Medical professionalism among emergency physicians in South Korea: a survey of perceptions and experiences of unprofessional behavior.

OBJECTIVE: The purpose of this study was to analyze the current situation concerning professionalism among emergency physicians in South Korea by conducting a survey regarding their perceptions and experiences of unprofessional behavior. METHODS: In October 2018, the authors evaluated the responses to a questionnaire administered to 548 emergency physicians at 28 university hospitals. The participants described their perceptions and experiences concerning 45 unprofessional behaviors classified into the following five categories: patient care, communication with colleagues, professionalism at work, research, and violent behavior and abusive language. Furthermore, the responses were analyzed by position (resident vs. faculty). Descriptive statistics were generated on the general characteristics of the study participants. To compare differences in responses by position and sex, the chi-square and Fisher exact tests were performed. RESULTS: Of the 548 individuals invited to participate in this study, 253 responded (response rate, 46.2%). In 34 out of 45 questionnaires, more than half of participants reported having experienced unprofessional behavior despite their negative perceptions. Eleven perception questions and 38 experience questions for unprofessional behavior showed differences by position. CONCLUSION: Most emergency physicians were well aware of what constituted unprofessional behavior; nevertheless, many had engaged in or observed such behavior.

Shed syndecan-2 enhances colon cancer progression by increasing cooperative angiogenesis in the tumor microenvironment.

Although shed syndecan-2 potentiated the tumorigenic activities of colon cancer cells, how shed syndecan-2 increases this tumorigenic potential remains unclear. Using an orthotopic mouse model of colon cancer, we show that shed syndecan-2 increases colon cancer progression by cooperatively promoting angiogenesis. Co-administration with a synthetic peptide of shed syndecan-2 (S2LQ) enhanced the survival and tumor engraftment of luciferase-expressing CT26 colon adenocarcinoma cells orthotopically implanted into the cecum of BALB/c mice. Intravenous injection of S2LQ further enhanced the growth of orthotopic tumors in the cecum, with increases in the tissue infiltration of macrophages and the formation of blood vessels, mainly in peripheral layers of the tumor facing the stroma. Furthermore, S2LQ stabilized HIF1α and enhanced the VEGF expression in human colon cancer cell lines, and increased the migration of RAW 264.7 murine macrophage cells and bone marrow-derived macrophages. Finally, S2LQ increased the tube formation of vascular endothelial cells in vitro. Together, these data demonstrate that shed syndecan-2 enhances tumorigenic activity by increasing the crosstalk of cancer cells with tumor-associated macrophages and endothelial cells to enhance angiogenesis for colon cancer progression in the tumor microenvironment.

Elimination of biosynthetic pathways for l-valine and l-isoleucine in mitochondria enhances isobutanol production in engineered Saccharomyces cerevisiae.

Saccharomyces cerevisiae has a natural ability to produce higher alcohols, making it a promising candidate for production of isobutanol. However, the several pathways competing with isobutanol biosynthesis lead to production of substantial amounts of l-valine and l-isoleucine in mitochondria and isobutyrate, l-leucine, and ethanol in cytosol. To increase flux to isobutanol by removing by-product formation, the genes associated with formation of l-valine (BAT1), l-isoleucine (ILV1), isobutyrate (ALD6), l-leucine (LEU1), and ethanol (ADH1) were disrupted to construct the S. cerevisiae WΔGBIALA1_2vec strain. This strain showed 8.9 and 8.6 folds increases in isobutanol concentration and yield, respectively, relative the corresponding values of the background strain on glucose medium. In a bioreactor fermentation with a gas trapping system, the WΔGBIALA1_2vec strain produced 662 mg/L isobutanol concentration with a yield of 6.71 mgisobutanol/gglucose. With elimination of the competing pathways, the WΔGBIALA1_2vec strain would serve as a platform strain for isobutanol production.

Molecular and functional evaluation of a novel HIF inhibitor, benzopyranyl 1,2,3-triazole compound.

Hypoxia occurs in a variety of pathological events, including the formation of solid tumors. Hypoxia-inducible factor (HIF)-1α is stabilized under hypoxic conditions and is a key molecule in tumor growth and angiogenesis. Seeking to develop novel cancer therapeutics, we investigated small molecules from our in-house chemical libraries to target HIF-1α. We employed a dual-luciferase assay that uses a luciferase (Luc) reporter vector harboring five copies of hypoxia-responsive element (HRE) in the promoter. Under hypoxic conditions that increased Luc reporter activity by four-fold, we screened 144 different compounds, nine of which showed 30-50% inhibition of hypoxia-induced Luc reporter activity. Among these, "Compound 12, a benzopyranyl 1,2,3-triazole" was the most efficient at inhibiting the expression of HIF-1α under hypoxic conditions, reducing its expression by 80%. Under hypoxic conditions, the half maximal IC50 of the compound was 24 nM in HEK-293 human embryonic kidney cells, and 2 nM in A549 human lung carcinoma cells. Under hypoxic conditions, Compound 12 increased hydroxylated HIF-1α levels and HIF-1α ubiquitination, and also dose-dependently decreased HIF-1α target gene expression as well as vascular endothelial growth factor (VEGF) secretion. Furthermore, this compound inhibited VEGF-induced in vitro angiogenesis in human umbilical vein endothelial cells (HUVECs), and in vivo, it inhibited chick chorioallantoic membrane angiogenesis. In allogaft assays, cotreatment with Compound 12 and gefitinib significantly inhibited tumor growth and angiogenesis. Compound 12 can be a novel inhibitor of HIF-1α by accelerating its degradation, and shows much potential as an anti-cancer agent through its ability to suppress tumor growth and angiogenesis.

Coexistence of follicular lymphoma and an unclassifiable myeloproliferative neoplasm in a treatment-naïve patient: A case report.

Myeloproliferative neoplasms are associated with lymphoproliferative diseases following the administration of cytotoxic drugs or exposure to radiation, but are rare prior to therapy. The present study reports the case of a 61-year-old female with a history of transient ischemic attack. The patient, who presented with a palpable mass in the epitrochlear area of the left arm, was simultaneously diagnosed with follicular lymphoma and an unclassifiable myeloproliferative neoplasm. Excisional lymph node biopsy revealed stage I follicular lymphoma (grade 1). Laboratory findings demonstrated leukocytosis, erythrocytosis, thrombocytosis and decreased erythropoietin. Biopsy of the bone marrow revealed hypercellularity, with predominance of erythroid cells, and large polylobated megakaryocytes with increased mitotic figures, but no evidence of lymphomatous infiltration. The janus kinase 2 V617F mutation was also detected in the cells derived from the bone marrow specimen. Following local excision of the lymph node in the left epitrochlear area, radiation was delivered to the involved field, at a dose of 24 Gy in 12 fractions. The patient was started on hydroxyurea (1 g twice per day, orally) 2 weeks subsequent to radiotherapy, and was administered 500 mg twice per day as maintenance therapy. At the six-month follow-up, the white blood cell count, hemoglobin levels and platelet count had reduced, and the patient was in a healthy condition. A computed tomography scan of the neck, chest and abdomen indicated no abnormalities. To the best of our knowledge, the present study is the first case report of follicular lymphoma coexisting with an unclassifiable myeloproliferative neoplasm in a previously healthy patient. Molecular and genetic studies are required to further evaluate this infrequent disease association.

Synthesis and Biological Evaluation of Manassantin Analogues for Hypoxia-Inducible Factor 1α Inhibition.

To cope with hypoxia, tumor cells have developed a number of adaptive mechanisms mediated by hypoxia-inducible factor 1 (HIF-1) to promote angiogenesis and cell survival. Due to significant roles of HIF-1 in the initiation, progression, metastasis, and resistance to treatment of most solid tumors, a considerable amount of effort has been made to identify HIF-1 inhibitors for treatment of cancer. Isolated from Saururus cernuus, manassantins A (1) and B (2) are potent inhibitors of HIF-1 activity. To define the structural requirements of manassantins for HIF-1 inhibition, we prepared and evaluated a series of manassantin analogues. Our SAR studies examined key regions of manassantin's structure in order to understand the impact of these regions on biological activity and to define modifications that can lead to improved performance and drug-like properties. Our efforts identified several manassantin analogues with reduced structural complexity as potential lead compounds for further development. Analogues MA04, MA07, and MA11 down-regulated hypoxia-induced expression of the HIF-1α protein and reduced the levels of HIF-1 target genes, including cyclin-dependent kinase 6 (Cdk6) and vascular endothelial growth factor (VEGF). These findings provide an important framework to design potent and selective HIF-1α inhibitors, which is necessary to aid translation of manassantin-derived natural products to the clinic as novel therapeutics for cancers.

Does physical activity moderate the association between depressive symptoms and disability in older adults?

OBJECTIVE: Depressive symptoms and disability are closely associated and known to have reciprocal relationships. This study examines whether physical activity moderates the association between depressive symptoms and disability in community-dwelling older adults. METHODS: Baseline and 1-year follow-up data of 645 persons aged 65 years or older from the Suwon Longitudinal Aging Study were analyzed. A 15-item Geriatric Depression Scale, Physical Functioning scale, and physical performance tests were used to assess the individual's depressive symptoms and functional disability. Physical activity was defined as the recommended level of exercise based on its frequency and intensity. Multiple regression analysis with generalized estimating equations was conducted to examine the physical activity's role as an effect modifier in the association between depressive symptoms and disability. RESULTS: Physical activity was a significant effect modifier in the 'depressive symptoms-disability' association, controlling for sociodemographic characteristics and health-related covariates. Moderate-intensity activity was as effective as vigorous activity in moderating the relationship. The moderating effect was notable among those displaying severe depressive symptoms and functional disability. Over time the strength of the association between depressive symptoms and disability tended to diminish for those engaging in physical activity. CONCLUSION: The association between depressive symptoms and disability is moderated by physical activity in older persons. The findings suggest that healthcare professionals need to promote moderate amount of physical activity as a potential intervention tool in attenuating the depression-disability connection in later life, especially among those with high levels of physical and mental impairments.

[Association of social support and social activity with physical functioning in older persons].

OBJECTIVES: According to Rowe and Kahn (1998), successful aging is the combination of a low probability of disease, high functioning, and active engagement with life. The purpose of this study was to assess the relationship between active engagement with life and functioning among the community-dwelling elderly. METHODS: Data were collected from Wave 2 of the Suwon Longitudinal Aging Study (SLAS), consisting of a sample of 645 persons aged 65 and older living in the community. A social activity checklist and social support inventory were used as measures of engagement with life, along with the Physical Functioning (PF) scale as a measure of functioning. The effects of social support and social activity on physical functioning, taking into account the covariates, were analyzed by hierarchical linear regression analysis. RESULTS: Maintenance of social activity and social support were significantly associated with higher physical function, after adjusting for sociodemographic and health-related covariates. Social support appeared to be more prominent than social activity in predicting physical functioning. CONCLUSIONS: Social support and social activity are potentially modifiable factors associated with physical function in older persons. Studies examining the role social engagement may play in preventing disability are warranted.

Health practices that predict recovery from functional limitations in older adults.

BACKGROUND: Although previous studies show the benefits of certain health behaviors in reducing physical disability in older people, their effects on functional limitation, an antecedent of disability, are not well established. This study aims to identify health behavioral practices that affect recovery from functional limitations in older adults. METHODS: A total of 312 community-dwelling adults aged 65 and older with functional limitations were examined in 2002 for functional recovery in 2003. Functional limitations were measured by self-reports of difficulty performing upper- and lower-body movements. Positive health practices included regular physical activity, normal body mass index (BMI), periodic medical checkups, and moderate alcohol consumption. Logistic regression models were fitted to identify individual as well as combined health practices that predict functional recovery, adjusting for sociodemographic and health-related covariates. RESULTS: Although each of the positive health practices was significantly associated with functional recovery in the bivariate analyses, only physical activity continued to be a strong independent predictor in the multivariate analysis. The likelihood of functional recovery tended to increase with the number of health practices adopted by the elderly. Physical activity, in combination with normal BMI, proved to be one of the most influential health practice profiles, resulting in a high percentage of functional recovery. CONCLUSIONS: Health behaviors, especially physical activity, contribute to an older person's functional independence. The benefit of an increased number of health practices on recovery from functional limitations suggests that targeting multiple behavioral risks may help delay the onset of disability in later life.