Towards a global partnership model in interprofessional education for cross-sector problem-solving.

OBJECTIVES: A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. METHODS: This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students' data. RESULTS: We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest-posttest differences in students' readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students' social interaction anxiety after the IPE simulation. CONCLUSIONS: The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education.

Students' interaction anxiety and social phobia in interprofessional education in Hong Kong: mapping a new research direction.

BACKGROUND: Interprofessional education (IPE) has been promoted as a breakthrough in healthcare because of the impact when professionals work as a team. However, despite its inception dating back to the 1960s, its science has taken a long time to advance. There is a need to theorize IPE to cultivate creative insights for a nuanced understanding of IPE. This study aims to propose a research agenda on social interaction by understanding the measurement scales used and guiding researchers to contribute to the discussion of social processes in IPE. METHOD: This quantitative research was undertaken in a cross-institutional IPE involving 925 healthcare students (Medicine, Nursing, Social Work, Chinese Medicine, Pharmacy, Speech Language Pathology, Clinical Psychology, Food and Nutritional Science and Physiotherapy) from two institutions in Hong Kong. Participants completed the Social Interaction Anxiety Scale (SIAS-6) and Social Phobia Scale (SPS-6). We applied a construct validation approach: within-network and between-network validation. We performed confirmatory factors analysis, t-test, analysis of variance and regression analysis. RESULTS: CFA results indicated that current data fit the a priori model providing support to within-network validity [RMSEA=.08, NFI=.959, CFI=.965, IFI=.965, TLI=.955]. The criteria for acceptable fit were met. The scales were invariant between genders, across year levels and disciplines. Results indicated that social interaction anxiety and social phobia negatively predicted behavioural engagement (F = 25.093, p<.001, R2=.065) and positively predicted behavioural disaffection (F = 22.169, p<.001, R2=.057) to IPE, suggesting between-network validity. CONCLUSIONS: Our data provided support for the validity of the scales when used among healthcare students in Hong Kong. SIAS-6 and SPS-6 have sound psychometric properties based on students' data in Hong Kong. We identified quantitative, qualitative and mixed methods research designs to guide researchers in getting involved in the discussion of students' social interactions in IPE.Key MessagesThe Social Anxiety Scale (SIAS-6) and Social Phobia Scale (SPS-6) scales have sound psychometric properties based on the large-scale healthcare students' data in IPE in Hong Kong.Social interaction anxiety and social phobia negatively predicted students' behavioural engagement with IPE and positively predicted behavioural disaffection. The scales are invariant in terms of gender, year level and discipline.Quantitative, qualitative and mixed methods studies are proposed to aid researchers to contribute in healthcare education literature using the SIAS-6 and SPS-6.

Youths' attitudes toward open discussion of suicide, preferred contexts, and the impact of Internet use: An exploratory sequential mixed-methods study in Hong Kong.

BACKGROUND: Although the necessity and benefits of having the open and public discussion about suicide have been recognized, youths' opinions regarding such discussion remain unknown. AIMS: To explore youths' attitudes toward open suicide discussion, particularly concerning their preference of discussion contexts and impacts of Internet use. METHOD: This exploratory sequential mixed-methods study targeted Hong Kong youths aged 15 to 19. A total of six focus groups and 12 individual interviews were held (N = 40). Topics included adolescents' views of open suicide discussion, concerns, perceived benefits, and preferred contexts. The questionnaire survey (N = 1,676) was conducted subsequently to investigate the prevalence of youths' perspectives on public discussion of suicide and relationships with discussion contexts, use of social media platforms, and motivations of online expression. RESULTS: Qualitative findings revealed three types of attitudes toward open suicide discussion: reluctance, support, and indifference. Major barriers included cultural norms, topic sensitivity, privacy concerns, contagion effect, fear of embarrassment, and unpleasant experiences in school programs. Results of quantitative analyses showed that reluctance was the dominant attitude among adolescents, and taboo was the top concern. Variations in youths' attitudes were related to gender, school academic banding, and suicide-related experiences. Notably, adolescents who had been exposed to suicide messages in contexts of peer networks and online platforms were more likely to endorse open suicide discussion. In addition, an increased likelihood of engaging in public suicide discussion was associated with the use of Instagram, WhatsApp, and Snapchat, and the motive of 'expressing emotions and opinions' online. CONCLUSIONS: Our results indicated a prevalent rejection among adolescents toward open suicide discussion, suggesting the issue of stigma, the need for tailored programs, the value of appropriate contexts, and the impact of Internet use. These findings may facilitate the development of school-based suicide prevention initiatives and the efficacy of online services for suicide-related communication.

The Use of Close Friends on Instagram, Help-Seeking Willingness, and Suicidality Among Hong Kong Youth: Exploratory Sequential Mixed Methods Study.

BACKGROUND: Social networking sites (SNSs) have gained popularity in recent years for help seeking and self-distress expression among adolescents. Although online suicidal expression is believed to have major benefits, various concerns have also been raised, particularly around privacy issues. Understanding youths' help-seeking behavior on SNSs is critical for effective suicide prevention; however, most research neglects the impacts of the private SNS context. OBJECTIVE: This study aims to examine youths' private SNS use via the new Instagram feature, Close Friends, and its association with both online and offline help-seeking willingness as well as youths' suicidality. METHODS: This study employed an exploratory sequential mixed methods approach with a combination of explorative qualitative interviews and a systematic quantitative survey, targeting youth aged 15-19 years in Hong Kong. The motivations for utilizing Close Friends and concerns regarding online expression were addressed in the focus group and individual interviews (n=40). A cross-sectional survey (n=1676) was conducted subsequently with eligible secondary school students to examine the prevalence of Close Friends usage, their online and offline help-seeking willingness, and suicide-related experiences. RESULTS: A total of 3 primary motives for using Close Friends were identified during interviews, including (1) interaction and help seeking, (2) release of negative emotions, and (3) ventilation and self-expression. Most participants also highlighted the privacy concerns associated with public online communication and the importance of contacting close friends for emotional support. Survey results showed that use of Close Friends was quite prevalent among adolescents (1163/1646, 70.66%), with around 46% (754/1646, 45.81%) of respondents being frequent users. Differences by gender and school academic banding were also revealed. Regarding help-seeking intentions, youths were generally positive about seeking help from peers and friends offline (1010/1266, 79.78%) yet negative about seeking assistance from online friends or professionals with whom they had not yet developed a real-world connection (173/1266, 13.67%). Most notably, frequencies of Close Friends usage were differentially associated with online and offline help-seeking willingness and youths' suicidality. Compared with nonusers, those who had ever used the feature were more likely to seek offline support (adjusted odds ratios [AORs] 1.82-2.36), whereas heavy use of Close Friends was associated with increased odds of online help-seeking willingness (AOR 1.76, 95% CI 1.06-2.93) and a higher risk of suicidality (AOR 1.53, 95% CI 1.01-2.31). CONCLUSIONS: The popularity of Close Friends reflects the increasing need for private online expression among youth. This study demonstrates the importance of Close Friends for self-expression and private conversation and inadequacy of peer support for suicidal adolescents. Further research is needed to identify the causal relationship between Close Friends usage and help-seeking willingness to guide the advancement of suicide prevention strategies. Researchers and social media platforms may cooperate to co-design a risk monitoring system tailored to the private SNS context, assisting professionals in identifying youth at risk of suicide.

Medical interns' views on the strategies for reducing antibiotic misuse in the hospitals-what guidelines do they follow?

Objectives: Although the topic of antibiotic misuse is taught in medical schools, interns (fresh medical graduates) still encounter barriers to appropriate antibiotic prescription when they practice in hospitals under supervision. The impact of teaching in medical school, antibiotics stewardship program (ASP), and prescription guidelines was uncertain. This study explored the medical interns' views on antibiotic use and resistance, and their perceived enablers to appropriate antibiotic prescription. Methods: Two focus groups were conducted among medical interns with rotation experiences in different public hospitals of Hong Kong. The identified themes about attitudes to antibiotic resistance and enablers to appropriate antibiotic prescription were further examined by a questionnaire survey with 77 respondents. Results: The interns had lower preferences for tackling antibiotic resistance as they feared of delayed prescriptions. Guidelines provided by international evidence-based clinical resources and the interns' working hospitals were stronger enablers to appropriate antibiotic use than education materials from schools and the government. Qualitative findings revealed that the interns were aware of the existing ASP but doubted its effectiveness as it failed to get the prescribers' attention. They followed guidelines in their wards but perceived guidelines from local health authorities user-unfriendly. Knowledge from medical school was not very applicable. Varying prescribing practices between hospitals and the densely placed hospital beds made it difficult to prevent the spread of antimicrobial resistance. Conclusions: Minimizing delayed prescription is of a higher priority than tackling antibiotic resistance in medical interns' perspective. Interventions should target guidelines in hospitals and simplify the interface of local guidelines.

Motivations for Online Expression, Willingness of Online Help-Seeking, and the Risk of Suicide Among Hong Kong Youths: A Mixed-Methods Study.

Despite widespread interest in social media use, little is known about the heterogeneity of underlying motivations for online engagement among at-risk adolescents. This study adopted a mixed-methods approach to evaluate the motives of online expression among Hong Kong youths aged 15-19, as well as their relationships to online help-seeking willingness and suicide risks. In total, 6 focus groups and 12 individual interviews were conducted (N = 40) to elicit information regarding online expression purposes and to construct questionnaire items. The cross-sectional survey (N = 1,676) was undertaken subsequently to determine the prevalence of motives, and their correlations with online help-seeking willingness and suicide risks. Qualitative interviews revealed two key themes: major motivations for online expression, and features of online expression and help-seeking among suicidal youths. Quantitative analyses demonstrated the prevalence of each online expression purpose, with most reporting on "emotional expression" and "life sharing and documentation," but variations identified by gender, school academic banding, and suicide-related experience. Notably, an ordinal logistic regression model revealed that motives of "emotional expression" and "image building" were associated with increased suicide risks, while the purpose of "life sharing" was associated with decreased suicide risks. Those who expressed online for "self-expression" and "friend making" showed a stronger willingness for online help-seeking. These findings provide a more holistic overview of the purposes of online expression, which suggested the likelihood of mental health issues and the need for support. Such insight may facilitate the development of more effective suicide prevention strategies and online intervention services.

Improving Public Toilet Environment and Hygiene Practices in an Asian City: Voices From Hong Kong Residents.

Toilet hygiene is an important preventive measure for infectious diseases, including severe acute respiratory syndrome (SARS) and COVID-19. This study explored public's opinions on improving toilet environment and hygiene practices in Hong Kong. A mixed-method approach was applied. We conducted 4 focus groups plus 3 individual interviews among the Hong Kong Chinese, followed by a questionnaire survey with 300 respondents recruited from various districts. Difference in response distributions between groups with different demographics was tested by Pearson χ2 test. Instead of advocating for advanced toilet facilities, respondents were mostly concerned about basic hygiene issues. Malfunctioning facilities resulting from poor toilet management, such as clogged toilets, stained facilities, and problematic flushing systems, were most cited as barriers to toilet hygiene practices. Three quarters of the survey respondents expressed concerns over worn and poorly maintained toilets, shortage of janitors, and cleansing supplies. However, respondents who were older (P < .001), less educated (P < .001), and had lower income (P = .001) were significantly more likely to find hygiene conditions in public toilets satisfactory. The findings reflected the substandard of the current provisions as a developed city in Asia. Enhanced efforts by the government to maintain basic toilet supplies and facilities is the key to improving public compliance to toilet hygiene practices.

Management of Domestic Violence by Primary Care Physicians in Hong Kong: Association With Barriers, Attitudes, Training, and Practice Background.

While primary care physicians (PCPs) have opportunities to recognize patients who encounter domestic violence (DV) by intimate partners, warning symptoms such as unexplained physical injury, bruising, anxiety, and depression are often missed during clinic visits. This study investigated the barriers of Hong Kong PCPs toward managing DV, including recognition, management, and referrals of these patients. Four focus group interviews were conducted to explore the in-depth opinions of PCPs on managing DV in Hong Kong. The themes identified were investigated in a questionnaire survey with data from 504 PCPs working in public and private sectors. Factor analysis of the survey data suggested four major barrier factors: (a) worries about the potential harms of intervening in patients' domestic affairs and DV issues, (b) lack of guidelines and support services, (c) limited skills and time in managing DV, and (d) patients' reluctance in disclosing DV issues. PCPs with more years of practice had more worries about intervening in domestic issues (Factor 1), while the younger PCPs tended to perceive limited skills and time in managing DV cases as barriers (Factor 3). PCPs working in the public setting were more likely to ask patients about DV (M = 5.4 vs. 2.9), suspected DV (M = 3.8 vs. 2.3), and managed DV (M = 1.7 vs. 1.0) in the past 5 years compared with the private PCPs. Some PCPs in the focus groups expressed the view that DV cases should be handled by social workers instead of doctors. Survey respondents who held such views about doctors' limited role in DV management also scored higher in all of the barrier factors. The findings suggest that there are boundaries between domestic and medical realms, especially in a Chinese context. Resolving PCPs' worries by training, provision of DV management guidelines, and referral pathway to social workers may be good starting points to bridge the gaps.

Factors that facilitate recognition and management of domestic violence by primary care physicians in a Chinese context - a mixed methods study in Hong Kong.

BACKGROUND: Domestic violence is common in the community. Many of its victims present to primary care physicians (PCPs) but are not being recognized and managed. The barriers, with specific reference to a Chinese cultural context, were investigated earlier. This paper explored the factors which facilitated the process of recognizing and managing suspected cases of domestic violence by PCPs in Hong Kong. METHODS: Four focus group interviews were conducted to explore in-depth the experiences of PCPs in recognition, management and referral of domestic violence cases from which facilitators were identified. The relevant themes were then investigated in a questionnaire survey with 504 PCPs working in public and private sectors. RESULTS: The focus group participants emphasized mood symptoms as useful indicators for probable abuse and continuity of care was important to unmask issues of domestic violence. The top facilitators perceived by the respondents of the survey included: a trusting doctor-patient relationship (99.8%), good communication skills (99.0%), patients' unexplained bruises (96.3%), medical history (94.6%), and mood symptoms (94.4%). Further, the survey found that PCPs with longer years of practice, a medical degree obtained from Western countries, and postgraduate training in family counselling or psychological medicine perceived more facilitators in managing domestic violence. CONCLUSIONS: Without a local screening policy and training protocol to manage domestic violence, PCPs regarded their skills in mental healthcare and good relationships with patients as the key facilitators. While training in mental health care helps PCPs manage domestic violence, a specific protocol emphasizing medical-social collaboration is anticipated to facilitate them to take a more proactive and effective stance from screening to management.

Associations between demographic factors and psychological distress among Chinese residents in Hong Kong: beyond socioeconomic classes.

Most studies highlighted the association between psychological distress and socioeconomic status (SES). There were weaker explanations for distress found in the middle classes, especially in Asian countries. We conducted a questionnaire survey with 1626 adult Chinese primary-care attenders from 13 private and 6 public clinics in different districts of Hong Kong. Their demographic background and distress level measured by GHQ-12 were analysed. We found that respondents with younger age, better education, and lower income were more likely to be distressed. In a multiple logistic regression model, age and income, but not education, were significant predictors for distress. Highest rates of distress were found among the unemployed (45.5%) and the students (37.1%), followed by service workers and shop sales workers (33.0%), associate professionals (32.0%), and clerks (29.2%). Craftworkers (9.1%), plant and machine operators (11.5%), and retired people (12.8%) were least likely to be distressed, followed by professionals (21.0%). Apart from SES, the findings suggest that young age, academic and job stressors, and low self-esteem are significant factors for distress. These factors may be intensified in a Chinese context by peer comparison resulting in a state of relative deprivation.

A mixed-methods study on toilet hygiene practices among Chinese in Hong Kong.

BACKGROUND: Public toilets are a common transmission vector of infectious diseases due to environmental contamination. Research on Chinese people's hygiene practices in public lavatories are lacking. This study examined Chinese people's hygiene practices in public lavatories in Hong Kong. METHODS: We conducted qualitative interviews and a self-administered questionnaire survey with local residents from June 2016 to April 2018. Four focus group discussions and three individual interviews informed the design of the questionnaire. We recruited interviewees and survey respondents via social service centers. The interviews and questionnaire focused on the public's daily practices and hygiene behaviors in public toilets. Content analysis of qualitative data was conducted. Multivariable logistic regressions were used to examine the association between age and toilet hygiene behaviors. RESULTS: Our qualitative component revealed a range of handwashing practices, from not washing at all, washing without soap, to washing for a longer time than instructions. Other toilet use practices were identified, such as not covering toilet lid before flushing and stepping on toilet seats due to dirtiness, and spitting into toilet bowls or hand basin. Totally, 300 respondents completed the questionnaire. Among them, 212 (70.9%) were female and 246 (86.1%) were aged 65 or below. More than two thirds always washed hands with soap (68.7%) and dried hands with paper towels (68.4%). Up to 16.2% reported stepping on toilet seats and 43.9% never covered the toilet lid before flushing. Over one fourth (26.4%) spit into squat toilets/ toilet bowl. Regression analyses showed that the elderly group were less likely to report stepping on toilet seats (adjusted odds ratio, AOR = 0.17, 95%CI 0.03-0.88), flushing with the toilet lid closed (AOR = 0.40, 0.16-0.96), but more likely to spit into squat toilets/ toilet bowl (AOR = 4.20, 1.50-11.74). CONCLUSIONS: Hong Kong Chinese's compliance to hygiene practices in public toilets is suboptimal. Stepping on toilet seat is a unique Chinese practice due to the dirtiness of toilet seats. Spitting practices may increase the risk of airborne infectious diseases and need improvement. Measures are needed to improve toilet hygiene behaviors, including public education campaigns and keeping toilet environment clean.

Perceptions of Chinese Towards Dementia in Hong Kong-Diagnosis, Symptoms and Impacts.

The increasing prevalence of dementia has become a public health issue worldwide including China. This study aims to explore the perception of Chinese in Hong Kong towards the diagnosis, symptoms and impacts of dementia. A cross-sectional survey was conducted among outpatients (without diagnosed dementia) attending a regional public hospital using a standard questionnaire. The results from 290 respondents showed that most preferred to be told about the diagnosis of dementia as soon as possible if they got it, in order to deal with the news and to access treatment and support early. Nearly two thirds of the respondents perceived practical issues (61.3%), physical health (61.0%), and emotional distress (58.4%) as their most fearful impacts, while legal issues (7.4%) were their least concerns. Family history/genes (79.1%) and brain injury (75.9%) were the most commonly perceived causes of dementia. For symptoms, respondents were more likely to identify cognitive impairments than undesirable behaviours. The accepting and proactive attitudes of the public indicate that there is a timely need of more public education about the disease, early screening and better continuity of care to fulfil the anticipated increase of the dementia patient population.

Views of Hong Kong Chinese primary care attenders on psychological distress: causes, management and recovery.

Background: Most of the previous studies of help seeking for psychological distress were conducted in Western countries. Chinese studies have had a stronger emphasis on psychosis. Objective: This study aims to understand how Hong Kong Chinese primary care attenders see psychological distress, including its causes, management approaches and recovery, and whether their views are different from Western views. Method: Nine focus groups and six individual interviews were conducted in Hong Kong among Chinese primary care attenders with/without known distress, patients' significant others and the general public, and a questionnaire survey was conducted with 1626 primary care attenders recruited from 13 private clinics and 6 public clinics. Results: More survey respondents agreed with psychological counselling (95.3%) than drugs (69.0%) to relieve psychological distress. Despite the belief in self-resilience (77.7%), only 34.8% respondents agreed that psychological distress could get better without professional help. Respondents with younger ages, better education and higher incomes tended to have stronger trust in counselling and self-resilience than drugs. Qualitative interviews revealed that although participants regarded psychological distress as a common problem in modern societies, distressed patients might be seen as being weak and troublesome. Some distressed patients found their recovery process painful because of discouragement from family and personnel at their workplace. Conclusions: Hong Kong Chinese patients' views of the causes and management approaches of psychological distress are similar to Western findings. However, help seeking and recovery are of greater concern in a Chinese context where patients may receive limited empathy for their conditions of psychological distress.

Semiautomated Alignment of High-Throughput Metabolite Profiles with Chemometric Tools.

The rapid increase in the use of metabolite profiling/fingerprinting techniques to resolve complicated issues in metabolomics has stimulated demand for data processing techniques, such as alignment, to extract detailed information. In this study, a new and automated method was developed to correct the retention time shift of high-dimensional and high-throughput data sets. Information from the target chromatographic profiles was used to determine the standard profile as a reference for alignment. A novel, piecewise data partition strategy was applied for the determination of the target components in the standard profile as markers for alignment. An automated target search (ATS) method was proposed to find the exact retention times of the selected targets in other profiles for alignment. The linear interpolation technique (LIT) was employed to align the profiles prior to pattern recognition, comprehensive comparison analysis, and other data processing steps. In total, 94 metabolite profiles of ginseng were studied, including the most volatile secondary metabolites. The method used in this article could be an essential step in the extraction of information from high-throughput data acquired in the study of systems biology, metabolomics, and biomarker discovery.

Five-year outcomes of western mental health training for Traditional Chinese Medicine practitioners.

BACKGROUND: There are increasing expectations for primary care practitioners to deal with mental health problems. In Hong Kong, 15 % of the general public consult Traditional Chinese Medicine (TCM) practitioners regularly for their primary health care needs. This study investigated the 5-year outcomes of a western mental health training course for TCM practitioners in Hong Kong. METHOD: Structured questionnaire surveys were conducted to compare the TCM practitioners' confidence and engagement in mental health care before and after the Course. The data collected during 2011-2015 were analyzed. RESULTS: A total of 151 TCM practitioners returned both pre- and post-Course questionnaires, with a response rate of 95.6 %. After the course, there were significant increases in the proportions of participants being confident of recognizing patients with psychological problems (62.9 % before the course vs 89.4 % after), diagnosing common mental health problems (47.7 % vs 77.5 %), and managing them (31.2 % vs 64.3 %). Overall, 66.9 % of the participants reported some increase in their confidence in recognizing patients with psychological problems, diagnosing or/and managing patients with common mental health problems. Qualitative responses illustrated the major improvements were increased awareness of mental symptoms, better understanding of classification of mental disorders and management approaches. On the other hand, barriers included difficulties in understanding medical terms in English, consultation time constraints, and a lack of formal referral system to psychiatrists. CONCLUSIONS: The Course has positive impact on TCM practitioners in handling mental health patients. The findings are useful for designing similar trainings on complementary and alternative medicine practitioners in other countries.

p21-Activated Kinases 1, 2 and 4 in Endometrial Cancers: Effects on Clinical Outcomes and Cell Proliferation.

p21-activated kinases (Paks) are serine/threonine protein kinases involved in biological events linked to malignant tumor progression. In this study, expression of Pak1, p-Pak2 Ser20, Pak4, pPak4 Ser474 in 21 normal endometrium, 16 hyperplastic endometrium without atypia, 17 atypical complex hyperplasia and 67 endometrial cancers was assessed by immunohistochemistry and correlated with clinicopathological parameters. We also accessed the proliferative role and downstream targets of Pak1 in endometrial cancer. Pak1 was expressed in cytoplasm whereas Pak4 and p-Pak4 were expressed in both cytoplasm and nucleus of endometrial tissues. In normal endometrium, significantly higher Pak1 (P = 0.028) and cytoplasmic p-Pak2 (P = 0.048) expression was detected in proliferative endometrium than secretory endometrium. Pak1, cytoplasmic and nuclear Pak4 and nuclear p-Pak4 was significantly overexpressed in endometrial cancer when compared to atrophic endometrium (all P<0.05). Moreover, type I endometrioid carcinomas showed significantly higher Pak1 expression than type II non-endometrioid carcinomas (P<0.001). On the other hand, Pak1, Pak4 and p-Pak4 expression negatively correlated with histological grade (all P<0.05) while p-Pak2 and cytoplasmic Pak4 expression inversely correlated with myometrial invasion (all P<0.05). Furthermore, patients with endometrial cancers with lower cytoplasmic Pak4 expression showed poorer survival (P = 0.026). Multivariate analysis showed cytoplasmic Pak4 is an independent prognostic factor. Functionally, knockdown of Pak1, but not Pak4, in endometrial cancer cell line led to reduced cell proliferation along with reduced cyclin D1, estrogen receptor (ERα) and progestogen receptor (PR) expression. Significant correlation between Pak1 and PR expression was also detected in clinical samples. Our findings suggest that Pak1 and cytoplasmic p-Pak2 may promote cell proliferation in normal endometrium during menstral cycle. Pak1, cytoplasmic and nuclear Pak4 and nuclear p-Pak4 are involved in the pathogenesis of endometrial cancer especially in postmenopausal women. Pak1 promote endometrial cancer cell proliferation, particular in type I endometrioid carcinoma. Cytoplasmic Pak4 can be potential prognostic marker in endometrial cancer.

Paradoxical impact of two folate receptors, FRα and RFC, in ovarian cancer: effect on cell proliferation, invasion and clinical outcome.

Despite being an essential vitamin, folate has been implicated to enhance tumor growth, as evidenced by reports on overexpression of folate receptor alpha (FRα) in carcinomas. The role of another folate transporter, reduced folate carrier (RFC), is largely unknown. This study investigated the roles of folate, FRα and RFC in ovarian cancers. We demonstrated FRα mRNA and protein overexpression and reduced RFC expression in association with FRα gene amplification and RFC promoter hypermethylation, respectively. FRα overexpression was associated with tumor progression while RFC expression incurred a favorable clinical outcome. Such reciprocal expression pattern was also observed in ovarian cancer cell lines. Folate was shown to promote cancer cell proliferation, migration and invasion in vitro, and down-regulate E-cadherin expression. This effect was blocked after either stable knockdown of FRα or ectopic overexpression of RFC. This hitherto unreported phenomenon suggests that, RFC can serve as a balancing partner of FRα and confer a protective effect in patients with high FRα-expressing ovarian carcinomas, as evidenced by their prolonged overall and disease-free survivals. In conclusion, we report on the paradoxical impact of FRα (putative oncogenic) and RFC (putative tumor suppressive) in human malignancies. FRα and RFC may potentially be explored as therapeutic target or prognostic marker respectively. We recommend caution and additional research on folate supplements in cancer patients.

Dissociating effects of subclinical anxiety and depression on cognitive control.

Even at subclinical levels, anxiety and depression are associated with impaired cognitive control. It is unclear, though, to what extent these deficits reflect a common underlying dysfunction. Using a non-affective hybrid masked prime-Simon task, we obtained several measures of within- and between- trial inhibitory behavioral control in 80 young, healthy volunteers, together with measures of their anxiety and depression levels. Neither depression nor anxiety affected low-level within-trial control, or any of the between-trial control measures. However, increased levels of depression, but not of anxiety, were associated with impaired high-level within-trial control (increased Simon effect). Results indicate that depression, but not anxiety, impairs voluntary online response-control mechanisms independent of affective content.

Overexpression of dedicator of cytokinesis I (Dock180) in ovarian cancer correlated with aggressive phenotype and poor patient survival.

AIMS: Dedicator of cytokinesis I (Dock180) is a novel guanine nucleotide exchange factor for Rho guanosine triphosphates (GTPases) important for cell migration. The aim of this study was to evaluate the role of Dock180 in ovarian carcinogenesis. METHODS AND RESULTS: Using immunohistochemistry, real-time polymerase chain reaction and Western blotting, overexpression of Dock180 RNA and protein was demonstrated in the nucleus and cytoplasm of ovarian cancer cell lines (n = 5) and clinical samples of ovarian borderline tumours (n = 21) and invasive cancers (n = 108) when compared with ovarian epithelial cell lines (n = 3) and benign cystadenomas (n = 10) (P < 0.05). High Dock180 cytoplasmic expression in ovarian cancer (n = 108) was associated significantly with serous histological type, high-grade cancer and advanced stage (P < 0.05), as well as poor overall and disease-free survival (P = 0.004). Using multivariate progression analysis, high Dock180 cytoplasmic expression and advanced cancer stage were found to be independent prognostic factors for short overall survival and disease-free survival (P < 0.05). Exogenous expression of Dock180 by transient transfection enhanced cancer cell migration and invasion, whereas knockdown of Dock180 by an siRNA approach retarded cancer cell migration and invasion in association with down-regulation of matrix metalloproteinase 2. CONCLUSIONS: Our findings suggest that Dock180 contributes to ovarian carcinogenesis and dissemination and is a potential prognostic marker and therapeutic target.

iASPP and chemoresistance in ovarian cancers: effects on paclitaxel-mediated mitotic catastrophe.

PURPOSE: iASPP is a specific regulator of p53-mediated apoptosis. Herein, we provided the first report on the expression profile of iASPP in ovarian epithelial tumor and its effect on paclitaxel chemosensitivity. EXPERIMENTAL DESIGN: Expression and amplification status of iASPP was examined in 203 clinical samples and 17 cell lines using immunohistochemistry, quantitative real-time PCR, and immunoblotting, and correlated with clinicopathologic parameters. Changes in proliferation, mitotic catastrophe, apoptosis, and underlying mechanism in ovarian cancer cells of different p53 status following paclitaxel exposure were also analyzed. RESULTS: The protein and mRNA expression of iASPP was found to be significantly increased in ovarian cancer samples and cell lines. High iASPP expression was significantly associated with clear cell carcinoma subtype (P = 0.003), carboplatin and paclitaxel chemoresistance (P = 0.04), shorter overall (P = 0.003), and disease-free (P = 0.001) survival. Multivariate analysis confirmed iASPP expression as an independent prognostic factor. Increased iASPP mRNA expression was significantly correlated with gene amplification (P = 0.023). iASPP overexpression in ovarian cancer cells conferred resistance to paclitaxel by reducing mitotic catastrophe in a p53-independent manner via activation of separase, whereas knockdown of iASPP enhanced paclitaxel-mediated mitotic catastrophe through inactivating separase. Both securin and cyclin B1/CDK1 complex were involved in regulating separase by iASPP. Conversely, overexpressed iASPP inhibited apoptosis in a p53-dependent mode. CONCLUSIONS: Our data show an association of iASPP overexpression with gene amplification in ovarian cancer and suggest a role of iASPP in poor patient outcome and chemoresistance, through blocking mitotic catastrophe. iASPP should be explored further as a potential prognostic marker and target for chemotherapy.