The mediating role of reflective functioning in the association between childhood trauma and suicide attempt.

BACKGROUND: Childhood trauma is intimately related with suicidal behaviour. Patients who have suffered childhood trauma develop impaired Reflective Functioning (RF), which refers to the capacity to understand ourselves and others in terms of intentional mental states. An improvement in RF has been associated with a reduction in suicidal attempts, but the mediating role of RF between childhood trauma and suicidal behaviour has not been addressed so far. OBJECTIVE: We aim to examine the potential mediating effect of RF among childhood trauma and suicide attempts. METHOD: We included 748 patients who had attempted suicide at least once. They were asked to complete the Reflective Functioning Questionnaire (RFQ-8), the Columbia-Suicide Severity Rating scale (CSSRS), and the Childhood Trauma Questionnaire-Short Form (CTQ-SF). We conducted linear regressions by simple mediating model to examine the role of RF in the indirect association between childhood trauma and the number of suicide attempts. RESULTS: Our results show significant indirect effects through hypo and hypermentalizing between Emotional Abuse (EA) and Sexual Abuse (SA) in childhood and the number of suicide attempts in lifetime. These results indicate that ineffective RF significantly mediates the association between childhood trauma and suicidality. CONCLUSION: This is the first study supporting the mediational role of RF in the relationship between EA and SA, and the number of suicide attempt in lifetime. These findings have important implications for reducing suicide rates and preventing future re-attempts. Further studies analysing this mediating role and focusing efforts on increasing RF-based interventions are required.

Efecto de la alteración de los niveles de expresión de microARN neurogénicos y su implicación en la agresividad de glioblastomas localizados en la región paraventricular / The effects of altered neurogenic microRNA levels and their involvement in the aggressiveness of periventricular glioblastoma

Introducción: El glioblastoma multiforme es el tumor cerebral primario más común y con el pronóstico más desfavorable del sistema nervioso central. A pesar de los numerosos estudios y avances en medicina, este sigue siendo letal, con una esperanza de vida promedio de 15 meses posteriores a la quimiorradioterapia.DesarrolloRecientemente, se han estudiado diversos factores asociados al diagnóstico y el pronóstico de pacientes con glioblastoma, como la localización tumoral, principalmente la zona subventricular; una de las áreas neurogénicas más activas del cerebro humano adulto. Los pacientes con glioblastoma asociados a esta zona en particular presentan generalmente una mayor agresividad, lo que resulta en un pronóstico desfavorable y una menor esperanza de vida. Actualmente, se ha profundizado en el estudio de los microARN, los cuales reflejan patrones de expresión distintos en condiciones fisiológicas o fisiopatológicas. Está reportado que los niveles de expresión de ciertos microARN, principalmente aquellos relacionados a procesos neurogénicos, se ven desregulados en eventos oncogénicos, favoreciendo así la gliomagénesis y la agresividad tumoral. En la presente revisión se discuten algunos de los microARN más importantes implicados en procesos neurogénicos de la zona subventricular y su asociación con la agresividad del glioblastoma.ConclusionesLa regulación y función de los microARN desempeña un rol importante en el desarrollo y la progresión del glioblastoma; en consecuencia, la comprensión de las alteraciones de los microARN implicados en la diferenciación, así como en la maduración neural y glial, podrían ayudar a entender mejor las características malignas del glioblastoma. (AU)

Introduction: Glioblastoma multiforme is the most common primary brain tumour, with the least favourable prognosis. Despite numerous studies and medical advances, it continues to be lethal, with an average life expectancy of 15 months after chemo-radiotherapy.DevelopmentRecent research has addressed several factors associated with the diagnosis and prognosis of glioblastoma; one significant factor is tumour localisation, particularly the subventricular zone, which represents one of the most active neurogenic niches of the adult human brain. Glioblastomas in this area are generally more aggressive, resulting in unfavourable prognosis and a shorter life expectancy. Currently, the research into microRNAs (miRNA) has intensified, revealing different expression patterns under physiological and pathophysiological conditions. It has been reported that the expression levels of certain miRNAs, mainly those related to neurogenic processes, are dysregulated in oncogenic events, thus favouring gliomagenesis and greater tumour aggressiveness. This review discusses some of the most important miRNAs involved in subventricular neurogenic processes and their association with glioblastoma aggressiveness.ConclusionsMiRNA regulation and function play an important role in the development and progression of glioblastoma; understanding the alterations of certain miRNAs involved in both differentiation and neural and glial maturation could help us to better understand the malignant characteristics of glioblastoma. (AU)

[Retrospective observational study of the persistence of SARS-CoV-2 infection in patients previously treated with rituximab]. / Estudio observacional retrospectivo de persistencia de infección por SARS-CoV-2 en pacientes tratados previamente con rituximab.

OBJECTIVE: Rituximab-induced immunosuppression could be a risk factor for mortality from COVID-19. The aim of the study was to describe the prevalence of SARS-CoV-2 infection in patients who have received rituximab and its association with a persistent viral infection. METHODS: Retrospective observational study of patients who received rituximab in the 6 months before to the onset of the pandemic. We analyzed the presence of infection and associated them with demographic variables, pathological history related to an increased risk of developing severe COVID-19, the doses of rituximab received, the type of ventilatory support, thromboembolic events, and the treatment received. A descriptive analysis of all the variables was carried out and infected and uninfected patients were compared. RESULTS: We screened a total of 68 patients who had received rituximab (median cumulative dose: 4,161mg (2,611-8,187.5)). 54.4% men, mean age 60.8 years (15.7; 25-87)). C + was confirmed for 22 patients. Of these, 45.5% had high blood pressure, 36.4% Diabetes Mellitus, 31.8% smokers/ex-smoker, 22.7% lung disease, 13.6% heart disease and 4.5% obesity. There were no statistically significant differences between C+ and C-. Only 2 patients developed immunity. For 10 patients (45.5%) did not have a negative CRP until the end of the follow-up. There was no association with cumulative dose of rituximab. The mortality rate was 22.7% in the C+. CONCLUSIONS: We observe that the persistence of the infection leads to a worse evolution of COVID-19. The use of alternatives should be considered during the pandemic, because of patients with decreased B-cell function may have high risk of fatal progression from COVID-19.

Aftas orales refractarias en tratamiento con adalimumab y apremilast en paciente con enfermedad de Behçet. Informe de un caso / Refractory oral aftas in treatment with adalimumab and apremilast in patient with Behçet syndrome. A case report

La enfermedad de Behçet es un trastorno inflamatorio multisistémico que se manifiesta de forma muy variada a nivel cutáneo, especialmente en forma de aftas orales frecuentemente refractarias. Los tratamientos con utilidad en la sintomatología de esta patología, resultan poco específicos y poco efectivos; teniendo que recurrir a veces a tratamientos sistémicos, como los biológicos: entre ellos, los anti-TNFα. Presentamos el caso de una paciente con enfermedad de Behçet, con aftas orales severas, recurrentes y refractarias a múltiples tratamientos. Actualmente, la paciente ha alcanzado la remisión clínica en tratamiento combinado de adalimumab y apremilast. (AU)

Behçet’s disease is a multisystemic inflammatory disorder that manifests itself in a variety of ways at the cutaneous level, especially in the form of oral thrush, very often very refractory. Treatments that are useful in the symptomatology of this pathology are not very specific and not very effective; sometimes it is necessary to resort to systemic treatments, such as biologi-cal ones: among them, anti-TNFα.We present the case of a patient diagnosed with Behçet’s disease, with severe oral aphthae, very recurrent and refractory to multiple treatments. Currently, the patient has reached clinical remission in combined treatment of adalimumab and apremilast. (AU)

Efecto de los fármacos modificadores del PH sobre los inhibidores de la tirosin quinasa: contrastando información / Effect of gastric-acid-reducing agents on the tyrosine kinasa inhibitors: contrasting information

Objetivos: Los inhibidores de la tirosin quinasa (ITK) comprenden un conjunto de moléculas ampliamente utilizadas actualmente en onco-hematología. Los ITK han supuesto una ventaja para los pacientes, de forma que la administración oral favorece su autonomía, pero a su vez, su absorción gastrointestinal y, por ende, su biodisponibilidad, puede verse alterada por el PH-gástrico. Las interacciones con los fármacos modificadores del PH son un problema conocido y una consulta frecuente. El objetivo del estudio fue analizar las interacciones ITK-fármacos modificadores del PH-gástrico y las discrepancias en diferentes bases de datos. Con los resultados, se elaboró una tabla, para proporcionar a los pacientes la información correcta y consensuada, y no generar así inseguridad que comprometa la adherencia al tratamiento o confianza hacia el profesional sanitario. Métodos: Se exportaron de la web de la Agencia Española del Medicamento y Productos Sanitarios los fármacos clasificados como ITK directos (ATC: L01XE). Se consultó la interacción de éstos con los IBP, Anti-H2 y antiácidos en diversas fuentes y se resumieron los hallazgos.Resultados y conclusiones: Para establecer una fuerte recomendación, es necesario consultar varias bases de datos, ya que las discrepancias o la información insuficiente pueden llevar a recomendaciones erróneas. Es importante establecer un consenso entre profesionales para realizar la recomendación correcta, y no ver comprometida la eficacia del tratamiento, con las importantes consecuencias que ello conllevaría. (AU)

Objectives: Tyrosine kinase inhibitors (TKIs) include a group of molecules widely used in oncohematology today. Using the oral administration route of TKIs offers an advantage for the patient; favoring patient autonomy, however, oral administration also causes relevant new problems. Gastrointestinal absorption and, therefore, bioavailability, can be altered by gastric PH. Interactions of these TKIs with gastric acid reducing (GAR) drugs are a known problem and a frequent query in clinical practice. The aim was to analyze ITK-GAR drugs interactions and discrepancies in different databases. Based on the results, a table was elaborated to provide the correct and consensed information, and thus not generate insecurity that compromises the adherence to the treatment or trust towards the healthcare professional.Methods: Drugs classified as direct ITKs (ATC: L01XE) were exported from the Spanish Agency for Medicines and Health Products website. Their interaction with PPIs, Anti-H2 and antacids was consulted in different databases and findings were summarized.Results and conclusions: To establish a strong recommendation, it is necessary to consult several databases, because of discrepancies or insufficient information can lead to erroneous recommendations. It is important to establish a consensus among professionals to make the correct recommendation, and not compromising the effectiveness of the treatment, which would entail important consequences. (AU)

COVID 19 y embarazo en Chile: Informe preliminar del estudio multicéntrico GESTACOVID / COVID-19 and pregnancy in Chile: preliminary report of the GESTACOVID multicenter study

INTRODUCCIÓN: En Chile, los efectos maternos y perinatales de la pandemia por SARS-CoV-2 son aún desconocidos. GESTACOVID es un estudio multicéntrico que incluye embarazadas y puérperas hasta el día 42 con COVID-19. El objetivo de este estudio es presentar un informe preliminar, describiendo el impacto de la enfermedad en las embarazadas, factores de riesgo asociados y resultados perinatales. MÉTODOS: Estudio de cohorte descriptivo que incluye 661 pacientes enroladas entre el 7 de marzo y el 6 de julio de 2020, en 23 centros hospitalarios del país. Se analizaron variables demográficas, comorbilidades, características clínicas y del diagnóstico de COVID-19 y resultado materno y perinatal. RESULTADOS: Las pacientes hospitalizadas por COVID-19 tuvieron mayor prevalencia de hipertensión arterial crónica [10% vs 3%; OR=3,1 (1,5-6,79); p=0,003] y de diabetes tipo 1 y 2 [7% vs 2%; OR=3,2 (1,3-7,7); p=0,009] que las pacientes manejadas ambulatoriamente. Un IMC >40 kg/mt2 se asoció con un riesgo dos veces mayor de requerir manejo hospitalizado [OR=2,4 (1,2 - 4,6); p=0,009]. Aproximadamente la mitad de las pacientes (54%) tuvo un parto por cesárea, y un 8% de las interrupciones del embarazo fueron por COVID-19. Hasta la fecha de esta publicación, 38% de las pacientes continuaban embarazadas. Hubo 21 PCR positivas en 316 neonatos (6,6%), la mayoría (17/21) en pacientes diagnosticadas por cribado universal. CONCLUSIONES: Las embarazadas con COVID-19 y comorbilidades como diabetes, hipertensión crónica y obesidad mórbida deben ser manejadas atentamente y deberán ser objeto de mayor investigación. La tasa de transmisión vertical requiere una mayor evaluación para diferenciar el mecanismo y tipo de infección involucrada.

INTRODUCTION: In Chile, effects of the SARS-CoV-2 infection in pregnant women are unknown. GESTACOVID is a multicenter collaborative study including pregnant women and those in the postpartum period (until 42 days) who have had COVID-19. The purpose of this study is to report our preliminary results describing the clinical impact of COVID-19 in pregnant women, the associated risk factors and perinatal results. METHODS: Descriptive cohort study including 661 patients between April 7th and July 6th, 2020, in 23 hospitals. Demographical, comorbidities, clinical and diagnostic characteristics of COVID-19 disease and maternal and perinatal outcomes were analyzed. RESULTS: Pregnant women with COVID-19 admitted to the hospital were more likely to have chronic hypertension [10% vs 3%; OR=3.1 (1.5-6.79); p=0,003] and diabetes type 1 and 2 [7% vs 2%; OR=3.2 (1.3-7.7); p=0.009] than those with outpatient management. A body mass index of >40 kg/mt2 was associated with two-fold higher risk of hospitalization [OR=2.4 (1.2-4.6); p=0.009]. Almost half of patients (54%) were delivered by cesarean section, and 8% of the medically indicated deliveries were due to COVID-19. So far, 38% of the patients are still pregnant. Among 316 newborns, there were 21 positive PCR tests (6.6%), mostly from asymptomatic mothers undergoing universal screening. CONCLUSIONS: Pregnant women with COVID-19 and comorbidities such as diabetes, chronic hypertension and morbid obesity need a close follow up and should be a matter for further research. Vertical transmission of COVID-19 should be thoroughly studied to define the mechanisms and type of infection involved.

The effects of altered neurogenic microRNA levels and their involvement in the aggressiveness of periventricular glioblastoma. / Efecto de la alteración de los niveles de expresión de microARN neurogénicos y su implicación en la agresividad de glioblastomas localizados en la región paraventricular.

INTRODUCTION: Glioblastoma multiforme is the most common primary brain tumour, with the least favourable prognosis. Despite numerous studies and medical advances, it continues to be lethal, with an average life expectancy of 15 months after chemo-radiotherapy. DEVELOPMENT: Recent research has addressed several factors associated with the diagnosis and prognosis of glioblastoma; one significant factor is tumour localisation, particularly the subventricular zone, which represents one of the most active neurogenic niches of the adult human brain. Glioblastomas in this area are generally more aggressive, resulting in unfavourable prognosis and a shorter life expectancy. Currently, the research into microRNAs (miRNA) has intensified, revealing different expression patterns under physiological and pathophysiological conditions. It has been reported that the expression levels of certain miRNAs, mainly those related to neurogenic processes, are dysregulated in oncogenic events, thus favouring gliomagenesis and greater tumour aggressiveness. This review discusses some of the most important miRNAs involved in subventricular neurogenic processes and their association with glioblastoma aggressiveness. CONCLUSIONS: MiRNA regulation and function play an important role in the development and progression of glioblastoma; understanding the alterations of certain miRNAs involved in both differentiation and neural and glial maturation could help us to better understand the malignant characteristics of glioblastoma.

Monitorización farmacocinética de niveles supraterapéuticos de adalimumab en paciente con enfermedad de Crohn / Pharmacokinetic monitoring of supratherapeutic adalimumab levels in patient with Crohn's disease

La monitorización farmacocinética de terapias biológicas dirigidas frente al factor de necrosis tumoral-a (TNF-a) ha sido recientemente introducida en nuestro centro hospitalario gracias a la iniciativa de nuestro equipo de enfermedad inflamatoria intestinal, formado por farmacéuticos, digestólogos y analistas clínicos, con la finalidad de optimizar la terapia en los pacientes que se mantienen en remisión clínica (monitorización "pro-activa"), o que presentan un fracaso terapéutico (monitorización "re-activa"). Se presenta un caso clínico de una paciente diagnosticada de enfermedad de Crohn y en tratamiento combinado con metotrexato y adalimumab. En septiembre de 2018, adalimumab fue intensificado de forma empírica a dosis de 40 mg administrados semanalmente por la aparición de manifestaciones extradigestivas (artralgias y parestesias en miembros inferiores). En febrero de 2019, la paciente se mantenía en remisión clínica con respecto a los síntomas intestinales, pero continuaba con las manifestaciones extradigestivas y refería aftas orales recurrentes. Por este motivo, se monitorizaron los niveles séricos de adalimumab, los cuales superaron ampliamente el intervalo terapéutico recomendado (5-12 mig/ml). En este sentido, se describe el seguimiento multidisciplinar del caso clínico y el ajuste posológico realizado en base a predicciones bayesianas, principios farmacocinéticos y farmacodinámicos y la clínica de la paciente. La monitorización farmacocinética de los niveles supraterapéuticos de adalimumab fue una herramienta útil para la optimización de dosis de adalimumab y la valoración objetiva de reacciones adversas en esta paciente. Este caso se ha notificado al Sistema Español de Farmacovigilancia

The pharmacokinetic monitoring of biological therapies against tumor necrosis-a (TNF-a) was recently introduced at our hospital thanks to the initiative of our inflammatory bowel disease team, composed of specialists in pharmacology, digestive system disease, and clinical analysis. The aim of the program was to optimize the therapy delivered to patients in clinical remission (pro-active monitoring) or clinical failure (reactive monitoring). We report the case of a patient diagnosed with Crohn's disease and under combined treatment with methotrexate and adalimumab. In September 2018, the dose of adalimumab was empirically increased to 40 mg/week due to the onset of extraintestinal manifestations (arthralgias and paraesthesias in lower limbs). In February 2019, the patient was in clinical remission with respect to the intestinal symptoms, but the extraintestinal manifestations persisted and the patient also reported anal aphthae. Consequently, serum adalimumab concentrations were monitored and found to widely exceed the recommended therapeutic interval (5-12 mig/ml). We report the multidisciplinary follow-up of the clinical case and the dosage adjustment based on Bayesian predictions, pharmacokinetic and pharmacodynamic principles, and the patient's clinical situation. Pharmacokinetic monitoring of supratherapeutic adalimumab levels proved to be a useful tool to achieve the optimal dosage of this drug and to objectively evaluate the patient's adverse reactions. The Spanish Pharmacosurveillance System has been notified of this case

Prenatal exposure to metals modified DNA methylation and the expression of antioxidant- and DNA defense-related genes in newborns in an urban area.

The developmental period in utero is a critical window for environmental exposure. Epigenetic fetal programming via DNA methylation is a pathway through which metal exposure influences the risk of developing diseases later in life. Genetic damage repair can be modified by alterations in DNA methylation, which, in turn, may modulate gene expression due to metal exposure. We investigated the impact of prenatal metal exposure on global and gene-specific DNA methylation and mRNA expression in 181 umbilical cord blood samples from newborns in Mexico City. Global (LINE1) and promoter methylation of DNA-repair (OGG1 and PARP1) and antioxidant (Nrf2) genes was evaluated by pyrosequencing. Prenatal metal exposure (As, Cu, Hg, Mn, Mo, Pb, Se, and Zn) was determined by ICP-MS analysis of maternal urine samples. Multiple regression analyses revealed that DNA methylation of LINE1, Nrf2, OGG1, and PARP1 was associated with potentially toxic (As, Hg, Mn, Mo, and Pb) and essential (Cu, Se, and Zn) elements, and with their interactions. We also evaluated the association between gene expression (mRNA levels quantified by p-PCR) and DNA methylation. An increase in OGG1 methylation at all sites and at CpG2, CpG3, and CpG4 sites was associated with reduced mRNA levels; likewise, methylation at the CpG5, CpG8, and CpG11 sites of PARP1 was associated with reduced mRNA expression. In contrast, methylation at the PARP1 CpG7 site was positively associated with its mRNA levels. No associations between Nrf2 expression and CpG site methylation were observed. Our data suggest that DNA methylation can be influenced by prenatal metal exposure, which may contribute to alterations in the expression of repair genes, and therefore, result in a lower capacity for DNA damage repair in newborns.

Exposure to diethylhexyl phthalate (DEHP) and monoethylhexyl phthalate (MEHP) promotes the loss of alveolar epithelial phenotype of A549 cells.

Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer that is metabolized to mono(2-ethylhexyl) phthalate (MEHP). Inhalation is an important exposure route for both phthalates, and their effects on lungs include inflammation, alteration of postnatal maturation (alveolarization), enlarged airspaces and cell differentiation changes, suggesting that alveolar epithelial cells-2 (AEC) are targets of phthalates. This study evaluated the cell progression, epithelial and mesenchymal markers, including surfactant secretion in A549 cells (AEC) that were exposed to DEHP (1-100 µM) or MEHP (1-50 µM) for 24-72 h. The results showed an increased cell proliferation at all concentrations of each phthalate at 24 and 48 h. Cell migration showed a concentration-dependent increase at 24 and 48 h of exposure to either phthalate and enlarged structures were seen. Decreased levels of both surfactants (SP-B/SP-C) were observed after the exposure to either phthalate at 48 h, and of SP-C positive cells exposed to MEHP, suggesting a loss of the epithelial phenotype. While a decrease in the epithelial marker E-cadherin and an increase in the mesenchymal marker fibronectin were observed following exposure to either phthalate. Our results showed that DEHP and MEHP altered the structure and migration of A549 cells and promoted the loss of the epithelial phenotype.

Epigenetic modulation of Nrf2 and Ogg1 gene expression in testicular germ cells by methyl parathion exposure.

Methyl parathion (Me-Pa) is an oxidizing organophosphate (OP) pesticide that generates reactive oxygen species (ROS) through its biotransformation. Some studies have also suggested that OP pesticides have the capacity to alkylate biomolecules, including DNA. In general, DNA methylation in gene promoters represses transcription. NRF2 is a key transcription factor that regulates the expression of antioxidant, metabolic and detoxifying genes through the antioxidant response element (ARE) situated in promoters of regulated genes. Furthermore, DNA repair genes, including 8-oxoguanine DNA glycosidase (OGG1), have been proposed as NRF2 target genes. Me-Pa exposure produces poor semen quality, genetic and oxidative damage in sperm cells, and reduced fertility. However, the Me-Pa effects on the methylation status and the expression of antioxidant (Nrf2) or DNA repair (Ogg1) genes in male germ cells have not been investigated. Therefore, mice were exposed to Me-Pa to evaluate the global (%5-mC) and specific methylation of Nrf2 and Ogg1 genes using pyrosequencing, gene expression, and total protein carbonylation in male germ cells. The results showed that Me-Pa significantly decreased the global DNA methylation pattern and significantly increased the methylation of two CpG sites within Ogg1 promoter and one CpG site within Nrf2 promoter. In addition, Ogg1 or Nrf2 expression did not change after Me-Pa exposure despite the oxidative damage produced. Altogether, our data suggest that Me-Pa toxicity alters Ogg1 and Nrf2 promoter methylation in male germ cells that may be modulating their gene expression.

Dismenorrea membranácea durante la menarquia / Membranous dysmenorrhea during menarche

La dismenorrea membranosa se caracteriza por dolor menstrual acompañado de la expulsión de la mucosa endometrial en forma de grandes fragmentos, e incluso en una única pieza, con la forma del molde de la cavidad uterina. Se presenta el caso de una paciente con expulsión de un gran molde de endometrio durante la menarquia. Se presentan las imágenes del molde endometrial íntegro de la cavidad uterina y el estudio anatomopatológico.

Membranous dysmenorrheal consist of menstrual pain accompanied by the expulsion of endometrial mucosa in the form of large fragments or even in one piece with the shape of the uterine cavity. We present the case of a patient with expulsion of endometrial during menarche. The pictures of endometrial piece, the shape of the uterine cavity and anatomo-pathological study has presented.

Intervenciones psicoterapéuticas y psicosociales para el manejo del estrés en esclerosis múltiple: aportación de intervenciones basadas en mindfulness / Psychotherapeutic and psychosocial interventions for managing stress in multiple sclerosis: the contribution of mindfulness-based interventions

La presencia de depresión o ansiedad asociada al diagnóstico de esclerosis múltiple (EM) se ha relacionado con una peor evolución de la enfermedad, con mayor número de brotes, con peor adherencia al tratamiento y una mayor disregulación del sistema inmune. Estudios recientes indican que intervenciones psicoterapéuticas dirigidas al manejo del estrés, entre ellas, intervenciones basadas en mindfulness (Mindfulness-Based Interventions, MBI), pueden mejorar la calidad de vida, la depresión, la ansiedad y la fatiga en pacientes con diagnóstico de EM. Mindfulness o atención plena fomenta la capacidad para observar las experiencias tal y como son y mejora la regulación emocional. Esta habilidad o actitud se aprende por entrenamiento y tiene la ventaja sobre otras intervenciones de que el efecto puede prolongarse a lo largo del tiempo al depender de la práctica personal. El objetivo del presente artículo es revisar la evidencia disponible sobre la eficacia de intervenciones psicosociales y psicoterapéuticas, específicamente MBI, en el manejo de la sintomatología ansioso-depresiva y del estrés percibido en pacientes con diagnóstico de EM

Depression or anxiety in multiple sclerosis (MS) has been linked to a more severe course of the disease and higher numbers of relapses, in addition to poorer treatment adherence and exacerbated immune system dysregulation. Recent investigations indicate that psychotherapeutic interventions for stress management, such as mindfulness-based interventions (MBIs), could improve quality of life, depression, anxiety, and fatigue in MS patients. Mindfulness fosters the ability to slow down and observe experiences as they truly are, which improves affect regulation. Mindfulness is acquired through training; its advantage over other psychotherapeutic interventions is that effects may remain over time, since cultivating mindfulness depends on regular practising of abilities learned during training. The objective of this article is to review the current evidence of psychotherapeutic and psychosocial interventions, including MBIs for stress management, and their beneficial effects on MS patients

Psychotherapeutic and psychosocial interventions for managing stress in multiple sclerosis: the contribution of mindfulness-based interventions.

Depression or anxiety in multiple sclerosis (MS) has been linked to a more severe course of the disease and higher numbers of relapses, in addition to poorer treatment adherence and exacerbated immune system dysregulation. Recent investigations indicate that psychotherapeutic interventions for stress management, such as mindfulness-based interventions (MBIs), could improve quality of life, depression, anxiety, and fatigue in MS patients. Mindfulness fosters the ability to slow down and observe experiences as they truly are, which improves affect regulation. Mindfulness is acquired through training; its advantage over other psychotherapeutic interventions is that effects may remain over time, since cultivating mindfulness depends on regular practising of abilities learned during training. The objective of this article is to review the current evidence of psychotherapeutic and psychosocial interventions, including MBIs for stress management, and their beneficial effects on MS patients.

Immunization of sea bream (Sparus aurata) juveniles against Photobacterium damselae subsp. piscicida by short bath: Effect on some pro-inflammatory molecules and the Mx gene expression.

Cytokines are a family of proteins derived from macrophages, lymphocytes, granulocytes, mast cells and epithelial cells and can be divided into interferons (IFNs), Interleukins (ILs) and Tumor Necrosis factors (TNFs) among others. The presence of cytokines in a wide number of fish species has been proved and several molecules types have been already cloned and sequenced. In this work some proinflamatory molecules and Mx gene were detected in the liver of vaccinated sea bream juveniles with an average body weight of 5 g. The method of immunization was by short bath and three different bacterins against the marine pathogen Photobacterium damselae subsp. piscicida were designed and used to immunize fish. Five genes encoding for five different molecules were analyzed by real time PCR: IL-1ß, IL Ir-2, Cox-2, Mx and TNFα. Gene expression was quantified along four days after fish immunization and results were compared among groups. Results show that the heat-inactivated vaccine stimulates the up-regulation of IL-1ß, IL Ir-2, Cox-2 and TNFα genes whereas the UV-light inactivated vaccine was the unique vaccine which stimulates the expression of Mx gene. The present is a novel study that shows by the first time the effect of the inactivation process of vaccines on the expression levels of genes involved in the defense against Photobacterium damselae subsp piscicida.

Hipercalcemia hipocalciúrica familiar: a veces no es lo que parece / Familial hypocalciuric hypercalcemia: sometimes it is not what it seems

La hipercalcemia hipocalciúrica familiar (HHF) constituye una causa poco común de hipercalcemia. Su prevalencia se estima que es de 1:78.000 personas. Mostramos un caso con presentación atípica con confirmación mediante diagnóstico genético. Se trata de una mujer de 74 años con osteoporosis remitida al servicio de Endocrinología por sospecha de hiperparatiroidismo primario (HPTP). Presentaba una hormona paratiroidea (PTH) elevada (96,3 pg/ml-límites normales (LN): 15-65 pg/ml) con niveles de calcio, fósforo y magnesio normales, además de una calciuria elevada. Posteriormente presentó cifras de PTH normales, niveles de calcio elevados junto con calciurias normales-elevadas. El cociente aclaramiento de calcio/aclaramiento de creatinina (CCCR, en mmol/l) osciló entre 0,011-0,02 mmol/l. El CCCR < 0,01 es sugestivo de HHF, y el CCCR > 0,02 de HPTP; este cociente se ve limitado en el rango entre 0,01-0,02 mmol/l, motivo por el que se justifica solicitar la prueba genética en todos los pacientes con PTH normales o alt as, hipercalcemia y CCCR < 0,02, requisitos que cumplía nuestro caso índice (AU)

Familial hypocalciuric hypercalcemia (FHH) is an uncommon cause of hypercalcemia. Its prevalence is estimated to be 1:78,000 people. We describe a case with atypical presentation confirmed by genetic diagnosis. This is a case of a woman of 74 years of age with osteoporosis referred to the endocrinology service with suspected primary hyperparathyroidism (HPTP). She presented with a high level of parathyroid hormone (96.3 pg/ml, normal limits (NL): 15-65 pg/ml), with normal levels of calcium, phosphorus and magnesium, as well as a raised level of calciuria. She subsequently presented with normal levels of PTH, raised levels of calcium, combined with normal -high calciuria. The calcium/creatinine clearance ratio (CCCR, in mmol/l) varied between 0.011 and 0.02 mmol/l. A CCCR < 0.01 is suggestive of FHH, and a CCCR > 0.02, of HPTP. This ratio is within the range between 0.01 and 0.02 mmol/l, a reason which justifies requesting a genetic test in all patients with normal or high PTH, hypercalcemia and CCCR < 0.02, requirements which our index case meets (AU)

Clinical effectiveness of exenatide in diabetic patients waiting for bariatric surgery.

BACKGROUND: Bariatric surgery constitutes the most effective treatment for severely obese type 2 diabetic patients. Exenatide is a glucagon-like peptide 1 receptor agonist that can improve glycemic control and cause weight loss in patients with type 2 diabetes. Clinical experience with exenatide in obese patients with type 2 diabetes waiting for bariatric surgery has not been reported. The aim of the study was to evaluate, in clinical practice, weight and metabolic effects of exenatide (after 3 and 6 months) in patients with type 2 diabetes and obesity waiting for bariatric surgery. METHODS: A total of 100 diabetic adult subjects with a BMI ≥ 35 kg/m(2) were included. Primary endpoints were changes in weight and HbA1c after 6 months of treatment. Secondary endpoints were changes from baseline of a variety of clinical measures (triglycerides levels, blood pressure, and waist circumference). Data were analyzed at 3 and 6 months of follow-up. RESULTS: Treatment for 6 months with exenatide decreased significantly body weight (-12.5 kg) and waist circumference (-13 cm). Twenty percent of patients reduced their BMI under 35 kg/m(2) and significantly improved their metabolic profile (HbA1c <7 %). Significant and maintained decreases in HbA1c of 1 % were observed in the 3 and 6 months cohorts. Triglycerides levels and blood pressure also decreased from baseline to the end of the study. Treatment was discontinued in 19 % of patients mainly due to drug inefficacy (6 %) or adverse events (4 %). CONCLUSIONS: Exenatide twice daily (BID) leads to early, robust, and significant weight loss in a subset of patients with diabetes and severe obesity before bariatric surgery. Clinical trials are needed to confirm the benefits of GLP-1 agonists in type 2 diabetic obese patients or high-risk super-obese patients waiting for bariatric surgery.

Extracellular vesicles and their synthetic analogues in aging and age-associated brain diseases.

Multicellular organisms rely upon diverse and complex intercellular communications networks for a myriad of physiological processes. Disruption of these processes is implicated in the onset and propagation of disease and disorder, including the mechanisms of senescence at both cellular and organismal levels. In recent years, secreted extracellular vesicles (EVs) have been identified as a particularly novel vector by which cell-to-cell communications are enacted. EVs actively and specifically traffic bioactive proteins, nucleic acids, and metabolites between cells at local and systemic levels, modulating cellular responses in a bidirectional manner under both homeostatic and pathological conditions. EVs are being implicated not only in the generic aging process, but also as vehicles of pathology in a number of age-related diseases, including cancer and neurodegenerative and disease. Thus, circulating EVs-or specific EV cargoes-are being utilised as putative biomarkers of disease. On the other hand, EVs, as targeted intercellular shuttles of multipotent bioactive payloads, have demonstrated promising therapeutic properties, which can potentially be modulated and enhanced through cellular engineering. Furthermore, there is considerable interest in employing nanomedicinal approaches to mimic the putative therapeutic properties of EVs by employing synthetic analogues for targeted drug delivery. Herein we describe what is known about the origin and nature of EVs and subsequently review their putative roles in biology and medicine (including the use of synthetic EV analogues), with a particular focus on their role in aging and age-related brain diseases.

The in vitro immunomodulatory effect of extracellular products (ECPs) of Vagococcus fluvialis L21 on European sea bass (Dicentrarchus labrax) leucocytes.

The immune associated genes, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor-α (TNF-α), ciclo-oxigenase-2 (COX-2), and Mx gene were studied by real-time PCR in head-kidney leucocytes of sea bass after incubation with the extracellular products (ECPs) of the probiotic strain Vagococcus fluvialis L21 and polyinosinic:polycytidylic acid (POLY I:C), at different times (T1.5, T6, T12, T24, T48 and T72). In general, we can observe how pro-inflammatory cytokines IL-1ß, TNF-α, IL-6 and COX-2 studied displayed a strong peak after stimulation with 1.5 h of ECPs of V. fluvialis L21, significant differences (P < 0.05) exist with other periods and with the POLY I: C at the same time. Similarly to the case of IL-10 also produced a statistically significant (P < 0.05) peak of expression on leukocytes that were stimulated with the ECPs of V. fluvialis L21. In the case of Mx gene expression, we note that in almost all sampling times there is an up-regulation of the Mx gene in leucocytes incubated with ECPs and POLY I:C compared to the control and Mx expression was higher in leucocytes that were stimulated with the ECPs of V. fluvialis for all times, except in T24. With these results we can consider that the ECPs of V. fluvialis L21 have a great power of stimulating the in vitro expression of immune-related genes and may even be useful as adjuvants for vaccine in aquaculture.