Alteraciones neuroanatómicas en los núcleos caudado y accumbens como marcador neurobiológico de mala respuesta al metilfenidato en el TDAH infantil

El Trastorno por Déficit de Atención con Hiperactividad (TDAH) es uno de los trastornos del neurodesarrollo más comunes que se inicia en la edad temprana y que se caracteriza por presentar un cuadro clínico de inatención, hiperactividad e impulsividad. Desde un punto de vista farmacológico, el metilfenidato (MFD) es el fármaco de primera elección para tratar el TDAH debido a la alta eficacia que presenta a la hora de mejorar los síntomas, no obstante, se ha estimado que un 30% de estos pacientes no responden de manera adecuada. Actualmente no se disponen de marcadores clínicos, genéticos o neurobiológicos que permitan identificar a los pacientes susceptibles de presentar una buena o mala respuesta al MFD. El objetivo del presente estudio ha sido identificar a través de técnicas de resonancia magnética (RM) y variables clínicas y neuropsicológicas si existen diferencias cerebrales y/o clínico-cognitivas entre los pacientes que presentan una respuesta favorable o desfavorable al MFD. Para ello, se ha utilizado un diseño ex post facto de casos y controles para estudiar una muestra de 27 pacientes TDAH (de entre 6 y 15 años de edad) naïve al tratamiento con MFD. La evaluación clínica de los pacientes al mes de iniciar el tratamiento farmacológico ha indicado que 16 sujetos han presentado una respuesta favorable y 11 desfavorable. Los resultados de RM han mostrado que los pacientes con una buena respuesta al MFD tienen una mayor concentración de sustancia gris en la cabeza de ambos núcleos caudados y en el núcleo accumbens derecho respecto a los pacientes que no responden de manera adecuada. En relación a las variables clínicas y neuropsicológicas, no se han encontrado diferencias entre los dos grupos antes de iniciar el tratamiento farmacológico, sin embargo sí se han hallado en la evaluación post-tratamiento en el cuestionario de Conners para padres y el test Continuous Performance Test. Asimismo, se ha encontrado una relación entre estas dos medidas y los volúmenes del núcleo caudado y accumbens de manera bilateral. Estos resultados no sólo apoyan la hipótesis sobre la implicación de estas estructuras en la fisiopatología del TDAH, sino que también ponen de manifiesto su implicación en la respuesta al tratamiento farmacológico y su relación con los síntomas tanto cognitivos como conductuales que se manifiestan en los pacientes con TDAH. Los resultados derivados de este trabajo podrían ser de gran utilidad para determinar un fenotipo neuroanatómico que permita diferenciar a los pacientes que presentarán una respuesta favorable o desfavorable al MFD en el momento del diagnóstico y predecir su grado de mejoría a nivel clínico y neuropsicológicoAttention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders occurring in childhood. The main symptoms are developmentally excessive levels of inattention, impulsivity and hyperactivity. Methylphenidate (MPH) is the drug of first choice for treating ADHD because of its high efficacy to reduce the symptoms. It has been estimated that 30% of patients with ADHD do not respond adequately to MPH. Presently, there are no clinical or biological markers distinguishing good and bad responders. The aim of this study was to evaluate whether anatomical and/or clinical/cognitive differences exist between these two types of patients (good and bad responders) by applying magnetic resonance (MR) procedures and clinical and neuropsychological assessments. A case-control study was implemented to analyze a sample of twenty-seven treatment-naïve patients with ADHD (between six and fifteen years old). MPH administration started one day after the MR acquisition. After a month, psychiatrists established the good or poor response to MPH according to clinical criteria. Sixteen patients showed good response to the MPH and eleven did a poor one. The results has showed the good responders had a higher concentration of gray matter in the both Caudate nucleus head and the right Accumbens nucleus than the bad responders. Before MPH treatment it has no found differences between groups regarding clinical and neuropsychological measures. However, statistical differences has found in the Conners' Parent Rating Scales (CPRS) and Continuous Performance Test (CPT) after treatment. Furthermore, a significant correlation has found between Caudate and Accumbens nuclei volume (bilaterally) and the CPRS and CPT improvement. These results support the hypothesis of the involvement of the Caudate and Accumbens nuclei in MPH response and in physiopathology of ADHD. Also, such findings could also be useful to determinate a neuroanatomical phenotype as an eventual sign that helps in characterizing, at the time of diagnosis, patients with good and bad response to MPH and predicting the clinical and neuropsychological improvement level

The hidden microbial ecosystem in the perennial ice from a Pyrenean ice cave.

Over the last years, perennial ice deposits located within caves have awakened interest as places to study microbial communities since they represent unique cryospheric archives of climate change. Since the beginning of the twentieth century, the temperature has gradually increased, and it is estimated that by the end of this century the increase in average temperature could be around 4.0°C. In this context of global warming the ice deposits of the Pyrenean caves are undergoing a significant regression. Among this type of caves, that on the Cotiella Massif in the Southern Pyrenees is one of the southernmost studied in Europe. These types of caves house microbial communities which have so far been barely explored, and therefore their study is necessary. In this work, the microbial communities of the Pyrenean ice cave A294 were identified using metabarcoding techniques. In addition, research work was carried out to analyze how the age and composition of the ice affect the composition of the bacterial and microeukaryotic populations. Finally, the in vivo effect of climate change on the cellular machinery that allow microorganisms to live with increasing temperatures has been studied using proteomic techniques

Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the disease

This is an open access article distributed under the terms of the Creative Commons Attribution License.[Introduction]: Fibromyalgia is a chronic pain syndrome with unknown etiology. Recent studies have shown some evidence demonstrating that oxidative stress may have a role in the pathophysiology of fibromyalgia. However, it is still not clear whether oxidative stress is the cause or the effect of the abnormalities documented in fibromyalgia. Furthermore, the role of mitochondria in the redox imbalance reported in fibromyalgia also is controversial. We undertook this study to investigate the role of mitochondrial dysfunction, oxidative stress, and mitophagy in fibromyalgia. [Methods]: We studied 20 patients (2 male, 18 female patients) from the database of the Sevillian Fibromyalgia Association and 10 healthy controls. We evaluated mitochondrial function in blood mononuclear cells from fibromyalgia patients measuring, coenzyme Q10 levels with high-performance liquid chromatography (HPLC), and mitochondrial membrane potential with flow cytometry. Oxidative stress was determined by measuring mitochondrial superoxide production with MitoSOX™ and lipid peroxidation in blood mononuclear cells and plasma from fibromyalgia patients. Autophagy activation was evaluated by quantifying the fluorescence intensity of LysoTracker™ Red staining of blood mononuclear cells. Mitophagy was confirmed by measuring citrate synthase activity and electron microscopy examination of blood mononuclear cells. [Results]: We found reduced levels of coenzyme Q10, decreased mitochondrial membrane potential, increased levels of mitochondrial superoxide in blood mononuclear cells, and increased levels of lipid peroxidation in both blood mononuclear cells and plasma from fibromyalgia patients. Mitochondrial dysfunction was also associated with increased expression of autophagic genes and the elimination of dysfunctional mitochondria with mitophagy. [Conclusions]: These findings may support the role of oxidative stress and mitophagy in the pathophysiology of fibromyalgia.This work was supported by grants FIS PI080500 and FIS EC08/00076, Ministerio de Sanidad, Spain. The authors dedicate this manuscript to FM patients and AFIBROSE (Asociación de Fibromialgia de Sevilla) for their unconditional help.Peer Reviewe

Augmentation of EMDR with multifocal transcranial current stimulation (MtCS) in the treatment of fibromyalgia : study protocol of a double-blind randomized controlled exploratory and pragmatic trial

Fibromyalgia (FM) is a generalized, widespread chronic pain disorder affecting 2.7% of the general population. In recent years, different studies have observed a strong association between FM and psychological trauma. Therefore, a trauma-focused psychotherapy, such as eye movement desensitization and reprocessing (EMDR), combined with a non-invasive brain stimulation technique, such as multifocal transcranial current stimulation (MtCS), could be an innovative adjunctive treatment option. This double-blind randomized controlled trial (RCT) analyzes if EMDR therapy is effective in the reduction of pain symptoms in FM patients and if its potential is boosted with the addition of MtCS. Forty-five patients with FM and a history of traumatic events will be randomly allocated to Waiting List, EMDR + active-MtCS, or EMDR + sham-MtCS. Therapists and patients will be kept blind to MtCS conditions, and raters will be kept blind to both EMDR and MtCS. All patients will be evaluated at baseline, post-treatment, and follow-up at 6 months after post-treatment. Evaluations will assess the following variables: sociodemographic data, pain, psychological trauma, sleep disturbance, anxiety and affective symptoms, and wellbeing. This study will provide evidence of whether EMDR therapy is effective in reducing pain symptoms in FM patients, and whether the effect of EMDR can be enhanced by MtCS. ClinicalTrials.gov . Registered on 2 August 2019. The online version contains supplementary material available at 10.1186/s13063-021-05042-w

Tomato POLLEN DEFICIENT 2 encodes a G-Type lectin receptor kinase required for viable pollen grain formation

Pollen development is a crucial biological process indispensable for seed set in flowering plants and for successful crop breeding. However, little is known about the molecular mechanisms regulating pollen development in crop species. This study reports a novel male-sterile tomato mutant, pollen deficient 2 (pod2), characterized by the production of non-viable pollen grains and resulting in the development of small parthenocarpic fruits. A combined strategy of mapping-by-sequencing and RNA interference-mediated gene silencing was used to prove that the pod2 phenotype is caused by the loss of Solanum lycopersicum G-Type lectin receptor kinase II.9 (SlG-LecRK-II.9) activity. In situ hybridization of floral buds showed that POD2/SlG-LecRK-II.9 is specifically expressed in tapetal cells and microspores at the late tetrad stage. Accordingly, abnormalities in meiosis and tapetum programmed cell death in pod2 occurred during microsporogenesis, resulting in the formation of four dysfunctional microspores leading to an aberrant microgametogenesis process. RNA-seq analyses supported the existence of alterations at the final stage of microsporogenesis, since we found tomato deregulated genes whose counterparts in Arabidopsis are essential for the normal progression of male meiosis and cytokinesis. Collectively, our results revealed the essential role of POD2/SlG-LecRK-II.9 in regulating tomato pollen development.This work was supported by research grants PID2019-110833RB-C31, PID2019-110833RB-C32, and PID2020-113324GB-100 funded by the Spanish Ministry of Science and Innovation (MCIN/AEI/10.13039/501100011033), and the Research and Innovation Programme of the European Union Horizon 2020 (BRESOV Project, ID 774244). A PhD fellowship to MGA was funded by the FPU Programme of the Spanish Ministry of Education and Culture (ref. AP2010-4528). RLe was supported by a Junta de Andalucía and FEDER research contract (DOC_01129)

Stabilization of apoptotic cells: generation of zombie cells

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.Apoptosis is characterized by degradation of cell components but plasma membrane remains intact. Apoptotic microtubule network (AMN) is organized during apoptosis forming a cortical structure beneath plasma membrane that maintains plasma membrane integrity. Apoptotic cells are also characterized by high reactive oxygen species (ROS) production that can be potentially harmful for the cell. The aim of this study was to develop a method that allows stabilizing apoptotic cells for diagnostic and therapeutic applications. By using a cocktail composed of taxol (a microtubule stabilizer), Zn2+ (a caspase inhibitor) and coenzyme Q10 (a lipid antioxidant), we were able to stabilize H460 apoptotic cells in cell cultures for at least 72 h, preventing secondary necrosis. Stabilized apoptotic cells maintain many apoptotic cell characteristics such as the presence of apoptotic microtubules, plasma membrane integrity, low intracellular calcium levels and mitochondrial polarization. Apoptotic cell stabilization may open new avenues in apoptosis detection and therapy.This work was supported by FIS PI10/00543 grant, Ministerio de Sanidad, Spain, and Fondo Europeo de Desarrollo Regional (FEDER-Unión Europea), SAS 111242 grant, Servicio Andaluz de Salud-Junta de Andalucía, Proyecto de Investigación de Excelencia de la Junta de Andalucía CTS-5725, BFU2012-38208 and by AEPMI (Asociación de Enfermos de Patología Mitocondrial).Peer Reviewe

Prevalence and Characterization of Psychological Trauma in Patients with Fibromyalgia: A Cross-Sectional Study

Preliminary evidence suggests that psychological trauma, especially childhood trauma, is a risk factor for the onset of fibromyalgia (FM).The main objective of this study consisted of evaluating the prevalence and detailed characteristics of psychological trauma in a sample of patients with FM, the chronology of trauma across the lifespan, and its clinical symptoms. We also calculated whether childhood trauma could predict the relationship with different clinical variables.Eighty-eight females underwent an interview to assess sociodemographic data, psychiatric comorbidities, level of pain, FM impact, clinical symptoms of anxiety, depression, insomnia, quality of life, and psychological trauma.The majority of participants (71.5%) met the diagnostic criteria for current post-traumatic stress disorder (PTSD). Participants reported having suffered traumatic events throughout their lifespan, especially in childhood and early adolescence, in the form of emotional abuse, emotional neglect, sexual abuse, and physical abuse. Traumatic events predict both poor quality of life and a level of pain in adulthood. All patients showed clinically relevant levels of anxiety, depression, insomnia, suicidal thoughts, and pain, as well as somatic comorbidities and poor quality of life. Pain levels predicted anxiety, depression, dissociation, and insomnia symptoms. 84% of the sample suffered one or more traumatic events prior to the onset of pain.Our data highlight the clinical complexity of patients with FM and the role of childhood trauma in the onset and maintenance of FM, as well as the high comorbidity between anxiety, depression, somatic symptoms, and FM. Our data also supports FM patients experiencing further retraumatization as they age, with an extremely high prevalence of current PTSD in our sample. These findings underscore the need for multidisciplinary programs for FM patients to address their physical pain and their psychiatric and somatic conditions, pay special attention to the assessment of psychological trauma, and provide trauma-focused interventions. Trial registration: ClinicalTrials.gov NCT04476316. Registered on July 20th, 2020.Copyright © 2022 Itxaso Gardoki-Souto et al

Supporting employees with mental illness and reducing mental illness-related stigma in the workplace: an expert survey

An expert survey was designed to support the development of a workplace-based multi-country intervention tackling depression, anxiety, and mental illness-related stigma in small- and medium-sized enterprises (SMEs). Academic experts and representatives of SME organisations, specific sector organisations, labour or advocacy groups, and occupational health organisations, were contacted across eight European countries and Australia. The survey comprised closed and open text questions to assess expert opinion about interventions for employees with mental health difficulties, interventions supporting their managers, and anti-stigma interventions. The survey was available in six languages. The online platform Qualtrics was used for data collection. Quantitative data was analysed through descriptive statistics and qualitative data was analysed through thematic analysis. Sixty-five of 146 experts responded, representing a 42% response rate. Results showed only 26.2% of experts agreed that employees could speak openly about mental health issues, and 81.5% of experts indicated a large or medium unmet need for support for employees with mental health issues. Psychoeducational materials, face-to-face workshops and interventions based on cognitive behavioural therapy were ranked most likely to be taken up by employees. Experts rated as most useful for managers’ guidelines on how to act if an employee has mental health issues (67.7%). The greatest number of experts indicated workshops of people with lived experience of mental illness (80.0%) and awareness campaigns (78.5%) were most required to tackle stigma. Responses were consistent between experts from different countries and areas of expertise. Experts in this multinational survey assessed that interventions supporting mental health in the workplace and tackling stigma are greatly needed. A multicomponent intervention with a wide range of materials and tools is supported.Additional co-authors: Doireann Ni Dhalaigh, Hanna Reich, Victoria Ross, Sarita Sanches, Katherine Thomson, Chantal Van Audenhove, Victor Pérez, Ella Arensman, Gyorgy Purebl, Benedikt L. Amann MENTUPP consortium members are Ainslie O’Connor, Andras Szekely, Anthony LaMontagne, Ariel Como, Arilda Dushaj, Asmae Doukani, Azucena Justicia, Birgit A. Greiner, Chris Lockwood, Cliodhna O’Connor, David McDaid, Dooyoung Kim, Eileen Williamson, Eve Griffin, Evelien Coppens, Genc Burazeri, Gentiana Qirjako, Grace Davey, Jaap van Weeghel, Joe Eustace, Joseph Kilroy, Juliane Hug, Kairi Kolves, Karen Mulcahy, Karen Michell, Kristian Wahlbeck, Lars de Winter, Laura Cox, Luigia D’Alessandro, Margaret Maxwell, Nicola Reavley, Peter Trembeczky, Paul Corcoran, Reiner Rugulies, Ruth Benson, Saara Rapeli, Sarah Ihinonvien, Sevim Mustafa, Sharna Mathieu, Stefan Hackel, Tanya King, Ulrich Hegerl, Vanda Scott & Wendy Orchar

High incidence of PTSD diagnosis and trauma-related symptoms in a trauma exposed bipolar I and II sample

Post-traumatic stress disorder (PTSD) is an established comorbidity in Bipolar Disorder (BD), but little is known about the characteristics of psychological trauma beyond a PTSD diagnosis and differences in trauma symptoms between BD-I and BD-II. (1) To present characteristics of a trauma-exposed BD sample; (2) to investigate prevalence and trauma symptom profile across BD-I and BD-II; (3) to assess the impact of a lifetime PTSD diagnosis vs. a history of trauma on BD course; and (4) to research the impacts of sexual and physical abuse. This multi-center study comprised 79 adult participants with BD with a history of psychological trauma and reports baseline data from a trial registered in Clinical Trials (; ref: NCT02634372). Clinical variables were gathered through clinical interview, validated scales and a review of case notes. The majority (80.8%) of our sample had experienced a relevant stressful life event prior to onset of BD, over half of our sample 51.9% had a lifetime diagnosis of PTSD according to the Clinician Administered PTSD scale. The mean Impact of Event Scale-Revised scores indicated high levels of trauma-related distress across the sample, including clinical symptoms in the PTSD group and subsyndromal symptoms in the non-PTSD group. Levels of dissociation were not higher than normative values for BD. A PTSD diagnosis (vs. a history of trauma) was associated with psychotic symptoms [2(1) = 5.404, p = 0.02] but not with other indicators of BD clinical severity. There was no significant difference between BD-I and BD-II in terms of lifetime PTSD diagnosis or trauma symptom profile. Sexual abuse significantly predicted rapid cycling [2(1) = 4.15, p = 0.042], while physical abuse was not significantly associated with any clinical indicator of severity. Trauma load in BD is marked with a lack of difference in trauma profile between BD-I and BD-II. Although PTSD and sexual abuse may have a negative impact on BD course, in many indicators of BD severity there is no significant difference between PTSD and subsyndromal trauma symptoms. Our results support further research to clarify the role of subsyndromic PTSD symptoms, and highlight the importance of screening for trauma in BD patients

High incidence of PTSD diagnosis and trauma-related symptoms in a trauma exposed bipolar I and II sample

Background: Post-traumatic stress disorder (PTSD) is an established comorbidity in Bipolar Disorder (BD), but little is known about the characteristics of psychological trauma beyond a PTSD diagnosis and differences in trauma symptoms between BD-I and BD-II. Objective: (1) To present characteristics of a trauma-exposed BD sample; (2) to investigate prevalence and trauma symptom profile across BD-I and BD-II; (3) to assess the impact of a lifetime PTSD diagnosis vs. a history of trauma on BD course; and (4) to research the impacts of sexual and physical abuse. Methods: This multi-center study comprised 79 adult participants with BD with a history of psychological trauma and reports baseline data from a trial registered in Clinical Trials (https://clinicaltrials.gov; ref: NCT02634372). Clinical variables were gathered through clinical interview, validated scales and a review of case notes. Results: The majority (80.8%) of our sample had experienced a relevant stressful life event prior to onset of BD, over half of our sample 51.9% had a lifetime diagnosis of PTSD according to the Clinician Administered PTSD scale. The mean Impact of Event Scale-Revised scores indicated high levels of trauma-related distress across the sample, including clinical symptoms in the PTSD group and subsyndromal symptoms in the non-PTSD group. Levels of dissociation were not higher than normative values for BD. A PTSD diagnosis (vs. a history of trauma) was associated with psychotic symptoms [2(1) = 5.404, p = 0.02] but not with other indicators of BD clinical severity. There was no significant difference between BD-I and BD-II in terms of lifetime PTSD diagnosis or trauma symptom profile. Sexual abuse significantly predicted rapid cycling [2(1) = 4.15, p = 0.042], while physical abuse was not significantly associated with any clinical indicator of severity. Conclusion: Trauma load in BD is marked with a lack of difference in trauma profile between BD-I and BD-II. Although PTSD and sexual abuse may have a negative impact on BD course, in many indicators of BD severity there is no significant difference between PTSD and subsyndromal trauma symptoms. Our results support further research to clarify the role of subsyndromic PTSD symptoms, and highlight the importance of screening for trauma in BD patients