Objective: Medical housemanship training has always been regarded as a highly stressful environment to doctors. This article described findings on stress, stressors and coping strategies among house officers in a Malaysian hospital. Methods: A cross-sectional study was conducted on house officers in a Malaysian hospital. The 12 items General Health Questionnaire (GHQ-12), General Stressors Questionnaire (GSQ) and Brief COPE inventory were administered to measure perceived stress, sources of stress and coping strategies among house officers respectively. Data was analysed using SPSS version 12. Results: Forty two house officers participated in this study. This study found that approximately 31% of the house officers were in distress. The top five stressors were fears of making mistakes that can lead to serious consequences, work overload, working with uncooperative colleagues, doing
work that mentally straining and feeling of being underpaid. The most frequent coping strategies used by house officers were religion, acceptance and self-distraction. Conclusion: This study found that there was a high percentage of distressed house officers. It also found that major stressors were related to performance pressure. The main coping strategy used by house officer was emotion-focused coping.
Pancreatic adenocarcinoma (PDAC) is a highly aggressive cancer with a high chance of recurrence, limited treatment options, and poor prognosis. A recent study has classified pancreatic cancers into four molecular subtypes: (1) squamous, (2) immunogenic, (3) pancreatic progenitor and (4) aberrantly differentiated endocrine exocrine. Among all the subtypes, the squamous subtype has the worst prognosis. This study aims to utilize large scale genomic datasets and computational systems biology to identify potential drugs targeting the squamous subtype of PDAC through combination therapy. Using the transcriptomic data available from the International Cancer Genome Consortium, Cancer Cell Line Encyclopedia and Connectivity Map, we identified 26 small molecules that could target the squamous subtype of PDAC. Among them include inhibitors targeting the SRC proto-oncogene (SRC) and the mitogen-activated protein kinase kinase 1/2 (MEK1/2). Further analyses demonstrated that the SRC inhibitors (dasatinib and PP2) and MEK1/2 inhibitor (pimasertib) synergized gemcitabine sensitivity specifically in the squamous subtype of PDAC cells (SW1990 and BxPC3), but not in the PDAC progenitor cells (AsPC1). Further analysis revealed that the synergistic effects are dependent on SRC or MEK1/2 activities, as overexpression of SRC or MEK1/2 completely abrogated the synergistic effects SRC inhibitors (dasatinib and PP2) and MEK1/2 inhibitor (pimasertib). In contrast, no significant toxicity was observed in the MRC5 human lung fibroblast and ARPE-19 human retinal pigment epithelial cells. Together, our findings suggest that combinations of SRC or MEK inhibitors with gemcitabine possess synergistic effects on the squamous subtype of PDAC cells and warrant further investigation.