clone 695 cells demonstrated a higher basal Oxygen Consumption Rate (OCR), ATP-linked OCR, and proton leak compared to PC3 cells. The elevation of mitochondrial function in clone 695 cells is accompanied by an increase in mitochondrial H2O2 production. These data suggest that H2O2 could reprogram PCa’s mitochondrial homeostasis, which allows the cancer to survive and regrow after RT. Upon exposure to RT, in addition to ROS production, we found that RT induces the release of extracellular vesicles (EVs) from PC3 cells (p < 0.05). Importantly, adding H2O2 to PC3 cells promotes EVs production in a dose-dependent manner and pre-treatment with polyethylene glycol-Catalase mitigates H2O2-mediated EV production. Both RT-derived EVs and H2O2-derived EVs carried higher levels of mitochondrial antioxidant proteins including, Peroxiredoxin 3, Glutathione Peroxidase 4 as well as mitochondrial-associated oxidative phosphorylation proteins. Significantly, adding isolated functional mitochondria 24 h prior to RT shows a significant increase in surviving fractions of PC3 cells (p < 0.05). Together, our findings reveal that H2O2 promotes the production of EVs carrying mitochondrial proteins and that functional mitochondria enhance cancer survival after RT.

Aberrant levels of reactive oxygen species (ROS) are potential mechanisms that contribute to both cancer therapy efficacy and the side effects of cancer treatment. Upregulation of the non-canonical redox-sensitive NF-kB family member, RelB, confers radioresistance in prostate cancer (PCa). We screened FDA-approved compounds and identified betamethasone (BET) as a drug that increases hydrogen peroxide levels in vitro and protects non-PCa tissues/cells while also enhancing radiation killing of PCa tissues/cells, both in vitro and in vivo. Significantly, BET increases ROS levels and exerts different effects on RelB expression in normal cells and PCa cells. BET induces protein expression of RelB and RelB target genes, including the primary antioxidant enzyme, manganese superoxide dismutase (MnSOD), in normal cells, while it suppresses protein expression of RelB and MnSOD in LNCaP cells and PC3 cells. RNA sequencing analysis identifies B-cell linker protein (BLNK) as a novel RelB complementary partner that BET differentially regulates in normal cells and PCa cells. RelB and BLNK are upregulated and correlate with the aggressiveness of PCa in human samples. The RelB-BLNK axis translocates to the nuclear compartment to activate MnSOD protein expression. BET promotes the RelB-BLNK axis in normal cells but suppresses the RelB-BLNK axis in PCa cells. Targeted disruptions of RelB-BLNK expressions mitigate the radioprotective effect of BET on normal cells and the radiosensitizing effect of BET on PCa cells. Our study identified a novel RelB complementary partner and reveals a complex redox-mediated mechanism showing that the RelB-BLNK axis, at least in part, triggers differential responses to the redox-active agent BET by stimulating adaptive responses in normal cells but pushing PCa cells into oxidative stress overload.

Abstract Background Syndecan-1 (Sdc1), a cell surface heparan sulfate proteoglycan normally expressed primarily by epithelia and plasma cells, is aberrantly induced in stromal fibroblasts of breast carcinomas. Stromal fibroblast-derived Sdc1 participates in paracrine growth stimulation of breast carcinoma cells and orchestrates stromal extracellular matrix fiber alignment, thereby creating a migration and invasion-permissive microenvironment. Here, we specifically tested the role of stromal Sdc1 in metastasis. Methods The metastatic potential of the aggressive mouse mammary carcinoma cell lines, 4T1 and E0776, was tested in wild-type and genetically Sdc1-deficient host animals. Metastatic lesions were characterized by immunohistochemical analysis. Results After orthotopic inoculation, the lung metastatic burden was reduced in Sdc1−/− animals by 97% and more than 99%, in BALB/cJ and C57BL/6 animals, respectively. The difference in metastatic efficiency was maintained when the tumor cells were injected into the tail vein, suggesting that host Sdc1 exerts its effect during later stages of the metastatic cascade. Co-localization studies identified Sdc1 expression in stromal fibroblasts within the metastatic microenvironment and in normal airway epithelial cells but not in other cells (endothelial cells, α-smooth muscle actin positive cells, leucocytes, macrophages). The Ki67 proliferation index and the rate of apoptosis of the metastatic tumor cells were diminished in Sdc1−/− vs. Sdc1+/+ animals, and leucocyte density was indistinguishable. Sdc1-mediated metastatic efficiency was abolished when the animals were housed at a thermoneutral ambient temperature of 31 °C, suggesting that the host Sdc1 effect on metastasis requires mild cold stress. Conclusions In summary, Sdc1 is induced in the lung microenvironment after mammary carcinoma cell dissemination and promotes outgrowth of metastases in a temperature-dependent manner.