Mindfulness rasgo y el potencial papel mediador de las estrategias de regulación emocional en el trastorno bipolar.

This cross-sectional study investigates the association between the main symptoms of Bipolar disorder (BD) and emotional regulation difficulties in adaptive and maladaptive emotional regulation strategies (ERS). In addition, this study examines the possible mediating effects of ERS with dispositional mindfulness and bipolar symptoms. Method. Twenty-four adults diagnosed with BD completed the Mindful Attention Awareness Scale (MAAS), the Beck Depression Inventory (BDI-II), the Altman Mania Self-Assessment Scale (ARSM), the Trait Anxiety Inventory (STAI-R), and the Cognitive Emotional Regulation Questionnaire (CERQ). Results. First, multiple regression analysis showed how depression was significantly positively related to self-blame, whereas trait anxiety was positively associated with self-blame and catastrophizing. Second, the results of the mediation analysis have shown a significant mediation effect for the self-blame in the relationship between mindfulness and depression (a*b = -.15; BCI 95% [-.36, -.03]) and between mindfulness and trait anxiety (a*b = -.09; BCI 95% [-.27, -.01]). Conclusions. Our results report the role of self-blame and catastrophizing in BD and how these might significantly mediate between dispositional mindfulness and symptoms of depression and anxiety. These results suggest that a meditation practice focused on reducing catastrophizing and self-blame may be especially helpful for symptoms of depression and anxiety in bipolar patients.En este estudio transversal se investiga la asociación entre los principales síntomas del Trastorno bipolar (TB) y las dificultades asociadas a las estrategias de regulación emocional (ERE) adaptativas y desadaptativas. Además, este estudio examina los efectos mediadores de las ERE con el mindfulness rasgo y el TB. Método. Veinticuatro adultos con TB completaron la Escala de Conciencia de Atención Plena (MAAS), el Inventario de Depresión de Beck (BDI-II), la Escala de Autoevaluación de Manía de Altman (ARSM), el Inventario de Ansiedad Rasgo (STAI-R), y el Cuestionario de Regulación Emocional Cognitiva (CERQ). Resultados. El análisis de regresión múltiple mostró cómo la depresión se relacionaba significativa y positivamente con la autoculpabilización, mientras que la ansiedad rasgo estaba positivamente asociada con la autoculpabilización y el catastrofismo. En segundo lugar, el análisis de mediación mostró un efecto de mediación significativo para la autoculpabilidad en la relación entre mindfulness y depresión (a*b = -.15; ICB 95% [-.36, -.03]) y entre mindfulness y ansiedad rasgo (a*b = -.09; ICB 95% [-.27, -.01]). Conclusiones. Nuestros resultados informan del papel de la auto-culpabilidad y el catastrofismo en el TB y de cómo éstas podrían mediar significativamente entre el mindfulness rasgo y el TB. Estos resultados sugieren que una práctica de meditación enfocada en el catastrofismo y la autoculpabilidad puede ser especialmente útil para reducir los síntomas en los pacientes bipolares

Mindfulness Rasgo y el potencial papel mediador de las estrategias de regulación emocional en el trastorno bipolar

This cross-sectional study investigates the association between the main symptoms of Bipolar disorder (BD) and emotional regulation difficulties in adaptive and maladaptive emotional regulation strategies (ERS). In addition, this study examines the possible mediating effects of ERS with dispositional mindfulnessand bipolar symptoms. Method.Twenty-four adults diagnosed with BD completed the Mindful Attention Awareness Scale (MAAS), the Beck Depression Inventory (BDI-II), the Altman Mania Self-Assessment Scale (ARSM), the Trait Anxiety Inventory (STAI-R), and the Cognitive Emotional Regulation Questionnaire (CERQ). Results. First, multiple regression analysis showed how depression was significantly positively related to self-blame, whereas trait anxietywas positively associated with self-blame and catastrophizing. Second, the results of the mediation analysis have shown a significant mediation effect for the self-blamein the relationship between mindfulnessand depression (a*b = -.15; BCI 95% [-.36, -.03]) and between mindfulnessand trait anxiety (a*b = -.09; BCI 95% [-.27, -.01]). Conclusions. Our results report the role of selfblame and catastrophizing in BD and how these might significantly mediate between dispositional mindfulness and symptoms of depression and anxiety. These results suggest that a meditation practice focused on reducing catastrophizing and self-blame may be especially helpful for symptoms of depression and anxiety in bipolar patients.En este estudio transversal se investiga la asociación entre los principales síntomas del Trastorno bipolar (TB) y las dificultades asociadas a las estrategias de regulación emocional (ERE) adaptativas y desadaptativas. Además, este estudio examina los efectos mediadores de las ERE con el mindfulnes rasgo y el TB. Método. Veinticuatro adultos con TB completa-ron la Escala de Conciencia de Atención Plena (MAAS), el Inventario de Depresión de Beck (BDI-II), la Escala de Autoevaluación de Manía de Al-tman (ARSM), el Inventario de Ansiedad Rasgo (STAI-R), y el Cuestiona-rio de Regulación Emocional Cognitiva (CERQ). Resultados. El análisis de regresión múltiple mostró cómo la depresión se relacionaba significativa y positivamente con la autoculpabilización, mientras que la ansiedad rasgo es-taba positivamente asociada con la autoculpabilización y el catastrofismo. En segundo lugar, el análisis de mediación mostró un efecto de mediación significativo para la autoculpabilidad en la relación entre mindfulnessy depresión (a*b = -.15; ICB 95% [-.36, -.03]) y entre mindfulness y ansiedad rasgo (a*b = -.09; ICB 95% [-.27, -.01]). Conclusiones. Nuestros resultados informan del papel de la auto-culpabilidad y el catastrofismo en el TB y de cómo éstas podrían mediar significativamente entre el mindfulness rasgo y el TB. Estos resultados sugieren que una práctica de meditación enfocada en el catastrofismo y la autoculpabilidad puede ser especialmente útil para reducir los síntomas en los pacientes bipolares

Selective Inhibition of Vascular Endothelial Growth Factor–Mediated Angiogenesis by Cyclosporin a: Roles of the Nuclear Factor of Activated T Cells and Cyclooxygenase 2

Cyclosporin A (CsA) is an immunosuppressive drug that inhibits the activity of transcription factors of the nuclear factor of activated T cells (NFAT) family, interfering with the induction of cytokines and other inducible genes required for the immune response. Here we show that CsA inhibits migration of primary endothelial cells and angiogenesis induced by vascular endothelial growth factor (VEGF); this effect appears to be mediated through the inhibition of cyclooxygenase (Cox)-2, the transcription of which is activated by VEGF in primary endothelial cells. Consistent with this, we show that the induction of Cox-2 gene expression by VEGF requires NFAT activation. Most important, the CsA-mediated inhibition of angiogenesis both in vitro and in vivo was comparable to the Cox-2 inhibitor NS-398, and reversed by prostaglandin E2. Furthermore, the in vivo corneal angiogenesis induced by VEGF, but not by basic fibroblast growth factor, was selectively inhibited in mice treated with CsA systemically. These findings involve NFAT in the regulation of Cox-2 in endothelial cells, point to a role for this transcription factor in angiogenesis, and may provide a novel mechanism underlying the beneficial effects of CsA in angiogenesis-related diseases such as rheumatoid arthritis and psoriasis

SARS-CoV-2 Infection in Multiple Sclerosis

To understand COVID-19 characteristics in people with multiple sclerosis (MS) and identify high-risk individuals due to their immunocompromised state resulting from the use of disease-modifying treatments. Retrospective and multicenter registry in patients with MS with suspected or confirmed COVID-19 diagnosis and available disease course (mild = ambulatory; severe = hospitalization; and critical = intensive care unit/death). Cases were analyzed for associations between MS characteristics and COVID-19 course and for identifying risk factors for a fatal outcome. Of the 326 patients analyzed, 120 were cases confirmed by real-time PCR, 34 by a serologic test, and 205 were suspected. Sixty-nine patients (21.3%) developed severe infection, 10 (3%) critical, and 7 (2.1%) died. Ambulatory patients were higher in relapsing MS forms, treated with injectables and oral first-line agents, whereas more severe cases were observed in patients on pulsed immunosuppressors and critical cases among patients with no therapy. Severe and critical infections were more likely to affect older males with comorbidities, with progressive MS forms, a longer disease course, and higher disability. Fifteen of 33 patients treated with rituximab were hospitalized. Four deceased patients have progressive MS, 5 were not receiving MS therapy, and 2 were treated (natalizumab and rituximab). Multivariate analysis showed age (OR 1.09, 95% CI, 1.04-1.17) as the only independent risk factor for a fatal outcome. This study has not demonstrated the presumed critical role of MS therapy in the course of COVID-19 but evidenced that people with MS with advanced age and disease, in progressive course, and those who are more disabled have a higher probability of severe and even fatal diseas

Cyclooxygenase-2 and prostaglandin E<inf>2</inf> signaling through prostaglandin receptor EP- 2 favor the development of myocarditis during acute trypanosoma cruzi infection

Inflammation plays an important role in the pathophysiology of Chagas disease, caused by Trypanosoma cruzi. Prostanoids are regulators of homeostasis and inflammation and are produced mainly by myeloid cells, being cyclooxygenases, COX-1 and COX-2, the key enzymes in their biosynthesis from arachidonic acid (AA). Here, we have investigated the expression of enzymes involved in AA metabolism during T. cruzi infection. Our results show an increase in the expression of several of these enzymes in acute T. cruzi infected heart. Interestingly, COX-2 was expressed by CD68+ myeloid heart-infiltrating cells. In addition, infiltrating myeloid CD11b+Ly6G- cells purified from infected heart tissue express COX-2 and produce prostaglandin E2 (PGE2) ex vivo. T. cruzi infections in COX-2 or PGE2- dependent prostaglandin receptor EP-2 deficient mice indicate that both, COX-2 and EP-2 signaling contribute significantly to the heart leukocyte infiltration and to the release of chemokines and inflammatory cytokines in the heart of T. cruzi infected mice. In conclusion, COX-2 plays a detrimental role in acute Chagas disease myocarditis and points to COX-2 as a potential target for immune intervention.This work was supported by (NG) grants from “Fondo de Investigaciones Sanitarias” (PS09/00538 and PI12/00289); “Universidad Autónoma de Madrid” and “Comunidad de Madrid” (CC08-UAM/SAL-4440/08); by (MF) grants from “Ministerio de Ciencia e Innovación” (SAF2010-17833); “Red de Investigación de Centros de Enfermedades Tropicales” (RICET RD12/0018/0004); European Union (HEALTH-FE-2008-22303, ChagasEpiNet); AECID Cooperation with Argentine (A/025417/09 and A/031735/10), Comunidad de Madrid (S-2010/BMD- 2332) and “Fundación Ramón Areces”. NAG was recipient of a ISCIII Ph.D. fellowship financed by the Spanish “Ministerio de Sanidad”. CCM and HC were recipients of contracts from SAF2010-17833 and PI060388, respectively.Peer Reviewe

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Hormonas tiroideas y desarrollo cerebral: regulación de la expresión de RC3/Neurogranina

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 10-12-1993RESUMEN Las hormonas tiroideas son esenciales para el correcto desarrollo cerebral en mamíferos. La deficiencia de hormonas tiroideas durante el periodo perinatal lleva asociadas numerosas alteraciones bioqufmicas, morfológicas y funcionales en el cerebro. Recientemente, nuestro gmpo ha identificado vanos mRNAs de expresión cerebral cuyos niveles se encuentran alterados como consecuencia del hipotiroidismo inducidom en ratas. Entre estos se encuentra RC3/neurogranina, un mRNA de expresión postnatal restringida a ciertas regiones del cerebro. Este mRNA codifica una proteína que une calmodulina y que es fosforilada por la proteína kinasa C. Su función es desconocida, aunque se cree que puede estar implicada en fenómenos de plasticidad sináptica y memoria. Tanto el hipotiroidismo fetal y neonatal, como el hipotiroidismo inducido en ratas jóvenes adultas, produce una disminución, de un 50 a un 70%. de los niveles del mRNA y de la proteína de RC3 en la corteza cerebral y el núcleo estriado. La administración de tiroxina (Tq) a las ratas hipotiroideas hace que se recuperen los niveles normales de expresión. El hipotiroidismo no afecta de forma general a la expresión g6nica en cerebro, ya que los niveles de los mRNAs de otros genes de expresión cerebral no se encuentran alterados. Otros estados asociados con el hipotiroidismo, como la disminución de la ingesta, no afectan a los niveles de expresión de RC3. El estudio molecular de la expresión de este gen, llevado a cabo mediante la medición de la actividad de su promotor. revela la presencia de un elemento de respuesta a ácido retinoico (RC3RARE), capaz de unir receptores de retinoides y de estimular la transcripción, a partir del promotor homólogo o de un promotor heterólogo, en respuesta ai ácido retinoico. El heterodfmero formado por el receptor de hormona tiroidea y RXR es capaz de unirse ai elemento RC3RARE. inhibiendo la estimulación mediada por el ácido retinoico. Los resultados obtenidos sugieren la posibilidad de que la acción de la hormona tiroidea "in vivo" sea debida a una interacci611,directa o indirecta, con la secuencia RC3RARE. sin descartar la posible existencia de elementos de respuesta a hormona tiroidea en zonas del gen aún no analizadas. El hecho de que la expresión de RC3 se encuentre regulada por hormonas tiroideas, podría suponer una correlación molecular a algunas de las alteraciones morfológicas y funcionales que tienen lugar en el cerebro de la rata como consecuencia del hipotiroidismo.ABSTRACT Thyroid hormones are essential for normal mammalian brain development. Thyroid hormone deficiency dunng the perinatal period causes severe changes in the brain at the morphological, biochemical and functional levels. Recently, our group has identified several brain mRNAs whose levels are altered as a consequence of hypothyroidism in rats. Among them is RC3Jneurogranin. a neuron-specific mRNA of postnatal onset of expression, highly enriched in some areas from the brain .This mRNA encodes a calmodulin-binding kinase C substrate protein. The function of RC3 is not known, although it could be involved in synaptic plasticity and memory. Neonatal, as well as adult onset hypothyroidism, induce a 2-3 fold decrease in RC3 mRNA and pmtein levels in cerebral cortex and striatum. The administration of thyroxine (T4) to hypothyroid rats increases RC3 mRNA to normal levels. Hypothyroidism does not affect brain expression in general, since the levels of other brainspecific mRNAs are not altered. Our results also mle out the possibility that nutritionai alterations as a consequence of hypothyroidism affect RC3 expression. The analysis of the RC3 promoter reveals the presence of a retinoic acid response element (RC3RARE) that binds retinoid receptors and transactivates in the context of the homologous or of an heterologous promoter in response to retinoic acid. Thyroid hormone receptor-RXR heterodimers bind to the RC3RARE element and inhibit the stimulation by retinoic acid. The results obtained suggest that thyroid hormone action "in vivo" is due to a direct or indirect interaction with the RARE, without discarding the possible presence of thyroid hormone response elements in other regions of the gene still not analyzed. The fact that RC3 expression is regulated by thyroid hormone represents the first disclosed molecular correlate of some morphological and functional alterations that take place in rat brain as a consequence of hypothyroidism

Interactions between Personality and Types of Mindfulness Practice in Reducing Burnout in Mental Health Professionals

Research on mindfulness-based interventions reports mainly on improvements at the group level. Thus, there is a need to elaborate on the individual differences in their effectiveness. The aim of this study was twofold: (1) to examine which personality factors could influence burnout reduction associated with different types of mindfulness practice and (2) to evaluate the interaction between personality factors and the amount of home practice; both aims were controlled for sociodemographic characteristics. A total of 104 Cuban mental health professionals, who participated in a crossover trial, were included. The effect of personality (Cattell’s 16 Personality Factors) was analyzed through regression analysis. First, the results revealed that Emotional Stability and Vigilance could negatively moderate the effectiveness of mindfulness-based interventions. Second, participants who scored low in Sensitivity or Vigilance could benefit more from the body-centered practices (i.e., body scan and Hatha yoga practices), but no significant results for the mind-centered practices (i.e., classical meditation) were found. Third, participants who scored high in Self-reliance could benefit more from informal practice. Other personality factors did not appear to moderate the effect of the interventions, though previous experience in related techniques must be considered. Recommendations and clinical implications are discussed. Trial registration number is NCT03296254 (clinicaltrials.gov)

Comparison of two brief mindfulness interventions for anxiety, stress and burnout in mental health professionals: a randomised crossover trial

BackgroundAnxiety, stress and burnout are a growing reality among mental health professionals, impacting negatively on them and their clients. Mindfulness-based interventions (MBIs) have demonstrated effectiveness in mitigating these sufferings. Nevertheless, there is a lack of knowledge on the impact of MBIs in Cuba.ObjectivesTo compare the effectiveness of two brief mindfulness-based interventions for reducing anxiety, work stress and burnout.MethodsA total of 104 mental health professionals from Havana (Cuba) participated in a randomised crossover trial. Group A received first an intervention involving body-centred practices (body scan and Hatha yoga) and a second intervention involving mind-centred practices (focused attention and open monitoring meditation). Group B received the same interventions but in reverse order. Four measures (anxiety, stress, burnout syndrome, and antecedents of burnout) were measured at baseline, posttest1, posttest2, and 6-months follow-up.ResultsAfter the first intervention, there was a between-group difference for burnout syndrome, but the ES was similar for both groups. After the second intervention (implementing both practises), groups showed the largest effect sizes, and there was a between-group difference for antecedents of burnout. Results were partially maintained at 6-month follow-up.ConclusionThese results suggest that mind-centred practises can be as effective as body-centred practises for stress, anxiety and burnout reduction. The combination of both types of practises could be the most effective way of teaching mindfulness. About the sequence of implementation, teaching mind-centred practises first and then body-centred practises could be most effective for reducing antecedents of burnout.Clinical Trial Registration: www.clinicaltrials.gov NCT03296254

Regulation of Cyclooxygenase-2 Expression in Human T Cells by Glucocorticoid Receptor-Mediated Transrepression of Nuclear Factor of Activated T Cells

Cyclooxygenase (COX) is the key enzyme in prostanoid synthesis from arachidonic acid (AA). Two isoforms, named COX-1 and COX-2, are expressed in mammalian tissues. The expression of COX-2 isoform is induced by several stimuli including cytokines and mitogens, and this induction is inhibited by glucocorticoids (GCs). We have previously shown that the transcriptional induction of COX-2 occurs early after T cell receptor (TCR) triggering, suggesting functional implications of this enzyme in T cell activation. Here, we show that dexamethasone (Dex) inhibits nuclear factor of activated T cells (NFAT)-mediated COX-2 transcriptional induction upon T cell activation. This effect is dependent on the presence of the GC receptor (GR), but independent of a functional DNA binding domain, as the activation-deficient GRLS7 mutant was as effective as the wild-type GR in the repression of NFAT-dependent transcription. Dex treatment did not disturb NFAT dephosphorylation, but interfered with activation mediated by the N-terminal transactivation domain (TAD) of NFAT, thus pointing to a negative cross-talk between GR and NFAT at the nuclear level. These results unveil the ability of GCs to interfere with NFAT activation and the induction of pro-inflammatory genes such as COX-2, and explain some of their immunomodulatory properties in activated human T cells