p21/Cyclin E pathway modulates anticlastogenic function of Bmi-1 in cancer cells.

Apart from regulating stem cell self-renewal, embryonic development and proliferation, Bmi-1 has been recently reported to be critical in the maintenance of genome integrity. In searching for novel mechanisms underlying the anticlastogenic function of Bmi-1, we observed, for the first time, that Bmi-1 positively regulates p21 expression. We extended the finding that Bmi-1 deficiency induced chromosome breaks in multiple cancer cell models. Interestingly, we further demonstrated that knockdown of cyclin E or ectopic overexpression of p21 rescued Bmi-1 deficiency-induced chromosome breaks. We therefore conclude that p21/cyclin E pathway is crucial in modulating the anticlastogenic function of Bmi-1. As it is well established that the overexpression of cyclin E potently induces genome instability and p21 suppresses the function of cyclin E, the novel and important implication from our findings is that Bmi-1 plays an important role in limiting genomic instability in cylin E-overexpressing cancer cells by positive regulation of p21.

Chemobrain: a critical review and causal hypothesis of link between cytokines and epigenetic reprogramming associated with chemotherapy.

One consequence of modern cancer therapy is chemotherapy related cognitive dysfunction or "chemobrain", the subjective experience of cognitive deficits at any point during or following chemotherapy. Chemobrain, a well-established clinical syndrome, has become an increasing concern because the number of long-term cancer survivors is growing dramatically. There is strong evidence that correlates changes in peripheral cytokines with the development of chemobrain in commonly used chemotherapeutic drugs for different types of cancer. However, the mechanisms by which these cytokines elicit change in the central nervous system are still unclear. In this review, we hypothesize that the administration of chemotherapy agents initiates a cascade of biological changes, with short-lived alterations in the cytokine milieu inducing persistent epigenetic alterations. These epigenetic changes lead to changes in gene expression, alterations in metabolic activity and neuronal transmission that are responsible for generating the subjective experience of cognition. This speculative but testable hypothesis should help to gain a comprehensive understanding of the mechanism underlying cognitive dysfunction in cancer patients. Such knowledge is critical to identify pharmaceutical targets with the potential to prevent and treat cancer-treatment related cognitive dysfunction and similar disorders.

Assessing the effect of a mind-body exercise, qigong Baduanjin, on sleep disturbance among women experiencing intimate partner violence and possible mediating factors: a randomized-controlled trial.

STUDY OBJECTIVES: To evaluate the effects of a mind-body exercise, qigong Baduanjin, on sleep disturbances in women experiencing intimate partner violence and explore the mediating role of depressive symptoms, perceived stress, and inflammation in producing the effects. METHODS: A subgroup of a parent randomized controlled trial was randomized for a 22-week Baduanjin intervention (n = 94) or wait-list control (n = 92). Questionnaires, including the General Sleep Disturbance Scale, Perceived Stress Scale, and Beck Depression Inventory version II, were administered at baseline, posttraining (6 weeks), and postintervention (22 weeks), and blood samples were collected to assess tumor necrosis factor and interleukin 6 levels at baseline and postintervention only. RESULTS: Of the 186 participants, 170 completed the study. Results indicate that the total sleep disturbance scores for the intervention group were significantly lower than those for the wait-list control group at week 6 (difference = -7.96; 95% confidence interval [CI], -13.63 to -2.30; P = .006) and week 22 (difference = -7.17; 95% CI, -12.58 to -1.76; P = .01). Mediation analysis showed a statistically significant indirect effect of the intervention on sleep improvement through reducing depressive symptoms (ß = 2.58, 95% CI, 0.69 to 5.09), while the mediating effects of perceived stress and inflammation were not significant. CONCLUSIONS: Qigong Baduanjin can be recommended for women who experience intimate partner violence and report sleep disturbances. More research is needed to understand the clinical significance of the observed sleep improvements. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Qigong Intervention Program for Abused Chinese Women; URL: https://clinicaltrials.gov/ct2/show/NCT02060123; Identifier: NCT02060123.

Effect of a Qigong Intervention on Telomerase Activity and Mental Health in Chinese Women Survivors of Intimate Partner Violence: A Randomized Clinical Trial.

Importance: Qigong is a mind-body exercise that may be an effective self-care intervention for improving the well-being of women survivors of intimate partner violence. Objective: To test whether a qigong intervention would increase telomerase activity and improve mental health in Chinese women who survived intimate partner violence. Design, Setting, and Participants: A single-blind randomized clinical trial among Chinese women (N = 271) who survived intimate partner violence in the past 2 years recruited from a community center in Hong Kong, China. The trial was conducted from March 12, 2014, to May 26, 2016. Data analysis was by intention to treat and performed from June 7 to August 24, 2018. Interventions: Randomization (1:1) to a 22-week qigong intervention (n = 136) that included 22 weeks of Baduanjin qigong group training (1-6 weeks: 2-hour sessions biweekly; 7-22 weeks: 1-hour follow-up sessions weekly) and self-practice (30 minutes per day for 22 weeks) or to a wait-list control group (n = 135) that received optional monthly health education sessions unrelated to qigong after 6 weeks (posttraining period) and qigong training after 22 weeks (postintervention period). Main Outcomes and Measures: The primary outcome was telomerase activity in peripheral blood mononuclear cells. The secondary outcomes included levels of proinflammatory cytokines (tumor necrosis factor and interleukin 6) in peripheral blood plasma, depressive symptoms (Beck Depression Inventory II score; score range, 0-63; higher scores represent more severe depressive symptoms), perceived stress (Perceived Stress Scale; score range, 0-40; higher scores represent higher stress), and perceived coping (Perceived Coping Scale; score range, 0-13; higher scores represent use of more coping strategies). Results: From 1611 Chinese women screened (mean [SD] age, 42.0 [8.8] years), 247 of 271 randomized participants completed the study (intervention group, 120; wait-list control group, 127). Telomerase activity of the intervention group participants after 22 weeks was not significantly different from that of the wait-list control group participants (5.18 U [95% CI, 5.05-5.31 U] in the intervention group vs 5.14 U [95% CI, 5.01-5.27 U] in the wait-list control group; P = .66). The mean change in telomerase activity from baseline was marginally significant in the intervention group (effect size [d], 0.13; 95% CI, 0.001-0.27) but not in the wait-list control group (d, -0.03; 95% CI, -0.16 to 0.10). Perceived stress and depressive symptoms were significantly lower in the intervention group than in the wait-list control group after 6 weeks (between-group differences: perceived stress: d, -1.81; 95% CI, -3.27 to -0.34; depressive symptoms: d, -3.57; 95% CI, -6.25 to -0.90), but not after 22 weeks (between-group differences: perceived stress: d, -1.03; 95% CI, -2.50 to 0.43; depressive symptoms: d, -1.78; 95% CI, -4.26 to 0.70). Conclusions and Relevance: The findings of this study do not support a significant benefit of Baduanjin qigong on telomerase activity in women who have survived intimate partner violence. However, outcomes related to mental health seem to be improved, which should be confirmed by additional studies. Trial Registration: ClinicalTrials.gov Identifier: NCT02060123.

Parental response to child's isolation during the SARS outbreak.

OBJECTIVES: To examine the needs, uncertainties, and experiences of parents during their child's hospitalization with highly suspected severe acute respiratory syndrome (HSS), and to identify ways to improve their psychological preparedness and communication with health care professionals and their isolated children during future infectious disease outbreaks. METHODS: Qualitative, semistructured interviews were conducted in July 2003 with parents of HSS pediatric patients. Seventeen HSS patients were hospitalized in a pediatric outpatient clinic of a major academic medical center in Hong Kong, between March 20 and May 28, 2003, during severe acute respiratory syndrome (SARS). Seven parents (41%) consented to participate in the study. RESULTS: Four major themes were identified from the interviews: 1) fear of immediate isolation and infection control procedures, 2) sources of anxiety, 3) coping, and 4) communication with children and health care professionals. CONCLUSIONS: Findings indicate a need to improve the psychological preparedness of the parents regarding the child's immediate isolation during hospitalization. Ample preparation and appropriate communication among parents, health care workers, and children might minimize fear and anxiety, sustain trust, and facilitate mutual understanding during an infectious disease outbreak.

Extremely stringent activation of p16INK4a prevents immortalization of uterine cervical epithelial cells without human papillomavirus oncogene expression.

Cervical epithelial cell immortalization with defined genetic factors without viral oncogenes has never been reported. Here we report that HPV-negative cervical epithelial cells failed to be immortalized by telomerase activation or the combination of p53 knockdown and telomerase activation. Under those conditions, p16INK4a expression was always elevated during the late stage of limited cell lifespan, suggesting that cervical epithelial cells possess an intrinsic property of uniquely stringent activation of p16INK4a, which may offer an explanation for the rarity of HPV-negative cervical cancer. Combining p16INK4a knockdown with telomerase activation resulted in efficient immortalization of HPV-negative cervical epithelial cells under ordinary culture conditions. Compared with the HPV16-E6E7-immortalized cell lines derived from the same primary cell sources, the novel HPV-negative immortalized cell lines had lower degrees of chromosomal instability, maintained more sensitive p53/p21 response to DNA damage, exhibited more stringent G2 checkpoint function, and were more resistant to replication-stress-induced genomic instability. The newly immortalized HPV-negative cervical epithelial cell lines were non-tumorigenic in nude mice. The cell lines can be used not only as much-needed HPV-negative non-malignant cell models but also as starting models that can be genetically manipulated in a stepwise fashion to investigate the roles of defined genetic alterations in the development of HPV-negative cervical cancer.

Hong Kong nurses' perceptions of and participation in continuing nursing education.

As medical technologies change, practicing nurses need to update their knowledge and skills to ensure quality health care for patients and to minimize possible health hazards in the workplace. This article describes a study that explored Hong Kong hospital nurses' perceptions of and participation in continuing nursing education. It found that Hong Kong nurses participate actively in continuing education out of a sense of professional responsibility and personal interest. However, consistent with findings from other studies, the major factors hindering nurses' participation are finances, family commitments, and time.

The knowledge level and precautionary measures taken by older adults during the SARS outbreak in Hong Kong.

The study aims to examine the knowledge and the practice of the precautionary measures taken by older adults in Hong Kong against the outbreak of severe acute respiratory syndrome (SARS). Overall, more than half the participants responded correctly that droplet transmission is one of the main transmission routes of SARS. Those who received formal education demonstrated that they acquired greater knowledge of the sources and precautionary measures for SARS. The types of precautionary measures used and the factors affecting their behaviours were discussed. The results of the study could help the health-care professionals develop appropriate health promotion and disease prevention programmes for older adults.

Balancing infection control practices and family-centred care in a cohort of paediatric suspected severe acute respiratory syndrome patients in Hong Kong.

OBJECTIVE: To identify key nursing issues for paediatric patients suspected of severe acute respiratory syndrome (SARS) in relation to the family-centred model of nursing care and to develop a data-based model of paediatric nursing care to be better applied in situations of suspected SARS or where outbreaks of other infectious diseases occur. METHODS: This is a retrospective descriptive case series, which analysed the medical and nursing records of all highly-suspected/suspected SARS patients admitted to a major acute hospital in Hong Kong. Key nursing personnel were also interviewed. RESULTS: The study included a total of 17 highly-suspected and 49 suspected SARS paediatric patients (age: 1-16). None of the paediatric patients was eventually diagnosed of SARS. Most cases presented fever (highly-suspected: 76.5%/ suspected: 100%), cough (64.7%/71.4%), nausea and vomiting (35.3%/28.6%). Nursing care was provided to the patients as necessary. Both the children and parents experienced fear of SARS, as well as separation anxiety arisen from hospitalization in a strict isolation setting. CONCLUSIONS: Infection control overshadowed the family-centred nursing practices in the management of SARS paediatric patients. A major nursing care issue for SARS paediatric patients was to achieve a careful balance between attending to patients' physical and psychological needs and adhering to the infection control guidelines, while at the same time offering psychological support to family members. The current philosophy and practice of family-centred nursing model neglect the special needs of children with infectious diseases and predominantly apply to children with non-infectious diseases that family visits are allowed and nursing care by parents are encouraged.

The impact of work-related risk on nurses during the SARS outbreak in Hong Kong.

Severe acute respiratory syndrome (SARS) is a highly infectious disease, with high potential for transmission to close contacts, particularly among healthcare workers. This is the first systematic study investigating hospital nurses' physical and psychological health status and the kinds of healthcare used-stratified by the level of contact with SARS patients-during the 2003 outbreak in Hong Kong. Nurses in moderate-risk areas appeared to have more stress symptoms than those working in high-risk areas. It is essential to design hospital support systems and occupational health policy to promote the psychological well-being of nurses during future outbreaks of emerging infections.