Impact of mind-body intervention on proinflammatory cytokines interleukin 6 and 1ß: A three-arm randomized controlled trial for persons with sleep disturbance and depression.

Depressed people are prone to sleep disturbance, which may in return perpetuate the depression. Both depression and sleep disturbance influence proinflammatory cytokines interleukin (IL) 6 and 1ß. Thus interventions for depression should consider the effect on sleep disturbance, and vice versa. Integrative Body-Mind-Spirit (IBMS) and Qigong interventions have been applied in a wide range of health and mental health conditions, including depression and sleep disturbance. This study aimed to evaluate the effect of these two mind-body therapies for persons with both depressive symptoms and sleep disturbance. A three-arm randomized controlled trial was conducted among 281 participants, who were randomly assigned to either IBMS, Qigong or wait list control group. Participants in IBMS and Qigong groups received eight weekly sessions of intervention. Outcome measures were plasma concentrations of IL-6 and IL-1ß, and a questionnaire containing Pittsburgh Sleep Quality Index, Center for Epidemiologic Studies Depression Scale, Somatic Symptom Inventory, Perceived Stress Scale and Body-Mind-Spirit Holistic Well-being Scale. Outcomes were assessed at baseline (T0), immediate post-intervention (T1) and at three-months post-intervention (T2). Besides intervention efficacy analysis, path analysis was performed to explore the relations among perceived stress, depression, sleep disturbance, and IL-6 and IL-1ß values. The study found both IBMS and Qigong reduced depression, sleep disturbance, painful and painless somatic symptoms, IL-6 and IL-1ß levels, and increased holistic well-being. The effect sizes of IBMS and Qigong, mostly in the medium magnitude range, were approximatively equivalent. Path analysis models revealed a predictive role of perceived stress in depression and sleep disturbance, a bidirectional relationship between depression and sleep disturbance, and significant influence of depression and sleep disturbance on IL-6 and IL-1ß. Compared with control, the findings support the efficacy of IBMS and Qigong interventions in relieving depression and sleep disturbance, and in reducing IL-6 and IL-1ß levels.

Role of Ocular Ultrasonography to Distinguish Papilledema From Pseudopapilledema.

BACKGROUND: We prospectively evaluated the sensitivity and specificity of ocular ultrasonography (OUS) to distinguish papilledema from pseudopapilledema. METHODS: Forty-nine study participants, with optic disc elevation, underwent neuro-ophthalmic evaluation, OUS, fundus photography, and optical coherence tomography (OCT) of the optic nerve head at the initial and follow-up visits (≤6 months apart). Participants were classified as having papilledema if there was a change in optic nerve appearance on fundus photographs, as determined by a masked observer, between initial and follow-up visits ≤6 months apart. OUS was considered positive when the optic nerve sheath width was >3.3 mm and the 30° test was positive. Ocular ultrasonographic findings were correlated in patients who had papilledema vs patients who had pseudopapilledema. In a subanalysis, OUS findings were also correlated with change in peripapillary retinal nerve fiber layer thickness on OCT of the optic nerve head between initial and follow-up visits. RESULTS: OUS was 68% (17/25) sensitive for papilledema and 54% (13/24) specific for pseudopapilledema. When using OCT parameters to define papilledema, the sensitivity of OUS to diagnose papilledema decreased to 62%. Positive OUS correlated with elevated opening pressure on lumbar puncture and with signs of increased intracranial pressure on MRI. CONCLUSION: OUS alone was less sensitive in diagnosing papilledema than previously thought. Therefore, OUS may not be helpful in distinguishing between papilledema and pseudopapilledema.

Comparing the efficacy of integrative body-mind-spirit intervention with cognitive behavioral therapy in patient-caregiver parallel groups for lung cancer patients using a randomized controlled trial.

Purposes/objectives: This paper reports the comparative efficacies of integrative body-mind-spirit intervention (I-BMS) and cognitive behavioral therapy (CBT) in patient-caregiver parallel groups for Chinese patients with lung cancer.Design: Randomized controlled trial (RCT).Methods: One hundred and fifty-seven patient-caregiver dyads with no marked functional impairment were randomized into one of the two interventions with eight weekly patient-caregiver parallel groups. Assessments were conducted at baseline, within one, eight- and sixteen-weeks post-intervention. Effects of treatment group across time were analyzed by multilevel modeling.Findings: CBT led to greater reduction in emotional vulnerability than I-BMS. I-BMS resulted in greater increase in overall QoL and spiritual self-care, and more reduction in depression than CBT. Patients in both interventions experienced improvement in physical, emotional and spiritual, except social, domains of QoL.Conclusion: I-BMS was more efficacious for diverse domains of QoL, and CBT was more effective for emotional well-being, despite the relatively small between-group effect sizes.Implications for psychosocial providers/policy: (1) With the expanding repertoire of psychosocial interventions for families facing lung cancer, it has become imperative to investigate the comparative efficacies of empirically supported and culturally adapted interventions. (2) Our findings show that I-BMS was more effective for diverse domains of QoL, while CBT was more efficacious with emotional well-being, although both interventions led to significant improvements in physical, emotional and spiritual domains of patient QoL. (3) Patient-caregiver parallel groups have been shown to be effective for enhancing QoL of Chinese lung cancer patients. (4) Care professionals are encouraged to dispense interventions based on the idiosyncratic needs and preferences of the patients to maximize the treatment effects.

Stress and psychosomatic symptoms in Chinese adults with sleep complaints: mediation effect of self-compassion.

Although stress has been widely acknowledged to link to psychosomatic dysfunctioning, the underlying mechanism that transmits the impact is not adequately investigated. This study examined self-compassion as a potential mediator that may explain the pathway from stress to depressive and somatic symptoms. Data in the present study were drawn from a baseline survey of 998 Chinese participants who enrolled in an intervention study on sleep disturbance in Hong Kong. Participants completed measures of perceived stress, self-compassion, depressive symptoms, and somatic symptoms. The results showed that stress was associated with depressive symptoms (r = .79, p < .01) and somatic symptoms (r = .47, p < .01). The path analyses showed that low levels of self-compassion mediated the association between stress and psychosomatic symptoms. Our findings provide insight into the pathway how stress affects psychosomatic symptoms. The intervention programs for stress management to improve psychological and physical functioning are recommended to consider self-compassion as a promising component in practice.

Integrative body-mind-spirit intervention for concurrent sleep and mood disturbances: sleep-specific daytime functioning mediates sleep and mood improvements.

Sleep disturbances and depressive symptoms are associated closely with daytime dysfunctions, yet few studies have investigated their temporal relationship in a randomized controlled trial. We investigated the inter-relationships among sleep, depressive symptoms and daytime functioning following an integrative body-mind-spirit (I-BMS) intervention. One hundred and eighty-five participants (mean age 55.28 years, 75.1% female) with co-existing sleep and depressive symptoms were randomized to I-BMS or waiting-list. Daytime functioning variables included the daytime dysfunction items of the Pittsburg Sleep Quality Index (PSQI-day), Somatic Symptom Inventory, Hospital Anxiety Depression Scale and Short Form Health Survey collected at baseline, post-treatment and 3-month follow-up. Sleep and depressive symptoms were measured by the sleep items of the PSQI (PSQI-night) and Center for Epidemiological Studies Depression Scale (excluding the sleep item) (CESD-M). Regression and path analyses were used to understand the role of daytime functioning in sleep and depressive symptoms. We found significant group and time effects on almost all daytime variables and significant group × time interactions on PSQI-day and somatic symptoms. The adjusted regression model showed that CESD-M was associated with all daytime variables. However, PSQI-night was associated only with PSQI-day. Path analyses indicated that PSQI-day bridged PSQI-night and CESD-M in a two-way direction after the I-BMS intervention. The conclusion was that, following I-BMS intervention, improvement in daytime functioning was related predominantly to improvement in depressive symptoms. Night-time sleep related only to daytime dysfunction that was specific to sleep disturbances. Therefore, 'sleep-specific daytime impairment' could be regarded as a major link from night-time sleep to depressive symptoms. More studies are required to understand the concept of 'sleep-specific daytime impairment'.

Dyadic associations between psychological distress and sleep disturbance among Chinese patients with cancer and their spouses.

BACKGROUND: Patients with cancer and their spouses usually both suffer, but the dyadic effects have not been thoroughly investigated. This study examined the dyadic effects of psychological distress on sleep disturbance in Chinese couples affected by cancer. METHODS: Patients with cancer and their spouses (N = 135) participated in this study. The Hospital Anxiety and Depression Scale and Pittsburgh Sleep Quality Index were used to measure anxiety, depression, and sleep disturbance. RESULTS: There were significant patient-spouse associations on anxiety (r = 0.48, P < .01), depression (r = 0.55, P < .01), and sleep disturbance (r = 0.30, P < .01). Analyses using the actor-partner interdependence model showed that anxiety had significant actor effects, rather than partner effects, on sleep disturbance in both patients and their spouses, but depression had both actor and partner effects. In addition to providing evidence for the concordance in distress and sleep disturbance in patients with cancer and their spouses, the findings indicate a mutual influence of depression on sleep disturbance among the couples. CONCLUSIONS: Clinicians and health care providers are suggested to integrate depression management as a component of sleep therapies and involve both patients and their spouses in treatment programs.

Study protocol on comparative effectiveness of mindfulness meditation and qigong on psychophysiological outcomes for patients with colorectal cancer: a randomized controlled trial.

BACKGROUND: Colorectal cancer imposes threats to patients' well-being. Although most physical symptoms can be managed by medication, psychosocial stressors may complicate survival and hamper quality of life. Mindfulness and Qigong, two kinds of mind-body exercise rooted in Eastern health philosophy, has been found effective in symptoms management, improving mental health, and reducing stress. With these potential benefits, a randomized controlled trial (RCT) is planned to investigate the comparative effectiveness of mindfulness and Baduanjin intervention on the bio-psychosocial wellbeing of people with colorectal cancer. METHODS/ DESIGN: A 3-arm RCT with waitlist control design will be used in this study. One hundred eighty-nine participants will be randomized into (i) Mindfulness, (ii) Baduanjin, or (iii) waitlist control groups. Participants in both the Baduanjin and mindfulness groups will receive 8-weeks of specific intervention. All three groups will undergo four assessment phases: (i) at baseline, (ii) at 4-week, (iii) at 8-week (post-intervention), and 6-month post-intervention (maintenance). All participants will be assessed in terms of cancer-related symptoms and symptom distress, mental health status, quality of life, stress level based on physiological marker. DISCUSSION: Based on prior research studies, participants in both the mindfulness and Baduanjn intervention group are expected to have better symptoms management, lower stress level, better mental health, and higher level of quality of life than the control group. This study contributes to better understanding on the common and unique effectiveness of mindfulness and Baduanjin qigong, as such patients and qualified healthcare professionals can select or provide practices which will produce maximum benefits, satisfaction, adherence, and sustainability. TRIAL REGISTRATION: The trial has been registered in the Clinical Trials Centre of the University of Hong Kong ( HKCTR-2198 ) on 08 March 2017.

Dimensionality of the Center for Epidemiologic Studies Depression Scale: an exploratory bi-factor analytic study.

OBJECTIVE: The Center for Epidemiologic Studies Depression Scale (CES-D) is a widely used instrument for measuring depressive symptoms. Though conventional factor analytic evaluations supported the use of four sub-scales for the CES-D, existing studies have yet to adopt the bi-factor analytic approach in psychometric assessment of the 20-item inventory. The present study aimed to apply both confirmatory factor analysis and exploratory bi-factor analysis to evaluate the dimensionality of the CES-D. METHODS: Current scoring practice of the CES-D (single-factor, four-factor, and second-order models) was tested using confirmatory factor analyses in a sample of 706 Chinese persons with insomnia and depressive symptoms. As an alternative, exploratory bi-factor analysis was conducted to examine the utility of the general depression factor and specific factors. RESULTS: Existing measurement models on the CES-D did not provide an adequate model fit to the data in terms of model fit indices and discriminant validity. The bi-factor model revealed a general depression factor that accounted for the majority of the item variance. The three specific factors (somatic symptoms, positive affect, and interpersonal problems) provided little unique information over and above the general factor and plausibly represent a methodological artifact rather than a substantive factor. CONCLUSION: The present study demonstrated empirical support for the bi-factor model as a realistic representation of the underlying structure of the CES-D. Researchers and clinicians are better served by simply using a single measure of depression.

Psychometric properties of the Chalder Fatigue Scale revisited: an exploratory structural equation modeling approach.

OBJECTIVE: Previous validation studies of the Chalder Fatigue Scale (CFS) suffer methodological shortcomings. The present study aimed to re-evaluate its psychometric properties using exploratory structural equation modeling (ESEM). METHODS: A Chinese sample of 1259 community-dwelling residents completed the 11-item Chinese CFS and a variety of health measures (anxiety, depression, exhaustion, sleep disturbance, and quality of life). In addition to traditional confirmatory factor analysis, ESEM was performed to assess the fit of two- and three-factor models using robust maximum likelihood estimation and oblique geomin rotation. Convergent validity of the CFS was examined via associations with five covariates (gender, age, exercise, perceived health, and life event) and the health measures in the ESEM model. RESULTS: The ESEM models displayed a superior fit to confirmatory factor models. The three-factor ESEM model showed a satisfactory model fit to the data but not for the two-factor model. The three factors were physical fatigue (three items, α = .800), low energy (four items, α = .821), and mental fatigue (four items, α = .861). The factors exhibited convergent validity with the model covariates and health measures. CONCLUSION: The results demonstrate the satisfactory reliability and convergent validity for the three-factor structure of the CFS as a valid measure of fatigue symptoms in the general population. Future psychometric studies could adopt the ESEM approach as a practical alternative to traditional confirmatory factor analysis.

Managing stress and anxiety through qigong exercise in healthy adults: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: An increasing number of studies have documented the effectiveness of qigong exercise in helping people reduce psychological stress and anxiety, but there is a scarcity of systematic reviews evaluating evidence from randomized controlled trials (RCTs) conducted among healthy subjects. METHODS: Thirteen databases were searched for RCTs from their inception through June 2013. Effects of qigong exercise were pooled across trials. Standardized mean differences (SMDs) were calculated for the pooled effects. Heterogeneity was assessed using the I2 test. The risk of bias was assessed using the Cochrane criteria. RESULTS: Seven RCTs met the inclusion criteria. Two RCTs suggested that qigong exercise immediately relieved anxiety among healthy adults, compared to lecture attendance and structured movements only. Four RCTs suggested qigong exercise relieved anxiety (pooled SMD = -0.75; 95% CI, -1.11 to -0.40), and three RCTs suggested that qigong exercise reduced stress (pooled SMD = -0.88; 95% CI, -1.22 to -0.55) among healthy subjects following one to three months of qigong practice, compared to wait-list controls. CONCLUSIONS: The available evidence suggests that qigong exercise reduces stress and anxiety in healthy adults. However, given the limited number of RCTs and their methodological flaws, further rigorously designed RCTs are needed.

Update on How to Approach a Patient with Locked-In Syndrome and Their Communication Ability.

Locked-in syndrome (LIS) is a rare and challenging condition that results in tetraplegia and cranial nerve paralysis while maintaining consciousness and variable cognitive function. Once acute management is completed, it is important to work with the patient on developing a plan to maintain and improve their quality of life (QOL). A key component towards increasing or maintaining QOL within this population involves the establishment of a functional communication system. Evaluating cognition in patients with LIS is vital for evaluating patients' communication needs along with physical rehabilitation to maximize their QOL. In the past decade or so, there has been an increase in research surrounding brain-computer interfaces to improve communication abilities for paralyzed patients. This article provides an update on the available technology and the protocol for finding the best way for patients with this condition to communicate. This article aims to increase knowledge of how to enhance and manage communication among LIS patients.

A self-administered moxibustion-cum-massage intervention for older adults with chronic pain in the community: A randomized controlled trial.

OBJECTIVES: To determine the effectiveness of a simple, self-administrable moxibustion-cum-massage intervention for relieving chronic pain and improving psychological well-being for older adults in the community. DESIGN: A randomized controlled trial. SETTING: Seventy-eight participants with chronic pain were randomly assigned to the intervention and waitlist control groups. INTERVENTIONS: Participants received two moxa sticks a day to use the moxibustion-cum-massage procedure with the help of trained volunteers or caregivers for five consecutive days. MAIN OUTCOME MEASURES: Participates' pain level, sleep quality, depression and subjective well-being were measured before the intervention (T0), immediately after the intervention (T1), and one week after the intervention (T2). RESULTS: Repeated measures ANOVA revealed a significant group × time interaction effect in subjective well-being with a medium effect size. Regarding within-group effects in the intervention group at post-intervention (T1), the subjective pain level was significantly reduced with a small effect size, while sleep quality and depression significantly improved with large effect sizes. The control group showed no significant within-group effects in these variables. Maintenance effects at follow-up (T2) were not significant. CONCLUSION: Despite the short intervention timeframe of five days, the study revealed preliminary evidence that the moxibustion-cum-massage intervention can be an effective, self-administrable pain relief regime for older adults. A longer period of intervention time is suggested for future studies.

Effects of Ving Tsun sticking-hand training on lower limb sensorimotor performance among community-dwelling middle-aged and older adults: a randomized controlled trial.

BACKGROUND: To explore the effects of Ving Tsun (VT) sticking-hand training on knee joint proprioception and leg muscular performance among community-dwelling middle-aged and older adults. METHODS: Thirty-three middle-aged and older adults were randomly assigned to either the VT or control group. The VT group received sticking-hand training twice/week for 3 months. Data were collected before and after the intervention period. The primary outcome was knee joint repositioning error, which was measured using knee joint active repositioning tests. The secondary outcomes included the maximum muscle strength and time to maximum muscle strength of the major leg muscles. RESULTS: No significant group, time, or group-by-time interaction effects were found for the knee joint repositioning error (p > 0.05). The maximum muscle strength of the knee flexors increased over time in the VT group only (p = 0.038). In addition, the time to maximum muscle strength in the hip extensors and flexors increased over time in both groups (p < 0.05). For the knee extensors and flexors, the time to maximum muscle strength increased in the control (p = 0.027) and VT (p = 0.019) groups, respectively, over time. CONCLUSIONS: VT sticking-hand training could improve the maximum muscle strength of the knee flexors but could not attenuate the age-related deterioration in leg muscle contraction speed nor improve knee joint proprioception among community-dwelling middle-aged and older adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT03318289. Registered on 23 October 2017.

A randomized controlled trial of qigong exercise on fatigue symptoms, functioning, and telomerase activity in persons with chronic fatigue or chronic fatigue syndrome.

BACKGROUND: Chronic fatigue is common in the general population. Complementary therapies are often used by patients with chronic fatigue or chronic fatigue syndrome to manage their symptoms. PURPOSE: This study aimed to assess the effect of a 4-month qigong intervention program among patients with chronic fatigue or chronic fatigue syndrome. METHODS: Sixty-four participants were randomly assigned to either an intervention group or a wait list control group. Outcome measures included fatigue symptoms, physical functioning, mental functioning, and telomerase activity. RESULTS: Fatigue symptoms and mental functioning were significantly improved in the qigong group compared to controls. Telomerase activity increased in the qigong group from 0.102 to 0.178 arbitrary units (p < 0.05). The change was statistically significant when compared to the control group (p < 0.05). CONCLUSION: Qigong exercise may be used as an alternative and complementary therapy or rehabilitative program for chronic fatigue and chronic fatigue syndrome.

A systematic review of the effectiveness of qigong exercise in supportive cancer care.

PURPOSE: Qigong as a complementary and alternative modality of traditional Chinese medicine is often used by cancer patients to manage their symptoms. The aim of this systematic review is to critically evaluate the effectiveness of qigong exercise in cancer care. METHODS: Thirteen databases were searched from their inceptions through November 2010. All controlled clinical trials of qigong exercise among cancer patients were included. The strength of the evidence was evaluated for all included studies using the Oxford Centre for Evidence-based Medicine Levels of Evidence. The validity of randomized controlled trials (RCTs) was also evaluated using the Jadad Scale. RESULTS: Twenty-three studies including eight RCTs and fifteen non-randomized controlled clinical trials (CCTs) were identified. The effects of qigong on physical and psychosocial outcomes were examined in 14 studies and the effects on biomedical outcomes were examined in 15 studies. For physical and psychosocial outcomes, it is difficult to draw a conclusion due to heterogeneity of outcome measures and variability of the results in the included studies. Among reviewed studies on biomedical outcomes, a consistent tendency appears to emerge which suggests that the patients treated with qigong exercise in combination with conventional methods had significant improvement in immune function than the patients treated with conventional methods alone. CONCLUSIONS: Due to high risk of bias and methodological problems in the majority of included studies, it is still too early to draw conclusive statements. Further vigorously designed large-scale RCTs with validated outcome measures are needed.

Prescribed Water Intake in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Arginine vasopressin promotes kidney cyst growth in autosomal dominant polycystic kidney disease (ADPKD). Increased water intake reduces arginine vasopressin and urine osmolality and may slow kidney cyst growth. METHODS: In this randomized controlled 3-year clinical trial, we randomly assigned adults with ADPKD who had a height-corrected total kidney volume in Mayo imaging subclass categories 1B to 1E and an estimated glomerular filtration rate of 30 ml/min/1.73 m2 or greater to (1) water intake prescribed to reduce 24-hour urine osmolality to 270 mOsmol/kg or less or (2) ad libitum water intake irrespective of 24-hour urine osmolality. The primary end point was the percentage annualized rate of change in height-corrected total kidney volume. RESULTS: A total of 184 patients participated in either the ad libitum water intake group (n=92) or the prescribed water intake group (n=92). Over 3 years, there was no difference in the annualized rate of change in height-corrected total kidney volume between the ad libitum (7.8% per year; 95% confidence interval [CI], 6.6 to 9.0) and prescribed (6.8% per year; 95% CI, 5.8 to 7.7) water intake groups (mean difference, −0.97% per year; 95% CI, −2.37 to 0.44; P=0.18). The difference in mean 24-hour urine osmolality between the ad libitum and prescribed water intake groups was −91 mOsmol/kg (95% CI, −127 to −54 mOsmol/kg), with 52.3% of patients achieving adherence to the target 24-hour urine osmolality and no reduction in serum copeptin over 3 years. The frequency of adverse events was similar between groups. CONCLUSIONS: For patients with ADPKD, prescribed water intake was not associated with excess adverse events and achieved the target 24-hour urine osmolality for half of the patients but did not reduce copeptin or slow the growth of total kidney volume over 3 years compared with ad libitum water intake. (Funded by the National Health and Medical Research Council of Australia [grant GNT1138533], Danone Research, PKD Australia, the University of Sydney, and the Westmead Medical Research Foundation; Australian New Zealand Clinical Trials Registry number, ACTRN12614001216606).

Physical activity, confidence and quality of life among cancer patient-carer dyads.

BACKGROUND: Physical activity (PA) has been positively associated with health-related quality of life (HRQoL) among cancer patients and family caregivers. However, there has been no relevant research for patient-caregiver dyads. METHODS: Path analysis, based on the actor-partner interdependence model (APIM), was used to examine the relationship between physical activity and health-related quality of life and explore the mediating role of emotional distress in 233 dyads. RESULTS: In both patients and caregivers, physical activity had a direct positive effect on physical quality of life (QoL) but not on mental. There was a significant indirect effect of physical activity on health-related quality of life via emotional distress for both dyad members. Patients' and caregivers' confidence in fighting cancer was negatively associated with their own emotional distress. Caregivers' confidence in fighting cancer was positively associated with their physical activity and also negatively associated with patients' emotional distress. CONCLUSIONS: Physical activity may be considered as a possible behavioral and rehabilitation strategy for improving health-related quality of life in patient-caregiver dyads and reducing negative symptoms. Future research and intervention may consider cancer patient-family caregiver dyad as a unit of care.

The Counterintuitive Relationship between Telomerase Activity and Childhood Emotional Abuse: Culture and Complexity.

BACKGROUND: A burgeoning literature has found relationships between telomere length, telomerase activity, and human health and longevity. Although some research links a history of childhood adversity with shortened telomere length, our review found no prior research on the relationship between child maltreatment history and telomerase activity in adulthood. We hypothesized a negative relationship between child maltreatment and telomerase activity and hypothesized that the association would be moderated by sex. METHODS: These relationships were tested on a sample of 262 Hong Kong Chinese adults (200 females versus 62 males) with mild to moderate depression. RESULTS: Counterintuitively, emotional abuse was positively associated with telomerase activity, while other maltreatment types were non-significant. The positive relationship between emotional abuse and telomerase activity was significantly moderated by the sex of the participant. CONCLUSIONS: We advance two possible explanations for this finding (1) a culturally informed resilience explanation and (2) a homeostatic complexity explanation. The two explanations are not mutually exclusive. This trial is registered under Hong Kong Clinical Trial Register number HKCTR-1929. SIGNIFICANCE STATEMENT: Emotional abuse was significantly positively associated with telomerase activity. There are at least two non-mutually exclusive explanations for the findings. Simply put, either (1) in the cultural context of Hong Kong emotional abuse was not a risk factor, and/or (2) the conceptualization of telomerase activity as a straightforward indicator of longevity is overly simplistic. The first story we might term a "resilience explanation" while the second we might call a "homeostatic complexity" story.

Repurposing hyperpolarization-activated cyclic nucleotide-gated channels as a novel therapy for breast cancer.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are members of the voltage-gated cation channel family known to be expressed in the heart and central nervous system. Ivabradine, a small molecule HCN channel-blocker, is FDA-approved for clinical use as a heart rate-reducing agent. We found that HCN2 and HCN3 are overexpressed in breast cancer cells compared with normal breast epithelia, and the high expression of HCN2 and HCN3 is associated with poorer survival in breast cancer patients. Inhibition of HCN by Ivabradine or by RNAi, aborted breast cancer cell proliferation in vitro and suppressed tumour growth in patient-derived tumour xenograft models established from triple-negative breast cancer (TNBC) tissues, with no evident side-effects on the mice. Transcriptome-wide analysis showed enrichment for cholesterol metabolism and biosynthesis as well as lipid metabolism pathways associated with ER-stress following Ivabradine treatment. Mechanistic studies confirmed that HCN inhibition leads to ER-stress, in part due to disturbed Ca2+ homeostasis, which subsequently triggered the apoptosis cascade. More importantly, we investigated the synergistic effect of Ivabradine and paclitaxel on TNBC and confirmed that both drugs acted synergistically in vitro through ER-stress to amplify signals for caspase activation. Combination therapy could suppress tumour growth of xenografts at much lower doses for both drugs. In summary, our study identified a new molecular target with potential for being developed into targeted therapy, providing scientific grounds for initiating clinical trials for a new treatment regimen of combining HCN inhibition with chemotherapy.