Identification of key genes for carcinogenic pathways associated with colorectal adenoma-to-carcinoma progression

Colorectal adenomas form a biologically and clinically distinct intermediate stage in development of colorectal cancer (CRC) from normal colon epithelium. Only 5% of adenomas progress into adenocarcinomas, indicating that malignant transformation requires other biological alterations than those involved in adenoma formation. The present study aimed to explore which cancer-related biological processes are affected during colorectal adenoma-to-carcinoma progression and to identify key genes within these pathways that can serve as tumor markers for malignant transformation. The activity of 12 cancer-related biological processes was compared between 37 colorectal adenomas and 31 adenocarcinomas, using the pathway analysis tool Gene Set Enrichment Analysis. Expression of six gene sets was significantly increased in CRCs compared to adenomas, representing chromosomal instability, proliferation, differentiation, invasion, stroma activation, and angiogenesis. In addition, 18 key genes were identified for these processes based on their significantly increased expression levels. For AURKA and PDGFRB, increased mRNA expression levels were verified at the protein level by immunohistochemical analysis of a series of adenomas and CRCs. This study revealed cancer-related biological processes whose activities are increased during malignant transformation and identified key genes which may be used as tumor markers to improve molecular characterization of colorectal tumors

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Trends in Work Conditions and Associations with Workers’ Health in Recent 15 Years: The Role of Job Automation Probability

Job automation and associated psychosocial hazards are emerging workplace challenges. This study examined the trends in work conditions and associations with workers&rsquo; health over time in jobs with different automation probabilities. We utilized data from six waves of national questionnaire surveys of randomly selected 95,762 employees between 2001 and 2016. The Job Content Questionnaire, the Copenhagen Burnout Inventory, and the Self-Rated Health Scale were applied, and working time was self-reported. Automation probability was derived for 38 occupations and then categorized into three groups. Trends in work conditions and the associations between automation probability, work conditions and health were examined. We observed a 7% decrease in high automation probability jobs, an overall increase in job demands for and prevalence of shift work, and a decrease in job control. Workers with high automation probability jobs had low job demands, low job control and high job insecurity. Low automation probability was associated with burnout in logistic regression models. The odds ratio of job insecurity, long working hours, and shift work relating to health was higher in the later years of the surveys. In conclusion, there has been a decrease in high automation probability jobs. Workers employed in jobs with different levels of automation probability encountered different work condition challenges

Information by healthcare professionals for decision-making of Type 2 Diabetes Mellitus management in Malaysia: comparison with shared decision-making model

Background: Relevant and sufficient information exchange between patients and healthcare professionals (HCPs) is imperative in the concept of shared decision-making. This concept is gaining attention as the patients are more satisfied with the decision and significant improvement in their health condition can also be seen. Objective: This paper aims to present the perceptions and experiences of patients and the HCPs on the information provided by the HCPs related decision-making in managing Type 2 Diabetes Mellitus (T2DM) in Malaysia. Further comparison of the gathered data was done against the shared decision-making model. Methods: Using an exploratory qualitative design, the perception of T2DM patients and the HCPs of three outpatient settings in the urban area of Malaysia were explored. Face-to-face in-depth interviews were conducted, over a period of six months, with 24 T2DM patients and 19 HCPs. Thematic analysis was used to analyse the data interpretively. Results: The following three important themes were emerged and discussed in this paper: (1) HCPs are giving instructions; (2) Other options are offered if necessary; (3) Insufficient information. Conclusion: Overall, the findings indicate that the practice of information provision in decision-making is still lacking among HCPs

Parents' experiences of caring for their child in a Paediatric Intensive Care Unit: a literature review

The objective is to identify the available literature on parents’ experiences in caring for children in the Paediatric Intensive Care Unit (PICU). Original research on parents experience in caring their child in PICU were identified from five online databases, namely CINAHL, Science Direct, Proquest, Cochrane, and Pubmed (2008–2018) using the terms “parent,” “experience,” “children”, “paediatric intensive care” and “caring.” We included articles addressing the parent's experiences while their child was admitted to PICU their needs and participation in the care of the child. Twenty-two papers have met the criteria for inclusion. Further review of these articles resulted in summarised topics – PICU parents’ experience, parental stressors, and parental needs. Current research demonstrates a diversity of parent's experiences while caring for their child; however, little is known about interventions to improve and support parents who are in a difficult situation when their child being treated in PICU

Being a parent of the sickest child: Malaysian perspectives

Mechanically ventilated children make up a small but growing segment of society's vulnerable population. The aim of the study was to understand the caring experiences of parents toward their mechanically ventilated children. This interpretive descriptive study was performed in the PICU of one tertiary hospital in Malaysia. The participants were purposively sampled. Semi-structured interviews were conducted with 21 parent caregivers of 18 children. Data were analysed by using Atlas.ti version 9. Thematic analysis was done and yielded the main theme, “The unpleasant experience in PICU” which emerged from two sub- themes: “The feeling of uncertainty” and “Recognizing the new child”. The study concluded that parents had fluctuating emotion throughout the stay. Positive parent-nurses interaction maintain the psychosocial health in embracing their journey

Health Literacy and Exercise to Treat Frailty in Community-Dwelling Older Adults: A National Survey Study

Aging is a major challenge facing modern society and has attracted global attention. Studies have provided some initial evidence that health literacy plays a role in determining frailty; however, most of these studies have used small convenience samples of individuals recruited from geographically limited areas, thus limiting the generalizability of their findings. The present study explored the relationships among health literacy, exercise, and frailty in Taiwanese older adults by using the data of a national population-based survey. We retrieved data from the Taiwan Longitudinal Study on Aging, a population-based survey. We gathered the 2015 data on the age, sex, education level, marital status, exercise habits, and activities of daily living (ADLs) of each eligible respondent. We evaluated the respondents&rsquo; health literacy by using a nine-item health literacy scale and categorized their health literacy level as low, medium, or high. Frailty was diagnosed according the Fried criteria. Our final sample consisted of 7702 community-dwelling older adults (3630 men and 4072 adults). Of these, 25.3% had low health literacy. The proportion of respondents who had two or more disabilities in terms of ADLs or instrumental ADLs was higher among the women (36.4% and 12.6%, respectively), and regular exercise was more common among the men (19.6%). Frailty was more prevalent among the women; the prevalence of frailty among the male and female respondents was 4.5% and 8.1%, respectively. High health literacy and regular exercise were protective factors for frailty. According to our results, poor health literacy is a risk factor for prefrailty and frailty, and regular exercise is significantly negatively associated with prefrailty and frailty. Additional studies are necessary to define practical strategies for reducing the risks of disability and death for older adults with low health literacy who do not exercise regularly, thereby improving their quality of life

Seroprevalence and clinical characteristics of viral hepatitis in transfusion-dependent thalassemia and hemophilia patients

Background/Aims Transfusion dependent subjects are at a great risk of viral hepatitis infection. We aimed to evaluate the prevalence and factors associated with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among transfusion-dependent patients in Taiwan. Methods: A total of 140 patients (67 thalassemic patients, 70 hemophilic patients, two patients with hereditary spherocytosis and one patient with von Willebrand disease) were prospectively enrolled to evaluate the prevalence and factors associated with viral hepatitis and spontaneous HCV clearance. All patients were tested for HBV and HCV serology and virology. Two consecutive serum samples, at least 1 year apart, were collected to clarify HCV seroclearance. Results: The seropositivity rate of hepatitis B surface antigen (HBsAg), HCV antibody (anti-HCV), and both HBsAg/anti-HCV were 6.4%, 45.7% and 5%, respectively. Logistic regression analysis of factors associated with anti-HCV seropositivity included age (odds ratio/95% confidence interval [OR/CI]: 1.12/1.07–1.18, P<0.001), serum alanine aminotransferase (ALT) (OR/CI: 1.04/1.02–1.06, P<0.001) and platelet counts (OR/CI: 0.995/0.991–0.998, P = 0.002). Age was the only factor independently associated with HBsAg seropositivity (OR/CI: 1.08/1.02–1.14.4, P = 0.007). Compared to patients born before 1992, the seroprevalence of HCV among thalassemic patients decreased dramatically in those born after 1992 (46.0% vs. 11.8%, p = 0.012). The seroprevalence of HCV among hemophilic patients also decreased significantly when comparing patients born before 1987 to those born after 1987 (79.5% vs. 11.5%, p<0.001). Similarly, the seroprevalence of HBV decreased significantly in the post-vaccination cohort compared to its counterpart (13.1%, vs. 1.3%, p = 0.005). The spontaneous clearance of HCV was observed in 25.4% (15/59) of patients, and ALT was the only factor associated with it (OR/CI 0.98/0.96–1.00, P = 0.02). Conclusions: Both HBV and HCV infections are prevalent among transfusion-dependent thalassemic and hemophilic patients in Taiwan. Nevertheless, seroprevalence decreased significantly and dramatically for HCV after universal blood screening and for HBV after implementation of a universal mass vaccination program