Efficacy of Internet-based rumination-focused cognitive behavioral therapy and mindfulness-based intervention with guided support in reducing risks of depression and anxiety: A randomized controlled trial.

Rumination and worry are common risk factors of depression and anxiety. Internet-based transdiagnostic interventions targeting individuals with these specific risks may be an effective way to prevent depression and anxiety. This three-arm randomized controlled trial compared the efficacy of Internet-based rumination-focused cognitive behavioral therapy (RFCBT), mindfulness-based intervention (MBI), and psychoeducation (EDU) control among 256 at-risk individuals. Participants' levels of rumination, worry, depressive, and anxiety symptoms were assessed at post-intervention (6 weeks), 3-month, and 9-month follow-ups. Linear mixed model analysis results showed similar levels of improvement in all outcomes across the three conditions. Changes in rumination differed comparing RFCBT and MBI, where a significant reduction in rumination was noted at a 3-month follow-up among participants in RFCBT, and no significant long-term effect among participants in MBI was noted at a 9-month follow-up. All three conditions showed similar reductions in risks and symptoms, implying that the two active interventions were not superior to EDU control. The high attrition at follow-ups suggested a need to exercise caution when interpreting the findings. Future studies should tease apart placebo effect and identify ways to improve adherence.

Conjugation of Vancomycin with a Single Arginine Improves Efficacy against Mycobacteria by More Effective Peptidoglycan Targeting.

Drug resistant bacterial infections have emerged as one of the greatest threats to public health. The discovery and development of new antimicrobials and anti-infective strategies are urgently needed to address this challenge. Vancomycin is one of the most important antibiotics for the treatment of Gram-positive infections. Here, we introduce the vancomycin-arginine conjugate (V-R) as a highly effective antimicrobial against actively growing mycobacteria and difficult-to-treat mycobacterial biofilm populations. Further improvement in efficacy through combination treatment of V-R to inhibit peptidoglycan synthesis and ethambutol to inhibit arabinogalactan synthesis underscores the ability to identify compound synergies to more effectively target the Achilles heel of the cell-wall assembly. Moreover, we introduce mechanistic activity data and a molecular model derived from a d-Ala-d-Ala-bound vancomycin structure that we hypothesize underlies the molecular basis for the antibacterial improvement attributed to the arginine modification that is specific to peptidoglycan chemistry employed by mycobacteria and distinct from Gram-positive pathogens.

Time-Dependent Changes in Depressive Symptoms Among Control Participants in Digital-Based Psychological Intervention Studies: Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Digital-based psychological interventions (DPIs) have been shown to be efficacious in many randomized controlled trials (RCTs) in dealing with depression in adults. However, the effects of control comparators in these DPI studies have been largely overlooked, and they may vary in their effects on depression management. OBJECTIVE: This meta-analytical study aimed to provide a quantitative estimate of the within-subject effects of control groups across different time intervals and explore the moderating effects of control types and symptom severity at baseline. METHODS: A systematic literature search was conducted in late September 2021 on selected electronic databases: PubMed; ProQuest; Web of Science; and the Ovid system with MEDLINE, PsycINFO, and Embase. The control conditions in 107 RCTs with a total of 11,803 adults with depressive symptoms were included in the meta-analysis, and effect sizes (Hedges g) were calculated using the standardized mean difference approach. Study quality was assessed using the Cochrane risk-of-bias tool for randomized trials version 2. RESULTS: The control conditions collectively yielded small to moderate effects in reducing depressive symptoms within 8 weeks since the baseline assessment (g=-0.358, 95% CI -0.434 to -0.281). The effects grew to moderate within 9 to 24 weeks (g=-0.549, 95% CI -0.638 to -0.460) and peaked at g=-0.810 (95% CI -0.950 to -0.670) between 25 and 48 weeks. The effects were maintained at moderate to large ranges (g=-0.769, 95% CI -1.041 to -0.498) beyond 48 weeks. The magnitude of the reduction differed across the types of control and severity of symptoms. Care as usual was the most powerful condition of all and produced a large effect (g=-0.950, 95% CI -1.161 to -0.739) in the medium term. The findings showed that waitlist controls also produced a significant symptomatic reduction in the short term (g=-0.291, 95% CI -0.478 to -0.104), refuting the previous suspicion of a nocebo effect. In addition, a large effect on depressive symptom reduction in the long term (g=-1.091, 95% CI -1.210 to -0.972) was noted among participants with severe levels of depressive symptoms at baseline. CONCLUSIONS: This study provided evidence that depressive symptoms generally reduced over time among control conditions in research trials of DPIs. Given that different control conditions produce variable and significant levels of symptomatic reduction, future intervention trials must adopt an RCT design and should consider the contents of control treatments when investigating the efficacy of DPIs. The results of waitlist controls confirmed previous findings of spontaneous recovery among people with mild to moderate depressive symptoms in face-to-face studies. Researchers may adopt watchful waiting as participants wait for the availability of digital-based psychological services.

Nonattachment at Work on Well-being Among Working Adults in Hong Kong.

Objectives: Nonattachment has been found to be a potentially important mental quality in mitigating psychological distress and promoting well-being across student and community adult populations. This study investigated the relationships between nonattachment and three workplace-related variables, namely control at work, psychological safety, and supervisor support, on mental well-being of a representative sample of working adults in Hong Kong. Methods: This is a cross-sectional investigation using the data provided by 1008 working adults who participated in a population-based telephone survey. Structural equation modeling (SEM) was performed to test how nonattachment may be related to mental well-being of working adults, with the relationship being mediated by three workplace-related variables. Results: Results indicated that nonattachment was positively associated with flourishing. This association was mediated by perceived supervisor support and control at work. In addition, nonattachment was negatively related to depression and anxiety symptoms and the association was only mediated by perceived supervisor support. Psychological safety did not significantly mediate the effect of nonattachment on mental well-being. Conclusions: This study provides suggestive evidence that staff's perception towards supervisors and level of control at work can bridge the relationship between nonattachment and employee well-being. Potential cultural nuance that may have contributed to the nonsignificance of psychological safety was discussed.

COVID-19 heterogeneity in islands chain environment.

BACKGROUND: It is critical to capture data and modeling from the COVID-19 pandemic to understand as much as possible and prepare for future epidemics and possible pandemics. The Hawaiian Islands provide a unique opportunity to study heterogeneity and demographics in a controlled environment due to the geographically closed borders and mostly uniform pandemic-induced governmental controls and restrictions. OBJECTIVE: The goal of the paper is to quantify the differences and similarities in the spread of COVID-19 among different Hawaiian islands as well as several other archipelago and islands, which could potentially help us better understand the effect of differences in social behavior and various mitigation measures. The approach should be robust with respect to the unavoidable differences in time, as the arrival of the virus and promptness of mitigation measures may vary significantly among the chosen locations. At the same time, the comparison should be able to capture differences in the overall pandemic experience. METHODS: We examine available data on the daily cases, positivity rates, mobility, and employ a compartmentalized model fitted to the daily cases to develop appropriate comparison approaches. In particular, we focus on merge trees for the daily cases, normalized positivity rates, and baseline transmission rates of the models. RESULTS: We observe noticeable differences among different Hawaiian counties and interesting similarities between some Hawaiian counties and other geographic locations. The results suggest that mitigation measures should be more localized, that is, targeting the county level rather than the state level if the counties are reasonably insulated from one another. We also notice that the spread of the disease is very sensitive to unexpected events and certain changes in mitigation measures. CONCLUSIONS: Despite being a part of the same archipelago and having similar protocols for mitigation measures, different Hawaiian counties exhibit quantifiably different dynamics of the spread of the disease. One potential explanation is that not sufficiently targeted mitigation measures are incapable of handling unexpected, localized outbreak events. At a larger-scale view of the general spread of the disease on the Hawaiian island counties, we find very interesting similarities between individual Hawaiian islands and other archipelago and islands.

Differential associations among social support, health promoting behaviors, health-related quality of life and subjective well-being in older and younger persons: a structural equation modelling approach.

BACKGROUND: Extensive studies have confirmed social support as a critical protective factor of people's health-related quality of life (HRQoL) and subjective well-being (SWB). However, health promoting behaviors as a potential mechanism and age differences in this mechanism has received fewer attention. This study aims to examine the associations among social support, health promoting behaviors, HRQoL and SWB in older and younger persons in Hong Kong. METHOD: A convenience sample of both younger (12-35 years old) and older persons (55 years old and above) were recruited from three non-government organizations to complete a survey. Structural Equation Model (SEM) was conducted to test both the measurement model and structural models to examine the relationship between social support, health promoting behaviors, HRQoL and SWB. Multi-group SEM was also performed and compared to test whether there were significant age differences in the pathways between the key variables. RESULTS: A final sample of 408 participants (older-persons: N = 200 (mean age: 71.63 (8.16); 180/200 female), younger-persons: N = 208 (mean age: 18.10 (5.04); 155/208 female) were included in the final analysis. Results showed that social support was positively associated with SWB directly and indirectly through health promoting behaviors for the whole sample (CFI = .95, IFI = .94, RMSEA = .07, SRMR = 0.056). Results suggested that the association between the variables differed across age samples. While social support showed a positive association with health promoting behaviors for both younger and older persons, how each of them associated with HRQoL and SWB was different. CONCLUSION: Findings suggest that the pathway which social support linked with HRQoL and SWB might differ across age groups. Age-specific strategies should be considered when promoting HRQoL and SWB among the younger and older population.

Mindfulness meditation for Chinese patients with psychosis: A systematic review and meta-analysis.

Mindfulness meditation (MM) and its alignment with the mind-body perspective of health in Chinese cultures indicate its potential to benefit Chinese patients with psychosis. This is the first systematic review and meta-analysis to address the following questions: (1) Does MM improve clinical, well-being, and third-wave outcomes (i.e., mindfulness, acceptance, and compassion levels) among Chinese patients with psychosis? (2) What are the patient- and/or intervention-specific factors that moderate the efficacy of MM? (3) Are improvements on third-wave outcomes associated with improvements on clinical and well-being outcomes? (4) What are the mechanisms underlying the effects of MM? Evidence synthesized from 23 relevant articles (20 studies) involving 1749 patients showed that (1) MM improved a wide range of patients' outcomes, most consistently and sustainably for insight, rehospitalization duration, recovery rate, and social functioning; (2) age and duration of illness, but not the cumulated intervention hours, moderated the overall efficacy of MM; (3) post-MM improvements on mindfulness and on clinical and well-being outcomes were related, and (4) the effects of MM on patients' outcomes may be driven by its ability to promote positive changes in personal growth and enhance one's coping with the illness and its symptoms. Our data showed preliminary support for the benefits of MM in Chinese patients with psychosis. However, results should be considered in light of the varying quality of included studies and their heterogeneity in multiple aspects. Further research is needed to deduce the sustainability of MM's effects, its active ingredients, underlying mechanisms, and additional moderators of its efficacy.

Socioeconomic Status, Mental Health, and Workplace Determinants among Working Adults in Hong Kong: A Latent Class Analysis.

This study provides insights on mental health correlates and work stress patterns in a representative sample of working adults in Hong Kong using an intersectional perspective. Using data from a cross-sectional, population-based telephone survey of 1007 working adults in Hong Kong, latent class analysis was conducted to identify socioeconomic classes within the sample. Three latent classes were identified, and they differed significantly in all the SES variables. Results suggested mental health to be the lowest in Class 1, the lowest income group. The three classes did not differ from their perceived level of job demand and control in work-related stress. Predictably, the highest income group perceived the lowest level of effort-reward imbalance. The lowest paid class was also reported perceiving the lowest level of relational justice. Different barriers to mental health services were also identified. Finally, cultural implications associated with work stress patterns, research, and practice implications are discussed. This study provides an empirical foundation for future studies to investigate patterns of job stress and mental health needs in a diverse population of working adults, with a particular focus on addressing the intersectional profiles of working adults and their needs in mental health services.

Evidence for a novel subcortical mechanism for posterior cingulate cortex atrophy in HIV peripheral neuropathy.

We previously reported that neuropathic pain was associated with smaller posterior cingulate cortical (PCC) volumes, suggesting that a smaller/dysfunctional PCC may contribute to development of pain via impaired mind wandering. A gap in our previous report was lack of evidence for a mechanism for the genesis of PCC atrophy in HIV peripheral neuropathy. Here we investigate if volumetric differences in the subcortex for those with neuropathic paresthesia may contribute to smaller PCC volumes, potentially through deafferentation of ascending white matter tracts resulting from peripheral nerve damage in HIV neuropathy. Since neuropathic pain and paresthesia are highly correlated, statistical decomposition was used to separate pain and paresthesia symptoms to determine which regions of brain atrophy are associated with both pain and paresthesia and which are associated separately with pain or paresthesia. HIV+ individuals (N = 233) with and without paresthesia in a multisite study underwent structural brain magnetic resonance imaging. Voxel-based morphometry and a segmentation/registration tool were used to investigate regional brain volume changes associated with paresthesia. Analysis of decomposed variables found that smaller midbrain and thalamus volumes were associated with paresthesia rather than pain. However, atrophy in the PCC was related to both pain and paresthesia. Peak thalamic atrophy (p = 0.004; MNI x = - 14, y = - 24, z = - 2) for more severe paresthesia was in a region with reciprocal connections with the PCC. This provides initial evidence that smaller PCC volumes in HIV peripheral neuropathy are related to ascending white matter deafferentation caused by small fiber damage observed in HIV peripheral neuropathy.

Objective and subjective cognitive functioning in relation to psychopathology among women with early psychosis.

BACKGROUND: Subjective cognitive impairment (SCI) among early psychosis is under-recognized and under-studied. However, SCI is as important as objective impairment to be understood, since it assesses cognitive difficulties in real-life situations from a personal perspective and is therefore an essence of individualized medicine. This study aims to explore the associations between the objective and subjective measures of cognitive impairments and to identify factors contributing to SCI among people with early psychosis. METHODS: Participants were 60 females (mean age 24.57 ± 8.28) who had a diagnosis of psychotic-spectrum disorder within 5 years. They completed a battery of neuropsychological tests assessing a range of cognitive functions including verbal learning, memory, attention, and executive functions. The Subjective Cognitive Impairment Scale (SCIS) was used to assess their perceived cognitive decline. Psychotic symptoms and depression were also assessed. RESULTS: SCIS was not correlated with any of the objective cognitive tests results. It was positively correlated with depression and positive symptoms. A hierarchical multiple regression model revealed that positive symptoms and depression together explained 31.9% of the total variance in SCIS and only depression significantly predicted SCI. Performances on the memory tests were correlated with, and predicted by negative symptoms. CONCLUSIONS: There was no correlation between SCI and objective cognitive performances in patients with early psychosis. Treatments should not only focus on symptomatic remission and performance of cognitive tests, but also place emphasis on improving moods and subjective cognitive functions of individuals with early psychosis.

Profile of gynaecology surgeries from Western Province, Solomon Islands.

INTRODUCTION: Evidence is lacking on the profile of gynaecological conditions affecting women in the Solomon Islands, including the availability and quality of surgical management. METHODS: Prospective analysis of hospital records was undertaken on all patients who underwent gynaecological surgery at Gizo Hospital, Western Province during a 6-day program led by volunteer Australian surgeons. Patient data on pre-operative history, investigation results, performed surgical procedures and postoperative recovery were collected. RESULTS: Of the 23 patients who presented with gynaecological problems requiring surgery, 20 underwent at least one surgical procedure during the study period. The most common presenting symptoms were pain and abnormal uterine bleeding. Median body mass index was 27, and 70% of patients were overweight or obese. Two surgeries were cancelled due to dengue fever. The surgeries performed were 12 vaginal operations, 8 laparoscopies and 9 laparotomies. Of surgical specimens collected, 61% were sent for histopathology testing. The median duration of postoperative hospital admission was 2 days (interquartile range, 1 day). CONCLUSION: The Solomon Islands presents a unique profile of challenges to surgical practice, including the impact of dengue infection on fitness for surgery, a mobile patient population dispersed across the islands, difficult access to pathology services, and increased length of stay. Despite this, most patients had surgical outcomes equivalent to those in a developed setting.

Efficacy and Moderation of Mobile App-Based Programs for Mindfulness-Based Training, Self-Compassion Training, and Cognitive Behavioral Psychoeducation on Mental Health: Randomized Controlled Noninferiority Trial.

BACKGROUND: Mindfulness-based interventions, self-compassion training, and cognitive behavioral therapy have garnered much evidence in its salutary effects on mental health. With increasing application of smartphone and mobile technology on health promotion, this study investigated the efficacy and possible moderators of mindfulness, self-compassion, and cognitive behavioral psychoeducation training mobile apps in the improvement of mental health. OBJECTIVE: The aim of this study was to examine the efficacy of 3 mobile app-based programs: mindfulness-based program, self-compassion program, and cognitive behavioral psychoeducation program in improving mental well-being and reducing psychological distress. Changes in mindful awareness and self-compassion were also assessed. To further delineate the suitability of each program for different types of individuals, individual difference variables (ie, discomfort with emotions and tolerance for ambiguity) were explored for potential moderation. METHODS: This study was a 3-arm, randomized, controlled, noninferiority trial examining the efficacy of mindfulness-based program, self-compassion program, and cognitive behavioral psychoeducation. Participants were randomized into either 1 of the 3 conditions. Throughout the 4-week, 28-session program, participants spent 10-15 min daily reviewing the course content and practicing various related exercises. At preprogram, postprogram, and 3-month follow-up, participants also completed Web-based measures of mental well-being, psychological distress, mindful-awareness, and self-compassion as well as the proposed moderators. RESULTS: Among the 2161 study participants, 508 and 349 completed the post- and 3-month follow-up assessment, respectively. All 3 conditions (mindfulness-based program: N=703; cognitive behavioral psychoeducation: N=753; self-compassion program: N=705) were found to be efficacious in improving mental well-being and reducing psychological distress. All conditions enhanced mindful awareness at postprogram. Significant interaction effect was found on self-compassion; cognitive behavioral psychoeducation and self-compassion program, but not mindfulness-based program, significantly enhanced self-compassion at postprogram. No significant differences regarding usage and users' satisfaction were found among the 3 conditions. None of the proposed moderators were found to be significant. CONCLUSIONS: Mindfulness-based, self-compassion, and cognitive behavioral psychoeducation mobile apps were efficacious in improving mental well-being and reducing psychological distress among adults at postprogram and 3-month follow-up. Future app-based psychological training programs should consider gamification and personalization of content or feedback to enhance engagement and mitigate the high attrition rates that are common in app-based health promotion programs. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) ChiCTR-TRC-13003468; http://www.chictr.org.cn/hvshowproject.aspx?id=6220 (Archived by WebCite at http://www.webcitation.org/734PlOz50).

Unraveling the insight paradox: One-year longitudinal study on the relationships between insight, self-stigma, and life satisfaction among people with schizophrenia spectrum disorders.

The promotion of insight among people with schizophrenia spectrum disorders has posed a dilemma to service providers as higher insight has been linked to positive clinical outcomes but negative psychological outcomes. The negative meaning that people attached to the illness (self-stigma content) and the recurrence of such stigmatizing thoughts (self-stigma process) may explain why increased insight is associated with negative outcomes. The present study examined how the presence of high self-stigma content and self-stigma process may contribute to the negative association between insight and life satisfaction. A total of 181 people with schizophrenia spectrum disorders were assessed at baseline. 130 and 110 participants were retained and completed questionnaire at 6-month and 1-year follow-up, respectively. Results showed that baseline insight was associated with lower life satisfaction at 6-month when self-stigma process or self-stigma content was high. Furthermore, baseline insight was predictive of better life satisfaction at 1-year follow-up when self-stigma process was low. Findings suggested that the detrimental effects of insight can be a result from both the presence of cognitive content and habitual process of self-stigma. Future insight promotion interventions should also address self-stigma content and process among people with schizophrenia spectrum disorders so as to maximize the beneficial effects of insight.

Flourishing With Psychosis: A Prospective Examination on the Interactions Between Clinical, Functional, and Personal Recovery Processes on Well-being Among Individuals with Schizophrenia Spectrum Disorders.

Well-being is not just the absence of mental disorder but also involves positive feelings and contentment (emotional well-being), meaningful engagement (psychological well-being), and contribution of one's community or society (social well-being). Recovery processes, which encompass mitigation of clinical symptomatology (clinical recovery), improvement in occupational, social, and adaptive functioning (functional recovery), and development of personally valued goals and identity (personal recovery), have demonstrated to be important markers of well-being. This study examined the relative contribution of clinical, functional, and personal recovery processes on well-being among individuals with schizophrenia and explored the effect of personal recovery on people with varying levels of symptom severity and functional ability. A longitudinal quantitative research design was used in which 181 people with schizophrenia spectrum disorders were assessed at baseline and 6 months. At baseline, 28.2% of the participants were considered as flourishing. Around half of the participants (52.5%) were moderately mentally healthy, while 19.3% were identified as languishing. Results showed that clinical recovery was predictive of better well-being at 6-month postbaseline. Personal recovery was found to positively predict well-being, above and beyond the effects of clinical and functional recovery. Moderation analysis showed that the effect of personal recovery on well-being did not depend on clinical and functional recovery, which implied that people with schizophrenia can participate in the process of personal recovery and enjoy positive well-being regardless of their clinical stability and functional competence. Given the robust salutogenic effect of personal recovery, greater emphasis should be placed on developing person-centered, strength-based, recovery-oriented services.

Autoimmunity Against the Heart and Cardiac Myosin in Children With Myocarditis.

BACKGROUND: Host autoimmune activity in myocarditis has been proposed to play a role in development of cardiac disease, but evidence of autoimmunity and relationship to outcomes have not been evaluated in pediatric myocarditis. METHODS: We performed a multi-institutional study of children with clinical myocarditis. Newly diagnosed patients were followed for up to 12 months and previously diagnosed patients at a single follow-up for serum levels of autoantibodies to human cardiac myosin, beta-adrenergic receptors 1 and 2, muscarinic-2 receptors, and antibody-mediated protein kinase A (PKA) activation in heart cells in culture. Results were compared with those of healthy control children. RESULTS: Both previously diagnosed patient at follow-up (P = .0061) and newly diagnosed patients at presentation (P = .0127) had elevated cardiac myosin antibodies compared with control subjects. Antibody levels were not associated with recovery status at follow-up in either group. PKA activation was higher at presentation in the newly diagnosed patients who did not recovery normal function (P = .042). CONCLUSIONS: Children with myocarditis have evidence of autoantibodies against human cardiac myosin at diagnosis and follow-up compared with control subjects. Differences in antibody-mediated cell signaling may contribute to differences in patient outcomes, as suggested by elevated antibody-mediated PKA activation in heart cells by the serum from nonrecovered patients.

High Frequency of Detection by PCR of Viral Nucleic Acid in The Blood of Infants Presenting with Clinical Myocarditis.

Specific viruses are associated with pediatric myocarditis, but the prevalence of viral DNAemia detected by blood polymerase chain reaction (PCR) is unknown. We evaluated the prevalence of known cardiotropic viruses (enterovirus, adenovirus, human herpesvirus 6, and parvovirus B19) in children with clinical myocarditis (n = 21). Results were compared to pediatric controls with similar viral PCR testing. The majority of positive PCR (89 %) was noted in children ≤12 months of age at diagnosis compared to older children. Infant myocarditis patients (8/10) had increased the prevalence of PCR positivity compared to infant pediatric controls (4/114) (p < 0.0001). Other than age, patient characteristics at diagnosis were similar between PCR-positive and PCR-negative patients. Both PCR-negative myocarditis infants had clinical recovery at follow-up. Of the PCR-positive myocarditis infants, 4 had clinical recovery, 2 developed chronic cardiomyopathy, 1 underwent heart transplant, and 1 died. Infants with clinical myocarditis have a high rate of blood viral positivity, which is higher compared to older children with myocarditis and healthy infant controls. Age-related differences in PCR positivity may be due to differences in host and/or virus characteristics. Our findings suggest that viral blood PCR may be a useful diagnostic tool and identify patients who would potentially benefit from virus-specific therapy.

A Low-Intensity Mindfulness-Based Intervention for Mood Symptoms in People with Early Psychosis: Development and Pilot Evaluation.

BACKGROUND: Depressive and anxiety symptoms are common in people suffering from early psychosis. Growing evidence shows that mindfulness-based intervention is an effective option in handling depression and anxiety disorders. Current article aims to provide documentation on the development and pilot study, before a RCT of larger scale, evaluating the acceptability and potential effects of a 7-week mindfulness-based intervention programme (MBI-p). METHOD: MBI-p was developed over nine months in 2014. A total of 14 people with early psychosis were recruited to three pilot trials of MBI-p. Eleven of them completed the programme and were interviewed. Eight of them were measured quantitatively at baseline and post-intervention on clinical symptoms, depression and anxiety levels, quality of life and mindfulness. RESULTS: Mixed qualitative and quantitative results supported MBI-p as an acceptable and feasible intervention. Significant statistical improvements were found in depression levels, mental quality of life, general psychopathology and ability to observe emotions and act with awareness. Qualitative comments suggested that the intervention was safe, enjoyable and had a positive impact on mood symptoms. In summary, these results provide a promising pilot support for a potentially effective and cost-efficient treatment option for people with early psychosis. Copyright © 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Depressive and anxiety symptoms are common in people with early psychosis but long received little attention. A low-intensity mindfulness-based intervention targeting depression and anxiety symptoms among people with early psychosis was developed and pilot tested. It is feasible and acceptable to use mindfulness-based intervention as a complementary treatment for psychosis.

Global analysis of alternative splicing during T-cell activation.

The role of alternative splicing (AS) in eliciting immune responses is poorly understood. We used quantitative AS microarray profiling to survey changes in AS during activation of Jurkat cells, a leukemia-derived T-cell line. Our results indicate that approximately 10-15% of the profiled alternative exons undergo a >10% change in inclusion level during activation. The majority of the genes displaying differential AS levels are distinct from the set of genes displaying differential transcript levels. These two gene sets also have overlapping yet distinct functional roles. For example, genes that show differential AS patterns during T-cell activation are often closely associated with cell-cycle regulation, whereas genes with differential transcript levels are highly enriched in functions associated more directly with immune defense and cytoskeletal architecture. Previously unknown AS events were detected in genes that have important roles in T-cell activation, and these AS level changes were also observed during the activation of normal human peripheral CD4+ and CD8+ lymphocytes. In summary, by using AS microarray profiling, we have discovered many new AS changes associated with T-cell activation. Our results suggest an extensive role for AS in the regulation of the mammalian immune response.

Differential expression of CD45 isoforms is controlled by the combined activity of basal and inducible splicing-regulatory elements in each of the variable exons.

The human CD45 gene encodes five isoforms of a transmembrane tyrosine phosphatase that differ in their extracellular domains as a result of alternative splicing of exons 4-6. Expression of the CD45 isoforms is tightly regulated in peripheral T cells such that resting cells predominantly express the larger CD45 isoforms, encoded by mRNAs containing two or three variable exons. In contrast, activated T cells express CD45 isoforms encoded by mRNAs lacking most or all of the variable exons. We have previously identified the sequences within CD45 variable exon 4 that control its level of inclusion into spliced mRNAs. Here we map the splicingregulatory sequences within CD45 variable exons 5 and 6. We show that, like exon 4, exons 5 and 6 each contain an exonic splicing silencer (ESS) and an exonic splicing enhancer (ESE), which together determine the level of exon inclusion in naïve cells. We further demonstrate that the primary activation-responsive silencing motif in exons 5 and 6 is homologous to that in exon 4 and, as in exon 4, binds specifically to the protein heterogeneous nuclear ribonucleoprotein L. Together these studies reveal common themes in the regulation of the CD45 variable exons and provide a mechanistic explanation for the observed physiological expression of CD45 isoforms.