The associates of anxiety among lung cancer patients: Dehydroepiandrosterone (DHEA) as a potential biomarker.

OBJECTIVE: Anxiety is a prevalent comorbidity in lung cancer (LC) patients associated with a decline in quality of life. Dehydroepiandrosterone (DHEA), a neuroactive steroid, levels rise in response to stress. Prior research on the association between DHEA and anxiety has yielded contradictory results and no study has investigated this association in LC patients. METHODS: A total of 213 patients with LC were recruited from a general hospital. Data on demographic and cancer-related variables were collected. Using the Chinese version of the Hospital Anxiety and Depression Scale (HADS), the degree of anxiety was determined. Cortisol, DHEA, and Dehydroepiandrosterone sulfate (DHEA-S) levels in saliva were measured. Adjusting for confounding variables, a multivariate regression analysis was conducted. RESULTS: 147 men and 66 women comprised our group with an average age of 63.75 years. After accounting for demographic and treatment-related factors, anxiety levels were significantly correlated with, post-traumatic stress symptoms (PTSSs) (ß = 0.332, p < 0.001) and fatigue (ß = 0.247, p = 0.02). Association between anxiety and three factors, including DHEA, PTSSs, and fatigue, was observed in patients with advanced cancer stages (III and IV) (DHEA ß = 0.319, p = 0.004; PTSS ß = 0.396, p = 0.001; fatigue ß = 0.289, p = 0.027) and those undergoing chemotherapy (DHEA ß = 0.346, p = 0.001; PTSS ß = 0.407, p = 0.001; fatigue ß = 0.326, p = 0.011). CONCLUSIONS: The association between anxiety and DHEA remained positive in advanced cancer stages and chemotherapy patients. Further study is necessary to determine whether DHEA is a potential biomarker of anxiety in LC patients.

Adapting the serious illness conversation guide for unhoused older adults: a rapid qualitative study.

BACKGROUND: Older adults experiencing homelessness (OAEH) age quickly and die earlier than their housed counterparts. Illness-related decisions are best guided by patients' values, but healthcare and homelessness service providers need support in facilitating these discussions. The Serious Illness Conversation Guide (SICG) is a communication tool to guide discussions but has not yet been adapted for OAEH. METHODS: We aimed to adapt the SICG for use with OAEH by nurses, social workers, and other homelessness service providers. We conducted semi-structured interviews with homelessness service providers and cognitive interviews with OAEH using the SICG. Service providers included nurses, social workers, or others working in homeless settings. OAEH were at least 50 years old and diagnosed with a serious illness. Interviews were conducted and audio recorded in shelters, transitional housing, a hospital, public spaces, and over Zoom. The research team reviewed transcripts, identifying common themes across transcripts and applying analytic notetaking. We summarized transcripts from each participant group, applying rapid qualitative analysis. For OAEH, data that referenced proposed adaptations or feedback about the SICG tool were grouped into two domains: "SICG interpretation" and "SICG feedback". For providers, we used domains from the Toolkit of Adaptation Approaches: "collaborative working", "team", "endorsement", "materials", "messages", and "delivery". Summaries were grouped into matrices to help visualize themes to inform adaptations. The adapted guide was then reviewed by expert palliative care clinicians for further refinement. RESULTS: The final sample included 11 OAEH (45% Black, 61 ± 7 years old) and 10 providers (80% White, 8.9 ± years practice). Adaptation themes included changing words and phrases to (1) increase transparency about the purpose of the conversation, (2) promote OAEH autonomy and empowerment, (3) align with nurses' and social workers' scope of practice regarding facilitating diagnostic and prognostic awareness, and (4) be sensitive to the realities of fragmented healthcare. Responses also revealed training and implementation considerations. CONCLUSIONS: The adapted SICG is a promising clinical tool to aid in the delivery of serious illness conversations with OAEH. Future research should use this updated guide for implementation planning. Additional adaptations may be dependent on specific settings where the SICG will be delivered.

Depressive Symptoms and Sleep Quality Mediate the Relationship Between Race and Quality of Life Among Patients With Heart Failure: A Serial Multiple Mediator Model.

BACKGROUND: Black patients with heart failure (HF) report worse quality of life (QoL) than White patients. Few investigators have examined mediators of the association between race and QoL, but depressive symptoms and sleep quality are associated with QoL. OBJECTIVE: The aim of this study was to determine whether depressive symptoms and sleep quality are mediators of the relationship between race and QoL among patients with HF. METHODS: This was a cross-sectional study. We included 271 outpatients with HF. Self-reported race (White/Black), depressive symptoms (Patient Health Questionnaire), sleep quality (Pittsburgh Sleep Quality Index), and QoL (Kansas City Cardiomyopathy Questionnaire) were collected at baseline. A serial multiple mediator analysis was conducted using the PROCESS macro for SPSS. RESULTS: Ninety-six patients (35.4%) were Black. Black participants reported higher levels of depressive symptoms and poorer sleep quality than White participants. Race was not directly associated with QoL but indirectly associated with QoL through depressive symptoms and poorer sleep quality. Because of higher levels of depressive symptoms and poorer sleep quality, Black participants reported poorer QoL than White participants. CONCLUSIONS: Depressive symptoms and sleep quality together mediated the relationship between race and QoL. These findings suggest that screening for depressive symptoms and sleep quality could identify patients at risk for poor QoL, especially in Black patients.

Perceived Control, Functional Status, Depressive Symptoms, and Anxiety: Mediating and Moderating Influences on Health-Related Quality of Life in Patients With Heart Failure.

BACKGROUND: Health-related quality of life (HRQoL) is poor in patients with heart failure. Psychological (ie, depressive symptoms [DS], anxiety, and perceived control) and physical (ie, functional status) factors are associated with HRQoL. The dynamic relationships among these variables and their impact on HRQoL remain unclear, limiting the ability to design effective interventions. PURPOSE: Our aim was to evaluate a moderated mediation model, in which the association between perceived control and HRQoL was hypothesized to be mediated by DS and anxiety in the presence of a moderator, functional status. METHODS: Patients (N = 426) with heart failure completed the Control Attitudes Scale-Revised to measure perceived control, Duke Activity Status Index for functional status, Patient Health Questionnaire-9 for DS, Brief Symptom Inventory for anxiety, and Minnesota Living with Heart Failure Questionnaire for HRQoL. We performed a moderated parallel mediation analysis. RESULTS: Higher levels of perceived control were associated with better HRQoL through lower levels of anxiety and DS in the presence of functional status (index of moderated mediation for DS, b = 0.029; 95% confidence interval, 0.016-0.045; for anxiety: b = 0.009, 95% confidence interval, 0.002-0.018). The effect of perceived control on psychological symptoms was stronger at low and moderate functional statuses; however, this effect diminished with increasing functional status. CONCLUSION: Functional status moderated the indirect effects of perceived control on HRQoL through DS and anxiety in patients with heart failure. Efforts to improve HRQoL by targeting perceived control may be more effective when considering DS and anxiety in patients with low to moderate levels of functional status.

Dietary Antioxidant Insufficiency Is Associated With Increased Inflammatory Markers and Poorer Health-Related Quality of Life in Patients With Heart Failure.

BACKGROUND: Antioxidant insufficiency, elevated inflammatory markers, and poor health-related quality of life (HRQOL) are prevalent in patients with heart failure (HF). OBJECTIVE: The objective of this study was to examine the associations among dietary antioxidant intake, inflammatory markers, and HRQOL in patients with HF. METHODS: This was a secondary analysis of 265 patients with HF who completed a 4-day food diary. We assessed intake of 10 antioxidants: alpha carotene, beta carotene, beta cryptoxanthin, lutein, zeaxanthin, lycopene, vitamins C and E, zinc, and selenium. Antioxidant insufficiency was reflected by a measured level for each antioxidant that was below the estimate average requirement or lower than median for antioxidants without an estimate average requirement. Inflammatory markers including serum C-reactive protein, cytokines (interleukins 6 and 10), tumor necrosis factor-alpha, and soluble receptors (sTNFR1 and sTNFR2) were assessed with enzyme immunoassay. Health-related quality of life was measured using the Minnesota Living with Heart Failure at 12 months. RESULTS: Dietary antioxidant insufficiency predicted C-reactive protein (ß = 0.135, P = .032) and interleukin 10 (ß = -.155, P = .027). Patients with higher antioxidant insufficiency had higher C-reactive protein and lower interleukin 10. Both antioxidant insufficiency (ß = 0.13, P = .049) and higher C-reactive protein (ß = 0.16, P = .019) were independently associated with poorer HRQOL while adjusting for covariates. CONCLUSIONS: Dietary antioxidant insufficiency was associated with increased markers of inflammation and poorer HRQOL. Improvement of diet quality among patients with HF may be a fruitful area of research for enhancing HRQOL.

Mediators of the Association Between Cognitive Function and Self-care Behaviors in Patients Hospitalized With an Exacerbation of Heart Failure.

BACKGROUND: Patients with heart failure (HF) must engage in self-care, yet their self-care is often poor. Cognitive function commonly is impaired in HF and is associated with poor self-care. Heart failure knowledge and self-care confidence also are needed to preform self-care. Few investigators have examined mediators of the association of cognitive function with self-care. OBJECTIVES: The aim of this study was to determine whether HF knowledge and self-care confidence mediated the association of cognitive function with self-care maintenance and management among patients with HF. METHODS: This was a cross-sectional observational study of 164 patients with HF. Cognitive function was assessed using the Montreal Cognitive Assessment. Self-care maintenance and self-care management behaviors and self-care confidence were measured using the Self-care of Heart Failure Index. Heart failure knowledge was measured using the Dutch Heart Failure Knowledge Scale. We conducted 2 parallel mediation analyses using the PROCESS macro in SPSS, one for self-care maintenance and one for self-care management. RESULTS: Cognitive function was indirectly associated with self-care maintenance through HF knowledge (indirect effect, 0.54; 95% confidence interval, 0.10-1.02) and self-care confidence (indirect effect, 0.26; 95% confidence interval, 0.04-0.54). Those with better cognitive function had more HF knowledge and self-care confidence. Better cognitive function was not directly associated with self-care management but indirectly associated with better self-care management through higher self-care confidence (indirect effect, 0.50; 95% confidence interval, 0.04-1.05). CONCLUSIONS: Both HF knowledge and self-care confidence mediated the association of cognitive function with self-care maintenance, and only self-care confidence mediated the association between cognitive function and self-care management. Interventions targeting HF knowledge and self-care confidence may improve self-care even for those with lower cognitive function and need to be developed and tested.

Mediation by Fatalism of the Association Between Symptom Burden and Self-care Management in Patients With Heart Failure.

BACKGROUND: Clinicians and researchers often assume that symptom burden is associated with self-care management (SCM) in patients with heart failure (HF). However, that association is often not borne out in simple regression analyses and may be because another variable mediates the association. Fatalism is an appropriate candidate for mediation and is the belief that circumstances are predetermined without opportunity for control by individuals. OBJECTIVE: Our objective was to determine whether fatalism mediated the relationship of symptom burden with SCM among adults with HF. METHODS: We conducted a secondary analysis (N = 95) from a clinical trial. We used Self-care of HF Index to measure SCM, the Memorial Symptom Assessment Scale-HF for symptom burden, and the Cardiovascular Disease Fatalism Instrument to measure fatalism. We used the PROCESS macro to evaluate mediation. RESULTS: Symptom burden was not directly associated with SCM (effect coefficient [C'] = 0.0805; 95% confidence interval, -0.048 to 0.209; P = .217). There was, however, an indirect pathway between symptom burden and SCM through fatalism (ab = -0.040; 95% confidence interval, -0.097 to -0.002). Those with higher symptom burden were more fatalistic (a = 0.004, P = .015), and greater fatalism was associated with worse SCM (b = -9.132, P = .007). CONCLUSION: Symptom burden, not directly associated with SCM, is associated through the mediator of fatalism. Interventions to improve SCM should include strategies to mitigate fatalistic views. Self-care management interventions should focus on promoting internal locus of control or increasing perceptions of perceived control to decrease fatalism and improve engagement in self-care.

Adverse effects of non-intubated airway suctioning: a clinical data-based study.

AIMS AND OBJECTIVES: The purpose of this study was to investigate the adverse effects of non-intubated suctioning. BACKGROUND: Airway hygiene aims to maintain a patent airway to ensure adequate ventilation. Nasopharyngeal, oropharyngeal or nasotracheal suctioning may be used in patients who require airway suctioning but do not have an artificial airway. However, no studies till date provide insight into the adverse effects of non-intubated airway suctioning. DESIGN: A clinical data-based retrospective design. METHOD: Using institutional and clinical databases of three university hospitals in 2008-2016, we conducted a study with a propensity score matching method of 3,326 hospitalised patients who had undergone suction therapy with or without a tracheotomy. Conditional logistic regression analyses were performed to investigate the link between suctioning and the probabilities of adverse effects. STROBE checklist was used to report the current study. RESULTS: Patients who required nasopharyngeal, oropharyngeal or nasotracheal suctioning had a higher risk of gastrointestinal ulcers than tracheotomised patients (adjusted OR 1.99; 95% CI, 1.24-3.20). Patients who received non-intubated suction had a higher risk of developing pneumonia (adjusted OR 1.59; 95% CI, 1.26-2.00), and the risk of aspiration pneumonia was three times higher than tracheotomised patients (adjusted OR 3.04; 95% CI, 1.40-6.60). CONCLUSIONS: Non-intubated patients who require suctioning for airway clearing are more susceptible to gastrointestinal ulcers, pneumonia and aspiration pneumonia. The findings would facilitate in alerting healthcare professionals to this group of patients. However, more clinical research is needed to elucidate the mechanisms of adverse effects in non-intubated patients who require suctioning. RELEVANCE TO CLINICAL PRACTICE: The adverse effects of suctioning can easily be overlooked in debilitated patients with no intubation. Professionals must be aware of the discomfort and risks that patients may experience.

Heart Failure Knowledge, Symptom Perception, and Symptom Management in Patients With Heart Failure.

BACKGROUND: Prevention of heart failure (HF) exacerbations requires that patients carefully self-manage their condition. Symptom perception is a key component in self-care for patients with HF that involves monitoring for HF symptoms and recognizing symptom changes. Heart failure knowledge is a prerequisite for better symptom perception and symptom management. However, the relationships among HF knowledge, symptom perception, and symptom management remain unclear. OBJECTIVE: The aim of this study was to explore the inter-relationships among HF knowledge, symptom monitoring, symptom recognition, and symptom response in patients with HF. METHOD: We included 185 patients with HF in this study. Heart failure knowledge was measured using the Dutch HF Knowledge Scale. Symptom monitoring, symptom recognition, and symptom response were measured using the Self-care of HF Index. Structural equation modeling was used for data analyses. RESULTS: Heart failure knowledge was associated with symptom monitoring (ß = .357, P < .001). Symptom monitoring was directly associated with both symptom recognition (ß = .371, P < .001) and symptom response (ß = .499, P < .001). Symptom recognition was directly associated with symptom response (ß = .274, P < .001). Heart failure knowledge was not directly associated with symptom recognition, nor with symptom response. Heart failure knowledge was indirectly associated with symptom recognition and symptom response through symptom monitoring. CONCLUSION: Symptom monitoring is associated with both symptom recognition and symptom response and is a mediator between HF knowledge and symptom recognition and between HF knowledge and symptom response. This finding suggests that it is important for clinicians not just to increase patients' HF knowledge but also to enhance their skills of symptom monitoring and symptom recognition and promote symptom monitoring among patients to improve symptom response in self-care.

Mind Your Heart: Exploring Feasibility, Acceptability, and Preliminary Effects of Phone-Delivered Mindfulness Training on Medication Adherence in Outpatients With Chronic Heart Failure.

BACKGROUND: Mindfulness training (MT) may promote medication adherence in outpatients with heart failure. OBJECTIVE: The aims of this study were to determine the feasibility and acceptability of MT (primary outcomes) and explore effects on medication adherence, functional capacity, cognitive function, depression, and mindfulness skills (secondary outcomes). METHODS: In this pre/post-design study, participants received a 30-minute phone-delivered MT session weekly for 8 weeks. RESULTS: We enrolled 33 outpatients (32% women; 69.7 White; mean age, 60.3 years). Retention was 100%, and session attendance was 91%. Overall, participants (97%) rated MT as enjoyable. Objectively assessed ( P < .05) adherence decreased post intervention, whereas improvements were noted in functional capacity ( P = .05), mindfulness ( P < .05), and cognitive function (reaching significance for Flanker scores). CONCLUSIONS: Phone-delivered MT was feasible and acceptable. Whereas no improvements were noted in medication adherence and depression, cognitive function, functional capacity, and mindfulness levels increased post intervention, suggesting MT may have beneficial effects in outpatients with heart failure.

Systematic identification of the interventional mechanism of Qingfei Xiaoyan Wan (QFXYW) in treatment of the cytokine storm in acute lung injury using transcriptomics-based system pharmacological analyses.

CONTEXT: Acute lung injury (ALI) is a complex, severe inflammation disease with high mortality, and there is no specific and effective treatment for ALI. Qingfei Xiaoyan Wan (QFXYW) has been widely used to treat lung-related diseases for centuries. OBJECTIVE: This study evaluates the potential effects and elucidates the therapeutic mechanism of QFXYW against LPS induced ALI in mice. MATERIALS AND METHODS: BALB/c Mice in each group were first orally administered medicines (0.9% saline solution for the control group, 0.5 mg/kg Dexamethasone, or 1.3, 2.6, 5.2 g/kg QFXYW), after 4 h, the groups were injected LPS (1.0 mg/kg) to induce ALI, then the same medicines were administered repeatedly. The transcriptomics-based system pharmacological analyses were applied to screen the hub genes, RT-PCR, ELISA, and protein array assay was applied to verify the predicted hub genes and key pathways. RESULTS: QFXYW significantly decreased the number of leukocytes from (6.34 ± 0.51) × 105/mL to (4.01 ± 0.11) × 105/mL, accompanied by the neutrophil from (1.41 ± 0.19) × 105/mL to (0.77 ± 0.10) × 105/mL in bronchoalveolar lavage fluid (BALF). Based on Degree of node connection (Degree) and BottleNeck (BN), important parameters of network topology, the protein-protein interaction (PPI) network screened hub genes, including IL-6, TNF-α, CCL2, TLR2, CXCL1, and MMP-9. The results of RT-PCR, ELISA, and protein chip assay revealed that QFXYW could effectively inhibit ALI via multiple key targets and the cytokine-cytokine signalling pathway. CONCLUSIONS: This study showed that QFXYW decreased the number of leukocytes and neutrophils by attenuating inflammatory response, which provides an important basis for the use of QFXYW in the treatment of ALI.

Health-Related Quality of Life Is a Mediator of the Relationship Between Medication Adherence and Cardiac Event-Free Survival in Patients with Heart Failure.

BACKGROUND: Health-related quality of life (HRQOL) is an important patient-reported outcome that is related to medication adherence, hospitalization and death. The nature of the relationships among medication adherence, HRQOL, and hospitalization and death is unknown. We sought to determine the relationships among medication adherence, HRQOL, and cardiac event-free survival in patients with heart failure. METHODS AND RESULTS: We enrolled 218 patients with heart failure. Patients' medication adherence was measured objectively using the Medication Event Monitoring System. HRQOL was assessed using the Minnesota Living with Heart Failure Questionnaire. Patients were followed for up to 3.5 years to collect hospitalization and mortality data. Mediation analysis was used to determine the nature of the relationships among the variables. Patients with better medication adherence had better HRQOL (P = .014). Medication adherence and HRQOL were associated with cardiac event-free survival (both P < .05). Patients with medication nonadherence were 1.86 times more likely to experience a cardiac event than those with better medication adherence (P = .038). Medication adherence was not associated with cardiac event-free survival after entering HRQOL in the model (P = .118), indicating mediation by HRQOL of the relationship between medication adherence and cardiac event-free survival. CONCLUSIONS: HRQOL mediated the relationship between medication adherence and cardiac event-free survival. It is important to assess medication adherence and HRQOL regularly and develop interventions to improve medication adherence and HRQOL to decrease hospitalization and mortality in patients with heart failure.

Dysregulation of the miR-30a/BiP axis by cigarette smoking accelerates oral cancer progression.

BACKGROUND: Cigarette smoking is the most significant cause of oral cancer progression. Cigarette smoke condensate (CSC) has been shown to induce endoplasmic reticulum (ER) stress. Binding immunoglobulin protein (BiP) being as an ER stress regulator, has been reported to be implicated in malignant behaviors. Therefore, the aim of this study was to investigate the role of the ER stress-responsive protein, BiP, in CSC-induced oral squamous cell carcinoma (OSCC) malignancy. METHODS: The biological role of BiP in CSC-induced tumor progression was investigated in OSCC cells (YD38 and SCC25) and in a tumor xenograft mouse model. The expressions of related genes were investigated using quantitative RT-PCR and Western blot analysis. Cell migration and invasion were assessed using scratch wound healing and Transwell invasion assays. The effects of conditioned media from OSCC cells on the angiogenic activities of endothelial cells were analyzed using a tube formation assay. The interaction between miR-30a and BiP mRNA was detected using a luciferase reporter assay. RESULTS: Our results demonstrated that CSC increased the expression of BiP in time- and dose-dependent manners in YD38 and SCC25 cells, and that silencing BiP abrogated CSC-induced cell invasion and tumor-associated angiogenesis. Notably, the putative miR-30a binding site was observed in the 3'untranslated region (UTR) of BiP mRNA, and miR-30a suppressed BiP expression by targeting 3'UTR of BiP transcript. In addition, CSC increased the expression of BiP in OSCC cells by downregulating miR-30a. We also showed that BiP promoted invasion and tumor-associated angiogenesis by increasing the production and secretion of vascular endothelial growth factor in CSC-exposed OSCC cells. Moreover, BiP inhibition suppressed OSCC growth and reduced tumor vessel density in tumor-bearing mice administered with CSC. CONCLUSIONS: These observations suggest that epigenetic regulation of BiP via miR-30a downregulation is involved in CSC-induced OSCC progression.

Pharmacokinetics and bioequivalence study of two ciprofloxacin hydrochloride tablets in healthy Chinese subjects under fasting and fed conditions: A randomized, open-label, two-formulation, two-sequence, two-period, single-dose crossover study.

OBJECTIVE: The study mainly aimed to determine the bioequivalence of two branded ciprofloxacin hydrochloride tablets (250 mg) under fasting and fed conditions. MATERIALS AND METHODS: The study was carried out in 48 healthy Chinese subjects under fasting and fed conditions with a randomized, open-label, two-formulation, two-sequence, two-period, single-dose crossover design. In each period of the study, the subjects were assigned to receive a single oral dose of 250 mg ciprofloxacin hydrochloride. Blood samples were collected from 1 hour before dosing to 36 hours after administration with 16 timepoints in total. The bioequivalence analysis was performed after ln-transformation of the ciprofloxacin pharmacokinetic parameters including Cmax, AUC0-t, and AUC0-∞. RESULTS: A total of 48 subjects were enrolled in the fasting and fed studies, and 1 of the subjects was excluded before drug administration. In the fasting study, the 90% CIs for the test/reference geometric mean ratios (GMRs) of the ln-transformed data for Cmax, AUC0-t, and AUC0-∞ were 85.41 - 100.97%, 95.40 - 100.27%, and 95.48 - 100.30%, respectively. For the fed study, the 90% CIs for the test/reference GMRs of the ln-transformed data for Cmax, AUC0-t, and AUC0-∞ were 90.15 - 113.75%, 99.10 - 103.77%, and 99.11 - 103.80%, respectively. These values all fell within the standard acceptance range of 80 - 125%. CONCLUSION: In the study, the generic (test) product of ciprofloxacin hydrochloride 250 mg was bioequivalent to the innovator (reference) product after single-, oral-dose administration under fasting and fed conditions.

AtJ3, a specific HSP40 protein, mediates protein farnesylation-dependent response to heat stress in Arabidopsis.

MAIN CONCLUSION: Despite AtJ3 and AtJ2 sharing a high protein-sequence identity and both being substrates of protein farnesyltransferase (PFT), AtJ3 but not AtJ2 mediates in Arabidopsis the heat-dependent phenotypes derived from farnesylation modification. Arabidopsis HEAT-INTOERANT 5 (HIT5)/ENHANCED RESPONSE TO ABA 1 (ERA1) encodes the ß-subunit of the protein farnesyltransferase (PFT), and the hit5/era1 mutant is better able to tolerate heat-shock stress than the wild type. Given that Arabidopsis AtJ2 (J2) and AtJ3 (J3) are heat-shock protein 40 (HSP40) homologs, sharing 90% protein-sequence identity, and each contains a CaaX box for farnesylation; atj2 (j2) and atj3 (j3) mutants were subjected to heat-shock treatment. Results showed that j3 but not j2 manifested the heat-shock tolerant phenotype. In addition, transgenic j3 plants that expressed a CaaX- abolishing J3C417S construct maintained the same capacity to tolerate heat shock as j3. The basal transcript levels of HEAT-SHOCK PROTEIN 101 (HSP101) in hit5/era1 and j3 were higher than those in the wild type. Although the capacities of j3/hsp101 and hit5/hsp101 double mutants to tolerate heat-shock stress declined compared to those of j3 and hit5/era1, they were still greater than that of the wild type. These results show that a lack of farnesylated J3 contributes to the heat-dependent phenotypes of hit5/era1, in part by the modulation of HSP101 activity, and also indicates that (a) mediator(s) other than J3 is (are) involved in the PFT-regulated heat-stress response. In addition, because HSP40s are known to function in dimer formation, bimolecular fluorescence complementation experiments were performed, and results show that J3 could dimerize regardless of farnesylation. In sum, in this study, a specific PFT substrate was identified, and its roles in the farnesylation-regulated heat-stress responses were clarified, which could be of use in future agricultural applications.

Dietary Vitamin C Deficiency Is Associated With Health-Related Quality of Life and Cardiac Event-free Survival in Adults With Heart Failure.

BACKGROUND: Vitamin C deficiency is prevalent in adults with heart failure (HF). Little is known about the relationship of dietary vitamin C deficiency with health outcomes in adults with HF. OBJECTIVE: The study's aim was to determine the relationships of vitamin C deficiency measured at baseline with health-related quality of life (HRQOL) and cardiac event-free survival in patients with HF measured 1 year later. METHOD: A total of 251 patients with HF completed a 4-day food diary. Dietary vitamin C deficiency was defined as daily intake less than the estimated average requirement from the Institute of Medicine of 75 mg/d for men and 60 mg/d for women. Health-related quality of life was assessed using the Minnesota Living with Heart Failure Questionnaire at 12 months. Patients were followed for a median of 1 year to determine time to the first event of cardiac-related hospitalization or death. Data were analyzed by hierarchical linear and Cox proportional hazards regressions. RESULTS: One hundred patients (40%) had vitamin C deficiency. Dietary vitamin C deficiency was associated with poorer HRQOL at 12 months (ß = 0.16, P = .02) after controlling for demographic and clinical variables. During the follow-up period, 59 patients (24%) had cardiac events. In Cox regression, vitamin C deficiency predicted shorter cardiac event-free survival after adjusting for the same covariates (hazards ratio, 1.95; 95% confidence interval, 1.08-3.51). CONCLUSION: Vitamin C deficiency was associated with poorer HRQOL and shorter cardiac event-free survival in patients with HF. The findings suggest that encouraging patients with HF to consume a diet rich in fruits/vegetables to prevent vitamin C deficiency may lead to better health outcomes.

Plasma L5 levels are elevated in ischemic stroke patients and enhance platelet aggregation.

L5, the most electronegative and atherogenic subfraction of low-density lipoprotein (LDL), induces platelet activation. We hypothesized that plasma L5 levels are increased in acute ischemic stroke patients and examined whether lectin-like oxidized LDL receptor-1 (LOX-1), the receptor for L5 on endothelial cells and platelets, plays a critical role in stroke. Because amyloid ß (Aß) stimulates platelet aggregation, we studied whether L5 and Aß function synergistically to induce prothrombotic pathways leading to stroke. Levels of plasma L5, serum Aß, and platelet LOX-1 expression were significantly higher in acute ischemic stroke patients than in controls without metabolic syndrome (P < .01). In mice subjected to focal cerebral ischemia, L5 treatment resulted in larger infarction volumes than did phosphate-buffered saline treatment. Deficiency or neutralizing of LOX-1 reduced infarct volume up to threefold after focal cerebral ischemia in mice, illustrating the importance of LOX-1 in stroke injury. In human platelets, L5 but not L1 (the least electronegative LDL subfraction) induced Aß release via IκB kinase 2 (IKK2). Furthermore, L5+Aß synergistically induced glycoprotein IIb/IIIa receptor activation; phosphorylation of IKK2, IκBα, p65, and c-Jun N-terminal kinase 1; and platelet aggregation. These effects were blocked by inhibiting IKK2, LOX-1, or nuclear factor-κB (NF-κB). Injecting L5+Aß shortened tail-bleeding time by 50% (n = 12; P < .05 vs L1-injected mice), which was prevented by the IKK2 inhibitor. Our findings suggest that, through LOX-1, atherogenic L5 potentiates Aß-mediated platelet activation, platelet aggregation, and hemostasis via IKK2/NF-κB signaling. L5 elevation may be a risk factor for cerebral atherothrombosis, and downregulating LOX-1 and inhibiting IKK2 may be novel antithrombotic strategies.

Medication Adherence Mediates the Relationship Between Heart Failure Symptoms and Cardiac Event-Free Survival in Patients With Heart Failure.

BACKGROUND: Heart failure (HF) symptoms such as dyspnea are common and may precipitate hospitalization. Medication nonadherence is presumed to be associated with symptom exacerbations, yet how HF symptoms, medication adherence, and hospitalization/death are related remains unclear. OBJECTIVE: The aim of this study was to explore the relationships among HF symptoms, medication adherence, and cardiac event-free survival in patients with HF. METHODS: At baseline, patient demographics, clinical data, and HF symptoms were collected in 219 patients with HF. Medication adherence was monitored using the Medication Event Monitoring System. Patients were followed for up to 3.5 years to collect hospitalization and survival data. Logistic regression and survival analyses were used for the analyses. RESULTS: Patients reporting dyspnea or ankle swelling were more likely to have poor medication adherence (P = .05). Poor medication adherence was associated with worse cardiac event-free survival (P = .006). In Cox regression, patients with HF symptoms had 2 times greater risk for a cardiac event than patients without HF symptoms (P = .042). Heart failure symptoms were not a significant predictor of cardiac event-free survival after entering medication adherence in the model (P = .091), indicating mediation. CONCLUSIONS: Medication adherence was associated with fewer HF symptoms and lower rates of hospitalization and death. It is important to develop interventions to improve medication adherence that may reduce HF symptoms and high hospitalization and mortality in patients with HF.

Associations of Vitamin D Intake and Sleep Quality With Cognitive Dysfunction in Older Adults With Heart Failure.

BACKGROUND: Low vitamin D intake and poor sleep quality are independently associated with cognitive dysfunction in healthy older adults. However, the relationships among vitamin D intake, sleep quality, and cognitive dysfunction are unknown in older adults with heart failure (HF). PURPOSE: The aim of this study was to determine the relationships of vitamin D intake and sleep quality with cognitive dysfunction in older adults with HF. METHODS: A total of 160 older adults with HF completed the Mini-Mental State Examination to assess cognitive function. Vitamin D deficiency was defined as less than 15 mcg/day of average intake determined using a 3-day food diary and use of dietary supplements. Sleep quality was measured by the Pittsburgh Sleep Quality Index (PSQI). Hierarchical regressions and mediation analysis were used for data analysis. RESULTS: Thirty-four patients (21.2%) had severe cognitive dysfunction (total Mini-Mental State Examination score ≤ 19), 88 (55%) had vitamin D deficiency, and 120 (75%) reported poor sleep quality (total PSQI score > 5). Increased daily vitamin D intake (ß = 0.305, P < .001) and poorer sleep quality indicated by the total PSQI score (ß = -0.312, P < .001) were associated with cognitive function. Vitamin D deficiency was associated with poor sleep quality (odds ratio, 2.22; P = .033). In mediation analysis, the relationship between vitamin D deficiency and cognitive function was mediated by sleep quality among older adults with HF. CONCLUSIONS: Both vitamin D deficiency and poor sleep quality are associated with cognitive dysfunction in older adults with HF. Interventions should be tested to target patients with poor sleep quality to improve cognitive function, particularly in those with vitamin D deficiency.

The Association Between Depressive Symptoms and N-Terminal Pro-B-Type Natriuretic Peptide With Functional Status in Patients With Heart Failure.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and depressive symptoms are each associated with functional status in patients with heart failure (HF), but their association together with functional status has not been examined. OBJECTIVE: The aim of this study was to determine whether functional status scores differ as a function of depressive symptoms and NT-proBNP levels considered together. METHODS: We studied 284 patients with HF who were divided into 4 groups based on the median split of NT-proBNP levels and cut point for depressive symptoms (Beck Depression Inventory ≥ 14): (1) low NT-proBNP of 562.5 pg/mL or less without depressive symptoms, (2) low NT-proBNP of 562.5 pg/mL or less with depressive symptoms, (3) high NT-proBNP of greater than 562.5 pg/mL without depressive symptoms, and (4) high NT-proBNP of greater than 562.5 pg/mL with depressive symptoms. The Duke Activity Status Index was used to assess functional status. RESULTS: Nonlinear regression demonstrated that patients without depressive symptoms were more than twice as likely to have higher (better) functional status scores than patients with depressive symptoms regardless of NT-proBNP levels after controlling for age, gender, prescribed antidepressants, and body mass index. Functional status levels of patients with low NT-proBNP did not differ from those with high NT-proBNP in the presence of depressive symptoms. CONCLUSION: When examined together, depressive symptoms rather than NT-proBNP levels predicted functional status. CLINICAL IMPLICATIONS: Adequate treatment of depressive symptoms may lead to better functional status regardless of HF severity.