Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells.

Human mononuclear phagocytes comprise phenotypically and functionally overlapping subsets of dendritic cells (DCs) and monocytes, but the extent of their heterogeneity and distinct markers for subset identification remains elusive. By integrating high-dimensional single-cell protein and RNA expression data, we identified distinct markers to delineate monocytes from conventional DC2 (cDC2s). Using CD88 and CD89 for monocytes and HLA-DQ and FcεRIα for cDC2s allowed for their specific identification in blood and tissues. We also showed that cDC2s could be subdivided into phenotypically and functionally distinct subsets based on CD5, CD163, and CD14 expression, including a distinct subset of circulating inflammatory CD5-CD163+CD14+ cells related to previously defined DC3s. These inflammatory DC3s were expanded in systemic lupus erythematosus patients and correlated with disease activity. These findings further unravel the heterogeneity of DC subpopulations in health and disease and may pave the way for the identification of specific DC subset-targeting therapies.

Induced-Pluripotent-Stem-Cell-Derived Primitive Macrophages Provide a Platform for Modeling Tissue-Resident Macrophage Differentiation and Function.

Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues. Co-culturing human or murine iMacs with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMacs differentiated in vivo into microglia after injection into the brain and into functional alveolar macrophages after engraftment in the lung. Finally, iPSCs from a patient with familial Mediterranean fever differentiated into iMacs with pro-inflammatory characteristics, mimicking the disease phenotype. Altogether, iMacs constitute a source of tissue-resident macrophage precursors that can be used for biological, pathophysiological, and therapeutic studies.

Human fetal dendritic cells promote prenatal T-cell immune suppression through arginase-2.

During gestation the developing human fetus is exposed to a diverse range of potentially immune-stimulatory molecules including semi-allogeneic antigens from maternal cells, substances from ingested amniotic fluid, food antigens, and microbes. Yet the capacity of the fetal immune system, including antigen-presenting cells, to detect and respond to such stimuli remains unclear. In particular, dendritic cells, which are crucial for effective immunity and tolerance, remain poorly characterized in the developing fetus. Here we show that subsets of antigen-presenting cells can be identified in fetal tissues and are related to adult populations of antigen-presenting cells. Similar to adult dendritic cells, fetal dendritic cells migrate to lymph nodes and respond to toll-like receptor ligation; however, they differ markedly in their response to allogeneic antigens, strongly promoting regulatory T-cell induction and inhibiting T-cell tumour-necrosis factor-α production through arginase-2 activity. Our results reveal a previously unappreciated role of dendritic cells within the developing fetus and indicate that they mediate homeostatic immune-suppressive responses during gestation.

COVID-19 and Well-Being of Non-local Students: Implications for International Higher Education Governance.

Non-local students have been one of the worst affected groups during the COVID-19 pandemic. Many of them live in foreign countries/regions with limited social and economic support. This study examines the effects of the COVID-19 pandemic and its control measures on the well-being of non-local students globally. It also examines the effectiveness of university support for the well-being of non-local students. Data were derived from a global survey on non-local students' knowledge, experiences, and well-being amidst the COVID-19 Pandemic, which was conducted in April 2020 (n = 583). A significant proportion (42.6%) of the students had low well-being. We found that being worried about COVID-19 (B = - 0.206, p = 0.048), perceived disruption of academic activities (B = - 0.155, p = 0.024), perceived disruption of social activities (B = - 0.153, p = 0.044), and feeling lonely (B = - 0.340, p = 0.000) were negatively associated with the students' well-being. However, informational support from universities was positively associated with their well-being (B = 0.225, p = 0.004). These findings are discussed in the context of higher education governance and practical changes necessary to promote non-local students' well-being during and after the pandemic.

Hallmarks of improved immunological responses in the vaccination of more physically active elderly females.

Physical inactivity is one of the leading contributors to worldwide morbidity and mortality. The elderly are particularly susceptible since the features of physical inactivity overlap with the outcomes of natural aging - including the propensity to develop cardiovascular diseases, cancer, diabetes mellitus, sarcopenia and cognitive impairment. The age-dependent loss of immune function, or immunosenescence, refers to the progressive depletion of primary immune resources and is linked to the development of many of these conditions. Immunosenescence is primarily driven by chronic immune activation and physical activity interventions have demonstrated the potential to reduce the risk of complications in the elderly by modulating inflammation and augmenting the immune system. Since poor vaccination outcome is a hallmark of immunosenescence, the assessment of vaccine efficacy provides a window to study the immunological effects of regular physical activity. Using an accelerator-based study, we demonstrate in a Singaporean Chinese cohort that elderly women (n=56) who walk more after vaccination display greater post-vaccination expansion of monocytes and plasmablasts in peripheral blood. Active elderly female participants also demonstrated lower baseline levels of IP-10 and Eotaxin, and the upregulation of genes associated with monocyte/macrophage phagocytosis. We further describe postive correlations between the monocyte response and the post-vaccination H1N1 HAI titres of participants. Finally, active elderly women reveal a higher induction of antibodies against Flu B in their 18-month second vaccination follow-up. Altogether, our data are consistent with better immunological outcomes in those who are more physically active and highlight the pertinent contribution of monocyte activity.

Longitudinal Study of Cellular and Systemic Cytokine Signatures to Define the Dynamics of a Balanced Immune Environment During Disease Manifestation in Zika Virus-Infected Patients.

Background: Since its unexpected reemergence, Zika virus (ZIKV) has caused numerous outbreaks globally. This study characterized the host immune responses during ZIKV infection. Methods: Patient samples were collected longitudinally during the acute, convalescence and recovery phases of ZIKV infection over 6 months during the Singapore outbreak in late 2016. Plasma immune mediators were profiled via multiplex microbead assay, while changes in blood cell numbers were determined with immunophenotyping. Results: Data showed the involvement of various immune mediators during acute ZIKV infection accompanied by a general reduction in blood cell numbers for all immune subsets except CD14+ monocytes. Importantly, viremic patients experiencing moderate symptoms had significantly higher quantities of interferon γ-induced protein 10, monocyte chemotactic protein 1, interleukin 1 receptor antagonist, interleukin 8, and placental growth factor 1, accompanied by reduced numbers of peripheral CD8+ T cells, CD4+ T cells, and double-negative T cells. Levels of T-cell associated mediators, including interferon γ-induced protein 10, interferon γ, and interleukin 10, were high in recovery phases of ZIKV infection, suggesting a functional role for T cells. The identification of different markers at specific disease phases emphasizes the dynamics of a balanced cytokine environment in disease progression. Conclusions: This is the first comprehensive study that highlights specific cellular changes and immune signatures during ZIKV disease progression, and it provides valuable insights into ZIKV immunopathogenesis.

Quality-of-life concerns of Chinese patients with advanced cancer.

This study aimed to examine the quality of life (QOL) of patients with advanced cancer in Hong Kong. Ninety participants were recruited from the oncology ward of the study hospital. They responded to a 28-item, 8-subscale multidimensional questionnaire and a single-item scale that measured QOL in a face-to-face interview. Participation in health care decisions, food-related concerns, and existential distress were some QOL concerns that require health care professionals' attention. Walking ability predicted the level of QOL in certain QOL domains that surfaces patients' need for rehabilitation. That the QOL domain value of life was the most important domain that predicted overall QOL calls for meaning-of-life interventions for palliative care.

Perceptions of a life review programme among Chinese patients with advanced cancer.

AIMS: The aim of this study was to elicit patients' perceptions of their participation in a life review programme for Chinese patients with advanced cancer. BACKGROUND: Empirical data have supported the suggestion that a life review is an effective psycho-spiritual intervention, particularly with older people. However, no life review programmes have been specifically designed for Chinese patients with advanced cancer, and their views on the life review therefore remain unknown. DESIGN: This study was a descriptive qualitative design. METHOD: In-depth individual interviews were conducted with a sample of 26 patients with advanced cancer receiving home-based palliative care from a hospice after the completion of the programme. RESULTS: The six categories identified in the analysis were as follows: (1) accepting one's unique life; (2) feelings of emotional relief; (3) bolstering a sense of meaning in life; (4) leaving a personal legacy; (5) making future orientations; and (6) barriers to a life review. CONCLUSION: Our life review programme is non-invasive care intervention for improving the psycho-spiritual well-being of Chinese patients with advanced cancer and helping them to prepare for death. This programme not only provides Chinese nurses with a new approach to meeting the unique needs of patients approaching death but also poses a challenge to customary beliefs about death, which is considered a social taboo in China. RELEVANCE TO CLINICAL PRACTICE: The life review programme can be integrated into the usual care arrangements to enhance the psycho-spiritual well-being of Chinese patients with advanced cancer. Nurses should be aware of the challenges involved in the process of conducting a life review.

Holistic concerns of Chinese stroke survivors during hospitalization and in transition to home.

AIM: This article is a report of a study conducted to explore the phenomenon of concerns as experienced by Chinese stroke survivors during hospitalization and in transition to home. BACKGROUND: Stroke is characterized by its sudden onset and prolonged residual problems, which affect survivors' holistic well-being. Many studies have focused on stroke consequences and their correlates with psychosocial outcomes. Very little is known about holistic concerns of stroke survivors, particularly in the transition from hospital to home. METHOD: We used purposive sampling of 15 stroke survivors who participated in semi-structured interviews after being discharged from stroke wards of a general hospital in Hong Kong from November 2008 to February 2009. The interviews were transcribed verbatim and analysed using Giorgi's phenomenological techniques. FINDINGS: Stroke survivors' physical, psychological, socio-cultural and spiritual concerns in hospital and transition to home emerged from the data analysis. The four major themes identified were: (a) dynamic interplay of holistic concerns, (b) cultural expression of illness experiences, (c) social support 'paradox' and (d) caring gaps in clinical management. CONCLUSION: Understanding the interwoven holistic concerns for the stroke survivors in hospital and after discharged home can help nurses to identify their health needs and plan for appropriate nursing interventions. The findings provide guidance for the development of culture-sensitive holistic care interventions with family involvement in Chinese stroke populations.

Advance directives and life-sustaining treatment: attitudes of Hong Kong Chinese elders with chronic disease.

OBJECTIVE: To examine the attitudes of Hong Kong Chinese elders with chronic disease with regard to advance directives and life-sustaining treatment. DESIGN: Cross-sectional questionnaire survey. SETTING: Medical unit of a regional teaching hospital in Hong Kong. PARTICIPANTS: In-patients aged 60 years or above with chronic disease. MAIN OUTCOME MEASURES: Demographic profiles and attitudes towards advance directives and life-sustaining treatment. RESULTS: A total of 219 elderly patients completed the questionnaire. Their mean age was 73 (standard deviation, 8) years; 133 (61%) were female. The majority had neither heard about advance directives (81%), nor discussed the issue with others (73%) before participating in this study. After they were informed of the concept of advance directives, about half (49%) said they would consider using it if it is legislated in Hong Kong. The respondents generally supported the withholding or withdrawing of life-sustaining treatment in medically futile situations. In all, 55% of them believed that the patient alone should make the decision on withholding or withdrawing life-sustaining treatment, if competent to do so. If the patient became not competent, 44% believed that the individual's family alone should make such a decision. CONCLUSION: The fact that most of the respondents had never heard about advance directives or discussed the concept with others points to a lack of knowledge and to the necessity to step up public education about such issues.

Seeking harmony in the provision of care to the stroke-impaired: views of Chinese family caregivers.

AIMS: To explore the coping strategies of Chinese family caregivers of stroke-impaired older relatives. BACKGROUND: Many stroke-impaired patients rely heavily on support from their families, and the daily lives of such family caregivers are severely impacted. However, services and support for family caregivers of stroke-impaired relatives in the home setting have received little attention. Appropriate and relevant information and support to family caregivers are important in facilitating the care-giving task. It is, therefore, necessary to understand the nature and demands of care-giving before planning specific educational and support programmes. DESIGN: Grounded theory. METHODS: Fifteen Chinese family caregivers of stroke-impaired older relatives were recruited and interviewed in 2003 and 2004. Theoretical sampling and constant comparative analysis were used to recruit the sample and perform data analysis. RESULTS: Seeking harmony to provide care for the stroke-impaired was the core category for describing and guiding the family care-giving process, with five main stages: (1) living with ambiguity, (2) monitoring the recovery progress, (3) accepting the downfalls, (4) meeting family obligations and (5) reconciling with harmony. These issues were seldom discussed openly with health professionals. CONCLUSIONS: The findings indicated that Chinese family caregivers determine their own needs by seeking harmony to continue to provide care without thinking about getting help from others or their own health problems. These findings help to define some of the complex dynamics that have an impact on the development of partnership care and might challenge nurses practising in the community. RELEVANCE TO CLINICAL PRACTICE: Community nurses should assess and understand the coping strategies of family caregivers and assist them to engage in stress-reducing practices. This is an important partnership to be formed in stroke care for family caregivers in the community. The study findings will guide further development of family care-giving aspects in nursing practice.

Evaluation of the psychometric properties of a modified Chinese version of the Caregiver Task Inventory--refinement and psychometric testing of the Chinese Caregiver Task Inventory: a confirmatory factor analysis.

AIM: To test the reliability and validity of the modified Chinese version of the Caregiver Task Inventory. BACKGROUND: The original Caregiver Task Inventory was developed in 1983 by Clark and Rakowski in the USA. It was used to measure Chinese family caregivers' needs in Hong Kong. Its failure to evaluate the psychometric properties of the instrument measuring the needs of family caregivers across cultures limited its scientific rigor. DESIGN: A quantitative study method was used to test the psychometrics of the modified Chinese version of the Caregiver Task Inventory. METHODS: A convenience sample of 114 family caregivers completed the Caregiver Task Inventory in 2005 to test different aspects of the validity and reliability and confirm items of the short form of the Chinese Caregiver Task Inventory-25. RESULTS: The content validity of the 25 items of the Chinese Caregiver Task Inventory was validated by six experts, who assessed the correlation between caregiving tasks and the five refined sub-scales. The construct validity was determined by confirmatory factor analysis (CFA). The χ(2) goodness-of-fit, χ(2): df ratio, goodness-of-fit index (GFI), adjusted GFI and root mean square residual were obtained and used to assess the fit of the model. The internal consistency and stability of the Chinese Caregiver Task Inventory-25 were determined by Cronbach's method (0·93) and the internal reliability (item total correlation) for the five refined sub-scales ranged from 0·67-0·86. CFA and internal consistency analysis showed a strong degree of fit between the conceptualisation and the development of the measurement. CONCLUSIONS: The Chinese Caregiver Task Inventory-25 is a relevant and culturally appropriate research instrument to measure the needs of Chinese family caregivers. RELEVANCE TO CLINICAL PRACTICE: This study reveals that stroke nurses should assess the impacts of caregiving tasks on caregivers' physical and psychological stress levels prior to planning relevant interventions.

Effectiveness of music intervention on the quality of life of older people.

AIM: This paper is a report of a study of the effect of music on the quality of life of community-dwelling older Chinese people in Hong Kong. BACKGROUND: Older people's quality of life can be improved by preparing for the transition into old age. Listening to music, as a vehicle for feeling, can facilitate the non-verbal expression of emotion, reaching people's inner feelings without being threatening, and it can be a tool for emotional catharsis. METHOD: A randomized controlled trial design was conducted from in 2007 in a community centre in Hong Kong. A total of 66 older people (31 in music group and 35 in control group), aged from 65 to 90 years were randomly assigned to undergo either a 30-minute music intervention or a rest period for 4 weeks; quality of life outcomes were then measured. RESULTS: Quality of life improved weekly in the music group, indicating a cumulative dose effect, and a statistically significantly better quality of life was found over time in each sub-score for those in the music group compared with the controls. However, in the music group, there were no statistically significant improvements of quality of life in each sub-score over the 4 weeks. CONCLUSION: Being engaged in music activities can help a person to connect with their life experiences and with other people, and to be more stimulated. Music is a non-invasive, simple and inexpensive therapeutic method of improving quality of life in community-dwelling elders.

The meaning of spirituality and spiritual care among the Hong Kong Chinese terminally ill.

AIM: This paper is a report of a study conducted to explore the phenomenon of spirituality and spiritual care among terminally ill Chinese patients. BACKGROUND: Meeting a patient's spiritual needs is a fundamental part of holistic nursing care. In the Western literature, spirituality is related to connectedness, faith, and hope. Contemporary scholars in the West suggest that spirituality is a broader term than religion. METHOD: Phenomenological interviews were conducted with a convenience sample of 15 terminally ill Chinese patients in 2007. FINDINGS: Participants found the term spirituality an abstract concept and described it as a unique personal belief which gives strength and relates to meaning of life. Spirituality is integrated with the body and mind and is a multidimensional concept. The acceptance of death as a process in life and 'letting go' leads to serenity and peace of mind. Other important themes include how the meaning of life is derived through relationships and connectedness, self-reflection of responsibilities, and obligations fulfilled. Inner spiritual well-being is attained from having faith and knowing possibilities in life and after death. Participants did not expect nurses to provide spiritual care, but when quality interpersonal care was given it gave them strength and spiritually supportive. CONCLUSION: If healthcare professionals can provide a compassionate and loving environment that facilitates acceptance and hope, the spiritual life of patients is enhanced. For dying individuals to experience love and for them to be understood as valuable even when no longer economically productive are both experiences of healing.

Healthcare professionals' perceptions of existential distress in patients with advanced cancer.

AIM: This paper is a report of an exploration of the phenomenon of existential distress in patients with advanced cancer from the perspectives of healthcare professionals. BACKGROUND: Existential distress is an important concern in patients with advanced cancer; it affects their well-being and needs to be addressed in the provision of holistic care. METHOD: Focus groups were conducted from November 2008 to February 2009 with physicians, nurses, social workers, occupational therapists, physiotherapists, and chaplains working in a palliative care unit that served patients with advanced cancer in Hong Kong. Data collection and analysis were guided by the grounded theory approach. All categories were saturated when five focus groups had been held with a total number of 23 participants. FINDINGS: We found three causal conditions of existential distress: anticipation of a negative future, failure to engage in meaningful activities and relationships, and having regrets. Three basic (caring, relating and knowing) and six specific (positive feedback, religious support, new experiences, task setting, exploring alternatives and relationship reconciliation) intervening strategies were identified. Whether the intervening strategies would be effective would depend on patients' openness and readiness; healthcare professionals' self-awareness, hopefulness, and interest in knowing the patients; and a trusting relationship between patients and healthcare professionals. A sense of peace in patients was considered a consequence of successful interventions. CONCLUSION: This paper acknowledges the lack of an accepted conceptual framework of existential distress in patients with advanced cancer. It is based on healthcare professionals' views, and further studies from the perspectives of patients and their families are needed.

The meaning of hope from the perspective of Chinese advanced cancer patients in Hong Kong.

AIM: This article reports a study to examine the meaning of hope from the perspective of Chinese advanced cancer patients in Hong Kong. METHODS: Semi-structured interviews were conducted with a convenience sample of advanced cancer patients recruited from the palliative care unit of a local hospital. Data were saturated after 17 participants were interviewed. Qualitative content analysis was adopted to analyse the data. FINDINGS: Hope as experienced by the participants was found to consist of five components: living a normal life, social support, actively letting go of control, reconciliation between life and death, and wellbeing of significant others. CONCLUSIONS: While hope is related to the wellbeing of patients with advanced cancer, successful palliative care partly depends on an awareness of the importance of hope in the end-of-life context and cultural sensitivity to the meanings behind it from the patients' own perspective.

The use of interdisciplinary seminars for the development of caring dispositions in nursing and social work students.

AIM: This paper is a report of a study to evaluate the influence of interdisciplinary seminars for undergraduate nursing and social work students on development of their understanding of the meaning of caring. BACKGROUND: There is growing international interest in interprofessional education, which is believed to have the potential to improve patient care. If interprofessional education and subsequent collaboration are truly to be patient-centred, it is important to identify a value base which creates a healthcare professional identity that facilitates collaboration. Caring, as a humanistic value, is found in both nursing and social work professionals. METHOD: A mixed method approach, primarily qualitative but with a quantitative component, was chosen for evaluation of the interprofessional seminars. The data were collected between 2007-2008 by videotape recordings of the sessions, follow-up telephone interviews and a questionnaire. FINDINGS: There was cultivation in the nursing students of a deeper understanding of caring based on openness and a non-judgmental approach, learned from their social work counterparts. Reciprocally, social work students learned about the nursing students' daily activities as they observed the natural process of trust and communication in the context of caring. CONCLUSION: Enhanced understanding of caring in practice is not possible via learning through a uni-professional approach. Students' reflections and dialogue enable their development of relation-centred caring, particularly in the realm of biomedical and technical environments.

Metformin Monotherapy Downregulates Diabetes-Associated Inflammatory Status and Impacts on Mortality.

Aging is the main risk factor for developing diabetes and other age-related diseases. One of the most common features of age-related comorbidities is the presence of low-grade chronic inflammation. This is also the case of metabolic syndrome and diabetes. At the subclinical level, a pro-inflammatory phenotype was shown to be associated with Type-2 diabetes mellitus (T2DM). This low to mid-grade inflammation is also present in elderly individuals and has been termed inflammaging. Whether inflammation is a component of aging or exclusively associated with age-related diseases in not entirely known. We used clinical data and biological readouts in a group of individuals stratified by age, diabetes status and comorbidities to investigate this aspect. While aging is the main predisposing factor for several diseases there is a concomitant increased level of pro-inflammatory cytokines. DM patients show an increased level of sTNFRll, sICAM-1, and TIMP-1 when compared to Healthy, Non-DM and Pre-DM individuals. These inflammatory molecules are also associated with insulin resistance and metabolic syndrome in Non-DM and pre-DM individuals. We also show that metformin monotherapy was associated with significantly lower levels of inflammatory molecules, like TNFα, sTNFRI, and sTNFRII, when compared to other monotherapies. Longitudinal follow up indicates a higher proportion of death occurs in individuals taking other monotherapies compared to metformin monotherapy. Together our finding shows that chronic inflammation is present in healthy elderly individuals and exacerbated with diabetes patients. Likewise, metformin could help target age-related chronic inflammation in general, and reduce the predisposition to comorbidities and mortality.

Mapping of γ/δ T cells reveals Vδ2+ T cells resistance to senescence.

BACKGROUND: Immune adaptation with aging is a major of health outcomes. Studies in humans have mainly focus on αß T cells while γδ T cells have been neglected despite their role in immunosurveillance. We investigated the impact of aging on γδ T cell subsets phenotypes, functions, senescence and their molecular response to stress. METHODS: Peripheral blood of young and old donors in Singapore have been used to assess the phenotype, functional capacity, proliferation capacity and gene expression of the various γδ T cell subsets. Peripheral blood mononuclear cells from apheresis cones and young donors have been used to characterize the telomere length, epigenetics profile and DNA damage response of the various γδ T cell subsets phenotype. FINDINGS: Our data shows that peripheral Vδ2+ phenotype, functional capacity (cytokines, cytotoxicity, proliferation) and gene expression profile are specific when compared against all other αß and γδ T cells in aging. Hallmarks of senescence including telomere length, epigenetic profile and DNA damage response of Vδ2+ also differs against all other αß and γδ T cells. INTERPRETATION: Our results highlight the differential impact of lifelong stress on γδ T cells subsets, and highlight possible mechanisms that enable Vδ2+ to be resistant to cellular aging. The new findings reinforce the concept that Vδ2+ have an "innate-like" behavior and are more resilient to the environment as compared to "adaptive-like" Vδ1+ T cells.