Antioxidant and Neuroprotective Effects of the First Tryptophyllin Found in Snake Venom (Bothrops moojeni).

In this study, we report the isolation, characterization, and synthesis of the peptide BmT-2 belonging to the tryptophyllins family, isolated from the venom of the snake Bothrops moojeni. This is the first time a tryptophyllin is identified in snake venom. We tested whether BmT-2 had cytotoxic effects and antioxidant activity in a set of experiments that included both in vitro and cell-based assays. BmT-2 presented a radical scavenging activity toward ABTS• and AAPH-derived radicals. BmT-2 protected fluorescein, DNA molecules, and human red blood cells (RBCs) from free radicals generated by the thermal decomposition of AAPH. The novel tryptophyllin was not toxic in cell viability tests, where it (up to 0.4 mg/mL) did not cause hemolysis of human RBCs and did not cause significant loss of cell viability, showing a CC50 > 1.5 mM for cytotoxic effects against SK-N-BE(2) neuroblastoma cells. BmT-2 prevented the arsenite-induced upregulation of Nrf2 in Neuro-2a neuroblasts and the phorbol myristate acetate-induced overgeneration of reactive oxygen species and reactive nitrogen species in SK-N-BE(2) neuroblastoma cells. Electronic structure calculations and full atomistic reactive molecular dynamics simulations revealed the relevant contribution of aromatic residues in BmT-2 to its antioxidant properties. Our study presents a novel peptide classified into the family of the tryptophyllins, which has been reported exclusively in amphibians. Despite the promising results on its antioxidant activity and low cytotoxicity, the mechanisms of action of BmT-2 still need to be further elucidated.

Components of Banisteriopsis caapi, a Plant Used in the Preparation of the Psychoactive Ayahuasca, Induce Anti-Inflammatory Effects in Microglial Cells.

Banisteriopsis caapi is used to prepare the psychoactive beverage ayahuasca, and both have therapeutic potential for the treatment of many central nervous system (CNS) conditions. This study aimed to isolate new bioactive compounds from B. caapi extract and evaluate their biological activity, and that of the known ß-carboline components of the plant (harmine, harmaline, and tetrahydroharmine), in BV-2 microglial cells, the in vivo activation of which is implicated in the physiopathology of CNS disorders. B. caapi extract was fractionated using semipreparative liquid chromatography (HPLC-DAD) and the exact masses ([M + H]+m/z) of the compounds in the 5 isolated fractions were determined by high-resolution LC-MS/MS: F1 (174.0918 and 233.1289), F2 (353.1722), F3 (304.3001), F4 (188.1081), and F5 (205.0785). Harmine (75.5-302 µM) significantly decreased cell viability after 2 h of treatment and increased the number of necrotic cells and production of reactive oxygen species at equal or lower concentrations after 24 h. F4 did not impact viability but was also cytotoxic after 24 h. Most treatments reduced proinflammatory cytokine production (IL-2, IL-6, IL-17, and/or TNF), especially harmaline and F5 at 2.5 µM and higher concentrations, tetrahydroharmine (9.3 µM and higher), and F5 (10.7 µM and higher). The results suggest that the compounds found in B. caapi extract have anti-inflammatory potential that could be explored for the development of treatments for neurodegenerative diseases.

The peptide secreted at the water to land transition in a model amphibian has antioxidant effects.

In addition to the morphophysiological changes experienced by amphibians during metamorphosis, they must also deal with a different set of environmental constraints when they shift from the water to the land. We found that Pithecopus azureus secretes a single peptide ([M + H]+ = 658.38 Da) at the developmental stage that precedes the onset of terrestrial behaviour. De novo peptide and cDNA sequencing revealed that the peptide, named PaT-2, is expressed in tandem and is a member of the tryptophyllins family. In silico studies allowed us to identify the position of reactive sites and infer possible antioxidant mechanisms of the compounds. Cell-based assays confirmed the predicted antioxidant activity in mammalian microglia and neuroblast cells. The potential neuroprotective effect of PaT-2 was further corroborated in FRET-based live cell imaging assays, where the peptide prevented lipopolysaccharide-induced ROS production and glutamate release in human microglia. In summary, PaT-2 is the first peptide expressed during the ontogeny of P. azureus, right before the metamorphosing froglet leaves the aquatic environment to occupy terrestrial habitats. The antioxidant activity of PaT-2, predicted by in silico analyses and confirmed by cell-based assays, might be relevant for the protection of the skin of P. azureus adults against increased O2 levels and UV exposure on land compared with aquatic environments.

Factors associated with alcohol use and abuse in Brazilian primary health care settings.

The main goal of this study was to identify the prevalence of alcohol use and associations with selected variables among clients in a primary healthcare setting. A quantitative, cross-sectional study was carried out using structured questionnaires to measure the pattern of alcohol consumption, quality of life and common mental disorders. The results showed that men, people between 18 and 40 years old, with income between $300.00 and 1200.00 and smokers were at a higher risk of problematic alcohol use. Healthcare professionals should include alcohol screening questions to identify the hazardous consumption of alcohol at an early stage and prevent negative consequences.

Assistance related to suicidal behavior at a mobile emergency service: Sociodemographic and clinical associated factors.

It is important to investigate the care given to people with suicidal behavior, as it is an important predictor of future death by suicide and there is a lack of studies on this issue in Brazil. This study had the objective of investigating assistance related to suicidal behavior at a mobile emergency service and sociodemographic and clinical associated factors. This was a quantitative, cross-sectional study based on documental information. The data were collected through manual consultation of nursing records in which call-outs for suicidal behavior in the year 2014 were documented. The data were analyzed using descriptive statistics, Chi-squared test, Fisher's exact test, correlation tests, and comparison of means tests. In the 313 records analyzed there was a predominance of adult women with self-inflicted drug poisoning, attended to in their own residence and referred to pre-hospital emergency medical services. There was a lack of documentation on signs, symptoms, and grievances in most cases. The interventions most carried out by the nurses were related to monitoring of clinical parameters. There were differences related to the victim's sex and lethality, suicide attempt method, referral to emergency services, and semester of occurrence (January-June, July-December). Suicide attempts through self-poisoning or self-inflicted injuries differed in relation to time of call-out, waiting time, lethality, documentation on clinical assessment and interventions, and referral to emergency services. This study enabled the charting of factors linked with suicidal behavior and associated factors; it offers reflections on limitations and nursing care potential in the prevention of reoccurrence of suicidal behavior.

Factors associated with common mental disorders and use of psychiatric drugs in cancer outpatients.

BACKGROUND: Considering the high incidence of cancer in Brazil and worldwide, the high prevalence and relevance of Common Mental Disorders (CMD) in the treatment of cancer patients, and the use of psychiatric drugs without reliably proven effectiveness, studies that contemplate this topic are needed to understand and provide rationale for the treatment of CMD in these individuals. OBJECTIVES: This study identified prevalence and factors associated with Common Mental Disorders (CMD) and psychotropic use in cancer outpatients. METHOD: This is a cross-sectional study with descriptive correlational design. It was developed in the chemotherapy sector of a hospital specialized in cancer. The tools used were: Self Reporting Questionnaire (SRQ-20) and structured questionnaires. FINDINGS: Among 403 respondents, CMD prevalence was 31.5% and psychotropic use was 25.8%. CMD were associated with gender, education, family income, psychotropic use and cancer surgery. Psychotropic use was associated with gender, employment status, cancer surgery, treatment period and other physical health conditions. Logistic regressions showed CMD were associated with gender and other physical health conditions; psychotropic use was associated with gender, employment status and other conditions.

Structure⁻Activity Relationship of Piplartine and Synthetic Analogues against Schistosoma mansoni and Cytotoxicity to Mammalian Cells.

Schistosomiasis, caused by helminth flatworms of the genus Schistosoma, is an infectious disease mainly associated with poverty that affects millions of people worldwide. Since treatment for this disease relies only on the use of praziquantel, there is an urgent need to identify new antischistosomal drugs. Piplartine is an amide alkaloid found in several Piper species (Piperaceae) that exhibits antischistosomal properties. The aim of this study was to evaluate the structure­function relationship between piplartine and its five synthetic analogues (19A, 1G, 1M, 14B and 6B) against Schistosoma mansoni adult worms, as well as its cytotoxicity to mammalian cells using murine fibroblast (NIH-3T3) and BALB/cN macrophage (J774A.1) cell lines. In addition, density functional theory calculations and in silico analysis were used to predict physicochemical and toxicity parameters. Bioassays revealed that piplartine is active against S. mansoni at low concentrations (5⁻10 µM), but its analogues did not. In contrast, based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, piplartine exhibited toxicity in mammalian cells at 785 µM, while its analogues 19A and 6B did not reduce cell viability at the same concentrations. This study demonstrated that piplartine analogues showed less activity against S. mansoni but presented lower toxicity than piplartine.

Physical and mechanical restraint in psychiatric units: Perceptions and experiences of nursing staff.

BACKGROUND: Physical restraint in psychiatric units is a common practice but extremely controversial and poorly evaluated by methodologically appropriate investigations. The cultural issues and professionals' perceptions and attitudes are substantial contributors to the frequency of restraint that tend to be elevated. Aim In this qualitative study, we aimed to understand the experiences and perceptions of nursing staff regarding physical restraint in psychiatric units. METHOD: Through theoretical sampling, 29 nurses from two Brazilian psychiatric units participated in the study. Data were collected from 2014 to 2016 from individual interviews and analyzed through thematic analysis, employing theoretical presuppositions of symbolic interactionism. RESULTS: Physical restraint was considered unpleasant, challenging, risky, and associated with dilemmas and conflicts. The nursing staff was often exposed to the risks and injuries related to restraint. Professionals sought strategies to reduce restraint-related damages, but still considered it necessary due to the lack of effective options to control aggressive behavior. CONCLUSIONS: This study provides additional perspectives about physical restraint and reveals the need for safer, humanized and appropriate methods for the care of aggressive patients that consider the real needs and rights of these patients.

Enhanced activation of eosinophils in peripheral blood and implications for eosinophilic esophagitis diagnosis.

BACKGROUND AND AIM: Eosinophils are markers of the eosinophilic esophagitis (EoE) disease, and this work aimed to assess whether activation of eosinophils could be a noninvasive test to contribute for EoE diagnosis. METHODS: The activation state of peripheral blood eosinophils in EoE patients and control subjects was assessed based on the morphological aspects of the eosinophil after adherence to slide. Cyclooxygenase-2 and 5-lipoxygenase expressions were evaluated by means of immunofluorescence microscopy to verify if and which eicosanoid pathway is triggered in eosinophils in blood in EoE. RESULTS: The eosinophils of patients with EoE were significantly more activated than those of control individuals. The lowest percentage of normal eosinophils for control subjects was 40%, while the highest percentage of eosinophils of normal aspect for patients with EoE was 32%. Considering 36% as a cutoff for normal eosinophils, this value differentiated all individuals with EoE from individuals without the disease with a sensitivity of 100%, considering the diagnosis of EoE as currently defined. Eosinophils of EoE patients showed higher expression of cyclooxygenase-2 than those of control subjects. CONCLUSIONS: The quantification of morphological changes in eosinophils is a feasible, easy, and reliable manner to identify EoE patients. Therefore, patients with symptoms of esophageal dysfunction showing higher than 36% activated eosinophils in peripheral blood could be a useful way to help definition and diagnostic criterion for EoE.

Emergency Nursing Experiences in Assisting People With Suicidal Behavior: A Grounded Theory Study.

AIM: To understand emergency nursing experiences in assisting people with suicidal behavior. METHOD: Grounded theory study with symbolic interactionism conducted in 2015 to 2016 in Brazil with 19 nurses. RESULTS: Assistance for people with suicidal behavior is critical, challenging, evokes different feelings and requires knowledge, skills and emotional control. Nurses did not feel prepared or supported, and identified recurrent gaps and problems. Nurses occupied a limited role, restricted to attending to physical needs. They predominantly manifested opposition, judgments and incomprehension about patients. CONCLUSION: This study presents key elements to be addressed in interventions and investigations regarding nursing support, training and supervision.

Quality of Life in Brazil's Family Health Strategy: Common Mental Disorders, Use of Psychotropic Drugs and Sociodemographic Factors.

The aim of the study was to evaluate the patients' quality of life in Brazil's Family Health Strategy and its association with sociodemographic factors, presence of common mental disorders, and use of psychotropic drugs. Were interviewed 442 patients. Tools were: World Health Organization Quality of Life Assessment-Bref and Self Reporting Questionnaire. Male and low education were strongly associated with higher quality of life. Use of psychotropic drugs and the presence of CMD were strongly associated with poor quality of life. There is a pressing need for primary health care professionals to invest in tracking, and in holistic interventions that are able to cover the healthcare needs of these vulnerable groups.

Factors Associated with Potential Drug-Drug Interactions in Patients Attended in Primary Health Care: A Focus on Mental Health.

There were no Brazilian studies regarding potential drug-drug interactions (DDIs) in primary health care (PHC) analysing common mental disorders (CMDs) and psychotropic medication. OBJECTIVES: To identify DDI prevalence in that setting; to classify DDI; to verify correlations with demographics, pharmacotherapeutics, psychotropic medication and CMDs. Among 430 patients interviewed 190 had more than two medications prescribed, 58.4% had DDI. Factors associated were age and number of medications. Nine types of severe DDI composed 28% patients' prescriptions, 71.9% involving psychotropic medication. Only the number of types of drugs contributed to the regression model. Results raise important aspects regarding patient safety in PHC units in Brazil are where patients with psychological complaints have to seek for health care firstly.

The Meaning of Stigma for People with Mental Disorders in Brazil.

OBJECTIVE: To understand the meaning of stigma for people with mental disorders. METHOD: A qualitative study with 46 Brazilian adults with mental disorders. Data were collected through semistructured interviews and nonparticipant observation and submitted for a thematic analysis with symbolic interactionism. RESULTS: Stigma was considered as an experience of incomprehension and suffering. The society has difficulty in empathizing, respecting differences and understanding the extent of the suffering of people with mental disorders. Participants recommended anti-stigma strategies that included promoting knowledge and respecting differences. CONCLUSIONS: The present study contributes new insights to be addressed in interventions to reduce the suffering and impact of stigma.

Factors Associated With Psychotropic Medication Use in Individuals in Brazilian Primary Health Care Units: A Descriptive, Cross-Sectional Study.

The current descriptive, cross-sectional study aimed to investigate the rate of psychotropic medication use and its association with sociodemographic factors, pharmacotherapy, health history, and presence of common mental disorders in individuals in Brazilian primary health care (PHC) units. A sample of 442 individuals was interviewed in 10 PHC units. Tools used included a structured questionnaire and the Self Reporting Questionnaire-20. The rate of psychotropic medication use was 38.7%. Demographic characteristics associated with psychotropic medication use were age 60 or older with common mental disorders and physical illness, a primary-level education or less, no occupation, and family income greater than three times the minimum wage. The strongest predictor of psychotropic medication use was monthly family income. The results highlight the need for interventions to improve patient outcomes. [Journal of Psychosocial Nursing and Mental Health Services, 55(3), 38-45.].

Meaning of Pharmacological Treatment for Families of People With Depression.

Medication adherence is related to patient satisfaction with family support. This research aimed to understand the meaning of pharmacotherapy to families of people with major depressive disorder. This qualitative study employed Grounded Theory and Symbolic Interactionism. Seventeen families of people with depression from a Brazilian clinic were included. Data was collected from 2013 to 2014, using open interviews, which were analyzed by open, axial, and selective coding. Medication represented "Tranquility and worry" because it re-established tranquility in family routine, but generated concerns. Thus, families were conflicted and ambivalent about medications, and they interfered with the promotion or impairment of adherence.

Adherence to Psychotropic Medications and Associated Factors in Primary Health Care.

The study aims were to analyze patients' adherence to psychotropic medications and its association with sociodemographic factors, therapeutic regimen, presence of common mental disorders, and illness factors. A descriptive cross-sectional study was carried out in ten Primary Health Care units in Brazil. The tools were the Measurement of Treatment Adherence Test and the Self Reporting Questionnaire. Nonadherence to psychotropic drugs was 88.9%. There was association between adherence and age and among patients positive for Common Mental Disorders (97.8%). In the multivariate analysis this association was not maintained. Findings indicate strategies are needed to improve medication adherence in the Primary Health Care services. However, no strategy will be effective if patients and their families are not involved in the process.

Common Mental Disorders in Primary Health Care Units: Associated Factors and Impact on Quality of Life.

BACKGROUND: Considering the high worldwide prevalence of common mental disorders (CMDs), characterizing the association between CMD and quality of life (QoL) constitute a valuable measure to gauge patient's functional impairment due to CMD symptoms. OBJECTIVE: To investigate factors associated with the incidence of CMD and its impact on the QoL in primary health care (PHC) patients. DESIGN: Cross-sectional study completed in a municipality in Brazil. Standardized tools included the Self-Reporting Questionnaire-20 to detect CMDs and the WHOQOL-brief to assess QoL, in addition to a sociodemographic and treatment-related questionnaire. RESULTS: A total of 41.4% of the patients met cutoff scores for a CMD, and the presence of a CMD was associated with female gender and marital status. Patients with CMDs had lower QoL scores than patients who were negative for a CMD. CONCLUSIONS: CMDs are highly prevalent in PHC settings and affect patients' QoL. The high frequency of CMD in those that seek care through PHC necessitate incorporating mental health services into the range of available services.

[Common mental disorders and use of psychotropic medications in women consulting at primary care units in a Brazilian urban area]. / Transtornos mentais comuns e uso de psicofármacos em mulheres atendidas em unidades básicas de saúde em um centro urbano brasileiro.

OBJECTIVE: To investigate the prevalence of common mental disorders (CMD) in women consulting at primary health care units in a Brazilian urban area, as well as to determine the impact of CMD on quality of life (QoL), the association of sociodemographic factors with CMD and QoL, and the prevalence and pattern of psychotropic medication use in the study sample. METHODS: In this quantitative, cross-sectional, correlational-descriptive study, a stratified sample of 365 women was interviewed between May 2012 and January 2013 in five primary health care units in Brazil. Data were collected using sociodemographic and drug use questionnaires. The self-reporting questionnaire (SRQ-20) was used to estimate the prevalence of CMD; and the World Health Organization Quality of Life (WHOQOL)-bref instrument was used to assess quality of life. To evaluate the impact of CMD on QoL, the t test and linear regression models were employed. The chi-square test was used to verify associations between CMD and sociodemographic variables. Descriptive analysis was used for psychotropic drug use. RESULTS: The prevalence of CMD was 44.1%. The prevalence of psychotropic medication use was 27.1%. Only 5.6% of participants had a psychiatric diagnosis recorded in their medical chart. Psychotropic drugs were used by 41.6% of participants with CMD according to the SRQ-20 and by 15.7% of those without CMD. There was no association between CMD and sociodemographic variables, but CMD and QoL were significantly associated. Women with CMD had the worst QoL, without impact of sociodemographic variables. CONCLUSIONS: Further attention should be given to the pattern of psychotropic medication use and prescription in primary care settings. Women with CMD had functional impairment, as shown by significantly lower QoL scores. The fact that sociodemographic factors did not impact the present results seems to support the notion of a different basis for CMD in women.

Antiviral Action against SARS-CoV-2 of a Synthetic Peptide Based on a Novel Defensin Present in the Transcriptome of the Fire Salamander (Salamandra salamandra).

The potential emergence of zoonotic diseases has raised significant concerns, particularly in light of the recent pandemic, emphasizing the urgent need for scientific preparedness. The bioprospection and characterization of new molecules are strategically relevant to the research and development of innovative drugs for viral and bacterial treatment and disease management. Amphibian species possess a diverse array of compounds, including antimicrobial peptides. This study identified the first bioactive peptide from Salamandra salamandra in a transcriptome analysis. The synthetic peptide sequence, which belongs to the defensin family, was characterized through MALDI TOF/TOF mass spectrometry. Molecular docking assays hypothesized the interaction between the identified peptide and the active binding site of the spike WT RBD/hACE2 complex. Although additional studies are required, the preliminary evaluation of the antiviral potential of synthetic SS-I was conducted through an in vitro cell-based SARS-CoV-2 infection assay. Additionally, the cytotoxic and hemolytic effects of the synthesized peptide were assessed. These preliminary findings highlighted the potential of SS-I as a chemical scaffold for drug development against COVID-19, hindering viral infection. The peptide demonstrated hemolytic activity while not exhibiting cytotoxicity at the antiviral concentration.

Isolation of Sporothrix schenckii from the claws of domestic cats (indoor and outdoor) and in captivity in São Paulo (Brazil).

Sporotrichosis is a subcutaneous mycosis and is also a zoonosis (sapro- and anthropozoonosis). The objective of the present study was to determine the occurrence of sporotrichosis in domestic cats and in wild or exotic felines in captivity through the isolation of Sporothrix spp. from claw impressions in a culture medium. The samples included 132 felines, of which 120 (91.0 %) were domestic cats, 11 (8.3 %) were wild felines, and one (0.7 %) was an exotic felid. Twenty-one (17.5 %) were outdoor cats. Of the total, 89 (67.4 %) had contact with other animals of the same species. It was possible to isolate Sporothrix schenckii from the claws of one (0.7 %) of the felids probed; this animal exhibited generalised sporotrichosis and had infected a female veterinarian. The potential pathogenic agents Microsporum canis and Malassezia pachydermatis were isolated in 12.1 and 5.3 % of the animals, respectively. The following anemophilous fungi, which were considered to be contaminants, were also isolated: Penicillium sp. (28 or 21.2 %), Aspergillus sp. (13 or 9.8 %), Rhodotorula sp. (5 or 3.8 %), Candida sp. (5 or 3.8 %), Trichoderma sp. (1 or 0.7 %), and Acremonium sp. (1 or 0.7 %). Due to the low magnitude of occurrence (0.7 %) of Sporothrix in feline claws, the potential of the cats evaluated in this study to be sources of infection in the city of São Paulo is considerably low.