A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart.

Cardiomyocytes are subjected to the intense mechanical stress and metabolic demands of the beating heart. It is unclear whether these cells, which are long-lived and rarely renew, manage to preserve homeostasis on their own. While analyzing macrophages lodged within the healthy myocardium, we discovered that they actively took up material, including mitochondria, derived from cardiomyocytes. Cardiomyocytes ejected dysfunctional mitochondria and other cargo in dedicated membranous particles reminiscent of neural exophers, through a process driven by the cardiomyocyte's autophagy machinery that was enhanced during cardiac stress. Depletion of cardiac macrophages or deficiency in the phagocytic receptor Mertk resulted in defective elimination of mitochondria from the myocardial tissue, activation of the inflammasome, impaired autophagy, accumulation of anomalous mitochondria in cardiomyocytes, metabolic alterations, and ventricular dysfunction. Thus, we identify an immune-parenchymal pair in the murine heart that enables transfer of unfit material to preserve metabolic stability and organ function. VIDEO ABSTRACT.

Maternal Factors and Placental Pathologies Associated with a Diagnosis of Chronic Villitis.

OBJECTIVE: To evaluate maternal risk factors associated with chronic villitis of unknown etiology (VUE) and to describe cooccurring placental pathologies. STUDY DESIGN: A retrospective case-control study was conducted using placental pathology records from deliveries ≥ 20 weeks between 2010 and 2018. Cases were placentas with documented chronic villitis without infectious cause, hereafter called VUE. Controls were placentas without this diagnosis, matched to the cases 2:1. Maternal and neonatal demographic and clinical data were collected. Descriptive statistics are reported with Fisher's exact test or a chi-squared test, as appropriate, and multivariable conditional logistic regression was conducted. RESULTS: Our study included 352 cases with VUE and 657 controls. A diagnosis of gestational diabetes (p = 0.03) and gestational hypertension (p = 0.06) was 1.5 times more likely to occur in those with a VUE diagnosis. A trend was also seen for chronic hypertension (odds ratio [OR] = 1.7, p = 0.07) and preeclampsia (OR = 1.5, p = 0.09) compared with controls. Placentas with VUE, specifically high-grade VUE, were more likely to be small for gestational age (p = 0.01), and to be diagnosed with other placental findings including lymphoplasmacytic or chronic deciduitis (p < 0.01), maternal (p < 0.01) and fetal vascular malperfusion (p = 0.02), and chorionitis (acute or chronic; p < 0.01). CONCLUSION: Gestational diabetes and hypertension were associated with a diagnosis of VUE, and overall, VUE placentas have more abnormal placental findings compared with control. Understanding VUE risk factors may facilitate prenatal care strategies and counseling to achieve the best outcomes for pregnant patients and their neonates. KEY POINTS: · VUE is a common inflammatory lesion of the placenta.. · Gestational diabetes and hypertension are associated with a VUE diagnosis.. · Findings of other placental pathologies increase in VUE..

Extracellular vesicles from neural stem cells transfer IFN-γ via Ifngr1 to activate Stat1 signaling in target cells.

The idea that stem cell therapies work only via cell replacement is challenged by the observation of consistent intercellular molecule exchange between the graft and the host. Here we defined a mechanism of cellular signaling by which neural stem/precursor cells (NPCs) communicate with the microenvironment via extracellular vesicles (EVs), and we elucidated its molecular signature and function. We observed cytokine-regulated pathways that sort proteins and mRNAs into EVs. We described induction of interferon gamma (IFN-γ) pathway in NPCs exposed to proinflammatory cytokines that is mirrored in EVs. We showed that IFN-γ bound to EVs through Ifngr1 activates Stat1 in target cells. Finally, we demonstrated that endogenous Stat1 and Ifngr1 in target cells are indispensable to sustain the activation of Stat1 signaling by EV-associated IFN-γ/Ifngr1 complexes. Our study identifies a mechanism of cellular signaling regulated by EV-associated IFN-γ/Ifngr1 complexes, which grafted stem cells may use to communicate with the host immune system.

Deep Convolutional Generative Adversarial Networks to Enhance Artificial Intelligence in Healthcare: A Skin Cancer Application.

In recent years, researchers designed several artificial intelligence solutions for healthcare applications, which usually evolved into functional solutions for clinical practice. Furthermore, deep learning (DL) methods are well-suited to process the broad amounts of data acquired by wearable devices, smartphones, and other sensors employed in different medical domains. Conceived to serve the role of diagnostic tool and surgical guidance, hyperspectral images emerged as a non-contact, non-ionizing, and label-free technology. However, the lack of large datasets to efficiently train the models limits DL applications in the medical field. Hence, its usage with hyperspectral images is still at an early stage. We propose a deep convolutional generative adversarial network to generate synthetic hyperspectral images of epidermal lesions, targeting skin cancer diagnosis, and overcome small-sized datasets challenges to train DL architectures. Experimental results show the effectiveness of the proposed framework, capable of generating synthetic data to train DL classifiers.

Neural Networks-Based On-Site Dermatologic Diagnosis through Hyperspectral Epidermal Images.

Cancer originates from the uncontrolled growth of healthy cells into a mass. Chromophores, such as hemoglobin and melanin, characterize skin spectral properties, allowing the classification of lesions into different etiologies. Hyperspectral imaging systems gather skin-reflected and transmitted light into several wavelength ranges of the electromagnetic spectrum, enabling potential skin-lesion differentiation through machine learning algorithms. Challenged by data availability and tiny inter and intra-tumoral variability, here we introduce a pipeline based on deep neural networks to diagnose hyperspectral skin cancer images, targeting a handheld device equipped with a low-power graphical processing unit for routine clinical testing. Enhanced by data augmentation, transfer learning, and hyperparameter tuning, the proposed architectures aim to meet and improve the well-known dermatologist-level detection performances concerning both benign-malignant and multiclass classification tasks, being able to diagnose hyperspectral data considering real-time constraints. Experiments show 87% sensitivity and 88% specificity for benign-malignant classification and specificity above 80% for the multiclass scenario. AUC measurements suggest classification performance improvement above 90% with adequate thresholding. Concerning binary segmentation, we measured skin DICE and IOU higher than 90%. We estimated 1.21 s, at most, consuming 5 Watts to segment the epidermal lesions with the U-Net++ architecture, meeting the imposed time limit. Hence, we can diagnose hyperspectral epidermal data assuming real-time constraints.

Evaluation of Preprocessing Methods on Independent Medical Hyperspectral Databases to Improve Analysis.

Currently, one of the most common causes of death worldwide is cancer. The development of innovative methods to support the early and accurate detection of cancers is required to increase the recovery rate of patients. Several studies have shown that medical Hyperspectral Imaging (HSI) combined with artificial intelligence algorithms is a powerful tool for cancer detection. Various preprocessing methods are commonly applied to hyperspectral data to improve the performance of the algorithms. However, there is currently no standard for these methods, and no studies have compared them so far in the medical field. In this work, we evaluated different combinations of preprocessing steps, including spatial and spectral smoothing, Min-Max scaling, Standard Normal Variate normalization, and a median spatial smoothing technique, with the goal of improving tumor detection in three different HSI databases concerning colorectal, esophagogastric, and brain cancers. Two machine learning and deep learning models were used to perform the pixel-wise classification. The results showed that the choice of preprocessing method affects the performance of tumor identification. The method that showed slightly better results with respect to identifing colorectal tumors was Median Filter preprocessing (0.94 of area under the curve). On the other hand, esophagogastric and brain tumors were more accurately identified using Min-Max scaling preprocessing (0.93 and 0.92 of area under the curve, respectively). However, it is observed that the Median Filter method smooths sharp spectral features, resulting in high variability in the classification performance. Therefore, based on these results, obtained with different databases acquired by different HSI instrumentation, the most relevant preprocessing technique identified in this work is Min-Max scaling.

Cost-effectiveness of a Contact Intervention and a Psychotherapeutic Program for Post-discharge Suicide Prevention.

OBJECTIVE: To determine the cost-effectiveness of 2 strategies for post-discharge suicide prevention, an Enhanced Contact intervention based on repeated in-person and telephone contacts, and an individual 2-month long problem-solving Psychotherapy program, in comparison to facilitated access to outpatient care following a suicide attempt. METHODS: We conducted a cost-effectiveness analysis based on a decision tree between January and December 2019. Comparative effectiveness estimates were obtained from an observational study conducted between 2013 and 2017 in Madrid, Spain. Electronic health care records documented resource use (including extra-hospital emergency care, mortality, inpatient admission, and disability leave). Direct cost data were derived from Madrid's official list of public health care prices. Indirect cost data were derived from Spain's National Institute of Statistics. RESULTS: Both augmentation strategies were more cost-effective than a single priority outpatient appointment considering reasonable thresholds of willingness to pay. Under the base-case scenario, Enhanced Contact and Psychotherapy incurred, respectively, €2,340 and 6,260 per averted attempt, compared to a single priority appointment. Deterministic and probabilistic sensitivity analyses showed both augmentation strategies to remain cost-effective under several scenarios. Enhanced Contact was slightly cost minimizing in comparison to Psychotherapy (base-case scenario: €-196 per averted attempt). CONCLUSIONS: Two post-discharge suicide prevention strategies based on Enhanced Contact and Psychotherapy were cost-effective in comparison to a single priority appointment. Increasing contacts between suicide attempters and mental health-care providers was slightly cost minimizing compared to psychotherapy.

Mindfulness-based mobile app reduces anxiety and increases self-compassion in healthcare students: A randomised controlled trial.

OBJECTIVE: To compare the effect of a mindfulness-based mobile application versus an in-person mindfulness-based training program in terms of reducing anxiety and increasing empathy, self-compassion, and mindfulness in a population of healthcare students. METHODS: The authors conducted a single-blind, randomised controlled trial with three parallel groups. Participants were allocated to the mobile app, the in-person mindfulness-based program (IMBP), or a control group. Assessments at baseline and postintervention (8 weeks) included measures of anxiety, empathy, self-compassion, and mindfulness. RESULTS: Of 168 students randomised, 84 were analysed on an intention-to-treat basis (app: n = 31; IMBP: n = 23; control: n = 30). The mobile app group showed a large effect size for reductions in trait anxiety compared with controls (g = 0.85, p = 0.003), and a medium, nonsignificant effect compared with the IMBP group (g = 0.52, p = 0.152). Participants from both interventions experienced a significant increase in self-compassion and mindfulness compared with controls. Levels of empathy remained unchanged for the 3 arms. CONCLUSIONS: A mobile app can be as effective as an IMBP in reducing anxiety and increasing self-compassion and mindfulness among healthcare students.

Nutraceutical Compounds Targeting Inflammasomes in Human Diseases.

The macromolecular complex known as "inflammasome" is defined as an intracellular multi-protein complex composed of a sensor receptor (PRR), an adaptor protein and an effector enzyme (caspase-1), which oligomerize when they sense danger, such as how the NLR family, AIM-2 and RIG-1 receptors protect the body against danger via cytokine secretion. Within the NLR members, NLRP3 is the most widely known and studied inflammasome and has been linked to many diseases. Nowadays, people's interest in their lifestyles and nutritional habits is increasing, mainly due to the large number of diseases that seem to be related to both. The term "nutraceutical" has recently emerged as a hybrid term between "nutrition" and "pharmacological" and it refers to a wide range of bioactive compounds contained in food with relevant effects on human health. The relationship between these compounds and diseases based on inflammatory processes has been widely exposed and the compounds stand out as an alternative to the pathological consequences that inflammatory processes may have, beyond their defense and repair action. Against this backdrop, here we review the results of studies using several nutraceutical compounds in common diseases associated with the inflammation and activation of the NLRP3 inflammasomes complex. In general, it was found that there is a wide range of nutraceuticals with effects through different molecular pathways that affect the activation of the inflammasome complex, with positive effects mainly in cardiovascular, neurological diseases, cancer and type 2 diabetes.

Clinical trials of psychological interventions cancelled due to the COVID-19 outbreak: how should we respond?

The measures to contain the spread of the COVID-19 outbreak have no precedent in the recent history of many countries. Around 2,000 million people in the world are in isolation or quarantine, and gatherings of people have been expressly banned in many countries. In Spain, this prohibition affects workplaces, schools, and the national health system, where most of the healthcare is being provided either on the phone or online.

A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia.

A high proportion of patients with acute myeloid leukemia who achieve minimal residual disease negative status ultimately relapse because a fraction of pathological clones remains undetected by standard methods. We designed and validated a high-throughput sequencing method for minimal residual disease assessment of cell clonotypes with mutations of NPM1, IDH1/2 and/or FLT3-single nucleotide variants. For clinical validation, 106 follow-up samples from 63 patients in complete remission were studied by sequencing, evaluating the level of mutations detected at diagnosis. The predictive value of minimal residual disease status by sequencing, multiparameter flow cytometry, or quantitative polymerase chain reaction analysis was determined by survival analysis. The sequencing method achieved a sensitivity of 10-4 for single nucleotide variants and 10-5 for insertions/deletions and could be used in acute myeloid leukemia patients who carry any mutation (86% in our diagnostic data set). Sequencing-determined minimal residual disease positive status was associated with lower disease-free survival (hazard ratio 3.4, P=0.005) and lower overall survival (hazard ratio 4.2, P<0.001). Multivariate analysis showed that minimal residual disease positive status determined by sequencing was an independent factor associated with risk of death (hazard ratio 4.54, P=0.005) and the only independent factor conferring risk of relapse (hazard ratio 3.76, P=0.012). This sequencing-based method simplifies and standardizes minimal residual disease evaluation, with high applicability in acute myeloid leukemia. It is also an improvement upon flow cytometry- and quantitative polymerase chain reaction-based prediction of outcomes of patients with acute myeloid leukemia and could be incorporated in clinical settings and clinical trials.

Mindfulness-based social cognition training (SocialMIND) versus psychoeducational multicomponent intervention for people with a first episode of psychosis: a study protocol for a randomised controlled trial.

BACKGROUND: People who suffer a first episode of psychosis experience higher levels of distress and suffering. Early intervention programs combine pharmacological and psychosocial strategies that include different components, such as cognitive-behavioural therapy, psychosocial interventions, medication adherence, family psychoeducation, counselling, etc. Among the complementary approaches, mindfulness-based interventions help participants to cultivate a radical acceptance of their psychotic experiences within a person-centered framework. They show promising results for people with longer duration of psychosis, but there is still no evidence for people who have recently experienced their first episode of psychosis. METHODS: The present parallel-group, single-blind (evaluator), randomised (1:1 ratio), controlled (versus active comparator), superiority, clinical trial will compare the effectiveness of SocialMIND on social functioning as measured by the Personal and Social Performance (PSP) scale. The active comparator will be a psychoeducational multicomponent intervention (PMI) that incorporates elements of early intervention programs that are effective for people who have suffered a first episode of psychosis. Both SocialMIND and PMI encompass eight weekly sessions, four bi-weekly sessions, and five monthly sessions. Changes in primary and secondary outcomes will be measured after weekly (8th week), bi-weekly (16th week) and monthly sessions (56th week), and 3 months after completing the intervention (68th week). Secondary outcomes include symptoms of psychosis, anxiety and depression, as well as indicators of general functioning. Tertiary outcomes are measures of social cognition, neurocognition, mindfulness, and indicators of inflammation and oxidative stress. A final sample of 80 participants is proposed to detect clinically significant differences in social functioning. DISCUSSION: This is the first mindfulness-based social cognition training for people with psychosis. SocialMIND aims to generate changes in the real-life functioning of people who have experienced a first episode of psychosis, and to be at least as effective as a psychoeducational multicomponent program. Adherence to the interventions is a common problem among young people with psychosis, so several difficulties are anticipated, and some methodological issues are discussed. TRIAL REGISTRATION: The trial was registered in ClinicalTrials.gov in October 2018 (NCT03309475).

Concurrent progressive multifocal leukoencephalopathy and central nervous system infiltration by multiple myeloma: A case report.

Progressive multifocal leukoencephalopathy rarely occurs in patients with multiple myeloma. Intracranial central nervous system invasion is also an uncommon event in multiple myeloma, occurring in less than 1% of cases. We describe herein an exceptional case of coexisting progressive multifocal leukoencephalopathy and intraparenchymal central nervous system myeloma infiltration. A 73-year-old woman with relapsed multiple myeloma was treated with 15 cycles of lenalidomide and dexamethasone, but therapy had to be stopped because of a hip fracture after a fall. During hospitalization, the patient developed progressive multifocal leukoencephalopathy caused by John Cunningham virus, and a prominent intra-parenchymal CD138-positive infiltrate was detected. VDJ rearrangements of the immunoglobulin heavy chain gene and the mutational profile of plasma cells in bone marrow at the time of diagnosis and in brain biopsy after progression were analyzed by next generation sequencing, showing genetic differences between medullary and extramedullary myeloma cells. The role of long-term treatment with lenalidomide and dexamethasone in the development progressive multifocal leukoencephalopathy or intraparenchymal central nervous system myeloma infiltration remains unknown. However, our results suggest that both events may have arisen as a consequence of treatment-related immunosuppression. Thus, an appropriate clinical approach compatible with the simultaneous treatment of progressive multifocal leukoencephalopathy and multiple myeloma should be developed.

Autophagic dysfunction in patients with Papillon-Lefèvre syndrome is restored by recombinant cathepsin C treatment.

BACKGROUND: Cathepsin C (CatC) is a lysosomal enzyme involved in activation of serine proteases from immune and inflammatory cells. Several loss-of-function mutations in the CatC gene have been shown to be the genetic mark of Papillon-Lefèvre syndrome (PLS), a rare autosomal recessive disease characterized by severe early-onset periodontitis, palmoplantar hyperkeratosis, and increased susceptibility to infections. Deficiencies or dysfunction in other cathepsin family proteins, such as cathepsin B or D, have been associated with autophagic and lysosomal disorders. OBJECTIVES: Here we characterized the basis for autophagic dysfunction in patients with PLS by analyzing skin fibroblasts derived from patients with several mutations in the CatC gene and reduced enzymatic activity. METHODS: Skin fibroblasts were isolated from patients with PLS assessed by using genetic analysis. Authophagic flux dysfunction was evaluated by examining accumulation of p62/SQSTM1 and a bafilomycin assay. Ultrastructural analysis further confirmed abnormal accumulation of autophagic vesicles in mutant cells. A recombinant CatC protein was produced by a baculovirus system in insect cell cultures. RESULTS: Mutant fibroblasts from patients with PLS showed alterations in oxidative/antioxidative status, reduced oxygen consumption, and a marked autophagic dysfunction associated with autophagosome accumulation. These alterations were accompanied by lysosomal permeabilization, cathepsin B release, and NLR family pyrin domain containing 3 (NLRP3) inflammasome activation. Treatment of mutant fibroblasts with recombinant CatC improved cell growth and autophagic flux and partially restored lysosomal permeabilization. CONCLUSIONS: Our data provide a novel molecular mechanism underlying PLS. Impaired autophagy caused by insufficient lysosomal function might represent a new therapeutic target for PLS.

Implementation of a suicide risk prevention program in the Autonomous Community of Madrid. The ARSUIC experience.

INTRODUCTION: This study evaluates the degree of compliance and effectiveness of the ARSUIC Suicide Risk Care Program. ARSUIC seeks to reduce the relapse risk that follows a suicide attempt by scheduling a high priority outpatient visit following hospital discharge. METHOD: Hospital-based retrospective study conducted between years 2012 and 2015. We included every suicide attempt treated at the La Paz University Hospital's mental healthcare resources network. We estimated the time between hospital discharge and the first outpatient visit; the proportion of visits that fulfill the program's objective - a follow-up within a maximum of 7 days; the suicide attempt rate; and the percentage of attempts corresponding to relapses, by study year. RESULTS: After program deployment, median time between discharge and the first visit decreased from 8.5 to 6 days, and the percentage of visits that fulfill the program's objective increased from 32 to 48.5%. Between years 2012 and 2015, the suicide attempt rate per person and year decreased from 1.20 to 1.08 and the proportion of attempts corresponding to relapses from 26.6% to 12.8%. CONCLUSION: Implementing the ARSUIC Program lowered the time between discharge and the first outpatient visit following a suicide attempt. The proportion of suicide attempts due to relapses and the suicide attempt rate per person decreased progressively. The program fulfilment proportion was under 50%, suggesting between-user differences regarding their effective access to the program.

Phenotypic, transcriptomic, and genomic features of clonal plasma cells in light-chain amyloidosis.

Immunoglobulin light-chain amyloidosis (AL) and multiple myeloma (MM) are 2 distinct monoclonal gammopathies that involve the same cellular compartment: clonal plasma cells (PCs). Despite the fact that knowledge about MM PC biology has significantly increased in the last decade, the same does not apply for AL. Here, we used an integrative phenotypic, molecular, and genomic approach to study clonal PCs from 24 newly diagnosed patients with AL. Through principal-component-analysis, we demonstrated highly overlapping phenotypic profiles between AL and both monoclonal gammopathy of undetermined significance and MM PCs. However, in contrast to MM, highly purified fluorescence-activated cell-sorted clonal PCs from AL (n = 9) showed almost normal transcriptome, with only 38 deregulated genes vs normal PCs; these included a few tumor-suppressor (CDH1, RCAN) and proapoptotic (GLIPR1, FAS) genes. Notwithstanding, clonal PCs in AL (n = 11) were genomically unstable, with a median of 9 copy number alterations (CNAs) per case, many of such CNAs being similar to those found in MM. Whole-exome sequencing (WES) performed in 5 AL patients revealed a median of 15 nonrecurrent mutations per case. Altogether, our results show that in the absence of a unifying mutation by WES, clonal PCs in AL display phenotypic and CNA profiles similar to MM, but their transcriptome is remarkably similar to that of normal PCs.

CCR5/CD4/CXCR4 oligomerization prevents HIV-1 gp120IIIB binding to the cell surface.

CCR5 and CXCR4, the respective cell surface coreceptors of R5 and X4 HIV-1 strains, both form heterodimers with CD4, the principal HIV-1 receptor. Using several resonance energy transfer techniques, we determined that CD4, CXCR4, and CCR5 formed heterotrimers, and that CCR5 coexpression altered the conformation of both CXCR4/CXCR4 homodimers and CD4/CXCR4 heterodimers. As a result, binding of the HIV-1 envelope protein gp120IIIB to the CD4/CXCR4/CCR5 heterooligomer was negligible, and the gp120-induced cytoskeletal rearrangements necessary for HIV-1 entry were prevented. CCR5 reduced HIV-1 envelope-induced CD4/CXCR4-mediated cell-cell fusion. In nucleofected Jurkat CD4 cells and primary human CD4(+) T cells, CCR5 expression led to a reduction in X4 HIV-1 infectivity. These findings can help to understand why X4 HIV-1 strains infection affect T-cell types differently during AIDS development and indicate that receptor oligomerization might be a target for previously unidentified therapeutic approaches for AIDS intervention.

Focus on Extracellular Vesicles: Physiological Role and Signalling Properties of Extracellular Membrane Vesicles.

Extracellular vesicles (EVs) are a heterogeneous population of secreted membrane vesicles, with distinct biogenesis routes, biophysical properties and different functions both in physiological conditions and in disease. The release of EVs is a widespread biological process, which is conserved across species. In recent years, numerous studies have demonstrated that several bioactive molecules are trafficked with(in) EVs, such as microRNAs, mRNAs, proteins and lipids. The understanding of their final impact on the biology of specific target cells remains matter of intense debate in the field. Also, EVs have attracted great interest as potential novel cell-free therapeutics. Here we describe the proposed physiological and pathological functions of EVs, with a particular focus on their molecular content. Also, we discuss the advances in the knowledge of the mechanisms regulating the secretion of EV-associated molecules and the specific pathways activated upon interaction with the target cell, highlighting the role of EVs in the context of the immune system and as mediators of the intercellular signalling in the brain.

Mindfulness-based cognitive therapy versus psychoeducational intervention in bipolar outpatients with sub-threshold depressive symptoms: a randomized controlled trial.

BACKGROUND: The presence of depressive subsyndromal symptoms (SS) in bipolar disorder (BD) increases the risk of affective relapse and worsens social, cognitive functioning, and quality of life. Nonetheless, there are limited data on how to optimize the treatment of subthreshold depressive symptoms in BD. Mindfulness-Based Cognitive Therapy (MBCT) is a psychotherapeutic intervention that has been shown effective in unipolar depression. The assessment of its clinical effectiveness and its impact on biomarkers in bipolar disorder patients with subsyndromal depressive symptoms and psychopharmacological treatment is needed. METHODS/DESIGN: A randomized, multicenter, prospective, versus active comparator, evaluator-blinded clinical trial is proposed. Patients with BD and subclinical or mild depressive symptoms will be randomly allocated to: 1) MBCT added to psychopharmacological treatment; 2) a brief structured group psychoeducational intervention added to psychopharmacological treatment; 3) standard clinical management, including psychopharmacological treatment. Assessments will be conducted at screening, baseline, post-intervention (8 weeks) and 4 month follow-up post-intervention. The aim is to compare MBCT intervention versus a brief structured group psychoeducation. Our hypothesis is that MBCT will be more effective in reducing the subsyndromal depressive symptoms and will improve cognitive performance to a higher degree than the psychoeducational treatment. It is also hypothesized that a significant increase of BDNF levels will be found after the MBCT intervention. DISCUSSION: This is the first randomized controlled trial to evaluate the effects of MBCT compared to an active control group on depressive subthreshold depressive symptoms in patients with bipolar disorder. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02133170. Registered 04/30/2014.

Impact of mindfulness training on attentional control and anger regulation processes for psychotherapists in training.

OBJECTIVES: Little empirical literature focuses on psychotherapists' cultivation of internal states of mind necessary for controlling attention and responding empathically to the client. We explore the effects of mindfulness training on emotional and attentional measures in Spanish resident intern psychiatrists and clinical psychologists. METHOD: One hundred and three residents were assigned to an experimental group (n = 60) that completed an 8-week mindfulness training versus a wait-list control group (n = 43). We evaluated emotional variables (sadness, anxiety, and anger, using standard instruments), state of mindfulness (using the Mindfulness Awareness Attention Scale), and attentional control variables using objective measures such as a continuous performance task and the Stroop task before and after mindfulness training. RESULTS: Our study provides data that suggest that mindfulness training significantly improves measures of trait anger and attentional control. CONCLUSIONS: Further research is needed to replicate these findings, explore the effects of mindfulness training on other aspects of emotional regulation and cognition, and evaluate the impact of these effects within clinical situations.