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BackgroundAmoebiasis, caused by Entamoeba histolytica infection, is a global public health problem. However, available drugs to treat amoebiasis are currently limited, and no effective vaccine exists. Therefore, development of new preventive measures against amoebiasis is urgently needed.Methodology/principal findingsHere, to develop new drugs against amoebiasis, we focused on E. histolytica adenosine 5'-phosphosulfate kinase (EhAPSK), an essential enzyme in Entamoeba sulfolipid metabolism. Fatty alcohol disulfates and cholesteryl sulfate, sulfolipids synthesized in Entamoeba, play important roles in trophozoite proliferation and cyst formation. These processes are closely associated with clinical manifestation and severe pathogenesis of amoebiasis and with disease transmission, respectively. We validated a combination approach of in silico molecular docking analysis and an in vitro enzyme activity assay for large scale screening. Docking simulation ranked the binding free energy between a homology modeling structure of EhAPSK and 400 compounds. The 400 compounds were also screened by a 96-well plate-based in vitro APSK activity assay. Among fifteen compounds identified as EhAPSK inhibitors by the in vitro system, six were ranked by the in silico analysis as having high affinity toward EhAPSK. Furthermore, 2-(3-fluorophenoxy)-N-[4-(2-pyridyl)thiazol-2-yl]-acetamide, 3-phenyl-N-[4-(2-pyridyl)thiazol-2-yl]-imidazole-4-carboxamide, and auranofin, which were identified as EhAPSK inhibitors by both in silico and in vitro analyses, halted not only Entamoeba trophozoite proliferation but also cyst formation. These three compounds also dose-dependently impaired the synthesis of sulfolipids in E. histolytica.Conclusions/significanceHence, the combined approach of in silico and in vitro-based EhAPSK analyses identified compounds that can be evaluated for their effects on Entamoeba. This can provide leads for the development of new anti-amoebic and amoebiasis transmission-blocking drugs. This strategy can also be applied to identify specific APSK inhibitors, which will benefit research into sulfur metabolism and the ubiquitous pathway terminally synthesizing essential sulfur-containing biomolecules.

Amoebiasis is caused by Entamoeba histolytica infection, a protozoan parasite belonging to the phylum Amoebozoa. This parasite undergoes a fundamental cell differentiation process from proliferative trophozoite to dormant cyst, termed “encystation.” The cysts formed by encystation are solely responsible for the transmission of amoebiasis; therefore, Entamoeba encystation is an important subject from both biological and medical perspectives. Here, we have established a flow cytometry strategy for not only determining the percentage of formed cysts but also for monitoring changes in cell populations during encystation. This strategy together with fluorescence microscopy enables visualization of the cell differentiation process of Entamoeba encystation. We also standardized another flow cytometry protocol for counting live trophozoites. These two different flow cytometry techniques could be integrated into 96-well plate-based bioassays for monitoring the processes of cyst formation and trophozoite proliferation, which are crucial to maintain the Entamoeba life cycle. The combined two systems enabled us to screen a chemical library, the Pathogen Box of the Medicine for Malaria Venture, to obtain compounds that inhibit either the formation of cysts or the proliferation of trophozoites, or both. This is a prerequisite for the development of new drugs against amoebiasis, a global public health problem. Collectively, the two different 96-well plate-based Entamoeba bioassay and flow cytometry analysis systems (cyst formation and trophozoite proliferation) provide a methodology that can not only overcome the limitations of standard microscopic counting but also is effective in applied as well as basic Entamoeba biology.

Objectives:To examine the relationships of retirement and reasons for retirement with psychological distress in men and women at the age of 45–79 years. Method:Data from 202,584 Australians participating in the large-scale 45 and Up Study was used. Psychological distress was measured by the Kessler psychological distress scale. Associations between different work status and reasons for retirement with psychological distress were assessed for men and women at different ages using logistic regression. Results:Being fully retired or unemployed was associated with the high levels of psychological distress compared to being in paid work for men and women aged 45–64 (p< 0.0001), and for men aged 65–74 years (p≤ 0.0014). At the age of 75–79 years, there was no difference in psychological distress between different work statuses. Among retirees, retirement due to ill health, being made redundant or caring duty was associated with the high level of psychological distress. Conclusion:The association between work and mental health underscores the importance of policies and strategies to encourage and enable people to continue in the workforce after age 55, particularly for men. Important reasons for retirement with worse mental health outcomes include redundancy, ill health and needing to care for family or a friend. These circumstances will affect whether a person can continue working and their risk of poor mental health, and both considerations should be addressed in developing approaches for maintaining older workers or assisting them with their retirement transition. [ABSTRACT FROM AUTHOR]

Objectives:The ability of older people to mobilise within and outside their community is dependent on a number of factors. This study explored the relationship between spatial mobility and psychological health among older adults living in Australia.Methods:The survey sample consisted of 260 community-dwelling men and women aged 75–80 years, who returned a postal survey measuring spatial mobility (using the Life Space Questionnaire) and psychological health (using the SF36 Health Related Quality of Life Profile). From the Life Space Questionnaire, participants were given a life-space score and multinomial regression was used to explore the potential effect of mental health on life-space score.Results:The study found a significant association between mental health and life space. However, gender, physical functioning, and ability to drive were most strongly associated with the extent of life space and spatial mobility. Compared to men, older women are more likely to experience less spatial mobility and restricted life space, and hence are more vulnerable to social isolation.Conclusion:Mental health and life space were associated for the older people in this study. These findings have important implications for health policy and highlight the need to support older persons to maintain independence and social networks, and to successfully age in place within their community. This study also highlights the utility of the Life Space Questionnaire in terms of identifying older persons at risk of poorer mental health. [ABSTRACT FROM PUBLISHER]

AbstractObjectivesMethodsResultsConclusionTo evaluate a co-designed intervention using digital resources “Vietnam Cancer Caring Coping” (V-CCC) on the health literacy, depression, and quality of life of caregivers supporting a cancer patient in oncology hospitals in Vietnam.A pre-post quantitative evaluation with adult cancer caregivers across regional Oncology hospitals in Vietnam (Ho Chi Minh City, Da Nang, Can Tho, and Hue). Participants completed baseline and follow-up measures of health literacy (HLS-SF12) depression (PHQ-9) and Health-related Quality of Life (5Q-5D-5L). Participants accessed and reviewed V-CCC for a 2-week period.Two hundred and thirty-four caregivers completed pre and post-tests. Most participants were female (n = 143, 61%), married (n = 165, 70%), aged 18–44 (n = 155, 66%), lived rurally (n = 157, 67%). All health literacy scores of participants in post-intervention were significantly higher than that in pre-intervention across all domain’s healthcare, disease prevention, and health promotion as well as the total score (p < 0.001). A significant reduction in the proportion of caregivers reporting PHQ-9 moderately severe/severe depression post-intervention was demonstrated (10.2 vs. 6.1%, respectively (p ≤ 0.001). No significant differences were observed pre and post-intervention across four 5Q-5D-5L health dimensions: mobility, self-care, usual activities, and pain/discomfort. Regarding anxiety/depression as measured by 5Q-5D-5L the proportion of participants who reported having moderate, severe, and extreme problems in pre- and post-intervention was statistically significant (32 vs. 24%), respectively (p = 0.0028).Co-designed digital resources can reduce health literacy inequities and improve psychological outcomes for cancer caregivers. [ABSTRACT FROM AUTHOR]