Platinum nanoparticle-based microreactors protect against the behavioral and neurobiological consequences of chronic stress exposure.

Excitotoxicity is described as the exacerbated activation of glutamate AMPA and NMDA receptors that leads to neuronal damage, and ultimately to cell death. Astrocytes are responsible for the clearance of 80-90% of synaptically released glutamate, preventing excitotoxicity. Chronic stress renders neurons vulnerable to excitotoxicity and has been associated to neuropsychiatric disorders, i.e., anxiety. Microreactors containing platinum nanoparticles (Pt-NP) and glutamate dehydrogenase have shown in vitro activity against excitotoxicity. The purpose of the present study was to investigate the in vivo effects of these microreactors on the behavioral and neurobiological effects of chronic stress exposure. Rats were either unstressed or exposed for 2 weeks to an unpredictable chronic mild stress paradigm (UCMS), administered intra-ventral hippocampus with the microreactors (with or without the blockage of astrocyte functioning), and seven days later tested in the elevated T-maze (ETM; Experiment 1). The ETM allows the measurement of two defensive responses, avoidance and escape, in terms of psychopathology respectively related to generalized anxiety and panic disorder. Locomotor activity in an open field was also measured. Since previous evidence shows that stress inhibits adult neurogenesis, we evaluated the effects of the different treatments on the number of cells expressing the marker of migrating neuroblasts doublecortin (DCX) in the dorsal and ventral hippocampus (Experiment 2). Results showed that UCMS induces anxiogenic effects, increases locomotion, and decreases the number of DCX cells in the dorsal and ventral hippocampus, effects that were counteracted by microreactor administration. This is the first study to demonstrate the in vivo efficacy of Pt-NP against the behavioral and neurobiological effects of chronic stress exposure.

Depression, anxiety and stress symptoms in Brazilian university students during the COVID-19 pandemic: Predictors and association with life satisfaction, psychological well-being and coping strategies.

BACKGROUND: The COVID-19 pandemic raises concerns about the mental health of the world population. Protection measures to prevention the disease impacted education and undergraduate students were exposed to additional stressors. OBJECTIVES: Analyze depression, anxiety and stress symptoms in undergraduates, their respective predictors and the association with satisfaction with life, psychological well-being and coping strategies. METHODS: An online cross-sectional study was conducted from September 14 to October 19, 2020, involving undergraduate students enrolled in 33 courses from 5 public university campuses in the state of Parana, Brazil, using: questionnaire with sociodemographic, academic, health and pandemic effects variables; Depression, Anxiety and Stress Scale-21 (DASS-21); Satisfaction with Life Scale (SWLS); Psychological Well-Being (PWB); BriefCOPE. The convenience sample was composed of 1,224 participants, with 18 years old or older, that completed all research instruments. Spearman correlation and logistic analysis (univariate and multivariate) were applied to the collected data. RESULTS: Most of the undergraduates presented symptoms of depression (60.5%), anxiety (52.5%) and stress (57.5%). Depression, anxiety and stress presented significant correlations in common: negative with satisfaction with life, all dimensions of psychological well-being, and 3 adaptive copings (active coping, planning, positive reframing); positive with 5 maladaptive copings (behavioral disengagement, denial, self-blame, self-distraction, substance use). In addition, there were 7 common predictors for symptoms of depression, anxiety and stress: female; age 18-24 years old; having a chronic disease; lower scores in 2 dimensions of psychological well-being (positive relations with others, self-acceptance); higher scores in 2 maladaptive copings (self-blame, substance use). CONCLUSIONS: The data indicate a high prevalence of symptoms of depression, anxiety and stress, and suggest that higher scores of satisfaction with life, psychological well-being dimensions and adaptive copings may present protective effects in undergraduates during a pandemic crisis.

Increased risk of health professionals to feel traumatized during the COVID-19 pandemic.

Health professionals may be a vulnerable group to posttraumatic stress symptoms (PTSS) during the Coronavirus disease 2019 (COVID-19) pandemic. To investigate how health professionals who experienced a traumatic event are expressing PTSS and factors related to risk for higher PTSS symptomatology can inform how health professionals are facing their role in this crisis. This was an Internet cross-sectional survey. Participants were 49,767 Brazilian health professionals who have ever faced a traumatic event, which was about 25.9% of an initial sample of health professionals. PTSS symptoms were assessed using the Impact of Event Scale-Revised (IES-R) and latent profile analysis (LPA) explored subpopulations within participants based on their scores. Distinct profiles were compared for psychological distress (e.g., depression and anxiety) and quality of life. Multinomial logistic regression analysis was conducted to investigate the relationship between IES-R profiles and COVID-19 related experiences, thoughts, and perceptions. A two-profile model was the most appropriate for the IES-R data pointing out a group with a high level of PTSS (named high-PTSS; n = 10,401, 20.9%) and another expressing a low level of symptoms (named low-PTSS; n = 39,366, 79.1%). The high-PTSS profile demonstrated worse psychological scores (global psychological distress, somatization, depression, and anxiety) and worse quality of life (physical, psychological, social, and environmental) with moderate magnitudes. Small but significant predictors of the high-PTSS profile included sociodemographic characteristics and COVID-19 related experiences, thoughts, and perceptions. Most individuals who experienced a traumatic event were not in the high-PTSS profile. For those who were, however, psychological and quality of life measures were much worse. During the initial phase of the COVID-19 pandemic, several characteristics emerged as risks to report trauma.

The Therapeutic Effect of Intranasal Administration of Dexamethasone in Neuroinflammation Induced by Experimental Pulmonary Tuberculosis.

Tuberculosis (TB) is an important infectious disease and a public health problem. The organs most frequently affected by TB are the lungs; despite this, it has been reported that TB patients suffer from depression and anxiety, which have been attributed to social factors. In previous experimental work, we observed that the extensive pulmonary inflammation characteristic of TB with high cytokine production induces neuroinflammation, neuronal death and behavioral abnormalities in the absence of brain infection. The objective of the present work was to reduce this neuroinflammation and avoid the psycho-affective disorders showed during pulmonary TB. Glucocorticoids (GCs) are the first-line treatment for neuroinflammation; however, their systemic administration generates various side effects, mostly aggravating pulmonary TB due to immunosuppression of cellular immunity. Intranasal administration is a route that allows drugs to be released directly in the brain through the olfactory nerve, reducing their doses and side effects. In the present work, dexamethasone's (DEX) intranasal administration was evaluated in TB BALB /c mice comparing three different doses (0.05, 0.25 and 2.5 mg/kg BW) on lung disease evolution, neuroinflammation and behavioral alterations. Low doses of dexamethasone significantly decreased neuroinflammation, improving behavioral status without aggravating lung disease.

Mental health and illness of medical students and newly graduated doctors during the pandemic of SARS-Cov-2/COVID-19.

INTRODUCTION: SARS-Cov-2 virus pandemic causes serious emotional consequences. It has occurred widespread medical courses suspension, and graduations were anticipated. Field hospitals, set up to treat patients with mild to moderate COVID-19, were the main workplaces of newly graduated doctors. OBJECTIVE: To assess the impact of SARS-Cov-2/COVID-19 pandemic on mental health of medical interns and newly graduated doctors. METHOD: This is a cross-sectional study performed using a digital platform. Links to forms were sent in two moments: moment 1 (M1), at the beginning of the pandemic, in the first half of April/2020 and moment 2 (M2), after six months of pandemic, in the second half of September/2020. All students from the medical internship and all doctors graduated since 2018 from the three medical schools in Sergipe-NE-Brazil were invited. RESULTS: 335 forms were answered in April and 148 in September. In M1 88.9% considered themselves exposed to excess of information about COVID-19, which was associated with anxiety symptoms (p = 0.04). Long family physical distance was also associated with these symptoms, as increased appetite (p = 0.01), feeling shortness of breath (p = 0.003) and sweating (p = 0.007). Fear of acquire COVID-19 was reported as intense by almost half of participants, and of transmitting by 85.7% in M1. In M2 41.2% reported the death of friends or relatives. Psychiatric illness was described by 38.5% and psychotropic drugs use by 30.1% in M1, especially those who lived alone (p = 0.03) and the single ones (p = 0.01). Alcohol intake was reported by 54.3%, and among doctors graduated in 2020 it increased from 50% in M1 to 85% in M2 (p = 0.04). CONCLUSION: The pandemic had a negative impact on the mental health of medical students and newly graduated doctors. Exposure to excessive COVID-19 information and family physical distance were associated to anxiety symptoms. Among doctors graduated in 2020, alcohol intake increased during pandemic evolution.

Exploratory study on the psychological impact of COVID-19 on the general Brazilian population.

The COVID-19 pandemic has become one of the main international concerns regarding its impact on mental health. The present study aims to investigate the prevalence of depression, anxiety, and stress symptoms, and behavioral aspects amidst the COVID-19 pandemic in a Brazilian population. An online survey was administered from May 22 to June 5, 2020 using a questionnaire comprising of sociodemographic information, the Depression, Anxiety, and Stress Scale (DASS-21), and the Coping Strategies Inventory. Participants comprised 3,000 people from Brazil's 26 states and the Federal District, with an average age of 39.8 years, women (83%), married (50.6%), graduates (70.1%) and employees (46.7%). Some contracted the virus (6.4%) and had dead friends or relatives (22.7%). There was more consumption of drugs, tobacco, medication, and food (40.8%). Almost half of participants expressed symptoms of depression (46.4%), anxiety (39.7%), and stress (42.2%). These were higher in women, people without children, students, patients with chronic diseases, and people who had contact with others diagnosed with COVID-19. The existence of a group more vulnerable to situations with a high stress burden requires greater attention regarding mental health during and after the pandemic. That said, it should be emphasized that these findings are preliminary and portray a moment still being faced by many people amid the pandemic and quarantine measures. Therefore, we understand that the magnitude of the impacts on mental health will only be more specific with continuous studies after total relaxation of the quarantine.

Differential modulation of the anterior cingulate and insular cortices on anxiogenic-like responses induced by empathy for pain.

Mice cohabiting with a conspecific in chronic pain display anxiogenesis in the elevated plus-maze (EPM). Given that the anterior cingulate (ACC) and insular (InC) cortices play a role in the modulation of anxiety, pain, and emotional contagion, we investigated (a) the FosB activation in both brain areas and (b) the effects of intra-ACC or -InC injection of cobalt chloride (CoCl2, a synaptic blocker), on the anxiety of mice cohabiting with a cagemate suffering pain. Twenty-one days after birth, male Swiss mice were housed in pairs for 14 days to establish familiarity. On the 14th day, mice were divided into two groups: cagemate sciatic nerve constriction (CNC; i.e., one animal of each pair was subjected to sciatic nerve constriction), and cagemate sham (CS; i.e., a similar procedure but without suffering nerve constriction). After that, both groups were housed again with the same pairs for the other 14 days. On the 28th day, mice had their brains removed for the immunoassays analyses (Exp. 1). For experiments 2 and 3, on the 23rd day, the cagemates received guide cannula implantation bilaterally in the ACC or InC and, on the 28th day, they received local injections of saline or CoCl2, and then were exposed to the EPM. Results showed that cohabitation with a conspecific with chronic pain decreases and increases neuronal activation (FosB) within the ACC and InC, respectively. Intra-ACC or InC injection of CoCl2 reversed the anxiogenic effect in those animals that cohabited with a conspecific in chronic pain. ACC and InC seem to modulate anxiety induced by emotional contagion in animals cohabitating with a conspecific suffering pain.

Hesperidin Ameliorates Anxiety-Depressive-Like Behavior in 6-OHDA Model of Parkinson's Disease by Regulating Striatal Cytokine and Neurotrophic Factors Levels and Dopaminergic Innervation Loss in the Striatum of Mice.

The mechanisms underlying the neuroprotective effects of hesperidin in a murine model of PD are not fully elucidated. The current study was carried out to investigate the ability of hesperidin in modulating proinflammatory cytokines, neurotrophic factors, and neuronal recovery in 6-hydroxydopamine (6-OHDA)-induced nigral dopaminergic neuronal loss. Adult male C57BL/6 mice were randomly assigned into four groups: (I) sham/vehicle, (II) sham/hesperidin, (III) 6-OHDA/vehicle, and (IV) 6-OHDA/hesperidin. Mice received a unilateral intrastriatal injection of 6-OHDA and treated with hesperidin (50 mg/kg; per oral) for 28 days. After hesperidin treatment, mice were submitted to behavioral tests and had the striatum removed for neurochemical assays. Our results demonstrated that oral treatment with hesperidin ameliorated the anxiety-related and depressive-like behaviors in 6-OHDA-lesioned mice (p < 0.05). It also attenuated the striatal levels of proinflammatory cytokines tumor necrosis factor-α, interferon-gamma, interleukin-1ß, interleukin-2, and interleukin-6 and increased the levels of neurotrophic factors, including neurotrophin-3, brain-derived neurotrophic factor, and nerve growth factor in the striatum of 6-OHDA mice (p < 0.05). Hesperidin treatment was also capable to increase striatal levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid and protects against the impairment of dopaminergic neurons in the substantia nigra pars compacta (SNpc) (p < 0.05). In conclusion, this study indicated that hesperidin exerts anxiolytic-like and antidepressant-like effect against 6-OHDA-induced neurotoxicity through the modulation of cytokine production, neurotrophic factors levels, and dopaminergic innervation in the striatum.

Mesenchymal Stem Cells Therapy Improved the Streptozotocin-Induced Behavioral and Hippocampal Impairment in Rats.

Sporadic Alzheimer's disease (sAD) is the most prevalent neurodegenerative pathology with no effective therapy until date. This disease promotes hippocampal degeneration, which in turn affects multiple cognitive domains and daily life activities. In this study, we hypothesized that long-lasting therapy with mesenchymal stem cells (MSC) would have a restorative effect on the behavioral alterations and cognitive decline typical of sAD, as they have shown neurogenic and immunomodulatory activities. To test this, we chronically injected intravenous human MSC in a sAD rat model induced by the intracerebroventricular injection of streptozotocin (STZ). During the last 2 weeks, we performed open field, Barnes maze, and marble burying tests. STZ-treated rats displayed a poor performance in all behavioral tests. Cell therapy increased exploratory behavior, decreased anxiety, and improved spatial memory and marble burying behavior, the latter being representative of daily life activities. On the hippocampus, we found that STZ promotes neuronal loss in the Cornus Ammoni (CA1) field and decreased neurogenesis in the dentate gyrus. Also, STZ induced a reduction in hippocampal volume and presynaptic protein levels and an exacerbated microgliosis, relevant AD features. The therapy rescued CA1 neurodegeneration but did not reverse the decrease of immature neurons, suggesting that the therapy effect varied among hippocampal neuronal populations. Importantly, cell therapy ameliorated microgliosis and restored hippocampal atrophy and some presynaptic protein levels in the sAD model. These findings, by showing that intravenous injection of human MSC restores behavioral and hippocampal alterations in experimental sAD, support the potential use of MSC therapy for the treatment of neurodegenerative diseases.

Chronic mild hyperhomocysteinemia induces anxiety-like symptoms, aversive memory deficits and hippocampus atrophy in adult rats: New insights into physiopathological mechanisms.

In the last decade, increased homocysteine levels have been implicated as a risk factor for neurodegenerative and psychiatric disorders. We have developed an experimental model of chronic mild hyperhomocysteinemia (HHcy) in order to observe metabolic impairments in the brain of adult rodents. Besides its known effects on brain metabolism, the present study sought to investigate whether chronic mild HHcy could induce learning/memory impairments associated with biochemical and histological damage to the hippocampus. Adult male Wistar rats received daily subcutaneous injections of homocysteine (0.03 µmol/g of body weight) twice a day, from the 30th to the 60th day of life or saline solution (Controls). After injections, anxiety-like and memory tests were performed. Following behavioral analyses, brains were sliced and hippocampal volumes assessed and homogenized for redox state assessment, antioxidant activity, mitochondrial functioning (chain respiratory enzymes and ATP levels) and DNA damage analyses. Behavioral analyses showed that chronic mild HHcy may induce anxiety-like behavior and impair long-term aversive memory (24 h) that was evaluated by inhibitory avoidance task. Mild HHcy decreased locomotor and/or exploratory activities in elevated plus maze test and caused hippocampal atrophy. Decrease in cytochrome c oxidase, DNA damage and redox state changes were also observed in hippocampus of adult rats subjected to mild HHcy. Our findings show that chronic mild HHcy alters biochemical and histological parameters in the hippocampus, leading to behavioral impairments. These findings might be considered in future studies aiming to search for alternative strategies for treating the behavioral impairments in patients with mild elevations in homocysteine levels.

Propiedades psicométricas del Cuestionario de ansiedad social para adultos (CASO) en Perú / Psychometric properties of the Social Anxiety Questionnaire for Adults (SAQ) in Peru

Resumen La investigación sobre la evaluación de la ansiedad social en Iberoamérica es escasa. En los últimos años se ha informado sobre las características psicométricas del "Cuestionario de ansiedad social para adultos" (CASO) en distintos países iberoamericanos, excepto Perú. El objetivo de este estudio fue analizar las pruebas de validez basadas en el constructo, las pruebas de validez basadas en la relación con otras variables de tipo convergente y la fiabilidad del CASO, utilizando una muestra no clínica de 3064 peruanos. El análisis factorial confirmatorio comprobó que el modelo de cinco factores relacionados se ajustaba mejor a los datos que el modelo jerárquico y se halló que el modelo unifactorial no tenía un buen ajuste. Las correlaciones entre los factores del CASO (de .608 a .709) indicaron que cada uno de ellos evalúa aspectos específicos del constructo y aportan, a su vez, a la medición global del mismo. Los coeficientes de fiabilidad fueron de aceptables a muy buenos (.78( (( .85, .75( (( .83). La alta correlación (r= .69) con la subescala de Ansiedad de la "Escala de ansiedad social de Liebowitz, versión de autoinforme" (LSAS-SR), apoya su relación con la variable convergente. Estas adecuadas características psicométricas del CASO respaldan su utilización con población peruana.

Abstract Research on the assessment of social anxiety in Ibero-America is scarce. In recent years, the psychometric characteristics of the Social Anxiety Questionnaire for adults (SAQ) have been reported in different Ibero-American countries except Peru. The aim of this study was to analyze the construct and the convergent validity, and the reliability of the SAQ, using a non-clinical sample of 3064 Peruvians. The confirmatory factorial analysis showed that the model of five-related factors was better adjusted to the data than the hierarchical model, and that the unifactorial model did not have a good fit. The correlations between their factors (from .608 to .709) indicate that each of them evaluates specific aspects of the construct and also contribute to the overall measurement of it. The reliability coefficients were from acceptable to very good (.78( (( .85, .75( (( .83). The high correlation (r= .69) with the Anxiety subscale of the "Liebowitz Social Anxiety Scale-Self-Report version" (LSAS-SR) supports its convergent validity. These appropriate psychometric characteristics of the questionnaire support its use with the Peruvian population.

Lifestyles, Depression, Anxiety, and Stress as Risk Factors in Nursing Apprentices: A Logistic Regression Analysis of 1193 Students in Lima, Peru.

Currently, it is considered that mental disorders are related to different types of chronic pathologies; for this reason, efforts to improve general health should also focus on preserving mental health. Therefore, the objective of this study was to determine through logistic regression if the independent variables (risk factors) such as (X1) age, (X2) sex, (X3) marital status, (X4) number of children, and (X5) occupation have influence on the dependent variables such as lifestyles, depression, anxiety, and stress in Peruvian nursing students. The research study was descriptive, transversal, and prospective; 1193 nursing students from Chorrillos, Ica, and Chincha were evaluated, which constituted the total population for the 2018 semester. The Health Promoting Life Profile-II (HPLP-II) and the Depression and Anxiety Stress Scale-21 (DASS-21) were used as instruments. 53.9% of nursing students had unhealthy lifestyles; however, they presented moderate (19.7%), slight (14.2%), severe (2.5%), and extremely severe (2.4%) anxiety. With respect to depression, it was found that 61.2% and 59.9% of affected students were stressed. A significant association was found only between depression and age (p=0.040) and OR = 2.0 (95% CI 1.3-3.1), anxiety and marital status (p=0.043) and OR = 1.7 (95% CI 1.0-2.6), and lifestyles and sex of the students (p=0.003) and OR = 1.1 (95% CI 1.1-2.3). Finally, it is concluded that Peruvian nursing students showed levels of anxiety ranging from moderate to extremely severe, while most of them had "normal" states of depression and stress and also showed unhealthy lifestyles.

Exposure to enriched environment rescues anxiety-like behavior and miRNA deregulated expression induced by perinatal malnutrition while altering oligodendrocyte morphology.

Maternal malnutrition is one of the major early-life adversities affecting the development of newborn's brain and is associated with an increased risk to acquire cognitive and emotional deficiencies later in life. Studies in rodents have demonstrated that exposure to an enriched environment (EE) can reverse the negative consequences of early adversities. However, rescue of emotional disorders caused by perinatal malnutrition and the mechanisms involved has not been determined. We hypothesized that exposure to an EE may attenuate the anxiety-like disorders observed in mice subjected to perinatal protein malnutrition and that this could be mediated by epigenetic mechanisms. Male CF-1 mice were subject to perinatal protein malnutrition until weaning and then exposed to an EE for 5 weeks after which small RNA-seq was performed. In parallel, dark-light box and elevated plus maze tests were conducted to evaluate anxiety traits. We found that exposure to an EE reverses the anxiety-like behavior in malnourished mice. This reversal is paralleled by the expression of three miRNAs that become dysregulated by perinatal malnutrition (miR-187-3p, miR-369-3p and miR-132-3p). The predicted mRNA targets of these miRNAs are mostly related to axon guidance pathway. Accordingly, we also found that perinatal malnutrition leads to reduction in the cingulum size and altered oligodendrocyte morphology. These results suggest that EE-rescue of anxiety disorders derived from perinatal malnutrition is mediated by the modulation of miRNAs associated with the regulation of genes involved in axonal guidance.

Differential effects of cholecystokinin (CCK-8) microinjection into the ventrolateral and dorsolateral periaqueductal gray on anxiety models in Wistar rats.

Cholecystokinin (CCK) is one of the main neurohormone peptide systems in the brain, and a major anxiogenic mediator. The periaqueductal gray (PAG) is a key midbrain structure for defensive behaviors, which could include anxiety, fear, or even panic. The CCK system has wide distribution in the PAG, where the dorsolateral region (DL) participates in active defensive behavior and the ventrolateral region (VL) in passive defensive behavior. The aim of this study was to assess the effect of CCK-8 microinjection into DL-PAG or VL-PAG on anxiety-like behavior through two tests: elevated plus maze (EPM) and defensive burying behavior (DBB). CCK-8 (0.5 and 1.0 µg/0.5 µL) presently microinjected into the DL-PAG produced an anxiogenic-like effect on the EPM evidenced by decreasing the time spent/number of entries in open arms compared to vehicle group. Additionally, the latency to burying decreased and burying time increased on the DBB test. Contrarily, CCK-8 microinjected into the VL-PAG resulted in greater open-arm time and more open-arm entries compared to the vehicle-microinjected group. The results on the DBB test confirmed an anxiolytic-like response of CCK-8 into the VL-PAG. In conclusion, CCK-8 microinjected into DL-PAG produced anxiety-like behavior on EPM, and for first time reported on DBB. Contrarily, CCK-8 microinjected into the VL-PAG reduced anxiety-like behavior also for first time reported using both behavioral models EPM and DBB.

Circulating catecholamines are associated with biobehavioral factors and anxiety symptoms in head and neck cancer patients.

Studies have shown that stress-related catecholamines may affect cancer progression. However, little is known about catecholamine secretion profiles in head and neck cancer patients. The present study investigated plasma norepinephrine and epinephrine levels in head and neck squamous cell carcinoma (HNSCC) patients and patients with oral leukoplakia, as well as their association with clinicopathological and biobehavioral variables and anxiety symptoms. A total of 93 patients with HNSCC and 32 patients with oral leukoplakia were included. Plasma norepinephrine and epinephrine levels were measured by high performance liquid chromatography with electrochemical detection (HPLC-ED), and psychological anxiety levels were measured by the Beck Anxiety Inventory (BAI). Plasma norepinephrine and epinephrine concentrations were significantly higher in patients with oral and oropharyngeal squamous cell carcinoma (SCC) compared to non-cancer patients. Oral SCC patients displayed plasma norepinephrine levels about six times higher than oropharyngeal SCC patients, and nine times higher than oral leukoplakia patients (p < .001). Plasma epinephrine levels in oral SCC patients were higher compared to the oropharyngeal SCC (p = .0097) and leukoplakia (p < .0001) patients. Oropharyngeal SCC patients had higher plasma norepinephrine (p = .0382) and epinephrine levels (p = .045) than patients with oral leukoplakia. Multiple regression analyses showed that a history of high alcohol consumption was predictive for reduced plasma norepinephrine levels in the oral SCC group (p < .001). Anxiety symptom of "hand tremor" measured by the BAI was an independent predictor for higher plasma norepinephrine levels in HNSCC patients (ß = 157.5, p = .0377), while the "heart pounding/racing" symptom was independently associated with higher plasma epinephrine levels in the oropharyngeal SCC group (ß = 15.8, p = .0441). In oral leukoplakia patients, sleep deprivation and worse sleep quality were independent predictors for higher plasma norepinephrine levels, while severe tobacco consumption and higher anxiety levels were factors for higher plasma epinephrine levels. These findings suggest that head and neck cancer patients display sympathetic nervous system hyperactivity, and that changes in circulating catecholamines may be associated with alcohol consumption, as well as withdrawal-related anxiety symptoms.

Impact of an animal-assisted therapy programme on physiological and psychosocial variables of paediatric oncology patients.

The objective of this study was to propose an intervention and safety protocol for performing animal-assisted therapy (AAT) and evaluating its efficacy in children under outpatient oncological treatment based on psychological, physiological, and quality of life indicators for the children and caregivers. The sample consisted of 24 children diagnosed with leukaemia and solid tumours (58% girls with a mean age of 8.0 years) who underwent an AAT programme consisting of three 30-min sessions in an open group. Two dogs (one Labrador retriever and one golden retriever) were used, and activities such as sensory stimulation, gait training, and socialization were conducted. The exclusion criteria were severe mental problems, inability to answer the questions included in the instruments used, allergy to animals, unavailability/lack of interest, isolation precaution, surgical wound, use of invasive devices, ostomy, no current blood count for evaluation, neutropaenia, infection, fever, diarrhoea, vomiting, respiratory symptoms at the beginning of the intervention or 1 week before the intervention, hospitalization or scheduled surgery, and non-completion of the AAT programme. The variables analysed using validated self or other evaluations were stress, pain, mood, anxiety, depression, quality of life, heart rate, and blood pressure. A quasi-experimental study design was used. We observed a decrease in pain (p = 0.046, d = -0.894), irritation (p = 0.041, d = -0.917), and stress (p = 0.005; d = -1.404) and a tendency towards improvement of depressive symptoms (p = 0.069; d = -0.801). Among the caregivers, an improvement was observed in anxiety (p = 0.007, d = -1.312), mental confusion (p = 0.006, d = -1.350), and tension (p = 0.006, d = -1.361). Therefore, the selection criteria and care protocols used for the AAT programme in the oncological context were adequate, and the programme was effective.

Environmental enrichment decreases avoidance responses in the elevated T-maze and delta FosB immunoreactivity in anxiety-related brain regions.

Environmental enrichment (EE) is an animal management technique, which seems to improve adaptation to the experimental conditions of housing in laboratory animals. Previous studies have pointed to different beneficial effects of the procedure in the treatment of several disorders, including psychiatric conditions such as depression. The anxiolytic effects induced by EE, on the other hand, are not as clear. In fact, it has been proposed that EE acts as a mild stressor agent. To better understand the relationship of EE with anxiety-related responses, the present study exposed rats to one week of EE and subsequently tested these animals in the inhibitory avoidance and escape tasks of the elevated T-maze (ETM). In clinical terms, these responses have been respectively related to generalized anxiety and panic disorder. All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. Additionally, analysis of delta FosB protein immunoreactivity (FosB-ir) was used to map areas activated by EE exposure and plasma corticosterone measurements were performed. The results obtained demonstrate that exposure to EE for one week impaired avoidance responses, an anxiolytic-like effect, without altering escape reactions. Also, in animals submitted to the avoidance task EE exposure decreased FosB-ir in the cingulate cortex, dorsolateral and intermediate lateral septum, hippocampus (cornus of Ammon), anterior and dorsomedial hypothalamus, medial and basolateral amygdala and ventral region of the dorsal raphe nucleus. Although no behavioral differences were observed in animals submitted to the escape task, EE exposure also decreased FosB-ir in the cingulate cortex, hippocampus (dentate gyrus), lateral amygdala, paraventricular, anterior and ventromedial hypothalamus, dorsomedial periaqueductal gray and ventral and dorsal region of the dorsal raphe. No changes in corticosterone levels, however, were observed. These results contribute to a better understanding of the effects of EE on anxiety.

Sex differences in the effects of pre- and postnatal caffeine exposure on behavior and synaptic proteins in pubescent rats.

Few studies have addressed the effects of caffeine in the puberty and/or adolescence in a sex dependent manner. Considering that caffeine intake has increased in this population, we investigated the behavioral and synaptic proteins changes in pubescent male and female rats after maternal consumption of caffeine. Adult female Wistar rats started to receive water or caffeine (0.1 and 0.3g/L in drinking water; low and moderate dose, respectively) during the active cycle at weekdays, two weeks before mating. The treatment lasted up to weaning and the offspring received caffeine until the onset of puberty (30-34days old). Behavioral tasks were performed to evaluate locomotor activity (open field task), anxious-like behavior (elevated plus maze task) and recognition memory (object recognition task) and synaptic proteins levels (proBDNF, BDNF, GFAP and SNAP-25) were verified in the hippocampus and cerebral cortex. While hyperlocomotion was observed in both sexes after caffeine treatment, anxiety-related behavior was attenuated by caffeine (0.3g/L) only in females. While moderate caffeine worsened recognition memory in females, an improvement in the long-term memory was observed in male rats for both doses. Coincident with memory improvement in males, caffeine increased pro- and BDNF in the hippocampus and cortex. Females presented increased proBDNF levels in both brain regions, with no effects of caffeine. While GFAP was not altered, moderate caffeine intake increased SNAP-25 in the cortex of female rats. Our findings revealed that caffeine promoted cognitive benefits in males associated with increased BDNF levels, while females showed less anxiety. Our findings revealed that caffeine promotes distinct behavioral outcomes and alterations in synaptic proteins during brain development in a sex dependent manner.

Hippocampal and cerebellar histological changes and their behavioural repercussions caused by brain ischaemic hypoxia experimentally induced by sodium nitrite.

INTRODUCTION: Brain ischaemic hypoxia can produce severe neurological damage that leads to behavioural disorders. This research analysed the hippocampal and cerebellar histological alterations caused by brain ischaemic hypoxia experimentally induced by sodium nitrite (NaNO2) and possible direct repercussions of this hypoxia on behaviour. METHODOLOGY: An experimental study was carried out by administering 60mg/kg NaNO2 to 10 Wistar rats at 3 months of age for 15 consecutive days. Ten control rats did not receive NaNO2. To assess behavioural repercussions, the animals were evaluated in Open Field, Elevated Plus-Maze (EPM), and Forced Swim tests before and after injury to evaluate locomotion, anxiety, and depression, respectively. Markers of stress were evaluated by measuring the blood levels of cortisol, glucose, cholesterol, and lactate. The presence of hippocampal lesions was verified by histologically studying the CA1-CA4 areas. Sections of the cerebellum were also evaluated because Purkinje cells are highly sensitive to ischaemic hypoxia and may serve as markers for this process. RESULTS: The number of neurons with lesions was significantly higher in animals exposed to NaNO2 in the hippocampus areas CA2, CA3, and CA4. The cerebellum was also very vulnerable to hypoxia, presenting extensive lesion áreas. These results are correlated with the parameters of the anxiety and depression tests. CONCLUSION: NaNO2 promoted brain damage due to ischaemic hypoxia in rats. Intoxicated animals showed decreased brain weights; damage in hippocampus and cerebellum; and anxiogenic and depressive behaviour.

Host and clinical aspects in patients with benign migratory glossitis.

OBJECTIVE: Investigate the association of clinical, cytological and genetic characteristics with benign migratory glossitis (BMG). STUDY DESIGN: Sample consisted of 175 patients, 44 with BMG and 131 control patients. Clinical examination and DMFT index were assessed. Cytological evaluation determined cell morphology and morphometry. Genetic evaluation was performed by analysing IL6 polymorphisms by real-time PCR. Univariate and multivariate analyses were performed (p<0.05). RESULTS: There was a higher level of anxiety, DMFT score and a prevalence of fissured tongue in BMG group. A high mean nuclear/cytoplasmic area ratio was observed in patients with BMG. There was predominance of Papanicolaou class II I BMG group. IL6 allele G rs2069843 polymorphism was associated with BMG in the dominant model. In multivariate analysis, DMFT and anxiety scale remained associated with BMG.