Exergame-based rehabilitation for cancer patients undergoing abdominal surgery: Effects on pain, anxiety, depression, and fatigue - A pilot study.

PURPOSE: This study aimed to determine the efficacy of an exergame rehabilitation program on pain, anxiety or depression, and fatigue in oncology patients undergoing abdominal surgery. METHODS: The randomized controlled trial evaluated the efficacy of exergame rehabilitation on Pain, Anxiety, Depression, and Fatigue in oncology patients undergoing abdominal surgery. Patients were recruited from October 2022-March 2023 and were randomly assigned to the intervention group (postoperative traditional rehabilitation plus an exergame rehabilitation program) or control group (postoperative traditional rehabilitation). Data were collected at three different times: on admission, in the first 48 h, and on the 7th day after surgery. Primary outcomes were evaluated and monitored with different validated instruments: numeric rating scale (NRS) for pain, Hospital Anxiety and Depression Scale (HADS) to assess the level of anxiety and depression, and the Fatigue Assessment Scale (FAS) to assess physical and psychological fatigue. The length of stay and program completion were secondary outcomes. RESULTS: A total of 128 postoperative patients were recruited. Of these, 58 patients were excluded from the study due to clinical complications related to the surgical procedure (n = 53) or healthcare staff-related reasons (n = 5). Both the control and intervention groups were the same size (n = 35). Lower pain scores were observed on the 7th postoperative day in the group subject to the "exergame rehabilitation program" (p = 0.006). No statistically significant differences were observed for anxiety and depression between the 2 groups. Regarding fatigue, statistically significant differences were observed on admission (p = 0.03), which disappeared 48 h after surgery (p = 0.143). Differences between the groups were observed again on the 7th day after surgery (p = 0.005). CONCLUSIONS: The intervention using exergames was effective in reducing the postoperative pain of the patient undergoing major abdominal surgery and in restoring the levels of fatigue before surgical intervention. However, no differences were observed for anxiety or depression. Future studies with larger samples should be carried out.

Scale for time and space experience in anxiety (STEA): Phenomenology and its clinical relevance.

Anxiety is a pervasive emotional state where, phenomenologically, subjects often report changes in their experience of time and space. However, a systematic and quantified examination of time and space experience in terms of a self-report scale is still missing which eventually could also be used for clinical differential diagnosis. Based on historical phenomenological literature and patients' subjective reports, we here introduce, in a first step, the Scale for Time and Space Experience of Anxiety (STEA) in a smaller sample of 19 subjects with anxiety disorders and, in a second step, validate its shorter clinical version (cSTEA) in a larger sample of 48 anxiety subjects. The main findings are (i) high convergent and divergent validity of STEA with both Beck Anxiety Inventory (BAI) (r = 0.7325; p < 0.001) and Beck Depression Inventory (BDI) (r = 0.7749; p < 0.0001), as well as with spontaneous mind wandering (MWS) (r = 0.7343; p < 0.001) and deliberate mind wandering (MWD) (r = 0.1152; p > 0.05), (ii) statistical feature selection shows 8 key items for future clinical usage (cSTEA) focusing on the experience of temporal and spatial constriction, (iii) the effects of time and space experience (i.e., for both STEA and cSTEA scores) on the level of anxiety (BAI) are mediated by the degree of spontaneous mind wandering (MWS), (iv) cSTEA allows for differentiating high levels of anxiety from the severity of comorbid depressive symptoms, and (v) significant reduction in the cSTEA scores after a therapeutic intervention (breathing therapy). Together, our study introduces a novel fully quantified and highly valid self-report instrument, the STEA, for measuring time-space experiences in anxiety. Further we develop a shorter clinical version (cSTEA) which allows assessing time space experience in a valid, quick, and simple way for diagnosis, differential diagnosis, and therapeutic monitoring of anxiety.

Inflammatory Myopathy: When Electromyography and Autoantibodies Don't Help the Diagnosis.

Inflammatory myopathies (IM) are the most treatable myopathies. Necrotizing autoimmune myositis is a distinct clinicopathologic entity that starts either acutely or subacutely. Autoimmunity is essencial in the pathogenesis of myositis and autoantibodies may be present in more than 50% of patients. We present the case of a 73-year-old man with elevated levels of CK and aldolase, and proximal symmetric muscle weakness and weight loss. The etiological investigation revealed, via muscle biopsy, a necrotizing autoimmune myositis, even though the majority of usual autoantibodies and electromyography were negative. The case demonstrates the importance of combining the patient's symptoms, neurological examination, and analytical changes to corroborate the suspicion of myopathy.

Impact of Exergames on the Rehabilitation of Cancer Patients Undergoing Major Abdominal Surgery: A Randomized Controlled Trial.

BACKGROUND: Exergames can be an appealing strategy that is integrated into post-abdominal surgery rehabilitation. OBJECTIVE: The aim of this study was to assess the effectiveness of exergame rehabilitation in improving independence in activities of daily living (ADLs) and patient balance after abdominal cancer surgery. METHODS: A randomized control-group study was carried out in an oncological hospital in Portugal. Seventy postoperative patients were included, and data collection took place between January 2023 and May 2023. The patients were randomly assigned to either an exergame rehabilitation program (n = 35) or a traditional rehabilitation program (n = 35). The assessed outcomes were the Barthel and Berg scales, and data collection occurred at 3 different time points: admission, 48 hours postoperatively, and on the seventh day after surgery. RESULTS: At the third assessment, a statistically significant difference was observed between the 2 groups for both indicators, ADLs and balance. CONCLUSIONS: There was an improvement in ADLs and balance in the exergames group. By the seventh day after surgery, the intervention group showed improvement in balance and ADLs compared with the control group. IMPLICATIONS FOR PRACTICE: The use of exergames can be a solution to the challenges of traditional rehabilitation methods after abdominal surgery for cancer for postoperative patients. This is the first study carried out in this specific population.

Interaction between NSCLC Cells, CD8+ T-Cells and Immune Checkpoint Inhibitors Potentiates Coagulation and Promotes Metabolic Remodeling-New Cues on CAT-VTE.

BACKGROUND: Cancer-associated thrombosis (CAT) and venous thromboembolism (VTE) are frequent cancer-related complications associated with high mortality; thus, this urges the identification of predictive markers. Immune checkpoint inhibitors (ICIs) used in cancer immunotherapy allow T-cell activation against cancer cells. Retrospective studies showed increased VTE following ICI administration in some patients. Non-small cell lung cancer (NSCLC) patients are at high risk of thrombosis and thus, the adoption of immunotherapy, as a first-line treatment, seems to be associated with coagulation-fibrinolysis derangement. METHODS: We pharmacologically modulated NSCLC cell lines in co-culture with CD8+ T-cells (TCD8+) and myeloid-derived suppressor cells (MDSCs), isolated from healthy blood donors. The effects of ICIs Nivolumab and Ipilimumab on NSCLC cell death were assessed by annexin V and propidium iodide (PI) flow cytometry analysis. The potential procoagulant properties were analyzed by in vitro clotting assays and enzyme-linked immunosorbent assays (ELISAs). The metabolic remodeling induced by the ICIs was explored by 1H nuclear magnetic resonance (NMR) spectroscopy. RESULTS: Flow cytometry analysis showed that TCD8+ and ICIs increase cell death in H292 and PC-9 cells but not in A549 cells. Conditioned media from NSCLC cells exposed to TCD8+ and ICI induced in vitro platelet aggregation. In A549, Podoplanin (PDPN) levels increased with Nivolumab. In H292, ICIs increased PDPN levels in the absence of TCD8+. In PC-9, Ipilimumab decreased PDPN levels, this effect being rescued by TCD8+. MDSCs did not interfere with the effect of TCD8+ in the production of TF or PDPN in any NSCLC cell lines. The exometabolome showed a metabolic remodeling in NSCLC cells upon exposure to TCD8+ and ICIs. CONCLUSIONS: This study provides some insights into the interplay of immune cells, ICIs and cancer cells influencing the coagulation status. ICIs are important promoters of coagulation, benefiting from TCD8+ mediation. The exometabolome analysis highlighted the relevance of acetate, pyruvate, glycine, glutamine, valine, leucine and isoleucine as biomarkers. Further investigation is needed to validate this finding in a cohort of NSCLC patients.

The Combined Heterozygosity of Factor V Leiden and G20210A Prothrombin Gene Mutation in a Patient With Venous Thromboembolism.

Venous thromboembolism (VTE) is a chronic illness that includes pulmonary embolism (PE) and deep vein thrombosis (DVT), and many risk factors are associated. Anticoagulation therapy remains the cornerstone of venous thromboembolism management, and the duration of anticoagulation depends on the risk of venous thromboembolism. We report a case of a female with a combined heterozygosity of factor V Leiden and G20210A prothrombin gene mutation.

Characterization and monitoring of nutritional risk and nutritional status in oncological patients admitted to an oncological surgery unit: A longitudinal study.

BACKGROUND AND AIMS: malnutrition is a common phenomenon in people with cancer and can occur at all stages of the disease trajectory. Prevention, early identification of patients at risk of malnutrition, nutritional diagnosis, and personalized intervention, monitoring and follow-up are essential measures to minimize the occurrence of malnutrition and its consequences. This study aims to evaluate if current institutional practices regarding nutritional intervention guarantees nutritional/dietary care for cancer patients. METHODS: adescriptive, analytical and longitudinal study was carried out, lasting five months, in a hospital inpatient surgical oncology unit. All patients admitted to the unit in the period between 1 March and 31 July 2022, who underwent nutritional screening at the time of admission to the service, were included. During hospitalization, they were subjected to periodic assessments of weight, body mass index and nutritional screening every 7 days until discharge. RESULTS: a total of 659 patients were admitted to the inpatient unit. The highest prevalence of malnutrition was observed in Head and Neck (37.6%), Genitourinary (30.8%) and Digestive (27.7%) cancers. Weight loss was especially significant in digestive, skin and sarcoma cancers, as well as genitourinary cancers, but not in breast cancer patients. During the hospitalization period, 14.0% of the hospitalized patients received nutrition-related nursing intervention, and 21.5% were referred for clinical dietetic intervention (by a registered dietitian). CONCLUSION: this work reinforces the high prevalence of malnutrition in oncological patients and the need to systematically track cancer patients throughout their disease/treatment trajectory, from admission to the hospital, to the day of admission to inpatient unit, and subsequent follow-up. We also propose expedited referrals to different specialized centres in nutritional support for cancer patients from the first day of hospitalization. Assessment of patients should always be accompanied by active referral capacity to a specialized and duly trained nutritional care team that is quick, proactive, and responsive.

The role of spirituality in people with amyotrophic lateral sclerosis and their caregivers: Scoping review.

BACKGROUND: There are few studies evaluating the role of spirituality and the role of spiritually integrated interventions in people with amyotrophic lateral sclerosis (PALS) and their caregivers. OBJECTIVES: A scoping review was conducted to examine the nature and breadth of peer-reviewed literature on the role of spirituality, interventions integrating spirituality, and outcomes for PALS and their caregivers. METHODS: A literature review was performed, following the methods from the Joanna Briggs Institute Reviewers, based on all articles published between January 2006 and April 2022, identified in the CINAHL Complete, MEDLINE Complete, MedicLatina, Psychology and Behavioral Sciences Collection, and SPORTDiscus with full-text databases using key terms. Extracted data included research aims, study design, population and characteristics, theme description, and measures or type of intervention. RESULTS: A total of 18 articles were included in this study: 14 qualitative, 3 quantitative, and 1 protocol of a quantitative study. Eight studies were based in Europe. The search identified different main themes related to spirituality for caregivers and patients, 2 spiritual measure scales, and one intervention. However, many studies were limited in sample size, generalizability, and transferability and used less sophisticated research designs. SIGNIFICANCE OF THE RESULTS: This scoping review illustrates the importance given to spirituality by caregivers and PALS and reveals a very heterogeneous response. Thus, experimental studies in the area of spirituality are needed to systematically explore the impact of spiritual interventions, and the results of these studies could advance practice and policy by enhancing the quality of life for PALS and their caregivers.

A New NOTCH3 Gene Mutation Associated With a CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy) Diagnosis.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common and best-known monogenic small vessel disease. This disease is caused by a genetic mutation in the neurogenic locus notch homolog protein 3 (NOTCH3) gene, inherited as an autosomal dominant trait, the presence of which confirms the diagnosis of CADASIL. Clinically, it can express itself in a variety of symptoms, including migraine with aura, mood disturbance, vascular dementia, ischemic stroke, and premature death. This case reports a 69-year-old man who was admitted for an etiological study of paresthesias and was later confirmed with a diagnosis of CADASIL with a NOTCH3 mutation.

Scale for Space and Time Experience in Psychosis: Converging Phenomenological and Psychopathological Perspectives.

INTRODUCTION: Abnormalities in the experience of space and time are fundamental to understanding schizophrenia spectrum disorders, but the precise relation between such abnormalities and psychopathological symptoms is still unclear. Therefore, the aim of our study was to introduce a novel scale for space and time experience in psychosis (STEP), specifically devised to assess schizophrenia spectrum disorders. METHODS: The STEP scale is a semiquantitative instrument developed on the basis of several items from previous scales and phenomenological reports addressing the experience of space and time. We applied the STEP scale to three groups of subjects (patients with schizophrenia spectrum disorders, patients with predominant affective symptoms, and healthy control subjects), to whom we also applied other more general psychopathological scales, such as the Positive and Negative Syndrome Scale and the Ego-Psychopathology Inventory. RESULTS: Patients with schizophrenia spectrum disorders scored significantly higher on general psychopatho--logical scales relative to subjects belonging to the other groups. The STEP scale provided good psychometric properties regarding reliability. We also tested convergent and divergent validity of the STEP scale and found that space and time subscale scores of STEP significantly correlated with each other, as well as with the remaining general psychopathological scores. DISCUSSION/CONCLUSION: We introduced the STEP scale as a novel instrument for the assessment of experience of space and time. Its psychometric properties showed high validity and reliability to identify psychopathological symptoms and enabled to differentiate patients with predominantly psychotic symptoms from those with predominantly affective symptoms. The STEP scale provides a standardized measure for assessing disturbances in the experience of space and time. Furthermore, it probably represents a leap forward toward the establishment of an additional dimension of symptoms proposed as "spatiotemporal psychopathology."

Effects of prolonged interruption of rehabilitation routines in amyotrophic lateral sclerosis patients.

OBJECTIVE: Patients with amyotrophic lateral sclerosis (ALS) experienced prolonged interruption of their rehabilitation palliative care routines due to restrictive COVID-19 pandemic public health measures. This study assesses the effects of before and after the lockdown on functionality rates and quality of life (QoL) in patients with ALS. METHODS: A longitudinal observational study was conducted. Participants were assessed three times - early January (T0), before mandatory lockdown (T1), and during lockdown (T2) - using the ALS Functional Rating Scale-revised (ALSFRS-R), Fatigue Severity Scale (FSS), and the ALS-Specific Quality of Life-Short Form (ALSSQOL-SF). The paired-sample t-test and Wilcoxon signed-rank test were used. RESULTS: Thirty-two patients were included with a mean age of 56.9 (SD 14.2) years and mean symptoms onset of 27.1 (SD 14.3) months. ALSFRS-R mean scores decayed significantly over time when comparing T0-T1 (0.26 ± 0.38) and T1-T2 (1.36 ± 1.43) slopes (p < 0.001). Significant differences were observed between T1 and T2 for ALSSQOL-SF scores (115.31 ± 17.06 vs. 104.31 ± 20.65), especially in four specific domains, and FSS scores (34.06 ± 16.84 vs. 40.09 ± 17.63). Negative correlations between negative emotions and physical symptoms assessed by ALSSQOL-SF and FSS were found. SIGNIFICANCE OF THE RESULTS: Rehabilitation treatment routines in palliative care, such as physiotherapy and speech therapy, appear to mitigate the ALSFRS-R slope. Prolonged interruption of rehabilitation during the lockdown may have accelerated the functional decline in ALS patients' motor skills with as measured after 2 months by the ALSFRS-R in the limb and bulbar subscores, but not respiratory subscore. Other short-term effects, increased fatigue and negative impact on QoL, were also verified.

The Use of Gamification in Patients Undergoing Hip Arthroplasty: Scoping Review.

Objective: The use of gamification can promote health-related behavior. This article is the first attempt to provide a historical overview of the use of games in patients undergoing hip arthroplasty. Materials and Methods: We conducted a scoping review to map and characterize the games used for the person undergoing hip arthroplasty. To perform this review, the respective descriptors were identified using search syntax appropriate to each of the databases: MEDLINE_ (Medical Literature Analysis and Retrieval System Online), CINAHL_ (Cumulative Index to Nursing and Allied Health Literature), SPORTDiscus, in the Psychology and Behavioral Sciences Collection, SCOPUS, SciELO (Scientific Electronic Library Online), and PEDRo (Physiotherapy Evidence Database). Results: An initial 968 articles were identified, of which 7 articles were included. The domains of the games under analysis essentially focus on aspects of rehabilitation (n = 5), or related (n = 2), and mostly exergames (n = 6). However, the instruments, characteristics, and procedures used to evaluate the games in the included studies have little depth and large variability. Conclusion: Few games exist that support people who have undergone hip arthroplasty. Most of the games under review were exergames to support rehabilitation. Consequently, we recommend developing another type of game with a focus on monitoring, counseling, and/or social support for selfmanagement training in persons undergoing hip arthroplasty.

Redox toxicology of environmental chemicals causing oxidative stress.

Living organisms are surrounded with heavy metals such as methylmercury, manganese, cobalt, cadmium, arsenic, as well as pesticides such as deltamethrin and paraquat, or atmospheric pollutants such as quinone. Extensive studies have demonstrated a strong link between environmental pollutants and human health. Redox toxicity is proposed as one of the main mechanisms of chemical-induced pathology in humans. Acting as both a sensor of oxidative stress and a positive regulator of antioxidants, the nuclear factor erythroid 2-related factor 2 (NRF2) has attracted recent attention. However, the role NRF2 plays in environmental pollutant-induced toxicity has not been systematically addressed. Here, we characterize NRF2 function in response to various pollutants, such as metals, pesticides and atmospheric quinones. NRF2 related signaling pathways and epigenetic regulations are also reviewed.

Neurotoxicity of e-cigarettes.

It appears that electronic cigarettes (EC) are a less harmful alternative to conventional cigarette (CC) smoking, as they generate substantially lower levels of harmful carcinogens and other toxic compounds. Thus, switching from CC to EC may be beneficial for smokers. However, recent accounts of EC- or vaping-associated lung injury (EVALI) has raised concerns regarding their adverse health effects. Additionally, the increasing popularity of EC among vulnerable populations, such as adolescents and pregnant women, calls for further EC safety evaluation. In this state-of-the-art review, we provide an update on recent findings regarding the neurological effects induced by EC exposure. Moreover, we discuss possible neurotoxic effects of nicotine and numerous other chemicals which are inherent both to e-liquids and EC aerosols. We conclude that in recognizing pertinent issues associated with EC usage, both government and scientific researchers must address this public health issue with utmost urgency.

Manganese Acts upon Insulin/IGF Receptors to Phosphorylate AKT and Increase Glucose Uptake in Huntington's Disease Cells.

Perturbations in insulin/IGF signaling and manganese (Mn2+) uptake and signaling have been separately reported in Huntington's disease (HD) models. Insulin/IGF supplementation ameliorates HD phenotypes via upregulation of AKT, a known Mn2+-responsive kinase. Limited evidence both in vivo and in purified biochemical systems suggest Mn2+ enhances insulin/IGF receptor (IR/IGFR), an upstream tyrosine kinase of AKT. Conversely, Mn2+ deficiency impairs insulin release and associated glucose tolerance in vivo. Here, we test the hypothesis that Mn2+-dependent AKT signaling is predominantly mediated by direct Mn2+ activation of the insulin/IGF receptors, and HD-related impairments in insulin/IGF signaling are due to HD genotype-associated deficits in Mn2+ bioavailability. We examined the combined effects of IGF-1 and/or Mn2+ treatments on AKT signaling in multiple HD cellular models. Mn2+ treatment potentiates p-IGFR/IR-dependent AKT phosphorylation under physiological (1 nM) or saturating (10 nM) concentrations of IGF-1 directly at the level of intracellular activation of IGFR/IR. Using a multi-pharmacological approach, we find that > 70-80% of Mn2+-associated AKT signaling across rodent and human neuronal cell models is specifically dependent on IR/IGFR, versus other signaling pathways upstream of AKT activation. Mn2+-induced p-IGFR and p-AKT were diminished in HD cell models, and, consistent with our hypothesis, were rescued by co-treatment of Mn2+ and IGF-1. Lastly, Mn2+-induced IGF signaling can modulate HD-relevant biological processes, as the reduced glucose uptake in HD STHdh cells was partially reversed by Mn2+ supplementation. Our data demonstrate that Mn2+ supplementation increases peak IGFR/IR-induced p-AKT likely via direct effects on IGFR/IR, consistent with its role as a cofactor, and suggests reduced Mn2+ bioavailability contributes to impaired IGF signaling and glucose uptake in HD models.

Post-translational modifications in MeHg-induced neurotoxicity.

Mercury (Hg) exposure remains a major public health concern due to its widespread distribution in the environment. Organic mercurials, such as MeHg, have been extensively investigated especially because of their congenital effects. In this context, studies on the molecular mechanism of MeHg-induced neurotoxicity are pivotal to the understanding of its toxic effects and the development of preventive measures. Post-translational modifications (PTMs) of proteins, such as phosphorylation, ubiquitination, and acetylation are essential for the proper function of proteins and play important roles in the regulation of cellular homeostasis. The rapid and transient nature of many PTMs allows efficient signal transduction in response to stress. This review summarizes the current knowledge of PTMs in MeHg-induced neurotoxicity, including the most commonly PTMs, as well as PTMs induced by oxidative stress and PTMs of antioxidant proteins. Though PTMs represent an important molecular mechanism for maintaining cellular homeostasis and are involved in the neurotoxic effects of MeHg, we are far from understanding the complete picture on their role, and further research is warranted to increase our knowledge of PTMs in MeHg-induced neurotoxicity.

Molecular Pathways Associated With Methylmercury-Induced Nrf2 Modulation.

Methylmercury (MeHg) is a potent neurotoxin that affects particularly the developing brain. Since MeHg is a potent electrophilic agent, a wide range of intracellular effects occur in response to its exposure. Yet, the molecular mechanisms associated with MeHg-induced cell toxicity have yet to be fully understood. Activation of cell defense mechanisms in response to metal exposure, including the up-regulation of Nrf2- (nuclear factor erythroid 2-related factor 2)-related genes has been previously shown. Nrf2 is a key regulator of cellular defenses against oxidative, electrophilic and environmental stress, regulating the expression of antioxidant proteins, phase-II xenobiotic detoxifying enzymes as well phase-III xenobiotic transporters. Analogous to other electrophiles, MeHg activates Nrf2 through modification of its repressor Keap1 (Kelch-like ECH-associated protein 1). However, recent findings have also revealed that Keap1-independent signal pathways might contribute to MeHg-induced Nrf2 activation and cytoprotective responses against MeHg exposure. These include, Akt phosphorylation (Akt/GSK-3ß/Fyn-mediated Nrf2 activation pathway), activation of the PTEN/Akt/CREB pathway and MAPK-induced autophagy and p62 expression. In this review, we summarize the state-of-the-art knowledge regarding Nrf2 up-regulation in response to MeHg exposure, highlighting the modulation of signaling pathways related to Nrf2 activation. The study of these mechanisms is important in evaluating MeHg toxicity in humans, and can contribute to the identification of the molecular mechanisms associated with MeHg exposure.

Single administration of agmatine reverses the depressive-like behavior induced by corticosterone in mice: Comparison with ketamine and fluoxetine.

Agmatine is a neuromodulator that has been proposed as a therapeutic strategy for the treatment of major depressive disorder (MDD). A previous study reported that agmatine caused a fast-acting effect in mice subjected to chronic mild stress without causing changes in the levels of synaptic proteins in the prefrontal cortex. We examined whether a single administration of agmatine is able to counteract the depressive-like behavior induced by chronic administration of corticosterone, a pharmacological model of stress, paralleled with the modulation of synaptic protein levels in the prefrontal cortex and hippocampus. Female mice received corticosterone (20 mg/kg, p.o.) for 21 days and, in the last day of treatment, were administered with a single dose of agmatine (0.1 mg/kg, p.o.), fluoxetine (10 mg/kg, p.o.; control for a conventional antidepressant) or ketamine (1 mg/kg, i.p.; control for a fast-acting antidepressant). Agmatine, similar to ketamine, reversed the depressive-like behavior induced by corticosterone in the tail suspension test (TST), an effect that was not observed in mice treated with fluoxetine. The immunocontent of GluA1 was increased by all the treatments in the hippocampus of control mice, whereas PSD95 was not significantly altered by treatments in any brain structure. Although the levels of synaptic proteins do not seem to account for the behavioral findings reported here, the present study provides clear evidence for the fast-acting antidepressant profile of agmatine in the TST, similar to ketamine.

Oxidative Stress in Methylmercury-Induced Cell Toxicity.

Methylmercury (MeHg) is a hazardous environmental pollutant, which elicits significant toxicity in humans. The accumulation of MeHg through the daily consumption of large predatory fish poses potential health risks, and the central nervous system (CNS) is the primary target of toxicity. Despite well-described neurobehavioral effects (i.e., motor impairment), the mechanisms of MeHg-induced toxicity are not completely understood. However, several lines of evidence point out the oxidative stress as an important molecular mechanism in MeHg-induced intoxication. Indeed, MeHg is a soft electrophile that preferentially interacts with nucleophilic groups (mainly thiols and selenols) from proteins and low-molecular-weight molecules. Such interaction contributes to the occurrence of oxidative stress, which can produce damage by several interacting mechanisms, impairing the function of various molecules (i.e., proteins, lipids, and nucleic acids), potentially resulting in modulation of different cellular signal transduction pathways. This review summarizes the general aspects regarding the interaction between MeHg with regulators of the antioxidant response system that are rich in thiol and selenol groups such as glutathione (GSH), and the selenoenzymes thioredoxin reductase (TrxR) and glutathione peroxidase (Gpx). A particular attention is directed towards the role of the PI3K/Akt signaling pathway and the nuclear transcription factor NF-E2-related factor 2 (Nrf2) in MeHg-induced redox imbalance.

Bleuler's Psychopathological Perspective on Schizophrenia Delusions: Towards New Tools in Psychotherapy Treatment.

The authors begin by addressing the historical evolution of the delusion concept and its different approaches, focusing afterwards mainly on the work of Bleuler, who stressed the proximity between delusions and the emotional life of patients with schizophrenia. I Therefore, the present work intends to review the main aspects of the theory of delusion formation in schizophrenia according to Bleuler's psychopathological perspective. For that purpose, first the role of delusions in the psychopathology of schizophrenia is explored in a close relation with the Bleuler's fundamental symptoms (Alogia, Autism, Ambivalence, and Affect Blunting) nowadays known as negative symptoms. Then, persecutory, grandiosity and sexual delusions in schizophrenia are described according to the tension between logic and affects, as well as, internal conflict, schizoid features, and auto-erotism as key psychopathological pathways. Thus, with this subjective perspective, it is intended to highlight Bleuler's psychopathological contribution to the affective and meaningful causality of delusions in schizophrenia. The former might be useful in the integration with other psychopathological phenomena (hallucinations and negative symptoms) and new forms of research and therapeutic approaches in this disorder that are complementary with the contemporary tendencies in psychopathology.