Serving an Indigenous community: Exploring the cultural competence of medical students in a rural setting

Since 2013, medical students from the International Medical University (IMU) in Malaysia have been providing primary healthcare services, under the supervision of faculty members, to the indigenous people living in Kampung Sebir. The project has allowed the students to learn experientially within a rural setting. This study aims to examine the cultural competence of IMU medical students through an examination of their perspective of the indigenous people who they serve and the role of this community service in their personal and professional development. Students who participated in the project were required to complete a questionnaire after each community engagement activity to help them reflect on the above areas. We analysed the responses of students from January to December 2015 using a thematic analysis approach to identify overarching themes in the students’ responses. Students had differing perceptions of culture and worldviews when compared to the indigenous people. However, they lacked the self-reflection skills necessary to understand how such differences can affect their relationship with the indigenous people. Because of this, the basis of their engagement with the indigenous community (as demonstrated by their views of community service) is focused on their agenda of promoting health from a student’s perspective rather than connecting and building relationships first. Students also lacked the appreciation that building cultural competency is a continuous process. The results show that the medical students have a developing cultural competence. The project in Kampung Sebir is an experiential learning platform of great value to provide insights into and develop the cultural competency of participating students. This study also reflects on the project itself, and how the relationship with stakeholders, the competence and diversity of academic staff, and the support of the university can contribute toward training in cultural competence

A genome-wide association study of Chinese and English language phenotypes in Hong Kong Chinese children

Funding: This study was partially supported by a Theme-based Research Scheme (T44-410/21-N) and a Collaborative Research Fund (CRF) (C4054-17W) from the Research Grants Council. HCS was partially supported by the KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research of Common Diseases, and the Hong Kong Branch of the Chinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics, as well as the Lo Kwee Seong Biomedical Research Fund.Dyslexia and developmental language disorders are important learning difficulties. However, their genetic basis remains poorly understood, and most genetic studies were performed on Europeans. There is a lack of genome-wide association studies (GWAS) on literacy phenotypes of Chinese as a native language and English as a second language (ESL) in a Chinese population. In this study, we conducted GWAS on 34 reading/language-related phenotypes in Hong Kong Chinese bilingual children (including both twins and singletons; total N = 1046). We performed association tests at the single-variant, gene, and pathway levels. In addition, we tested genetic overlap of these phenotypes with other neuropsychiatric disorders, as well as cognitive performance (CP) and educational attainment (EA) using polygenic risk score (PRS) analysis. Totally 5 independent loci (LD-clumped at r2 = 0.01; MAF > 0.05) reached genome-wide significance (p 0.3 and having at least 2 correlated SNPs (r2 > 0.5) with p < 1e-3). The loci were associated with a range of language/literacy traits such as Chinese vocabulary, character and word reading, and rapid digit naming, as well as English lexical decision. Several SNPs from these loci mapped to genes that were reported to be associated with EA and other neuropsychiatric phenotypes, such as MANEA and PLXNC1. In PRS analysis, EA and CP showed the most consistent and significant polygenic overlap with a variety of language traits, especially English literacy skills. To summarize, this study revealed the genetic basis of Chinese and English abilities in a group of Chinese bilingual children. Further studies are warranted to replicate the findings.Peer reviewe

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

A multi-modal intervention for managing the fatigue–sleep disturbance–depressed mood symptom cluster in breast cancer patients undergoing chemotherapy: A pilot study

Objective: To examine the feasibility and acceptability of a multi-modal intervention for managing the cancer-related fatigue–sleep disturbance–depressed mood (F-S-D) symptom cluster in patients with breast cancer (BC) and receiving chemotherapy in Hong Kong, and the preliminary effects of such intervention on the occurrence of the F-S-D symptom cluster in these patients. Methods: This study was a single-blind randomized controlled trial. Patients with BC scheduled for chemotherapy were recruited. Intervention participants received a weekly nurse-led multi-modal intervention lasting 7 weeks. The feasibility parameters and adverse events were assessed using logbook records. Acceptability was evaluated using a program evaluation questionnaire. F-S-D symptoms and quality of life (QOL) were measured at baseline (T0), upon intervention completion (T1), and 3 months after intervention completion (T2). Generalized estimating equation analyses were used. Results: Fifty participants were enrolled. The eligibility and enrollment rates were 11% and 87.7%, respectively. The rate of adherence to the intervention was 96%. No adverse events were reported. All participants were satisfied with the intervention, which had significant effects in terms of reducing the occurrence of the F-S-D symptom cluster at T2 (P ​= ​0.035) and improving QOL at T1 and T2 (T1: P ​= ​0.035; T2: P ​= ​0.012). Conclusions: The multi-modal intervention is a feasible, acceptable, and safe intervention that demonstrated preliminary positive effects in managing the F-S-D symptom cluster and improving QOL in patients with BC and receiving chemotherapy in Hong Kong. This study provides key insights into F-S-D symptom cluster management in patients with BC. Trial registration: ChiCTR2100047819 (Chinese Clinical Trial Register)

Oncology Nurses' Perspectives and Practices Toward the Delivery of Cancer Survivorship Care in Hong Kong

BACKGROUND: Despite tremendous progress in understanding the unmet needs of cancer survivors, our understanding of oncology nurses' perspectives and practices in the delivery of survivorship care is inadequate.OBJECTIVES: The aims of this study were to assess oncology nurses' perceptions about their responsibility and frequency of delivery of survivorship care to cancer patients and to examine the factors influencing such care.METHODS: A cross-sectional survey was administered to 81 nurses working in the oncology unit of hospitals in Hong Kong. Participants completed an investigator-developed questionnaire designed to assess oncology nurses' perceptions of responsibility, practices, and barriers regarding the provision of survivorship care for cancer patients.RESULTS: Results revealed discrepancies between oncology nurses' perceptions of responsibility and practices, with high levels of perceptions of various survivorship care as their responsibility but low levels in delivery of such care. Despite that discussing and managing pain was agreed by most oncology nurses as their responsibility (95.1%), 34.6% of them have never managed survivors' pain. Besides, 33.3% of nurses have never discussed and managed survivors' sexuality issues. Lack of time (79.0%), inadequate educational resources for family members (59.3%), and lack of knowledge and skills (54.4%) were major factors that impeded survivorship care provision.CONCLUSIONS: This study provides further evidence for inadequacies of oncology nurses in delivering survivorship care and their perceived barriers. Further studies are required to enhance our understanding of the strategies for improving the quality of cancer survivorship care.IMPLICATIONS FOR PRACTICE: Results underscore the need to develop educational resources and enhance training in survivorship care for oncology nurses.</p

Plasma Angiotensin Converting Enzyme 2 (ACE2) Activity in Healthy Controls and Patients with Cardiovascular Risk Factors and/or Disease

Angiotensin converting enzyme 2 (ACE2) is an endogenous negative regulator of the renin-angiotensin system, a key factor in the development of cardiovascular disease (CVD). ACE2 is also used by SARS-CoV-2 for host cell entry. Given that COVID-19 is associated with hypercoagulability, it is timely to explore the potential relationship between plasma ACE2 activity and the coagulation profile. In this cross-sectional study, ACE2 activity and global coagulation assays (GCA) including thromboelastography, thrombin, and fibrin generation were measured in adult healthy controls (n = 123; mean age 41 &plusmn; 17 years; 35% male) and in patients with cardiovascular risk factors and/or disease (n = 258; mean age 65 &plusmn; 14 years; 55% male). ACE2 activity was significantly lower in controls compared to patients with cardiovascular risk factors and/or disease (median 0.10 (0.02, 3.33) vs. 5.99 (1.95, 10.37) pmol/mL/min, p &lt; 0.001). Of the healthy controls, 48% had undetectable ACE2 activity. Controls with detectable ACE2 had lower maximum amplitude (p &lt; 0.001). In patients with cardiovascular risk factors and/or disease, those in the 3rd tertile were older and male (p = 0.002), with a higher Framingham grade and increased number of cardiovascular risk factors (p &lt; 0.001). In conclusion, plasma ACE2 activity is undetectable to very low in young healthy controls with minimal clinically relevant associations to GCA. Patients with cardiovascular risk factors and/or disease have increased plasma ACE2 activity, suggesting that it may be an important biomarker of endothelial dysfunction and atherosclerosis

Non-mitotic proliferation of malignant cancer cells revealed through live-cell imaging of primary and cell-line cultures

Abstract Introduction Anti-mitosis has been a key strategy of anti-cancer therapies, targeting at a fundamental property of cancer cells, their non-controllable proliferation due to overactive mitotic divisions. For improved anti-cancer therapies, it is important to find out whether cancer cells can proliferate independent of mitosis and become resistant to anti-mitotic agents. Results In this study, live-cell imaging was applied to both primary-cultures of tumor cells, and immortalized cancer cell lines, to detect aberrant proliferations. Cells isolated from various malignant tumors, such as Grade-III hemangiopericytoma, atypical meningioma, and metastatic brain tumor exhibit distinct cellular behaviors, including amoeboid sequestration, tailing, tunneling, nucleic DNA leakage, as well as prokaryote-like division such as binary fission and budding-shedding, which are collectively referred to and reported as ‘non-mitotic proliferation’ in this study. In contrast, benign tumors including Grade-I hemangiopericytoma and meningioma were not obvious in such behaviors. Moreover, when cultured in medium free of any anti-cancer drugs, cells from a recurrent Grade-III hemangiopericytoma that had been subjected to pre-operation adjuvant chemotherapy gradually shifted from non-mitotic proliferation to abnormal mitosis in the form of daughter number variation (DNV) and endomitosis, and eventually regular mitosis. Similarly, when treated with the anti-cancer drugs Epirubicin or Cisplatin, the cancer cell lines HeLa and A549 showed a shift from regular mitosis to abnormal mitosis, and further to non-mitosis as the dominant mode of proliferation with increasing drug concentrations. Upon removal of the drugs, the cells reversed back to regular mitosis with only minor occurrences of abnormal mitosis, accompanied by increased expression of the stem cell markers ALDH1, Sox, Oct4 and Nanog. Conclusions The present study revealed that various types of malignant, but not benign, cancer cells exhibited cellular behaviors indicative of non-mitotic proliferation such as binary fission, which was typical of prokaryotic cell division, suggesting cell level atavism. Moreover, reversible transitions through the three modes of proliferation, i.e., mitosis, abnormal mitosis and non-mitosis, were observed when anticancer drug concentrations were grossly increased inducing non-mitosis or decreased favoring mitosis. Potential clinical significance of non-mitotic proliferation in cancer drug resistance and recurrence, and its relationship with cancer stem cells are worthy of further studies

A genome-wide association study of Chinese and English language phenotypes in Hong Kong Chinese children

Dyslexia and developmental language disorders are important learning difficulties. However, their genetic basis remains poorly understood, and most genetic studies were performed on Europeans. There is a lack of genome-wide association studies (GWAS) on literacy phenotypes of Chinese as a native language and English as a second language (ESL) in a Chinese population. In this study, we conducted GWAS on 34 reading/language-related phenotypes in Hong Kong Chinese bilingual children (including both twins and singletons; total N = 1046). We performed association tests at the single-variant, gene, and pathway levels. In addition, we tested genetic overlap of these phenotypes with other neuropsychiatric disorders, as well as cognitive performance (CP) and educational attainment (EA) using polygenic risk score (PRS) analysis. Totally 5 independent loci (LD-clumped at r2 = 0.01; MAF &gt; 0.05) reached genome-wide significance (p &lt; 5e-08; filtered by imputation quality metric Rsq&gt;0.3 and having at least 2 correlated SNPs (r2 &gt; 0.5) with p &lt; 1e-3). The loci were associated with a range of language/literacy traits such as Chinese vocabulary, character and word reading, and rapid digit naming, as well as English lexical decision. Several SNPs from these loci mapped to genes that were reported to be associated with EA and other neuropsychiatric phenotypes, such as MANEA and PLXNC1. In PRS analysis, EA and CP showed the most consistent and significant polygenic overlap with a variety of language traits, especially English literacy skills. To summarize, this study revealed the genetic basis of Chinese and English abilities in a group of Chinese bilingual children. Further studies are warranted to replicate the findings.<br/