Lived Experience of Violence Perpetrated by Treated Patients and Their Visitors in Intensive Care Units: A Qualitative Study of Nurses.

BACKGROUND: Patient and visitor violence (PVV) is a widespread problem for health professionals. Nurses working in intensive care units (ICUs) face a relatively high risk of experiencing PVV, which significantly impacts both the health of nurses and the institution as a whole. The subjective perceptions of ICU nurses regarding PVV are inadequately explored in the literature. PURPOSE: The purpose of this study was to explore the perspectives, experiences, and perceptions of PVV in ICU nurses and to better understand the precipitating factors of violence. METHODS: A phenomenological qualitative design and purposive sampling were used. A semistructured interview guide was used to conduct in-depth interviews with 12 ICU nurses with PVV experiences. Giorgi's method of analysis was used to discover and identify the essential categories of experience. RESULTS: Five main experience categories were identified: family and patient factors as flashpoints, managing suppressed emotions by weathering the emotional storm, spiritual awakening after violence, and strategies for surviving further violence. The participants' experiences with PVV included a range of caring and mental health difficulties. In ICU settings, patient progress is often unpredictable, resulting in discrepancies between patient/family expectations and reality. Because feelings of frustration and powerlessness can eventually cause exhaustion in ICU nurses, implementing effective emotional management, stress adjustment, psychological counseling, team support, and violence intervention programs are crucial. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study provides new information on the process by which nurses can progress from inner trauma to self-recovery, moving from a negative affectivity disposition to a better understanding of threat appraisals and coping response options. Nurses should increase their awareness of the complexity of the phenomenon and of the interplay among the factors underlying PVV. The results of this study suggest that routine confusion and delirium assessments to rule out patients with ICU delirium in ICUs are important to preventing PVV. This study considers some of the implications of the research findings for nursing managers. Interventions, training programs, and/or management action should be used to ensure psychological and mental support is extended to all witnesses of PVV events and not only to those targeted by violence.

Effects of Integrated Workplace Violence Management Intervention on Occupational Coping Self-Efficacy, Goal Commitment, Attitudes, and Confidence in Emergency Department Nurses: A Cluster-Randomized Controlled Trial.

Patient and visitor violence (PVV), the most prevalent source of workplace violence, is largely ignored, underreported, and a persistent problem in emergency departments. It is associated with physical injuries, psychological distress, and occupational stress in nurses. A randomized controlled trial was conducted in Taiwan from January to December 2020. This study aimed to test the efficacy of an integrated Workplace Violence Prevention and Management Training Program on PVV in 75 emergency department (ED) nurses from a hospital. Cluster sampling was used because the policy of subdivision strategy was enforced during the COVID-19 pandemic. ED nurses received either the intervention or 1-hour in-service class. Data were collected from questionnaires. Data were analyzed mainly by the repeated measure analysis of variance and generalized estimating equations. The intervention had positive effects on developing stronger goal commitment, improving occupational coping self-efficacy, increasing confidence in ability to deal with violent situations, and modifying attitudes toward the causes and management of PVV in ED nurses (p < 0.05). The marginal R2 of the generalized estimating equation model for goal commitment, occupational coping self-efficacy, confidence, attitudes toward aggression in ED and aggressive behavior variables was high as 0.54 (p < 0.001), 0.45 (p < 0.001), 0.58 (p < 0.001), 0.29 (p < 0.05), and 0.72 (p < 0.001), respectively. These study models could effectively predict changes in the mean values. The benefit was driven by the effect of the intervention in ED nurses. Thus, the intervention, when applied in conjunction with routine in-service class, could exert synergistic improvements on outcomes measured in nurses.

Dilemmas and Repercussions of Workplace Violence against Emergency Nurses: A Qualitative Study.

Nurses received the highest rate of workplace violence due to their close interaction with clients and the nature of their work. There have been relatively few qualitative studies focus on nurses' perceptions of and experiences with the antecedents, dilemma and repercussions of the patient and visitor violence (PVV), leaving a considerable evidence gap. The aim of this study was to explore nurses' experience of PVV in emergency department, the impact of PVV on quality of care, and supports needed after exposure to such incidents. We conducted semi-structured interviews with a purposive and snowball sample of nurses, and analyzed the content of the interview transcripts. A total of 10 nurses were approached and agreed to participate. Those participants ranged in age from 24 to 41 years old, eight female and two male nurses, and the majority of them (80%) held a university Bachelor degree in nursing. The average time in nursing practice was 7.2 years. We conceptualized five analytical themes, which comprised: (1) multifaceted triggers and causes of PVV; (2) experiences following PVV; (3) tangled up in thoughts and struggle with the professional role; (4) self-reflexivity and adjustment; and, (5) needs of organizational efforts and support following PVV. This paper provides compelling reasons to look beyond solely evaluating the existence of workplace, and considering the perceived professional inefficacy, impacts of being threatened or assaulted in nurses. There are also urgent needs in provision of prevention and management of workplace training programs to ensure the high-quality nursing care.

Effects of Integrated Moral Reasoning Development Intervention for Management of Violence in Schizophrenia: A Randomized Controlled Trial.

Moral cognition is an important and multidimensional, but often overlooked, determinant of violence. Very few interventions have systematically examined the role of moral reasoning, anger management and problem-solving together in violence. A randomized controlled trial was conducted to comprehensively evaluate the sustained effects of an integrated Moral Reasoning Development Intervention (MRDI) in the management of repetitive violence in schizophrenia. This study placed special emphasis on essential components related to moral reasoning and violence in patients with schizophrenia. Evaluations, including measures of violence, moral reasoning, ethical valuation and judgement, decision-making, conflict management style, and personality traits, were performed at baseline, end of intervention, and 1-month follow-up after intervention. We found that MRDI was superior to treatment-as-usual, in improving moral reasoning and related variables and violence outcomes (p < 0.05). In comparison with the treatment-as-usual group (n = 22), patients in the MRDI group (n = 21) showed improved levels of moral reasoning, with decreased levels of violent behaviors. The MRDI participants also experienced significantly greater improvements or changes (p < 0.05) in their ethical valuation and judgement, decision-making style and preferences, and conflict management style. Our findings provide important implications for risk assessment and violence management and prevention.

A Systematic Review of Effectiveness of Omega-3 Fatty Acid Supplementation on Symptoms, Social Functions, and Neurobiological Variables in Schizophrenia.

BACKGROUND: Disturbance of lipid, particularly omega-3 polyunsaturated fatty acid (PUFA), metabolism is associated with the etiology and symptoms of schizophrenia. Numerous clinical studies have tried to evaluate whether omega-3 PUFA supplementation can ameliorate the disorder, but the results are inconclusive. OBJECTIVES: This systematic review integrates and refines the research evidence of the effectiveness of omega-3 PUFA nutritional supplementation on schizophrenia during the different developmental phases of the disease (prodromal, first-episode, and chronic phases) and examines whether different developmental stages modulate the efficacy of omega-3 PUFA supplementation. DATA SOURCES: Scientific articles from 2000 to 2020 in PubMed/Medline, Allied Health Literature, PsychINFO, and SCOPUS following the Preferred Reporting Items for Systematic Reviews guidelines. METHODS: A systematic review was performed. We reviewed electronic databases and identified 1,266 clinical studies. Of these, 26 met the inclusion criteria. RESULTS: The effectiveness of omega-3 dietary supplementation on symptoms varies among different phases of illness. Omega-3 supplementation significantly improves positive and negative symptoms at the prodromal phase, improves mainly the negative symptoms in patients with the first-episode, and effects symptoms partly in patients with chronic schizophrenia. DISCUSSION: The effectiveness of omega-3 PUFA dietary supplementation is modulated by age, duration of untreated psychosis and illness, baseline levels of omega-3 fatty acids, and status of antioxidant capacity of patients. The important implications for psychiatric research and clinical practice developments as well as nursing care are presented and discussed.

Use of Charlson Comorbidity Index and Nomogram to Predict Mortality in Elderly Patients with Late-Life Schizophrenia.

Objectives: Comorbid illness burden signifies a poor prognosis in schizophrenia. The aims of this study were to estimate the severity of comorbidities in elderly patients with schizophrenia, determine risk factors associated with mortality, and establish a reliable nomogram for predicting 1-, 3- and 5-year mortality and survival. Methods: This population-based study rigorously selected schizophrenia patients (≥65 years) having their first admission due to schizophrenia during the study period (2000-2013). Comorbidity was scored using the updated Charlson Comorbidity Index (CCI). Results: This study comprised 3827 subjects. The mean stay of first admission due to schizophrenia was 26 days. Mean numbers of schizophrenia and non-schizophrenia-related hospitalization (not including the first admission) were 1.80 and 3.58, respectively. Mean ages at death were 73.50, 82.14 and 89.32 years old, and the mean times from first admission to death were 4.24, 3.33, and 1.87 years in three different age groups, respectively. Nearly 30% were diagnosed with ≥3 comorbidities. The most frequent comorbidities were dementia, chronic pulmonary disease and diabetes. The estimated 1-, 3- and 5-year survival rates were 90%, 70%, and 64%, respectively. Schizophrenia patients with comorbid diseases are at increased risk of hospitalization and mortality (p < 0.05). Conclusion: The nomogram, composed of age, sex, the severity of comorbidity burden, and working type could be applied to predict mortality risk in the extremely fragile patients.

Effects of Integrated Violence Intervention on Alexithymia, Cognitive, and Neurocognitive Features of Violence in Schizophrenia: A Randomized Controlled Trial.

Patients with schizophrenia and repetitive violence express core impairments that encompass multiple domains. To date, there have been few interventions integrating neurocognition, social cognition, alexithymia, and emotion regulation together as an approach to manage repetitive violence. The aim of this open-label randomized controlled trial was to examine more comprehensively the effectiveness of a novel Integrated Cognitive Based Violence Intervention Program on management of repetitive violence in patients with schizophrenia (vSZ). Sixty recruited patients were aged ≥20 years, diagnosed with schizophrenia for >2 years, had repetitive violent behavior within one year, and were psychiatrically hospitalized. The vSZ patients were randomly allocated to two groups and received either the intervention or treatment as usual. The intervention module, consisting of all defined 11 cognitive and social cognitive domains as well as emotion regulation, which were grouped into four modules. The intervention placed emphasis on the patients' behavioral problems or intrinsic conflicts in relation to repetitive violence. The results indicate a statistically significant trend toward reducing impulsivity, anger with resentment, physical aggression, suspicion, and hostility (p < 0.05). The intervention significantly alleviated the intensity of cognitive failure, improved the management of alexithymic features and attribution styles and errors, and fostered adequate decision-making styles and emotion regulation capacity (p < 0.05). The intervention, when applied in conjunction with psychiatric standard care, could exert synergistic effects on alexithymia and cognitive, clinical, and neurocognitive features of repetitive violence in schizophrenia. This intervention provided patients a more active role to manage their violent behavior with the involvement of alexithymia.

Subsequent Dyslipidemia and Factors Associated with Mortality in Schizophrenia: A Population-Based Study in Taiwan.

Background: Persons with schizophrenia are at greater risk of developing subsequent medical conditions. To date, few studies have examined comprehensively the risks, mortality and survival rates in schizophrenia and subsequent dyslipidemia over different time periods. The objective of this study was to evaluate the occurrence of subsequent dyslipidemia after the diagnosis of schizophrenia, and factors associated with mortality and survival rate in patients with schizophrenia. Methods: We used a population-based cohort from Taiwan National Health Insurance Research Database, to investigate in patients whom were first diagnosed with schizophrenia during the period from 1997 through 2009, the risk of subsequent dyslipidemia during follow-up. Cumulative incidences and hazard ratios after adjusting for competing mortality risks were calculated. Results: A total of 20,964 eligible patients were included. Risks (i.e., comorbidity) and protective factors (i.e., statin use) have significant impacts on mortality. The mortality exhibits a U-shaped pattern by age. After 50, the risk of death increases with age. Risk of mortality before 50 increases with a decrease in age. Risks differed by the duration time to subsequent dyslipidemia after schizophrenia. Mean duration was 63.55 months in the survive group, and 43.19 months in the deceased group. The 5-, 10-, and 15-year survival rates for patients with schizophrenia and subsequent dyslipidemia were 97.5, 90, and 79.18%, respectively. Conclusion: Early occurrence of subsequent dyslipidemia is associated with increased overall mortality in patients with schizophrenia.

Beneficial effects of omega-3 fatty acid supplementation in schizophrenia: possible mechanisms.

BACKGROUND: Schizophrenia is a serious long-term psychotic disorder marked by positive and negative symptoms, severe behavioral problems and cognitive function deficits. The cause of this disorder is not completely clear, but is suggested to be multifactorial, involving both inherited and environmental factors. Since human brain regulates all behaviour, studies have focused on identifying changes in neurobiology and biochemistry of brain in schizophrenia. Brain is the most lipid rich organ (approximately 50% of brain dry weight). Total brain lipids is constituted of more than 60% of phospholipids, in which docosahexaenoic acid (DHA, 22:6n-3) is the most abundant (more than 40%) polyunsaturated fatty acid (PUFA) in brain membrane phospholipids. Results from numerous studies have shown significant decreases of PUFAs, in particular, DHA in peripheral blood (plasma and erythrocyte membranes) as well as brain of schizophrenia patients at different developmental phases of the disorder. PUFA deficiency has been associated to psychotic symptoms and cognitive deficits in schizophrenia. These findings have led to a number of clinical trials examining whether dietary omega-3 fatty acid supplementation could improve the course of illness in patients with schizophrenia. Results are inconsistent. Some report beneficial whereas others show not effective. The discrepancy can be attributed to the heterogeneity of patient population. METHODS: In this review, results from recent experimental and clinical studies, which focus on illustrating the role of PUFAs in the development of schizophrenia were examined. The rationale why omega-3 supplementation was beneficial on symptoms (presented by subscales of the positive and negative symptom scale (PANSS), and cognitive functions in certain patients but not others was reviewed. The potential mechanisms underlying the beneficial effects were discussed. RESULTS: Omega-3 fatty acid supplementation reduced the conversion rate to psychosis and improved both positive and negative symptoms and global functions in adolescents at ultra-high risk for psychosis. Omega-3 fatty acid supplementation could also improve negative symptoms and global functions in the first-episode patients with schizophrenia, but improve mainly total or general PANSS subscales in chronic patients. Patients with low PUFA (particularly DHA) baseline in blood were more responsive to the omega-3 fatty acid intervention. CONCLUSION: Omega-3 supplementation is more effective in reducing psychotic symptom severity in young adults or adolescents in the prodromal phase of schizophrenia who have low omega-3 baseline. Omega-3 supplementation was more effective in patients with low PUFA baseline. It suggests that patients with predefined lipid levels might benefit from lipid treatments, but more controlled clinical trials are warranted.

Effectiveness of a physical activity program on weight, physical fitness, occupational stress, job satisfaction and quality of life of overweight employees in high-tech industries: a randomized controlled study.

Introduction. This study aimed to examine the effectiveness of a physical activity (PA) program on weight control, physical fitness, occupational stress, job satisfaction and quality of life of overweight and sedentary employees in high-tech industries. Methods. Participants in the intervention group (n = 37) were instructed to carry out a PA program at moderate intensity for 60 min/session, 3 sessions/week for 12 weeks. Those in the control group (n = 38) received no PA program and were asked to continue their routine lifestyle. Evaluations were performed at baseline and at the end of the intervention. Results of structured questionnaires and blood biochemistry tests and evaluations of physical fitness were analyzed. Results. The PA program effectively reduced the number of risk factors for metabolic syndrome and body fat percentage, and improved physical fitness such as flexibility, muscular strength and endurance and cardiorespiratory endurance. The intervention also significantly decreased levels of serum triglyceride, total cholesterol and low-density lipoprotein cholesterol. Significant positive effects on work control, interpersonal relationships at work, global job satisfaction and quality of life were also demonstrated. Conclusion. This study showed that a PA program can be helpful in improving physical, physiological and psychological outcomes for overweight and sedentary employees in high-tech industries.

Increased circulating endothelial progenitor cells and improved short-term outcomes in acute non-cardioembolic stroke after hyperbaric oxygen therapy.

BACKGROUND: Acute ischemic stroke is a leading cause of mortality and long-term disability, and profiles of endothelial progenitor cells (EPCs) reflect the degree of endothelial impairment. This study tested the hypothesis that hyperbaric oxygen therapy (HBOT) both improves the clinical short-term outcomes and increases the number of circulating EPCs and antioxidant capacity. METHODS: The numbers of circulating EPCs [CD133+/CD34+ (%), KDR+/CD34+ (%)], biomarkers for oxidative stress (thiols and thiobarbituric acid-reactive substances), and clinical scores (National Institutes of Health Stroke Scale [NIHSS], Barthel index [BI], and modified Rankin Scale [MRS]) were prospectively evaluated in 25 patients with acute non-cardioembolic stroke under HBOT at two time points (pre- and post-HBOT). The biomarkers and clinical scores were compared with those of 25 age- and sex-matched disease controls. RESULTS: The numbers of KDR+/CD34+ (%) in the HBOT group following HBOT increased significantly, whereas the numbers of CD133+/CD34+ (%) also showed a tendency to increase without statistical significance. The mean high-sensitivity C-reactive protein levels showed significant decrease post-HBOT follow-up in the HBOT group. The changes in KDR+/CD34+EPC (%) numbers were positively correlated with changes in clinical outcomes scores (BI, NIHSS, and MRS) in the HBOT group. CONCLUSIONS: Based on the results of our study, HBOT can both improve short-term clinical outcomes and increase the number of circulating EPCs in patients with acute non-cardioembolic stroke.

Omega-3 polyunsaturated fatty acid supplementation in prevention and treatment of maternal depression: Putative mechanism and recommendation.

BACKGROUND: Women are vulnerable to depression during their childbearing years, and giving birth to a child precipitates postpartum depression (PPD) in some women. This review focuses on comparing the effectiveness of omega-3 polyunsaturated fatty acid supplementation on depression during pregnancy or PPD after childbirth. METHODS: MEDLINE, PubMed, PsycINFO, and the Cochrane Collaboration Registry of Controlled Trials etc. through July 2017 were searched. Studies of dietary intake and plasma and/or milk levels of omega-3 fatty acids and trials of benefits and effects of omega-3 fatty acids supplements on pregnant or postpartum women with depression were specifically selected. RESULTS: Omega-3 fatty acid deficiency, due to inadequate intake, fast depletion during pregnancy and lactation, is one of the risk factors of PPD. Associations between neuroinflammation (elevated pro-inflammatory cytokines) and aberrant neurotransmission (low serotonergic transmission activity) and risk of PPD have also been reported by numerous studies. Supplementation with eicosapentaenoic acid (EPA)-rich oil can effectively reduce depression during pregnancy and PPD after childbirth. Long term treatment with docosahexaenoic acid (DHA)-rich oil can be effective in reducing the risk of PPD in healthy women, but not in lactating women. Supplementation of DHA-rich oil to women begun at pregnancy and continued after childbirth exerts no beneficial effect on depression. CONCLUSIONS: Dietary supplementation with omega-3 fatty acids rich in EPA during pregnancy or postpartum reduces some symptoms associated with depression. DHA supplementation to healthy pregnant women can also reduce the risk of PPD.

Effects of a Psychoeducational Intervention in Patients With Breast Cancer Undergoing Chemotherapy.

BACKGROUND: Compelling evidence has yet to be published regarding the positive effect of psychoeducational interventions (PEIs) on psychological distress in patients with breast cancer. The impact of PEIs on self-efficacy, resilience, and quality of life is also unclear. PURPOSE: The aim of this study was to assess the effects of a PEI on anxiety, depression, disease-specific care knowledge, self-efficacy, resilience and quality of life in patients with breast cancer during and after chemotherapy. The intervention was administered before and during five rounds of chemotherapy treatment. METHODS: A randomized controlled trial was conducted. Patients with breast cancer (N = 40) were randomly assigned to either the experimental or control group. The experimental group participated in PEI, a brief and highly structured program consisting of two parts: (a) an educational manual that addressed depression, anxiety, disease-specific care knowledge, self-efficacy, and resilience and (b) a self-assessment of learning. The control group received only traditional pamphlet education. Data were collected at four time points: before the first chemotherapy session (T1), during the third chemotherapy session (T2), during the fifth chemotherapy session (T3), and at 2 weeks after the final chemotherapy session (T4). RESULTS: Anxiety, depression, resilience, and quality of life in the experimental group showed significant differences at T4. Significant differences became apparent at T2 for knowledge and at T3 for self-efficacy. The effects of knowledge, resilience, and quality of life remained significant when group and time interactions were included in the model, showing a positive relationship between PEI and the variables of knowledge, resilience, and quality of life. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Face-to-face PEI for patients with breast cancer is potentially effective in improving knowledge, resilience, and quality of life during and after chemotherapy. In the current study, PEI significantly improved disease care techniques, reduced chemotherapy-related discomfort, and improved quality of life for participants in the experimental group.

Role of adiponectin gene variants, adipokines and hydrometry-based percent body fat in metabolically healthy and abnormal obesity.

OBJECTIVE: Metabolically healthy obesity (MHO) subjects have better metabolic parameters than metabolically abnormal obesity (MAO) subjects, but the possible mechanisms underlying this remain unknown. Our study was designed to investigate the interrelationships among genes, adipokines, body fat and its distribution in MHO and MAO. METHODS: From 2007 to 2009, 103 males and 131 females aged 18-50 years were enrolled by an intention-to-treat design in a weight management clinic. Participants were divided into MHO and MAO groups. Percent body fat (PBF) was measured by a deuterium oxide dilution method. Four polymorphic variants, including PPARγ2 (Pro12Ala and C1431T) and adiponectin (T45G and G276T) genes, and three adipokines (adiponectin, leptin and resistin) were obtained. RESULTS: Of the 234 obese subjects, 130 (55.6%) were MHO. In the univariate analysis, the MAO group has significantly higher anthropometric, metabolic indices and leptin levels than the MHO group. Logistic regression analysis revealed that age, male gender, the T allele of adiponectin T45G polymorphism, leptin and PBF were positively associated with MAO. ANCOVA analysis revealed that the T allele of adiponectin T45G polymorphism was associated with higher fasting and postprandial glucose levels. We further found that TT genotype has a lower high molecular weight (HMW)/low molecular weight (LMW) adiponectin ratio than GG genotype. CONCLUSIONS: The factors associated with MAO are age, male gender, the T allele of adiponectin T45G polymorphism, leptin, and PBF. The net effects of T45G polymorphism on the MAO phenotype may be achieved by changes in the adiponectin oligomer ratio and glucose levels.

Adjunctive Hyperbaric Oxygen Therapy for Healing of Chronic Diabetic Foot Ulcers: A Randomized Controlled Trial.

PURPOSE: The purpose of this study was to compare the effect of standard wound care with adjunctive hyperbaric oxygen therapy (HBOT) to standard wound care alone on wound healing, markers of inflammation, glycemic control, amputation rate, survival rate of tissue, and health-related quality of life in patients with diabetic foot ulcers (DFUs). DESIGN: Prospective, randomized, open-label, controlled study. SUBJECTS AND SETTING: The sample comprised 38 patients with nonhealing DFUs who were deemed poor candidates for vascular surgery. Subjects were randomly allocated to an experimental group (standard care plus HBOT, n = 20) or a control group (standard care alone, n = 18). The study setting was a medical center in Kaohsiung City, Taiwan. METHODS: Hyperbaric oxygen therapy was administered in a hyperbaric chamber under 2.5 absolute atmospheric pressure for 120 minutes; subjects were treated 5 days a week for 4 consecutive weeks. Both groups received standard wound care including debridement of necrotic tissue, topical therapy for Wagner grade 2 DFUs, dietary control and pharmacotherapy to maintain optimal blood glucose levels. Wound physiological indices were measured and blood tests (eg, markers of inflammation) were undertaken. Health-related quality of life was measured using the Medical Outcomes Study 36-Item Short Form. RESULTS: Complete DFU closure was achieved in 5 patients (25%) in the HBOT group (n = 20) versus 1 participant (5.5%) in the routine care group (n = 18) (P = .001). The amputation rate was 5% for the HBOT group and 11% for the routine care group (χ = 15.204, P = .010). The HBOT group showed statistically significant improvements in inflammation index, blood flow, and health-related quality of life from pretreatment to 2 weeks after the last therapy ended (P < .05). Hemoglobin A1c was significantly lower in the HBOT group following treatment (P < .05) but not in the routine care group. CONCLUSIONS: Adjunctive HBOT improved wound healing in persons with DFU. Therapy also reduced the risk of amputation of the affected limb. We assert that at least 20 HBOT sessions are required to be effective.

JKB-122 is effective, alone or in combination with prednisolone in Con A-induced hepatitis.

Con A-induced hepatitis in mice is an established model of autoimmune hepatitis (AIH). JKB-122, a toll-like receptor 4 (TLR4) antagonist, was tested for hepatotprotectant activity. Within several hours of Con A challenge (15mg/kg iv), increased production of proinflammatory cytokines with inflammatory infiltrate occurred in the liver. The severity of tissue necrosis and the amount of circulating liver enzymes peak at 24h post Con A challenge. JKB-122 was given 24 and 16h before, then concurrently, and 4 and 8h (× 5 doses) after challenge with Con A. Serum and liver were harvested at 3, 9 and 24h post Con A challenge. JKB-122 at 20 and 50mg/kg po prevented the increase of serum liver enzymes by 47% and 95% respectively vs vehicle control 24h post Con A. JKB-122 significantly inhibited Con A-induced pathological lesions in the liver and the amount of IFN-γ IL-1ß, IL-4, IL-5, IL-6, IL-17A and TNF-α starting as early as 3h post Con A. Moreover, JKB-122 given concurrently (× 3 doses) with Con A showed similar effect. Finally, JKB-122 enhanced the therapeutic effects of submaximal dose of prednisolone with improved lesion score. It is concluded that JKB-122 at 20 and 50mg/kg po caused dose-dependent inhibition of elevated liver enzymes in Con A-induced hepatitis in mice, indicating hepatoprotectant activity. The results suggest that JKB-122 as monotherapy or in combination with prednisolone may offer a viable approach to the treatment of AIH.

Dose-Response Relationships of Multisensory Intervention on Hospitalized Patients With Chronic Schizophrenia.

BACKGROUND: Patients with chronic schizophrenia often show negative emotional responses because of cognitive impairment. Multisensory stimulation therapy has been shown effective in improving cognitive and emotional functions in cognitively impaired patients with dementia. However, very few studies have applied this multisensory intervention to patients with chronic schizophrenia. Furthermore, it is not known whether a dose-response relationship exists between the frequency and efficacy of this intervention. PURPOSE: The objective of this study was to evaluate the relationship between the effects and dose-response of the multisensory intervention on patients with chronic schizophrenia in a mental rehabilitation hospital. METHODS: A crossover study design with a sample size of 60 was conducted. Participants were divided equally between an experimental group and a control group. The experimental group received the intervention in a multisensory stimulation room. Six sessions of the 30-minute sensory intervention were conducted on experimental group participants, who were allowed to select their preferred stimulants. In contrast, the control group received routine care only. After a 2-week washout period, participants in the experimental group were reassigned to the control group, and those in the control group were reassigned to the experimental group. Standardized questionnaires were applied to evaluate psychotic symptoms, emotional responses, and well-being of all participants. The NeXus-4 model wireless biofeedback system was used to measure the psychological-physiological parameters of participants at baseline and after the first, third, and sixth sessions of the multisensory intervention. A generalized estimating equation model was used to analyze the effects of the intervention RESULTS:: Although multisensory stimulation therapy had no significant effect on psychotic symptoms and well-being, this intervention may improve the negative emotional reactions of patients. In particular, the intervention significantly reduced the subjective anxiety level of participants and stabilized their objective respiratory and heart rates. Moreover, a positive correlation was found between the efficacy of the treatment and the frequency of the intervention. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Evidence from this study validated the multisensory stimulation therapy protocol. Therefore, this protocol may be incorporated into clinical interventions to improve quality of care and to alleviate the negative emotions of patients with chronic schizophrenia.

Effects of nurse-led child- and parent-focused violence intervention on mentally ill adult patients and victimized parents: A randomized controlled trial.

BACKGROUND: Child-to-parent violence is an often hidden serious problem for parental caregivers of mentally ill adult children who experience violence toward them. To date, the comprehensive dyadic parent-adult child intervention to manage child-to-parent violence is scarce. OBJECTIVE: To evaluate the effect of Child- and Parent-focused Violence Program, an adjunctive intervention involved with both violent adult children with mental illness and their victimized biological parent (parent-adult child dyads) on violence management. DESIGN: Open-label randomized controlled trial. SETTING: A psychiatric ward in a teaching hospital and two mental hospitals in Southern Taiwan. PARTICIPANTS: Sixty-nine patients aged ≥20 years, with thought or mood disorders, having violent behavior in the past 6 months toward their biological parent of either gender were recruited. The violent patients' victimized biological parents who had a major and ongoing role in provision of care to these patients, living together with and being assaulted by their violent children were also recruited. The parent-adult child dyads were selected. METHODS: The intervention was carried out from 2011 to 2013. The parent-adult child dyads were randomly assigned to either the experimental group (36 dyads), which received Child- and Parent-focused Violence Intervention Program, or to the control group (33 dyads), which received only routine psychiatric care. The intervention included two individualized sessions for each patient and parent, separately, and 2 conjoint sessions for each parental-child dyad for a total of 6 sessions. Each session lasted for at least 60-min. Data collection was conducted at 3 different time frames: pre-treatment, post-treatment, and treatment follow-up (one month after the completion of the intervention). RESULTS: Occurrence of violence prior to intervention was comparable between two groups: 88.9% (n=32) parents in the experimental group versus 93.9% (n=31) in the control group experienced verbal attack, and 50% (n=18) versus 48.5% (n=16) received body attack and were injured. The intervention significantly reduced violence, improved impulsivity, changed patients' and parents' violence attributions, and fostering active coping processes in the experimental group as compared to the control group (p<0.05). No significant reductions were found in verbal aggression, cognitive and social reactions in the parent's reactions to assault, attentional subscale of impulsivity and wishful thinking (p>0.05). CONCLUSIONS: Child- and Parent-focused Violence Intervention Program is effective on child-to-parent violence management in parent-adult child dyads. Thus, the intervention can be helpful for patients who have just been diagnosed with mental illness and had an episode of violence toward their parents within a narrow time frame.

GPCR dimerization in brainstem nuclei contributes to the development of hypertension.

BACKGROUND AND PURPOSE: µ-Opioid receptors, pro-opiomelanocortin and pro-enkephalin are highly expressed in the nucleus tractus solitarii (NTS) and µ receptor agonists given to the NTS dose-dependently increased BP. However, the molecular mechanisms of this process remain unclear. In vitro, µ receptors heterodimerize with α2A -adrenoceptors. We hypothesized that α2A -adrenoceptor agonists would lose their depressor effects when their receptors heterodimerize in the NTS with µ receptors. EXPERIMENTAL APPROACH: We microinjected µ-opioid agonists and antagonists into the NTS of rats and measured changes in BP. Formation of µ receptor/α2A -adrenoceptor heterodimers was assessed with immunofluorescence and co-immunoprecipitation methods, along with proximity ligation assays. KEY RESULTS: Immunofluorescence staining revealed colocalization of α2A -adrenoceptors and µ receptors in NTS neurons. Co-immunoprecipitation revealed interactions between α2A -adrenoceptors and µ receptors. In situ proximity ligation assays confirmed the presence of µ receptor/α2A -adrenoceptor heterodimers in the NTS. Higher levels of endogenous endomorphin-1 and µ receptor/α2A -adrenoceptor heterodimers were found in the NTS of hypertensive rats, than in normotensive rats. Microinjection of the µ receptor agonist [D-Ala(2) , MePhe(4) , Gly(5) -ol]-enkephalin (DAMGO), but not that of the α2A -adrenoceptor agonist guanfacine, into the NTS of normotensive rats increased µ receptor/α2A -adrenoceptor heterodimer formation and BP elevation. The NO-dependent BP-lowering effect of α2A -adrenoceptor agonists was blunted following increased formation of µ receptor/α2A -adrenoceptor heterodimers in the NTS of hypertensive rats and DAMGO-treated normotensive rats. CONCLUSIONS AND IMPLICATIONS: Increases in endogenous µ receptor agonists in the NTS induced µ receptor/α2A -adrenoceptor heterodimer formation and reduced the NO-dependent depressor effect of α2A -adrenoceptor agonists. This process could contribute to the pathogenesis of hypertension.

Apolipoprotein J, a glucose-upregulated molecular chaperone, stabilizes core and NS5A to promote infectious hepatitis C virus virion production.

BACKGROUND & AIMS: Hepatitis C virus (HCV) infection leads to glucose abnormality. HCV depends on lipid droplets (LDs) and very-low density lipoproteins for assembly/releasing; however, the components and locations for this process remain unidentified. Apolipoprotein J (ApoJ), upregulated by glucose, functions as Golgi chaperone of secreted proteins and resides abundantly in very-low density lipoproteins. This study investigates the interplay between glucose, ApoJ and HCV virion production. METHODS: The effects of high glucose on ApoJ expression and HCV production were evaluated with cultivated HuH7.5, primary human hepatocytes, and in treatment naive chronic hepatitis C patients. How ApoJ affects HCV lifecycle was assessed using siRNA knockdown strategy in JFH1 infected and subgenomic replicon cells. The interactions and locations of ApoJ with viral and host components were examined by immunoprecipitation, immunofluorescence and subcellular fractionation experiments. RESULTS: HCV infection increased ApoJ expression, which in parallel with HCV infectivity was additionally elevated with high glucose treatment. Serum ApoJ correlated positively with fasting blood glucose concentration and HCV-RNA titre in patients. ApoJ silencing reduced intracellular and extracellular HCV infectivity and extracellular HCV-RNA, but accumulated intracellular HCV-RNA in HCV-infected cells. ApoJ interacted with HCV core and NS5A and stabilized the dual protein complex. HCV infection dispersed cytoplasmic ApoJ from the compact zones of the Golgi to encircle LDs, where co-localization of the core, NS5A, HCV-RNA, subcellular markers for LDs, endoplasmic reticulum (ER), Golgi, and membrane contact sites occurred. CONCLUSIONS: ApoJ facilitates infectious HCV particle production via stabilization of core/NS5A, which might surround LDs at the ER-Golgi membrane contact site.