Inhibition of caspase pathways limits CD4+ T cell loss and restores host anti-retroviral function in HIV-1 infected humanized mice with augmented lymphoid tissue.

The study of HIV infection and pathogenicity in physical reservoirs requires a biologically relevant model. The human immune system (HIS) mouse is an established model of HIV infection, but defects in immune tissue reconstitution remain a challenge for examining pathology in tissues. We utilized exogenous injection of the human recombinant FMS-like tyrosine kinase 3 ligand (rFLT-3 L) into the hematopoietic stem cell (HSC) cord blood HIS mouse model to significantly expand the total area of lymph node (LN) and the number of circulating human T cells. The results enabled visualization and quantification of HIV infectivity, CD4 T cell depletion and other measures of pathogenesis in the secondary lymphoid tissues of the spleen and LN. Treatment with the Caspase-1/4 inhibitor VX-765 limited CD4+ T cell loss in the spleen and reduced viral load in both the spleen and axillary LN. In situ hybridization further demonstrated a decrease in viral RNA in both the spleen and LN. Transcriptomic analysis revealed that in vivo inhibition of caspase-1/4 led to an upregulation in host HIV restriction factors including SAMHD1 and APOBEC3A. These findings highlight the use of rFLT-3 L to augment human immune system characteristics in HIS mice to support investigations of HIV pathogenesis and test host directed therapies, though further refinements are needed to further augment LN architecture and cellular populations. The results further provide in vivo evidence of the potential to target inflammasome pathways as an avenue of host-directed therapy to limit immune dysfunction and virus replication in tissue compartments of HIV+ persons.

Association Between Benefit Finding and Self-care Management in Heart Failure Patient-Caregiver Dyads: The Mediating Role of Mutuality.

BACKGROUND: Inadequate self-care management has been reported in patients with heart failure (HF) and their family caregivers. However, evidence on the influencing factors and corresponding action paths for self-care management within a dyadic context is limited. OBJECTIVE: The aim of this study was to examine dyadic associations between benefit finding and self-care management in HF patient-caregiver dyads and the mediating role of mutuality in these associations. METHODS: This cross-sectional study was conducted in China, and a convenience sample of 253 HF patient-caregiver dyads was included in the analysis. Dyadic benefit finding and mutuality, patients' self-care management, and caregivers' contributions to self-care management were measured using self-reported questionnaires. The actor-partner interdependence model and actor-partner interdependence mediation model were adopted to analyze the data. RESULTS: Patients' benefit finding had an actor effect on their own self-care management (ß = 0.134, P < .05) and a partner effect on caregivers' contributions to self-care management (ß = 0.130, P < .05). Similarly, caregivers' benefit finding had an actor effect on their contributions to self-care management (ß = 0.316, P < .01) and a partner effect on patients' self-care management (ß = 0.187, P < .01). Moreover, patients' mutuality completely mediated the actor effect of their benefit finding on self-care management (ß = 0.127; 95% confidence interval, 0.032-0.233), and caregivers' mutuality partially mediated the actor effect of their benefit finding on contributions to self-care management (ß = 0.060; 95% confidence interval, 0.012-0.124). In addition, caregivers' mutuality completely mediated the partner effect of patients' benefit finding on caregivers' contributions to self-care management (ß = 0.036; 95% confidence interval, 0.009-0.081). CONCLUSIONS: The findings revealed the importance of benefit finding and mutuality, 2 modifiable factors positively associated with dyadic HF self-care management. Dyadic interventions targeting on enhancing benefit finding and mutuality should be designed and implemented to improve HF self-care management.

Dyadic Associations Between Burden and Depressive Symptoms Among Patients With Heart Failure and Their Caregivers: The Mediating Role of Perceived Stress.

BACKGROUND: Depressive symptoms are prevalent in patients with heart failure and their family caregivers. Given the interpersonal interactions between dyadic individuals with intimate relationship, it is essential to consider the dyads as a unit when exploring the factors associated with depressive symptoms in heart failure patient-caregiver dyads. OBJECTIVE: The aims of this study were to explore the dyadic effects of burden on depressive symptoms in heart failure patient-caregiver dyads and investigate whether perceived stress acts as a mediator in these relationships. METHODS: In this cross-sectional study, 237 heart failure patient-caregiver dyads were recruited from 3 hospitals in China between November 2018 and June 2019. Symptom burden, caregiving burden, perceived stress, and depressive symptoms were assessed using self-report questionnaires. The actor-partner interdependence model and actor-partner interdependence mediation model were used to analyze the data. RESULTS: Patients' symptom burden had an actor effect on their own depressive symptoms and a partner effect on their caregivers' depressive symptoms. Similarly, caregivers' caregiving burden had an actor effect on their own depressive symptoms and a partner effect on patients' depressive symptoms. The actor effects between burden and depressive symptoms were partially mediated by their own perceived stress in heart failure patient-caregiver dyads. Furthermore, the partner effect between caregivers' caregiving burden and patients' depressive symptoms was completely mediated by patients' perceived stress. CONCLUSIONS: Patients' symptom burden and caregivers' caregiving burden aggravated their depressive symptoms by increasing their own perceived stress. Moreover, patients' symptom burden led to caregivers' depressive symptoms, and caregivers' caregiving burden contributed to patients' depressive symptoms through patients' perceived stress. These interdependent relationships suggest that dyadic interventions focused on reducing burden and perceived stress may be beneficial for relieving depressive symptoms in heart failure patient-caregiver dyads.

Psychosocial factors associated with career success among nurses: A latent profile analysis.

AIM: In this study, a person-centred approach was used to analyse career success profiles and explore the associated psychosocial factors among nurses. DESIGN: A cross-sectional study was conducted from 15 April to 15 October 2019. METHODS: A total of 1155 registered Chinese nurses were recruited from two general hospitals using convenience sampling. Participants completed a printed questionnaire, including the Maslach Burnout Inventory, Stress of Conscience Questionnaire, Practice Environment Scale, and Career Success Scale. Latent profile analysis and multinomial logistic regression were performed. The data were analysed with Mplus 8.3 and SPSS version 26.0. RESULTS: Three latent profiles of career success were identified: high, moderate and low. Nurses with lower educational levels, more years of work experience, lower emotional exhaustion, higher personal achievement, lower stress of conscience and higher participation in hospital affairs were more likely to have higher career success than the other profiles. CONCLUSIONS: Burnout, stress of conscience, practice environment, educational level and years of work experience were associated with career success among nurses. Targeting interventions may help enhance nurses' career success. Future research should combine subjective and objective indicators (salary, title and so on) to assess career success and explore other determinants for formulating interventions to enhance nurses' career success. IMPACT: The heterogeneity and psychosocial factors associated with nurses' career success provide valuable evidence for the formulation of individualized interventions. Nursing managers should understand the importance of career success, develop interventions to reduce nurses' burnout and stress of conscience, and improve the practice environment to enhance their career success. NO PATIENT OR PUBLIC CONTRIBUTIONS: This study was designed to examine the psychosocial factors associated with nurses' career success. The study was not conducted using suggestions from the patient groups or the public.

Relationships between job burnout, ethical climate and organizational citizenship behaviour among registered nurses: A cross-sectional study.

AIM: This study aimed to investigate the levels of nurses' organizational citizenship behaviour and the associations between job burnout and ethical climate with organizational citizenship behaviour. BACKGROUND: Organizational citizenship behaviour improves adverse outcomes led by nursing shortage. However, the associations between three dimensions of job burnout and organizational citizenship behaviour are inconsistent, and little is known about whether ethical climate is related to organizational citizenship behaviour in nurses. METHODS: In this cross-sectional study, 1157 nurses were selected using convenience sampling from April to October 2019. Self-report surveys assessed nurses' organizational citizenship behaviour, emotional exhaustion, depersonalization, personal accomplishment and perceptions of ethical climate. RESULTS: Mean organizational citizenship behaviour was high among nurses. The regression model showed that job burnout and ethical climate explained an additional 38.6% of the variance in organizational citizenship behaviour over and above sociodemographic factors, with 44.9% of the total variance. CONCLUSION: Nurses' organizational citizenship behaviour was at a relatively high level. Depersonalization was negatively associated with organizational citizenship behaviour while personal accomplishment and ethical climate were positively related to organizational citizenship behaviour. Therefore, nurse leaders are encouraged to take measures to help nurses reduce job burnout and create a favourable ethical climate for increasing nurses' organizational citizenship behaviour.

The effects of weight management on heart failure: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Weight management is an important part of disease management in patients with heart failure. However, the effectiveness of reported weight management interventions is inconclusive. AIMS: The aim of this systematic review and meta-analysis was to assess the effects of weight management on functional status, heart failure-related hospitalizations, and all-cause mortality in patients with heart failure. METHODS: PubMed, Web of Science, Embase, and the Cochrane Library were searched on April 3, 2022. This study was registered with PROSPERO (CRD42021283817). Eligible studies assessed functional status, heart failure-related hospitalizations, and all-cause mortality in patients with heart failure. Two researchers independently screened the articles, extracted data, and evaluated the risk bias of each study. Dichotomous variables were presented as OR with a 95% confidence interval (CI). The data were analyzed using a fixed effect or random effect model, and heterogeneity was determined using I2 statistics. All statistical analyses were conducted using RevMan 5.3. RESULTS: Among 4279 studies screened, seven randomized controlled trials were included in this study. The results showed that weight management significantly improved functional status (OR = 0.15, 95% CI [0.07, 0.35], I2 = 52%) and reduced the risk of all-cause mortality (OR = 0.54, 95% CI [0.34, 0.85], I2 = 0%), but had no significant effect on heart failure-related hospitalizations (OR = 0.72, 95% CI [0.20, 2.66]). LINKING EVIDENCE TO ACTION: Weight management has effects on improved functional status and reduced all-cause mortality in patients with heart failure. It is necessary to strengthen the weight management interventions of patients with heart failure to improve patients' functional status and reduce all-cause mortality.

Sedentary behavior and health outcomes in patients with heart failure: a systematic review and meta-analysis.

A better understanding of the association between sedentary behavior and heart failure is essential for the development of interventions to improve patients' outcomes. Therefore, a systematic review was conducted to determine the association between sedentary behavior and all-cause mortality, health-related quality of life, and depression in heart failure patients. We searched Web of Science, PubMed, Embase, and Cochrane Library and articles in references on 7 May 2021. The search results were limited to articles on heart failure patients over the age of 18, observational studies investigating the association between sedentary behavior and heart failure, and studies reporting one or more outcomes of interest. Two reviewers independently screened the literature and extracted data. Strengthening the Reporting of Observational Studies in Epidemiology was used to assess the quality of articles. Nine observational studies were included, of which, four were of high quality. Four cohort studies indicated that sedentary behavior was significantly associated with increased all-cause mortality (hazard ratio: 1.97; 95% confidence interval: 1.60 to 2.44; I2 = 38.9%). In addition, subgroup analysis based on geographical regions was conducted (hazard ratio: 1.82; 95% confidence interval: 1.46 to 2.29; I2 = 0%). Sedentary behavior was associated with worse health-related quality of life in patients with heart failure, and the regression coefficients ranged from 0.004 to 0.033 (95% confidence interval: 0.0004 to 0.055). Although sedentary behavior was associated with increased all-cause mortality and worse quality of life in patients with heart failure, further studies are needed to determine whether this association is causal.

The Relationship Between Uncertainty in Illness and Quality of Life in Patients With Heart Failure: Multiple Mediating Effects of Perceived Stress and Coping Strategies.

BACKGROUND: Previous investigators have demonstrated that uncertainty in illness is associated with quality of life (QoL) in patients with chronic illness. However, little is known about the mechanism underlying the relationship in patients with heart failure. OBJECTIVE: The aim of this study was to examine the multiple mediating effects of perceived stress and coping strategies on the relationship between uncertainty in illness and QoL in patients with heart failure. METHODS: We conducted a cross-sectional study in 302 patients with heart failure recruited at a general hospital in China from October 2016 to September 2017. Uncertainty in illness, perceived stress, coping strategies, and QoL were assessed using self-reported questionnaires. The multiple mediation model was tested using the PROCESS macro for SPSS. RESULTS: Of the 302 patients, 51.7% had poor physical QoL and 45.7% had poor mental QoL (physical component summary or mental component summary score of <50 points). Uncertainty in illness had a significantly negative indirect effect on mental QoL through perceived stress and acceptance-resignation (indirect effect, -0.02; 95% confidence interval, -0.04 to -0.01). Uncertainty in illness also had a significantly negative indirect effect on mental QoL via perceived stress only (indirect effect, -0.18; 95% confidence interval, -0.26 to -0.09). CONCLUSIONS: Poor QoL is prevalent in patients with heart failure. Perceived stress and acceptance-resignation are important mediating factors between uncertainty in illness and mental QoL in patients with heart failure. Interventions aimed at reducing perceived stress and acceptance-resignation coping may be beneficial for improving mental QoL in patients with heart failure.

The Heterogeneity of Physical and Anxiety Symptoms and Quality of Life Among Patients With Heart Failure: A Latent Class Analysis.

BACKGROUND: Patients with heart failure (HF) experience a severe burden of symptoms and reduced quality of life (QoL). However, little is known about the heterogeneity of these symptoms and the association with QoL. OBJECTIVES: The aims of this study were to conduct a latent class analysis on co-occurring physical and anxiety symptoms and to determine whether the underlying subgroups differ regarding the QoL among patients with HF. METHODS: The authors of this cross-sectional study recruited 329 patients with HF from 2 hospitals. Patients' symptoms and QoL were self-reported, and data were analyzed using latent class analysis, χ 2 test, analysis of variance, and hierarchical linear regression analysis. RESULTS: Three latent classes (all low, all high, and high physical-partial anxiety) were identified based on the occurrence of patients' physical and anxiety symptoms. Patients with a lower body mass index, a worse New York Heart Association class, and a longer disease duration were more likely to belong to the all-high class. Hierarchical linear regression analysis showed that distinct subgroups (all low vs all high: ß = -0.299, P < .001; all low vs high physical-partial anxiety: ß = -0.228, P < .001) were significantly associated with the physical summary component score for QoL. Likewise, distinct subgroups (all low vs all high: ß = -0.509, P < .001; all low vs high physical-partial anxiety: ß = -0.128, P = .012) were significantly associated with the mental summary component score for QoL. CONCLUSIONS: Patients with HF showed heterogeneity in physical and anxiety symptoms; the subgroup with severe symptoms exhibited a poor QoL. The associations between symptom subgroups and QoL require targeted symptom-based interventions.

Association between sleep and quality of life in heart failure patient-caregiver dyads and mediation of fatigue: An actor-partner interdependence mediation model.

AIMS: Quality of life is essential to heart failure patients and their family caregivers. This study aimed to examine the mediating role of fatigue in the association between sleep and quality of life in heart failure patient-caregiver dyads. DESIGN: A cross-sectional descriptive study was conducted from November 2017 to August 2018. METHODS: A total of 269 heart failure patient-caregiver dyads at two hospitals in China were included. The Chinese version of the Pittsburgh Sleep Quality Index, the Chalder Fatigue Scale and the 12-item Short-Form Health Survey were used to collect data on heart failure patients and their family caregivers. The structural equation model was employed in the dyadic analysis based on the actor-partner interdependence mediation model. RESULTS: Regarding the actor effects, poor sleep was negatively associated with physical and mental quality of life in heart failure patients and their family caregivers, respectively, and the relationship was mediated by their fatigue. Regarding the partner effects, caregivers' fatigue was positively associated with patients' physical quality of life and mediated the association between caregivers' sleep and patients' physical quality of life. CONCLUSIONS: Heart failure patients and their family caregivers experience reduced quality of life when they have poor sleep and fatigue, and caregivers' fatigue is related to patients' improved physical quality of life. Hence, dyadic interventions targeting to improving sleep and fatigue may be beneficial to their quality of life. IMPACT: This study highlights the importance of routinely measuring and managing sleep and fatigue for heart failure patients and their family caregivers. Effective dyadic-based interventions that maintain equal attention to family caregivers should be considered by healthcare providers to maximize the improvement of patients' quality of life.

Cross-cultural differences in nurse burnout and the relationship with patient safety: An East-West comparative study.

AIMS: To compare levels of nurse burnout across eastern and western cultures, as well as examine the influence of burnout on patient safety cross-culturally. DESIGN: Comparative cross-sectional study. METHODS: Survey data were collected from nurses between August and October 2017 in Australia (n = 730) and between April and October 2019 in China (n = 1107). Variables included burnout (emotional exhaustion, depersonalization, personal accomplishment), nurse leadership and support, staffing and resource adequacy, and perceived patient safety. Data were analysed separately for each jurisdiction using bootstrapped hierarchical regressions, which tested the relationships between burnout indicators and patient safety, controlling for support resources. RESULTS: Emotional exhaustion and depersonalization scores were significantly higher in the Australian sample compared with the Chinese sample. Australian participants reported significantly lower patient safety grades than Chinese participants and were less likely to agree that support resources were present in their current job. Separate regressions indicated that patient safety was significantly associated with staffing and resource adequacy, nurse leadership and support, and depersonalization among Australian participants (30% of variance explained in the final regression model), while staffing and resource adequacy, nurse leadership and support, personal accomplishment and emotional exhaustion predicted patient safety for Chinese participants (22% of variance explained in the final model). CONCLUSION: Australian nurses are at greater risk of burnout than Chinese nurses. Burnout dimensions are differentially associated with patient safety across cultures. Culturally relevant interventions may be more optimal than universal approaches for improving burnout and patient safety in nursing. IMPACT: This study increased understanding of cross-cultural differences in nurse burnout and the relationship with patient safety. Australian nurses were at greater risk of burnout than Chinese nurses. Emotional exhaustion, depersonalization and personal accomplishment influenced patient safety distinctively across the countries. These findings inform interventions designed to reduce nurse burnout and improve patient safety internationally.

The Relationship Between Caregiver Reactions and Psychological Distress in Family Caregivers of Patients With Heart Failure.

BACKGROUND: Providing care often causes negative reactions and psychological distress in family caregivers of patients with heart failure. How these 2 constructs are related has not been fully explored. OBJECTIVE: The aims of this study were to describe caregiver reactions to caregiving and psychological distress and to determine the associations between caregiver reactions to caregiving and psychological distress in family caregivers of patients with heart failure. METHODS: In this secondary analysis of a cross-sectional study, the sample included 231 patients and their family caregivers. The Chinese version of the Hospital Anxiety and Depression Scale was used to assess psychological distress (ie, symptoms of anxiety and depression), and the Caregiver Reaction Assessment was used to measure both negative and positive caregiver reactions to caregiving, including financial problems, impact on schedule, health problems, lack of family support, and self-esteem. RESULTS: Of the participants, 15.2% and 25.5% of caregivers reported symptoms of depression and anxiety, respectively. Impact on schedule was the most common caregiver reaction, followed by financial problems. Impact on schedule was related to both the caregivers' symptoms of depression (odds ratio [OR], 1.705; P = .001) and anxiety (OR, 1.306; P = .035), whereas financial problems were only related to symptoms of anxiety (OR, 1.273; P = .011). CONCLUSIONS: The findings suggest that interventions for reducing the negative impact on schedule of caregiving and helping to solve the caregivers' financial concerns might help to relieve their symptoms of depression and anxiety.

Functional status mediates the association of nutritional status with depressive symptoms in patients with heart failure.

AIMS: The decline of nutritional status and depressive symptoms are pandemic in heart failure patients and functional status may play a pivotal role between these. This study aimed to determine whether nutritional status is associated with depressive symptoms and whether functional status mediates this relationship in heart failure patients. DESIGN: This was a secondary analysis of a cross-sectional study. METHODS: The data were collected from November 2015-April 2016. Heart failure patients (N = 254) being hospitalized were included in this secondary analysis. The Depression Sub-Scale of the Hospital Anxiety and Depression Scale and the Duke Activity Status Index were used to assess patients' depressive symptoms and functional status. The nutritional status of patients was calculated using the Geriatric Nutritional Risk Index. RESULTS: In this study, the average scores of depressive symptoms, nutritional status and functional status were 4.91 (SD 3.12), 102.38 (SD 6.57) and 20.58 (SD 8.96) respectively. Out of the 254 patients, 46 patients (18.1%) had significant depressive symptoms (the score of Depression Sub-Scale of the Hospital Anxiety and Depression Scale ≥ 8) and 55 (21.7%) suffered from malnutrition (the score of Geriatric Nutritional Risk Index ≤ 98). In the multiple regression analyses, nutritional status was negatively associated with depressive symptoms (ß = -0.142, p = .02) and functional status mediated the relationship between nutritional status and depressive symptoms. CONCLUSIONS: Many patients with heart failure have malnutrition and depressive symptoms. Functional status plays a mediating role in the relationship between nutritional status and depressive symptoms. IMPACT: To relieve depressive symptoms in patients with heart failure, it is of importance to improve the functional status, especially for those with poor nutritional status.

Priming and Activation of Inflammasome by Canarypox Virus Vector ALVAC via the cGAS/IFI16-STING-Type I IFN Pathway and AIM2 Sensor.

Viral vectors derived from different virus families, including poxvirus (canarypox virus vector ALVAC) and adenovirus (human Ad5 vector), have been widely used in vaccine development for a range of human diseases including HIV/AIDS. Less is known about the mechanisms underlying the host innate response to these vectors. Increasing evidence from clinical vaccine trials testing different viral vectors has suggested the importance of understanding basic elements of host-viral vector interactions. In this study, we investigated the innate interactions of APCs with two commonly used HIV vaccine vectors, ALVAC and Ad5, and identified AIM2 as an innate sensor for ALVAC, triggering strong inflammasome activation in both human and mouse APCs. Microarray and comprehensive gene-knockout analyses (CRISPR/Cas9) identified that ALVAC stimulated the cGAS/IFI16-STING-type I IFN pathway to prime AIM2, which was functionally required for ALVAC-induced inflammasome activation. We also provided evidence that, in contrast to ALVAC, the Ad5 vector itself was unable to induce inflammasome activation, which was related to its inability to stimulate the STING-type I IFN pathway and to provide inflammasome-priming signals. In preconditioned APCs, the Ad5 vector could stimulate inflammasome activation through an AIM2-independent mechanism. Therefore, our study identifies the AIM2 inflammasome and cGAS/IFI16-STING-type I IFN pathway as a novel mechanism for host innate immunity to the ALVAC vaccine vector.

5-HT2C Receptor Knockdown in the Amygdala Inhibits Neuropathic-Pain-Related Plasticity and Behaviors.

Neuroplasticity in the amygdala drives pain-related behaviors. The central nucleus (CeA) serves major amygdala output functions and can generate emotional-affective behaviors and modulate nocifensive responses. The CeA receives excitatory and inhibitory inputs from the basolateral nucleus (BLA) and serotonin receptor subtype 5-HT2CR in the BLA, but not CeA, has been implicated anxiogenic behaviors and anxiety disorders. Here, we tested the hypothesis that 5-HT2CR in the BLA plays a critical role in CeA plasticity and neuropathic pain behaviors in the rat spinal nerve ligation (SNL) model. Local 5-HT2CR knockdown in the BLA with stereotaxic injection of 5-HT2CR shRNA AAV vector decreased vocalizations and anxiety- and depression-like behaviors and increased sensory thresholds of SNL rats, but had no effect in sham controls. Extracellular single-unit recordings of CeA neurons in anesthetized rats showed that 5-HT2CR knockdown blocked the increase in neuronal activity (increased responsiveness, irregular spike firing, and increased burst activity) in SNL rats. At the synaptic level, 5-HT2CR knockdown blocked the increase in excitatory transmission from BLA to CeA recorded in brain slices from SNL rats using whole-cell patch-clamp conditions. Inhibitory transmission was decreased by 5-HT2CR knockdown in control and SNL conditions to a similar degree. The findings can be explained by immunohistochemical data showing increased expression of 5-HT2CR in non-GABAergic BLA cells in SNL rats. The results suggest that increased 5-HT2CR in the BLA contributes to neuropathic-pain-related amygdala plasticity by driving synaptic excitation of CeA neurons. As a rescue strategy, 5-HT2CR knockdown in the BLA inhibits neuropathic-pain-related behaviors.SIGNIFICANCE STATEMENT Neuroplasticity in the amygdala has emerged as an important pain mechanism. This study identifies a novel target and rescue strategy to control abnormally enhanced amygdala activity in an animal model of neuropathic pain. Specifically, an integrative approach of gene transfer, systems and brain slice electrophysiology, behavior, and immunohistochemistry was used to advance the novel concept that serotonin receptor subtype 5-HT2C contributes critically to the imbalance between excitatory and inhibitory drive of amygdala output neurons. Local viral vector-mediated 5-HT2CR knockdown in the amygdala normalizes the imbalance, decreases neuronal activity, and inhibits neuropathic-pain-related behaviors. The study provides valuable insight into serotonin receptor (dys)function in a limbic brain area.

Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection.

Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, C. albicans-specific CD4 T cells are highly permissive to HIV in vitro. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on C. albicans- and CMV-specific CD4 T-cell immunity in vivo. We found a sequential dysfunction and preferential depletion for C. albicans-specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1ß) functional subsets, the Th17 functional subsets (IL-17, IL-22) of C. albicans-specific CD4 T cells were more permissive to HIV in vitro and impaired earlier in HIV-infected subjects. Infection history analysis showed that C. albicans-specific CD4 T cells were more susceptible to HIV in vivo, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that C. albicans-specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis.

Self-efficacy for self-regulation and fear of failure as mediators between self-esteem and academic procrastination among undergraduates in health professions.

Academic procrastination has been a widespread problem behavior among undergraduates. This study aimed to examine the prevalence of academic procrastination among undergraduates in health professions, and explore the mediation effects of self-efficacy for self-regulation and fear of failure in the relationship between self-esteem and academic procrastination. A cross-sectional design was used to study 1184 undergraduates in health professions from China. Participants completed measures of academic procrastination, self-esteem, self-efficacy for self-regulation and fear of failure. We used Pearson product-moment correlation to examine the bivariate correlations between study variables, and path analysis to examine mediation. Among the 1184 undergraduates, 877 (74.1%) procrastinated on at least one type of academic task. The total score for academic procrastination was negatively correlated with scores for self-esteem and self-efficacy for self-regulation, and positively correlated with the score for fear of failure. Moreover, the relationship between self-esteem and academic procrastination was fully mediated by self-efficacy for self-regulation (indirect effect: ß = - .15, 95% bootstrap CI - .19 to - .11) and fear of failure (indirect effect: ß = - .06, 95% bootstrap CI - .09 to - .04). These findings suggest that interventions targeting the enhancement of self-efficacy for self-regulation and the conquest of fear of failure may prevent or reduce academic procrastination among undergraduates in health professions, especially for those with lower self-esteem.

Family Caregiver Contribution to Self-care of Heart Failure: An Application of the Information-Motivation-Behavioral Skills Model.

BACKGROUND: Adherence to self-care behaviors improves outcomes of patients with heart failure (HF). Caregivers play an important role in contributing to self-care. OBJECTIVE: We aimed to explore the relationships among HF knowledge, perceived control, social support, and family caregiver contribution to self-care of HF, based on the Information-Motivation-Behavioral Skills Model. METHODS: Two hundred forty-seven dyads of eligible patients with HF and family caregivers were recruited from a general hospital in China. Structural equation modeling was used to analyze the data obtained with the Caregiver Contribution to Self-care of Heart Failure Index, the Heart Failure Knowledge Test, the Control Attitudes Scale, and the Social Support Rating Scale. RESULTS: In this model, caregiver contribution to self-care maintenance was positively affected by perceived control (ß = .148, P = .015) and caregiver confidence in contribution to self-care (ß = .293, P < .001). Caregiver contribution to self-care management was positively affected by HF knowledge (ß = .270, P < .001), perceived control (ß = .140, P = .007), social support (ß = .123, P = .019), caregiver confidence in contribution to self-care (ß = .328, P < .001), and caregiver contribution to self-care maintenance (ß = .148, P = .006). Caregiver confidence in contribution to self-care was positively affected by HF knowledge (ß = .334, P < .001). CONCLUSIONS: Heart failure knowledge, perceived control, and social support facilitated family caregiver contribution to self-care of HF. Targeted interventions that consider these variables may effectively improve family caregiver contributions to self-care.

Coping Styles Mediate the Relationship Between Self-esteem, Health Locus of Control, and Health-Promoting Behavior in Chinese Patients With Coronary Heart Disease.

BACKGROUND: Health-promoting behavior plays an important role in reducing the burden of coronary heart disease. Self-esteem and health locus of control may contribute to health-promoting behavior, and coping styles may mediate these associations. OBJECTIVE: The aims of our study were to examine whether self-esteem and health locus of control are associated with health-promoting behavior and examine the possible mediating effect of coping styles in patients with coronary heart disease. METHODS: Health-promoting behavior, self-esteem, health locus of control, and coping styles were assessed in 272 hospitalized patients (60 ± 12 years, 61% male) with coronary heart disease. Hierarchical regression analysis was conducted to analyze the relationships between health-promoting behavior and other variables. Mediation effect was examined according to the methods of Baron and Kenny. RESULTS: The mean score for health-promoting behavior was 2.57 ± 0.51; 38.2% of patients (n = 104) scored lower than 2.5. Self-esteem (ß = .139, P < .05), confrontation coping style (ß = .491, P < .001), disease duration (≥6 months, ß = .147, P < .05), and monthly income (≥1000 RMB [approximately US$154], ß = .111, P < .05) were positively associated with health-promoting behavior, accounting for 47.5% of its variance (F = 19.828). Confrontation partly mediated the association between self-esteem and health-promoting behavior and completely mediated the relationship between internal health locus of control and health-promoting behavior. CONCLUSIONS: Confrontation plays a mediating role in the association among self-esteem, internal health locus of control, and health-promoting behavior. Strategies should be undertaken to encourage the use of confrontation coping style, which will facilitate health-promoting behavior.

Attributions, future time perspective and career maturity in nursing undergraduates: correlational study design.

BACKGROUND: Career maturity is an important parameter as nursing undergraduates prepare for their future careers. However, little is known regarding the relationships between attributions, future time perspective and career maturity among nursing undergraduates. The purpose of this study was to investigate the degree of career maturity and its relationship with attributions and future time perspective. METHODS: A cross-sectional survey was designed. This survey was administered to 431 Chinese nursing undergraduates. Independent-sample t-tests and one-way ANOVA were performed to examine the mean differences between categories of binary and categorical demographic characteristics, respectively. Pearson correlations and multiple linear regressions were used to test the relationships between attributions, future time perspective and career maturity. RESULTS: The degree of career maturity was moderate among nursing undergraduates and that internal attributions of academic achievement, future efficacy and future purpose consciousness were positively associated with career maturity (all p < 0.01). These three factors accounted for 37.6% of the variance in career maturity (adjusted R(2) = 0.376). CONCLUSIONS: These findings might assist nursing educators and career counselors to improve nursing undergraduate career maturity by elucidating the imperative roles of internal attributions and future time perspective and to facilitate their transition from school to clinical practice.