Diet and exercise advice and referrals for cancer survivors: An integrative review of medical and nursing perspectives

Purpose: To examine the perspectives of medical and nursing health professionals concerning their roles and responsibilities in providing dietary and exercise advice to cancer survivors, and referrals to allied health professionals. Methods: An integrative review. PubMed, CINAHL, PsycINFO, Embase, Web of Science databases, and bibliographies of relevant studies were searched from December 2011 to June 2021. All studies were eligible for inclusion. The Mixed-Methods Appraisal Tool (MMAT) was used to critically appraise included studies. Data were extracted and synthesised regarding the perspectives of medical and nursing health professionals on their roles, responsibilities, barriers, and facilitators. Results: Twenty-one studies involving 3401 medical and nursing health professionals and 264 cancer survivors of diverse cancer types were included. Ten quantitative, nine qualitative, and two mixed-methods studies were eligible. All included studies met at least 80% of the quality criteria in the MMAT. Major findings include the following: (1) medical and nursing health professionals were unclear on their roles in providing dietary and exercise advice to cancer survivors but agreed they play a key role in referrals to dietitians and exercise professionals; (2) most cancer survivors valued the involvement of their general practitioner when receiving dietary and exercise advice. Conclusion: Although medical and nursing health professionals understand that referrals to allied health professionals form part of their role, there is a lack of clarity regarding their roles to provide dietary and exercise advice to cancer survivors. Future studies should address barriers and facilitators of dietary and exercise advice and referral by medical and nursing health professionals

Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy

Parkin, an E3 ubiquitin ligase implicated in Parkinson's disease, promotes degradation of dysfunctional mitochondria by autophagy. Using proteomic and cellular approaches, we show that upon translocation to mitochondria, Parkin activates the ubiquitin–proteasome system (UPS) for widespread degradation of outer membrane proteins. This is evidenced by an increase in K48-linked polyubiquitin on mitochondria, recruitment of the 26S proteasome and rapid degradation of multiple outer membrane proteins. The degradation of proteins by the UPS occurs independently of the autophagy pathway, and inhibition of the 26S proteasome completely abrogates Parkin-mediated mitophagy in HeLa, SH-SY5Y and mouse cells. Although the mitofusins Mfn1 and Mfn2 are rapid degradation targets of Parkin, we find that degradation of additional targets is essential for mitophagy. These results indicate that remodeling of the mitochondrial outer membrane proteome is important for mitophagy, and reveal a causal link between the UPS and autophagy, the major pathways for degradation of intracellular substrates

Effect of Intravenous Golimumab on Fatigue and the Relationship with Clinical Response in Adults with Active Ankylosing Spondylitis in the Phase 3 GO-ALIVE Study

INTRODUCTION: We studied the effect of intravenous (IV)-golimumab on fatigue and the association of fatigue improvement with clinical response post hoc in adults with active ankylosing spondylitis (AS) in the GO-ALIVE trial. METHODS: Patients were randomized to IV-golimumab 2 mg/kg (N = 105) at week (W) 0, W4, then every 8 W (Q8W) or placebo (N = 103) at W0, W4, W12, crossover to IV-golimumab 2 mg/kg at W16, W20, then Q8W through W52. Fatigue measures included Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question #1 (fatigue; 0 [none], 10 [worst]; decrease indicates improvement) and 36-Item Short Form Health Survey (SF-36) vitality subscale (0 [worst], 100 [best]; increase indicates improvement). Minimum clinically important difference is ≥ 1 for BASDAI-fatigue and ≥ 5 for SF-36 vitality. GO-ALIVE primary endpoint was Assessment of SpondyloArthritis international Society ≥ 20% improvement criteria (ASAS20). Other clinical outcomes assessed included other ASAS responses, Ankylosing Spondylitis Disease Activity Score, and Bath Ankylosing Spondylitis Functional Index score. The distribution-based minimally important differences (MIDs) were determined for BASDAI-fatigue and SF-36 vitality. The relationship between improvement in fatigue and clinical outcomes was assessed via multivariable logistic regression. RESULTS: Mean changes in BASDAI-fatigue/SF-36 vitality scores were greater with IV-golimumab versus placebo at W16 (- 2.74/8.46 versus - 0.73/2.08, both nominal p ≤ 0.003); by W52 (after crossover), differences between groups narrowed (- 3.18/9.39 versus - 3.07/9.17). BASDAI-fatigue/SF-36 vitality MIDs were achieved by greater proportions of IV-golimumab-treated versus placebo-treated patients at W16 (75.2%/71.4% versus 42.7%/35.0%). A one-point/five-point improvement in BASDAI-fatigue/SF-36 vitality scores at W16 increased likelihood of achieving ASAS20 (odds ratios [95% confidence intervals]: 3.15 [2.21, 4.50] and 2.10 [1.62, 2.71], respectively) and ASAS40 (3.04 [2.15, 4.28] and 2.24 [1.68, 3.00], respectively) responses at W16; concurrent improvements and clinical response at W52 were consistent. A one-point/five-point improvement in BASDAI-fatigue/SF-36 vitality scores at W16 predicted increased likelihood of achieving ASAS20 (1.62 [1.35, 1.95] and 1.52 [1.25, 1.86], respectively) and ASAS40 (1.62 [1.37, 1.92] and 1.44 [1.20, 1.73], respectively) responses at W52. CONCLUSIONS: IV-golimumab provided important and sustained fatigue improvement in patients with AS that positively associated with achieving clinical response. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02186873

Binding of Soluble Yeast β-Glucan to Human Neutrophils and Monocytes is Complement-Dependent

The immunomodulatory properties of yeast β-1,3/1,6 glucans are mediated through their ability to be recognized by human innate immune cells. While several studies have investigated binding of opsonized and unopsonized particulate β-glucans to human immune cells mainly via complement receptor 3 (CR3) or Dectin-1, few have focused on understanding the binding characteristics of soluble β-glucans. Using a well-characterized, pharmaceutical grade, soluble yeast β-glucan, this study evaluated and characterized the binding of soluble β-glucan to human neutrophils and monocytes. The results demonstrated that soluble β-glucan bound to both human neutrophils and monocytes in a concentration-dependent and receptor-specific manner. Antibodies blocking the CD11b and CD18 chains of CR3 significantly inhibited binding to both cell types, establishing CR3 as the key receptor recognizing the soluble β-glucan in these cells. Binding of soluble β-glucan to human neutrophils and monocytes required serum and was also dependent on incubation time and temperature, strongly suggesting that binding was complement-mediated. Indeed, binding was reduced in heat-inactivated serum, or in serum treated with methylamine or in serum reacted with the C3-specific inhibitor compstatin. Opsonization of soluble β-glucan was demonstrated by detection of iC3b, the complement opsonin on β-glucan-bound cells, as well as by the direct binding of iC3b to β-glucan in the absence of cells. Binding of β-glucan to cells was partially inhibited by blockade of the alternative pathway of complement, suggesting that the C3 activation amplification step mediated by this pathway also contributed to binding

AKL1, a botanical mixture for the treatment of asthma: a randomised, double-blind, placebo-controlled, cross-over study

BACKGROUND: Despite effective treatments, asthma outcomes remain suboptimal. Interest exists in complementary therapies, particularly in herbal remedies for asthma treatment, currently with inconclusive evidence of efficacy. The encapsulated botanical mixture AKL1 has anecdotal evidence of effectiveness in asthma. METHODS: We performed a randomised controlled cross over study comparing the effectiveness of AKL1 with indistinguishable placebo as add-on therapy in patients uncontrolled on standard asthma treatment. Thirty two adult asthmatics completed a 36 week trial consisting of a 4 week single blind run in period, during which placebo was added to usual treatment, a 12 week double blind active phase in which subjects received AKL1 or placebo, a single blind 8 week washout period receiving placebo and a final 12 week double blind cross-over active treatment phase. Daily diaries were kept of peak expiratory flow and symptoms, and spirometry, validated symptom and health status questionnaire scores and adverse events were monitored at study visits. Paired T tests were used to compare the effects of placebo and AKL1 on outcomes. Changes in outcome measures over treatment phases are presented as means and 95% confidence intervals (CI) of means. RESULTS: No significant differences in lung function (active-placebo) were found (Forced Expiratory Volume in 1 second: mean difference [95% CI] = 0.01 [-0.12 to 0.14] L, p = 0.9. Peak Expiratory Flow: -4.08 [-35.03 to 26.89]. L/min, p = 0.8). Trends to clinical improvements favouring active treatment were however consistently seen in the patient-centered outcomes: Asthma Control Questionnaire mean difference (active – placebo) [95% CI] = -0.35 [-0.78 to 0.07], p = 0.10, Asthma Quality of Life Questionnaire mean difference 0.42 [-0.08 to 0.93], p = 0.09, Leicester Cough Questionnaire mean difference 0.49, [-0.18 to 1.16], p = 0.15. Nine exacerbations occurred during placebo treatment and five whilst on AKL1. No significant adverse events were noted. CONCLUSION: AKL1 treatment was well tolerated. No significant improvements in lung function, symptoms, or quality of life were seen, although consistent trends were seen to improvements in patient-centered outcomes. Further studies are needed

Effects of age, education and gender in the Consortium to Establish a Registry for the Alzheimer's Disease (CERAD)-Neuropsychological Assessment Battery for Cantonese-speaking Chinese elders

Background: The Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-NAB) offers information on the clinical diagnosis of Alzheimer's disease (AD) and gives a profile of cognitive functioning. This study explores the effects of age, education and gender on participants' performance on eight subtests in the Chinese-Cantonese version of the CERAD-NAB. Methods: The original English version of the CERAD-NAB was translated and content-validated into a Chinese-Cantonese version to suit the Hong Kong Chinese population. The battery was administered to 187 healthy volunteers aged 60 to 94 years. Participants were excluded if they had neurological, medical or psychiatric disorders (including dementia). Stepwise multiple linear regression analyses were performed to assess the relative contribution of the demographic variables to the scores on each subtest. Results: The Cantonese version of CERAD-NAB was shown to have good content validity and excellent inter-rater reliability. Stepwise multiple regression analyses revealed that performances on seven and four out of eight subtests in the CERAD-NAB were significantly influenced by education level and age, respectively. Age and education had significant effects on participants' performance on many tests. Gender also showed a significant effect on one subtest. Conclusions: The preliminary data will serve as an initial phase for clinical interpretation of the CERAD-NAB for Cantonese-speaking Chinese elders

What the Public Was Saying about the H1N1 Vaccine: Perceptions and Issues Discussed in On-Line Comments during the 2009 H1N1 Pandemic

During the 2009 H1N1 pandemic, a vaccine was made available to all Canadians. Despite efforts to promote vaccination, the public's intent to vaccinate remained low. In order to better understand the public's resistance to getting vaccinated, this study addressed factors that influenced the public's decision making about uptake. To do this, we used a relatively novel source of qualitative data – comments posted on-line in response to news articles on a particular topic. This study analysed 1,796 comments posted in response to 12 articles dealing with H1N1 vaccine on websites of three major Canadian news sources. Articles were selected based on topic and number of comments. A second objective was to assess the extent to which on-line comments can be used as a reliable data source to capture public attitudes during a health crisis. The following seven themes were mentioned in at least 5% of the comments (% indicates the percentage of comments that included the theme): fear of H1N1 (18.8%); responsibility of media (17.8%); government competency (17.7%); government trustworthiness (10.7%); fear of H1N1 vaccine (8.1%); pharmaceutical companies (7.6%); and personal protective measures (5.8%). It is assumed that the more frequently a theme was mentioned, the more that theme influenced decision making about vaccination. These key themes for the public were often not aligned with the issues and information officials perceived, and conveyed, as relevant in the decision making process. The main themes from the comments were consistent with results from surveys and focus groups addressing similar issues, which suggest that on-line comments do provide a reliable source of qualitative data on attitudes and perceptions of issues that emerge in a health crisis. The insights derived from the comments can contribute to improved communication and policy decisions about vaccination in health crises that incorporate the public's views

Transcriptomic Approaches to Modelling Long Term Changes in Human Cardiac Electrophysiology

Slow changes in the activity of the heart occur with time scales from days through to decades, and may in part result from changes in cardiomyocyte properties. The cellular mechanisms of the cardiomyocyte action potential have time scales from < ms to hundreds of ms. Although the quantitative dynamic relations between mRNA transcription, protein synthesis, trafficking, recycling, and membrane protein activity are unclear, mRNA-Seq can be used to inform parameters in cell excitation equations. We use such transcriptomic data from a non-human primate to scale maximal conductances in the O’Hara-Rudy (2011) family of human ventricular cell models, and to predict diurnal changes in human ventricular action potential durations. These are related to circadian changes in the incidence of sudden cardiac deaths. Transcriptomic analysis of human fetal hearts between 9 and 16 weeks gestational age is beginning to be used to inform ventricular cell and tissue models of the electrophysiology of the developing fetal heart

Interaction of hope and optimism with anxiety and depression in a specific group of cancer survivors: a preliminary study

<p>Abstract</p> <p>Background</p> <p>Anxiety and depression have been identified as a common psychological distress faced by the majority of cancer patients. With the increasing number of cancer cases, increasing demands will be placed on health systems to address effective psychosocial care and therapy. The objective of this study was to assess the possible role of hope and optimism on anxiety and depression. We also wanted to investigate if there is a specific component of hope that could play a role in buffering anxiety and depression amongst cancer patients.</p> <p>Methods</p> <p>A retrospective cross sectional study was conducted in the outpatient station of the Oral and Maxillofacial Surgery at the University of Hong Kong, Hong Kong SAR, PR-China. Fifty patients successfully treated for OC cancer were recruited after their informed consents had been obtained during the review clinic. During their regular follow-up controls in the outpatient clinic the patients compiled the hospital anxiety and depression scale (HADS), hope scale (HS) and the life orientation scale-revised (LOT-R).</p> <p>Results</p> <p>Hope was negatively correlated with depression (<it>r </it>= -.55, <it>p </it>< .001) and anxiety (r = -.38, <it>p </it>< .05). Similar pattern was found between optimism and the latter adjustment outcomes (depression: <it>r </it>= -.55, <it>p </it>< .001; anxiety: <it>r </it>= -.35, <it>p </it>< .05). Regression analyses indentified that both hope and optimism were significant predictors of depression. Hope and optimism had equal association with depression (hope: <it>β </it>= .40 versus optimism: <it>β </it>= .38). Hope and optimism together were significantly predictive of anxiety, whereas neither hope nor optimism alone was significant individual predictors of anxiety.</p> <p>Conclusions</p> <p>Hope and optimism both negatively correlated with patients' level of anxiety and depression. Besides theoretical implications, this study brings forward relevant findings related to developing specific clinical psychological care in the field of oncology that to date has not been researched specifically in the field of oncology. The results of this study will help guide the direction of future prospective studies in the field of oncology. This will contribute significantly to increasing patients quality of life as well enabling health care facilities to provide all cancer patients a more holistic cancer care.</p

Targeting enhancer switching overcomes non-genetic drug resistance in acute myeloid leukaemia.

Non-genetic drug resistance is increasingly recognised in various cancers. Molecular insights into this process are lacking and it is unknown whether stable non-genetic resistance can be overcome. Using single cell RNA-sequencing of paired drug naïve and resistant AML patient samples and cellular barcoding in a unique mouse model of non-genetic resistance, here we demonstrate that transcriptional plasticity drives stable epigenetic resistance. With a CRISPR-Cas9 screen we identify regulators of enhancer function as important modulators of the resistant cell state. We show that inhibition of Lsd1 (Kdm1a) is able to overcome stable epigenetic resistance by facilitating the binding of the pioneer factor, Pu.1 and cofactor, Irf8, to nucleate new enhancers that regulate the expression of key survival genes. This enhancer switching results in the re-distribution of transcriptional co-activators, including Brd4, and provides the opportunity to disable their activity and overcome epigenetic resistance. Together these findings highlight key principles to help counteract non-genetic drug resistance