ER-mitochondria communication is involved in NLRP3 inflammasome activation under stress conditions in the innate immune system.

Endoplasmic reticulum (ER) stress and mitochondrial dysfunction, which are key events in the initiation and/or progression of several diseases, are correlated with alterations at ER-mitochondria contact sites, the so-called "Mitochondria-Associated Membranes" (MAMs). These intracellular structures are also implicated in NLRP3 inflammasome activation which is an important driver of sterile inflammation, however, the underlying molecular basis remains unclear. This work aimed to investigate the role of ER-mitochondria communication during ER stress-induced NLRP3 inflammasome activation in both peripheral and central innate immune systems, by using THP-1 human monocytes and BV2 microglia cells, respectively, as in vitro models. Markers of ER stress, mitochondrial dynamics and mass, as well as NLRP3 inflammasome activation were evaluated by Western Blot, IL-1ß secretion was measured by ELISA, and ER-mitochondria contacts were quantified by transmission electron microscopy. Mitochondrial Ca2+ uptake and polarization were analyzed with fluorescent probes, and measurement of aconitase and SOD2 activities monitored mitochondrial ROS accumulation. ER stress was demonstrated to activate the NLRP3 inflammasome in both peripheral and central immune cells. Studies in monocytes indicate that ER stress-induced NLRP3 inflammasome activation occurs by a Ca2+-dependent and ROS-independent mechanism, which is coupled with upregulation of MAMs-resident chaperones, closer ER-mitochondria contacts, as well as mitochondrial depolarization and impaired dynamics. Moreover, enhanced ER stress-induced NLRP3 inflammasome activation in the immune system was found associated with pathological conditions since it was observed in monocytes derived from bipolar disorder (BD) patients, supporting a pro-inflammatory status in BD. In conclusion, by demonstrating that ER-mitochondria communication plays a key role in the response of the innate immune cells to ER stress, this work contributes to elucidate the molecular mechanisms underlying NLRP3 inflammasome activation under stress conditions, and to disclose novel potential therapeutic targets for diseases associated with sterile inflammation.

Association between premenstrual dysphoric disorder and perinatal depression: a systematic review.

Premenstrual dysphoric disorder (PMDD) affects 1.2 to 5% of women of reproductive age. Besides significant suffering and social, occupational, and interpersonal impairment, it has been suggested that this syndrome is associated with other affective disorders, in different reproductive phases, such as pregnancy and the postpartum period. However, the literature on this association is scarce and presents great variability in terms of adopted methodology and mixed results. To analyze the relationship between PMDD and other affective disorders, aiming to contribute to the clarification of whether PMDD can be considered a risk factor for perinatal depression (PND). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive literature search in PubMed, EMBASE, CINAHL, PsycINFO databases. Seven original studies were included. Only one study linked PMDD with depression during pregnancy, with evidence of a positive association between PMDD and PND. This and five other studies show a positive relationship between PMDD and postpartum depression (PPD), assessed in periods ranging from 2 to 4 days to 1 year after birth. Only one study found no significant association between PMDD and PPD, assessed at 4 weeks postpartum. There seems to be a positive and significant association between PMDD and the development of perinatal depression, particularly postpartum depression. This review supports the relevance of health professionals systematically evaluating the presence of premenstrual dysphoric disorder, when monitoring women throughout the perinatal period.

Systematic Review and Meta-Analysis on MS-Based Proteomics Applied to Human Peripheral Fluids to Assess Potential Biomarkers of Bipolar Disorder.

Bipolar disorder (BD) is a clinically heterogeneous condition, presenting a complex underlying etiopathogenesis that is not sufficiently characterized. Without molecular biomarkers being used in the clinical environment, several large screen proteomics studies have been conducted to provide valuable molecular information. Mass spectrometry (MS)-based techniques can be a powerful tool for the identification of disease biomarkers, improving prediction and diagnosis ability. Here, we evaluate the efficacy of MS proteomics applied to human peripheral fluids to assess BD biomarkers and identify relevant networks of biological pathways. Following PRISMA guidelines, we searched for studies using MS proteomics to identify proteomic differences between BD patients and healthy controls (PROSPERO database: CRD42021264955). Fourteen articles fulfilled the inclusion criteria, allowing the identification of 266 differentially expressed proteins. Gene ontology analysis identified complement and coagulation cascades, lipid and cholesterol metabolism, and focal adhesion as the main enriched biological pathways. A meta-analysis was performed for apolipoproteins (A-I, C-III, and E); however, no significant differences were found. Although the proven ability of MS proteomics to characterize BD, there are several confounding factors contributing to the heterogeneity of the findings. In the future, we encourage the scientific community to use broader samples and validation cohorts, integrating omics with bioinformatics tools towards providing a comprehensive understanding of proteome alterations, seeking biomarkers of BD, and contributing to individualized prognosis and stratification strategies, besides aiding in the differential diagnosis.

Systematic Review and Meta-Analysis of Mass Spectrometry Proteomics Applied to Human Peripheral Fluids to Assess Potential Biomarkers of Schizophrenia.

Mass spectrometry (MS)-based techniques can be a powerful tool to identify neuropsychiatric disorder biomarkers, improving prediction and diagnosis ability. Here, we evaluate the efficacy of MS proteomics applied to human peripheral fluids of schizophrenia (SCZ) patients to identify disease biomarkers and relevant networks of biological pathways. Following PRISMA guidelines, a search was performed for studies that used MS proteomics approaches to identify proteomic differences between SCZ patients and healthy control groups (PROSPERO database: CRD42021274183). Nineteen articles fulfilled the inclusion criteria, allowing the identification of 217 differentially expressed proteins. Gene ontology analysis identified lipid metabolism, complement and coagulation cascades, and immune response as the main enriched biological pathways. Meta-analysis results suggest the upregulation of FCN3 and downregulation of APO1, APOA2, APOC1, and APOC3 in SCZ patients. Despite the proven ability of MS proteomics to characterize SCZ, several confounding factors contribute to the heterogeneity of the findings. In the future, we encourage the scientific community to perform studies with more extensive sampling and validation cohorts, integrating omics with bioinformatics tools to provide additional comprehension of differentially expressed proteins. The produced information could harbor potential proteomic biomarkers of SCZ, contributing to individualized prognosis and stratification strategies, besides aiding in the differential diagnosis.

Inflammation in Bipolar Disorder (BD): Identification of new therapeutic targets.

Bipolar disorder (BD) is a chronic and cyclic mental disorder, characterized by unusual mood swings between mania/hypomania and depression, raising concern in both scientific and medical communities due to its deleterious social and economic impact. Polypharmacy is the rule due to the partial effectiveness of available drugs. Disease course is often unremitting, resulting in frequent cognitive deficits over time. Despite all research efforts in identifying BD-associated molecular mechanisms, current knowledge remains limited. However, the involvement of inflammation in BD pathophysiology is increasingly consensual, with the immune system and neuroinflammation playing a key role in disease course. Evidence includes altered levels of cytokines and acute-phase proteins, pathological microglial activation, deregulation of Nrf2-Keap1 system and changes in biogenic amines neurotransmitters, whose expression is regulated by TNF-α, a pro-inflammatory cytokine highly involved in BD, pointing out inflammation as a novel and attractive therapeutic target for BD. As result, new therapeutic agents including non-steroidal anti-inflammatory drugs, N-acetylcysteine and GSK3 inhibitors have been incorporated in BD treatment. Taking into consideration the latest pre-clinical and clinical trials, in this review we discuss recent data regarding inflammation in BD, unveiling potential therapeutic approaches through direct or indirect modulation of inflammatory response.

Slower access to visual awareness but otherwise intact implicit perception of emotional faces in schizophrenia-spectrum disorders.

Schizophrenia-spectrum disorders are characterized by deficits in social domains. Extant research has reported an impaired ability to perceive emotional faces in schizophrenia. Yet, it is unclear if these deficits occur already in the access to visual awareness. To investigate this question, 23 people with schizophrenia or schizoaffective disorder and 22 healthy controls performed a breaking continuous flash suppression task with fearful, happy, and neutral faces. Response times were analysed with generalized linear mixed models. People with schizophrenia-spectrum disorders were slower than controls in detecting faces, but did not show emotion-specific impairments. Moreover, happy faces were detected faster than neutral and fearful faces, across all participants. Although caution is needed when interpreting the main effect of group, our findings may suggest an elevated threshold for visual awareness in schizophrenia-spectrum disorders, but an intact implicit emotion perception. Our study provides a new insight into the mechanisms underlying emotion perception in schizophrenia-spectrum disorders.

Serum uric acid as a predictor of bipolarity in individuals with a major depressive episode.

OBJECTIVES: There are no well-established biomarkers to predict the risk of conversion to bipolar disorder (BD) in patients with depression. Given the putative role of purinergic neurotransmission dysfunction in BD, the purpose of our study was to evaluate if higher serum uric acid (UA) levels could predict BD conversion in depressed inpatients. METHODS: We reviewed retrospectively the records of subjects hospitalized between June 2007 and June 2010 with a diagnosis of major depressive disorder (MDD) who had undergone routine UA levels testing at admission. At an approximate 10-year follow-up we identified subjects with a subsequent diagnosis of BD. We compared UA levels between the BD-converter and non-BD converter groups, performed Receiver operating characteristic curve analysis to evaluate the prognostic accuracy of serum UA levels and calculated the clinical utility index (CUI) as a risk biomarker for conversion to BD. RESULTS: The study included 250 subjects (55 "BD-converters" and 195 "No BD-converters"). "BD-converters" had significantly higher plasma UA levels compared to "No BD-converters" in their index hospitalization irrespective of gender (males: 403.84 ± 91.76 vs 270.81 ± 53.58 µmol/L; U = 94.5, P < 0.001 and females 302.19 ± 52.64 vs 202.69 ± 48.93 µmol/L; t = 10.75, P < 0.001). Serum UA levels showed a very good to excellent accuracy for predicting conversion to BD in inpatients with MDD (area under the curve [AUC]: 0.90; 95% CI: 0.86, 0.94) and had a good to excellent CUI- and a moderate to good CUI+ grading for discriminating BD-converter cases from non-BD converters. CONCLUSIONS: Our study suggests that depressed patients with higher levels of serum UA are at greater risk of a subsequent manic or hypomanic episode. The purinergic system could prove a promising path for the search of biomarkers in BD.

Treatment Options for Insomnia in Schizophrenia: A Systematic Review.

BACKGROUND: Insomnia is a common feature of schizophrenia. Although several studies have been published about the influence of certain drugs on schizophrenia patients' sleep, there are no well-grounded recommendations about insomnia treatment in this clinical setting. The present review aimed to identify relevant empirical evidence on available treatments of insomnia in patients with schizophrenia, assessing their safety and efficacy. METHODS: This is a systematic review of clinical trials investigating the effect of treatments for insomnia in patients with a diagnosis of schizophrenia. Data were obtained from Medline/PubMed, Embase, PsycInfo, and the Cochrane Library. Risk of bias was assessed in individual studies for selection, performance, detection, attrition, and reporting bias. RESULTS: Four studies met inclusion criteria; 2 using melatonin, 1 using paliperidone, and 1 with eszopiclone. All reported positive results: melatonin increased sleep efficiency and total duration of sleep; paliperidone decreased sleep latency onset and increased total sleep time and sleep efficiency; eszopiclone decreased insomnia severity index. CONCLUSIONS: Despite a very limited number of specific studies on this matter, all 4 studies have shown good benefit/risk ratios and reviewed options-melatonin, paliperidone, and eszopiclone-might represent valid options for residual insomnia in schizophrenia.

High-throughput sequencing reveals a novel closterovirus in arracacha (Arracacia xanthorrhiza).

High-throughput sequencing analysis detected a clostero-like virus from arracacha plants (Arracacia xanthorrhiza) in Brazil. The complete genome sequence, confirmed by RACE and Sanger sequencing, consists of 15,763 nucleotides with nine predicted open reading frames (ORFs) in a typical closterovirus genome organisation. The putative RNA-dependent RNA polymerase (RdRp), heat shock protein 70 homologue (Hsp70h), and coat protein showed 55-65, 38-44, and 20-36% amino acid sequence identity, respectively, to the homologous proteins of known closteroviruses. Phylogenetic analysis of Hsp70h showed that this putative novel arracacha plant virus was related to members of the genus Closterovirus in the family Closteroviridae. These results suggest that this virus, tentatively named "arracacha virus 1" (AV-1), is a novel member of the genus Closterovirus. This is the first closterovirus identified in arracacha plants.

Smoking and antidepressants pharmacokinetics: a systematic review.

BACKGROUND: Despite an increasingly recognized relationship between depression and smoking, little is known about how smoking influences antidepressant response and treatment outcomes. The aim of this study was to systematically review the evidence of the impact of smoking on new-generation antidepressants with an emphasis on the pharmacokinetic perspective. METHODS: We present a systematic review of clinical trials comparing the serum levels of new-generation antidepressants in smokers and nonsmokers. Data were obtained from MEDLINE/PubMed, Embase, and other sources. Risk of bias was assessed for selection, performance, detection, attrition, and reporting of individual studies. RESULTS: Twenty-one studies met inclusion criteria; seven involved fluvoxamine, two evaluated fluoxetine, sertraline, venlafaxine, duloxetine or mirtazapine, and escitalopram, citalopram, trazodone and bupropion were the subject of a single study. No trials were found involving other common antidepressants such as paroxetine or agomelatine. Serum levels of fluvoxamine, duloxetine, mirtazapine and trazodone were significantly higher in nonsmokers compared with smokers. CONCLUSIONS: There is evidence showing a reduction in the concentration of serum levels of fluvoxamine, duloxetine, mirtazapine and trazodone in smoking patients as compared to nonsmokers. The evidence regarding other commonly used antidepressants is scarce. Nonetheless, smoking status should be considered when choosing an antidepressant treatment, given the risk of pharmacokinetic interactions.

The other side of recovery: validation of the Portuguese version of the subjective experiences of psychosis scale.

BACKGROUND: The aim of this study was to develop and validate a Portuguese version of The Subjective Experiences of Psychosis Scale (SEPS) for use in Portuguese-speaking populations in order to provide a self-report instrument to assess and monitor dimensions of psychotic experiences, translating patient's perspective and experience in terms of recovery from psychosis. METHODS: The sample consisted of 30 participants with psychotic disorders who had recently experienced delusions or hallucinations. The SEPS was completed along with other observer-based assessments and self-report questionnaires, such as the Brief Psychiatric Rating Scale, the Insight and Treatment Attitudes Questionnaire and the Function Assessment Short Test. RESULTS: Two main factors representing the positive and negative components of each subscale were identified. We obtained good internal consistency and test-retest reliability for the positive and negative components of all subscales. The subscales of SEPS correlated with observer-based assessments and self-report questionnaires. CONCLUSIONS: The Portuguese version of the SEPS is a useful tool in the assessment and monitoring of psychotic symptoms.

Large-scale production of non-conventional edible plants for biodiverse school meals.

Introduction: School feeding programs are important for ensuring food security and promoting child health and development, particularly in low-income countries. In view of this importance, it is possible to increase the quality of these meals by diversifying the vegetables offered and incorporating underutilized plants to improve dietary diversity and nutritional quality into school meals. Methods: This study was carried out using the action research methodology following the implementation and development of the "Inova na Horta" project in the city of Jundiaí, São Paulo, Brazil. The project was based on the existing and functioning physical and organizational structure of a municipal organic farm. Vegetables were selected from among 210 non-conventional species and varieties, which were further selected for continuous production based on 8 nutritional, culinary and cultivation criteria. Results: Thirty-four vegetables were selected for continuous cultivation and provisions to the school kitchens. Nine tons of vegetables were produced and provided to 90 municipal schools from 2020-2023. Leafy vegetables accounted for most the production, with a total weight of 6441 kg corresponding to 71.6% of the total harvest. Kitchen teams were trained throughout the project duration. Discussion: The feasibility of the production and culinary use of 34 biodiverse, nutrient-rich and underutilized food vegetables for school meals was demonstrated. The selected vegetables are nutrient-rich and contain higher amounts of minerals and proteins than the control vegetables (conventional vegetables), thus complementing several nutrients in school meals. This methodology can be replicated by municipalities of various sizes as a public policy of food and nutritional security associated with the valorization of local biodiversity.

European Autism GEnomics Registry (EAGER): protocol for a multicentre cohort study and registry.

INTRODUCTION: Autism is a common neurodevelopmental condition with a complex genetic aetiology that includes contributions from monogenic and polygenic factors. Many autistic people have unmet healthcare needs that could be served by genomics-informed research and clinical trials. The primary aim of the European Autism GEnomics Registry (EAGER) is to establish a registry of participants with a diagnosis of autism or an associated rare genetic condition who have undergone whole-genome sequencing. The registry can facilitate recruitment for future clinical trials and research studies, based on genetic, clinical and phenotypic profiles, as well as participant preferences. The secondary aim of EAGER is to investigate the association between mental and physical health characteristics and participants' genetic profiles. METHODS AND ANALYSIS: EAGER is a European multisite cohort study and registry and is part of the AIMS-2-TRIALS consortium. EAGER was developed with input from the AIMS-2-TRIALS Autism Representatives and representatives from the rare genetic conditions community. 1500 participants with a diagnosis of autism or an associated rare genetic condition will be recruited at 13 sites across 8 countries. Participants will be given a blood or saliva sample for whole-genome sequencing and answer a series of online questionnaires. Participants may also consent to the study to access pre-existing clinical data. Participants will be added to the EAGER registry and data will be shared externally through established AIMS-2-TRIALS mechanisms. ETHICS AND DISSEMINATION: To date, EAGER has received full ethical approval for 11 out of the 13 sites in the UK (REC 23/SC/0022), Germany (S-375/2023), Portugal (CE-085/2023), Spain (HCB/2023/0038, PIC-164-22), Sweden (Dnr 2023-06737-01), Ireland (230907) and Italy (CET_62/2023, CEL-IRCCS OASI/24-01-2024/EM01, EM 2024-13/1032 EAGER). Findings will be disseminated via scientific publications and conferences but also beyond to participants and the wider community (eg, the AIMS-2-TRIALS website, stakeholder meetings, newsletters).

Emotional interference and attentional control in schizophrenia-spectrum disorders: The special case of neutral faces.

BACKGROUND AND OBJECTIVES: Schizophrenia-spectrum disorders (SSD) are characterized by impaired emotion processing and attention. SSD patients are more sensitive to the presence of emotional distractors. But despite growing interest on the emotion-attention interplay, emotional interference in SSD is far from fully understood. Moreover, research to date has not established the link between emotional interference and attentional control in SSD. This study thus aimed to investigate the effects of facial expression and attentional control in SSD, by manipulating perceptual load. METHODS: Twenty-two SSD patients and 22 healthy controls performed a target-letter discrimination task with task-irrelevant angry, happy, and neutral faces. Target-letter was presented among homogenous (low load) or heterogenous (high load) distractor-letters. Accuracy and RT were analysed using (generalized) linear mixed-effect models. RESULTS: Accuracy was significantly lower in SSD patients than controls, regardless of perceptual load and facial expression. Concerning RT, SSD patients were significantly slower than controls in the presence of neutral faces, but only at high load. No group differences were observed for angry and happy faces. LIMITATIONS: Heterogeneity of SSD, small sample size, lack of clinical control group, medication. CONCLUSIONS: One possible explanation is that neutral faces captured exogenous attention to a greater extent in SSD, thus challenging attentional control in perceptually demanding conditions. This may reflect abnormal processing of neutral faces in SSD. If replicated, these findings will help to understand the interplay between exogenous attention, attentional control, and emotion processing in SSD, which may unravel the mechanism underlying socioemotional dysfunction in SSD.

Psychological burden in Portuguese university students during the COVID-19 pandemic.

Background: University students are a risk population for mental health problems. This study aims to evaluate the psychological burden of the COVID-19 pandemic in Portuguese university students and to uncover factors associated with worse psychological indicators. Methods: We used an online survey to perform a cross-sectional study that evaluated students' perceptions, lifestyle, and psychological well-being during the pandemic. Depression symptoms and risk were measured by the Patient Health Questionnaire-9, and resilience levels were quantified by the 9-item Resilience Evaluation Scale. Self-perceived levels of anxiety and current mental health status were evaluated. Results: From a population of around 30,000 students invited to participate, 1751 responses were obtained and 1447 were included. Most students were female (72.3%) and were taking a master's degree (58.4%). The course with more responses was engineering (25.5%), followed by medicine (13.2%). The prevalence rates for higher anxiety levels, depression risk, and low resilience levels were 66.7%, 37.3%, and 24.9%, respectively. The factors associated with better psychological outcomes were being male, spending more time studying, having a job, performing extracurricular activities, physical exercise, and relaxing activities. By contrast, spending more time watching news, difficulty accessing online lectures, and absence of contact with family or friends were associated with worse psychological indicators. Although all courses presented substantial levels of depressive symptoms, architectures/arts, sciences, and humanities scored significantly more in the depression scale. Medicine students had significantly higher resilience levels compared with other courses. Conclusions: Our findings identify factors associated with worse psychological outcomes and can be used to create protective measures for the mental health of university students during current and future pandemics.

Brain Hemispheric Asymmetry in Schizophrenia and Bipolar Disorder.

BACKGROUND: This study aimed to compare brain asymmetry in patients with schizophrenia (SCZ), bipolar disorder (BPD), and healthy controls to test whether asymmetry patterns could discriminate and set boundaries between two partially overlapping severe mental disorders. METHODS: We applied a fully automated voxel-based morphometry (VBM) approach to assess structural brain hemispheric asymmetry in magnetic resonance imaging (MRI) anatomical scans in 60 participants (SCZ = 20; BP = 20; healthy controls = 20), all right-handed and matched for gender, age, and education. RESULTS: Significant differences in gray matter asymmetry were found between patients with SCZ and BPD, between SCZ patients and healthy controls (HC), and between BPD patients and HC. We found a higher asymmetry index (AI) in BPD patients when compared to SCZ in Brodmann areas 6, 11, and 37 and anterior cingulate cortex and an AI higher in SCZ patients when compared to BPD in the cerebellum. CONCLUSION: Our study found significant differences in brain asymmetry between patients with SCZ and BPD. These promising results could be translated to clinical practice, given that structural brain changes detected by MRI are good candidates for exploration as biological markers for differential diagnosis, besides helping to understand disease-specific abnormalities.

The Impact of COVID-19 on Anxious and Depressive Symptomatology in the Postpartum Period.

Background: Women in the postpartum period may be particularly vulnerable to the psychological effects of the COVID-19 pandemic. The aim of our study was to evaluate the impact of the coronavirus pandemic on postpartum depression and anxiety levels and the role of the fear of COVID-19 in its development. Methods: Women who delivered at the Bissaya Barreto Maternity Hospital, between 16 March and 16 June 2020 (Group 1: Birth in COVID-19 period, n = 207), recruited in the postpartum period, filled in a set of self-reported validated questionnaires: Perinatal Depression Screening Scale, Perinatal Anxiety Screening Scale, Profile of Mood States, Perseverative Thinking Questionnaire, Dysfunctional Beliefs Towards Maternity Scale, and the Fear of COVID-19 Scale. Levels of depressive and anxious symptomatology, negative affect, negative repetitive thinking, and the dysfunctional beliefs towards motherhood of these women were compared with data from samples of previous studies that included women whose delivery had occurred at the same Maternity Hospital before the COVID-19 pandemic period (Group 2: Birth before the COVID-19 period, n = 212). Results: Based on the cutoff points of the screening scales, the prevalence of clinically relevant depressive and anxious symptoms in Group 1 was 40.1% and 36.2%, respectively. Women in Group 1 had significantly higher levels of anxious and depressive symptoms, negative affect, negative repetitive thinking, and dysfunctional beliefs towards motherhood than women in Group 2 (p < 0.05). Fear of COVID-19 in the postpartum period was a predictor of depressive (ß = 0.262) and anxious (ß = 0.371) symptoms, explaining 6.9% and 13.7% of their variability, respectively (p < 0.001). Conclusion: During the COVID-19 pandemic, women in the postpartum period present greater depressive and anxious symptomatology, as well as increased risk factors.

Mitochondria Fusion upon SERCA Inhibition Prevents Activation of the NLRP3 Inflammasome in Human Monocytes.

Sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) is a crucial component of the cellular machinery responsible for Ca2+ homeostasis. The selective inhibition of SERCA by thapsigargin (TG) leads to perturbations in Ca2+ signaling, which can trigger endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) pathway is activated in response to ER stress and induces an adaptive response to preserve cell survival or committee cells to programmed death, depending on stress duration and/or level. Early stages of ER stress stimulate mitochondrial metabolism to preserve survival but under chronic ER stress conditions, mitochondrial dysfunction is induced, which, in turn, can enhance inflammation through NLRP3 inflammasome activation. This study was aimed at investigating the role of SERCA inhibition on NLRP3 inflammasome activation in human monocytes, which was evaluated in primary monocytes isolated from healthy individuals and in the THP-1 human monocytic cell line. Findings obtained in both THP-1 and primary monocytes demonstrate that SERCA inhibition triggered by TG does not activate the NLRP3 inflammasome in these innate immune cells since IL-1ß secretion was not affected. Results from THP-1 monocytes showing that SERCA inhibition increases mitochondrial Ca2+ content and fusion, in the absence of changes in ROS levels and membrane potential, support the view that human monocytes counteract ER stress that arises from inhibition of SERCA through modulation of mitochondrial morphology towards mitochondria fusion, thus preventing NLRP3 inflammasome activation. Overall, this work contributes to a better understanding of the molecular mechanisms that modulate the activity of the NLRP3 inflammasome leading to sterile inflammation, which are still poorly understood.

Portuguese Version of the Stigma Scale: Preliminary Psychometric Characteristics.

INTRODUCTION: Stigma is associated with poor prognosis of illness and reduced help-seeking behavior, self-esteem and treatment compliance. The aims of this study were to study the reliability and construct validity of the King's et al Stigma Scale, and its association with Illness and Help-Seeking Behaviors scale (IHSBS) scores. MATERIAL AND METHODS: One hundred and forty mental health patients filled out the Stigma scale and the Illness and Help-Seeking Behaviors scale. The exploratory factor analysis of the stigma scale was performed, and its reliability studied. The correlation analysis was used and mean differences in Stigma Scale scores among IHSBS groups were explored. RESULTS: The exploratory factor analysis indicated four factors (F): F1-Disclosure, F2-Discrimination, F3-Acceptance and F4-Personal Growth, which showed acceptable/good internal consistency (α from 0.70 to 0.91). Help-seeking behaviors were not associated with stigma. The levels of Discrimination were high in the group with global high-IHSB and in patients with medium/high illness behavior (IB) and health-related worries (HW). Additionally, Disclosure and overall stigma levels were higher in groups with high-HW and with medium-IB scores (when compared with the group with low-IB). The group with low-IB also had lower levels of Acceptance and Personal Growth when compared with the groups with medium-IB and high-IB, respectively. CONCLUSION: The Stigma Scale (27 items) is a valid, reliable instrument and useful tool to assess stigma in mental health patients.

Introdução: O estigma está associado a pior prognóstico de doença e redução da procura de ajuda, autoestima e adesão ao tratamento. Os objetivos deste estudo foram estudar a fidedignidade a validade de construto da Escala de Estigma de King et al e a sua associação com as pontuações da Escala de Comportamento de Procura de Ajuda e de Doença (ECPAD). Material e Métodos: Cento e quarenta doentes psiquiátricos preencheram a Escala de Estigma e a ECPAD. Foi realizada a análise fatorial exploratória da escala de estigma e a sua fidelidade estudada. Foram realizadas análises de correlação e exploradas as diferenças nas médias das pontuações da escala de estigma nos grupos de ECPAD. Resultados: A análise fatorial exploratória indicou quatro fatores (F): F1-Divulgação, F2-Discriminação, F3-Aceitação e F4-Crescimento Pessoal (α de 0.70 a 0.91). Os comportamentos de procura de ajuda não se associaram ao estigma. Os níveis de Discriminação foram altos no grupo com CPAD total-elevado e nos grupos com comportamentos de doença (CD) e com preocupações com a saúde (PS) médios/elevados. Adicionalmente, os níveis de Divulgação e Estigma total foram superiores no grupo com PS-elevado e no grupo com CD-médio (quando comparado com o grupo CD-baixo). O grupo com CD-baixo também revelou níveis inferiores de Aceitação e Crescimento Pessoal em comparação com os grupos com CD-médio e CD-elevado, respectivamente. Conclusão: A escala de estigma (27 itens) é um instrumento válido, fidedigno e útil para avaliar o estigma em doentes psiquiátricos.