Development and characterization of liposomal formulations containing sesquiterpene lactones for the treatment of chronic gout.

Gout and hyperuricemia are characterized by high uric acid levels, and their treatment involves medications that have adverse effects. In this study, we evaluated oral liposomal formulations with eremantholide C and goyazensolide as a novel approach to reduce the toxicity associated with these substances while maintaining their anti-hyperuricemic activity. We characterized the formulations and evaluated them based on encapsulation efficiency and stability over 12 months and under simulated physiological environments. We determined the toxicity of the liposomal formulations in Caco-2 cells and the anti-hyperuricemic activity in rats. The formulations exhibited nanometric size, a narrow size distribution, and a negative zeta potential, indicating their stability and uniformity. The efficient encapsulation of the sesquiterpene lactones within the liposomes emphasizes their potential for sustained release and therapeutic efficacy. Stability evaluation revealed a small decrease in the eremantholide C concentration and a remarkable stability in the goyazensolide concentration. In Caco-2 cells, the liposomes did not exert toxicity, but did exhibit an antiproliferative effect. In vivo assays demonstrated that the liposomes reduced serum uric acid levels. Our study represents an advancement in gout and hyperuricemia treatment. The liposomal formulations effectively reduced the toxicity associated with the sesquiterpene lactones while maintaining their therapeutic effects.

The Potential of Allelochemicals from Microalgae for Biopesticides.

Improvements in agricultural productivity are required to meet the demand of a growing world population. Phytopathogens, weeds, and insects are challenges to agricultural production. The toxicity and widespread application of persistent synthetic pesticides poses a major threat to human and ecosystem health. Therefore, sustainable strategies to control pests are essential for agricultural systems to enhance productivity within a green paradigm. Allelochemicals are a less persistent, safer, and friendly alternative to efficient pest management, as they tend to be less toxic to non-target organisms and more easily degradable. Microalgae produce a great variety of allelopathic substances whose biocontrol potential against weeds, insects, and phytopathogenic fungi and bacteria has received much attention. This review provides up-to-date information and a critical perspective on allelochemicals from microalgae and their potential as biopesticides.

Validation of the Opening Minds Scale for Health Care Providers (OMS-HC): Factor Structure and Psychometric Properties of the Brazilian Version.

Stigma towards people with mental illness is also present among health professionals. The study validated and estimated the reliability, dimensionality and structure of the Opening Minds Stigma Scale for Health Care Providers (OMS-HC) scale in Brazil. In this methodological study, health professionals (n = 199) from Family Health Units in Brazil were recruited by convenience sampling. The EFA conducted with 16 items resulted in four factors. The Cronbach's Alpha for the OMS scale was 0.74, which is considered to reflect reasonable reliability. The data presented contribute to the use of the scale in studies that investigate the level of stigma among health professionals towards people with mental illness, as well as in the development of anti-stigma interventions in this context.

Mental Health Care in Primary Health Care: An Integrative Review.

In this study, we analyzed recent studies on mental health approaches developed in primary health care to identify the emphasis of such interventions, their technical feasibility for the setting in question, and their levels of evidence. An integrative review was conducted of primary studies from the LILACS, PubMed, Embase, CINAHL, and Web of Science databases using the PRISMA search strategy. Nineteen studies were identified with a high level of evidence that contribute to the advancement of knowledge in the area. However, academic, cultural, and linguistic barriers still need to be overcome to facilitate sharing of such interventions' findings and protocols.

Intentional self-poisoning with medications: Occurrence, recurrence and suicide deaths.

This study aimed to identify the sociodemographic and clinical factors associated with the occurrence and recurrence of intentional self-poisoning with medications (ISP-M), and suicide deaths by ISP-M in the state of Mato Grosso, Brazil. In this cross-sectional analytical study, we used logistic regression models to analyze data obtained through health information systems. Factors associated with use of ISP-M as a method were female gender, white skin color, occurrence in urban areas and at home. The ISP-M as a method was less reported in people presumed under the influence of alcohol. Lower chance of death by suicide using ISP-M was found among young people and adults (under 60 years old).

Psychosocial factors and physical activity among workers in Brazil.

BACKGROUND: Complex behaviors, such as physical activity (PA), may be related to different levels of influence. OBJECTIVE: To analyze the role of social support, mood and alcohol consumption as psychosocial predictors on the engagement in PA among Brazilian workers. METHODS: This is a quantitative, cross-sectional analytical study. A sample of 395 participants answered a sociodemographic questionnaire, the Alcohol Use Disorder Identification Test (AUDIT), the Baecke Habitual Physical Activity Questionnaire, the Social Support Scale for Physical Activities (SSSPA) and the Brunel Mood Scale (BRUMS). RESULTS: Analysis via Pearson's Correlation Test indicated a negative correlation between PA and depression and fatigue, and a positive correlation between PA and alcohol consumption, vigor and the four variables of social support (support of family members for walking; support of friends for walking; support of family members for moderate and vigorous physical activity; support of friends for moderate and vigorous physical activity). A positive relationship between PA and low-risk alcohol consumption was also identified. A hierarchical multiple regression analysis showed that family support for walking, friends support for moderate and vigorous physical activity, vigor and alcohol consumption are predictors of PA. Hayes' moderation analysis indicated that social support has a moderating effect on the relationship between alcohol use and PA. CONCLUSION: Different factors may be involved in engaging in PA. A broader approach that addresses the singularities of individuals, especially in actions for different patterns of alcohol consumption, is recommended.

Evaluation of software for mental health promotion of undergraduate nursing students in the early years of college.

OBJECTIVE: To evaluate mental health promotion software for students in the early years of undergraduate nursing course. METHOD: Descriptive study developed with 41 undergraduates from a private higher education institution in an inland city of the state of São Paulo, approved by the Research Ethics Committee. Data collection was carried out remotely from April to October 2021, using a sociodemographic characterization questionnaire and student assessment of the software. The results were analyzed by descriptive statistics. RESULTS: Most respondents rated the tool and the clarity of its content as excellent. The modules considered most relevant were those related to solving problems with future implications. The students considered the advice very applicable to everyday life and a good correspondence between problem situations and real life. CONCLUSION: This type of intervention is configured as one more option in the list of strategies to promote nursing students' mental health, although it does not replace face-to-face care.

Donepezil Hydrochloride BCS Class Ambiguity: Relevant Aspects to be Considered in Drug Classification.

Donepezil hydrochloride (DH) is the most used anti-Alzheimer's disease drug, however, its classification according to the Biopharmaceutics Classification System (BCS) is not clear in the literature. BCS is one of the accepted criteria used to grant biowaiver (waiver of in vivo bioequivalence studies) of new drug products. So, the purpose of this work was to elucidate the BCS classification of DH and to raise the discussion about the possibility of biowaiver for new medicines containing it. The polymorphic form was previously identified as form III of DH. The drug showed high solubility in the entire pH range evaluated (1.2 to 6.8, at 37 °C) with a pH-dependent solubility profile. The effective permeability (Peff) values obtained with different DH concentrations, using in situ closed-loop perfusion model were statistically similar (p > 0.05), even when compared to high permeability control used (ketoprofen), demonstrating that DH has high permeability which, associated with its high solubility, allows to classify DH as BCS class 1. Relevant data to evaluate for granting a biowaiver for new medicines were also reviewed from the literature. Based on information reunited new immediate-release drug products containing DH should be eligible for BCS-based biowaiver.

Biopharmaceutics studies applied to goyazensolide: a drug candidate from Lychnophora species.

OBJECTIVES: To predict the substance's behaviour in vivo and determine the viability of the bioactive substance to become a drug, this work aimed to evaluate the biopharmaceutics characteristics of goyazensolide. METHODS: Differential scanning calorimetry (DSC) and thermogravimetry (TG) were applied for the characterization of goyazensolide. The biopharmaceutics characteristics were evaluated using in-silico and in-vitro (shake-flask and Parallel Artificial Membrane Permeability Assay) methods. KEY FINDINGS: DSC curve showed a single endothermic peak. According to the TG curve, goyazensolide has thermal stability close to 221.0°C and 210.0°C, under a nitrogen and oxygen atmosphere, respectively. In-silico data indicated that goyazensolide has high solubility and low permeability. The high solubility was confirmed by equilibrium solubility studies determined by the shake-flask method. The dose/solubility ratio values were 175.16 ml (pH 1.2), 194.99 ml (pH 4.5) and 222.07 ml (pH 6.8). The effective permeability of 0.03 × 10-6 cm/s was obtained for goyazensolide. This value is lower than furosemide (1.03 × 10-6 cm/s), confirming the low permeability of goyazensolide. CONCLUSIONS: Biopharmaceutics characteristics of goyazensolide are similar to drugs available on the market and attest to the feasibility of starting the process of developing a formulation containing this substance.

Chemical Analysis of Eruca sativa Ethanolic Extract and Its Effects on Hyperuricaemia.

In vivo assays and chemical analyses were performed on the ethanolic extract from leaves of Eruca sativa. UHPLC-ESI-QTOF analysis confirmed the presence of glucosinolates and flavonol glucosides. The major flavonoid of the ethanolic extract, kaempferol-3,4'-di-O-ß-glucoside, was isolated, a HPLC-DAD method developed and validated to quantify its content in the extract. In vivo experiments were carried out on Wistar rats with hyperuricaemia induced by potassium oxonate and uric acid. A hypouricaemic effect was observed in hyperuricaemic Wistar rats treated with ethanolic extract at dose of 125 mg/kg and kaempferol-3,4'-di-O-ß-glucoside at dose of 10 mg/kg. The main anti-hyperuricaemic mechanism observed in the extract was uricosuric. Kaempferol-3,4'-di-O-ß-glucoside was identified as an important component responsible for the total activity of the ethanolic extract and was considered as a good chemical and biological marker of the ethanolic extract of E. sativa. The obtained results indicated the potential of E. sativa in the treatment of hyperuricaemia and its comorbidities.

Evaluation of software for mental health promotion of undergraduate nursing students in the early years of college / Evaluación de un software de promoción de la salud mental para estudiantes de graduación en enfermería en los primeros años de curso / Avaliação de um software de promoção da saúde mental para graduandos de enfermagem dos anos iniciais

ABSTRACT Objective: To evaluate mental health promotion software for students in the early years of undergraduate nursing course. Method: Descriptive study developed with 41 undergraduates from a private higher education institution in an inland city of the state of São Paulo, approved by the Research Ethics Committee. Data collection was carried out remotely from April to October 2021, using a sociodemographic characterization questionnaire and student assessment of the software. The results were analyzed by descriptive statistics. Results: Most respondents rated the tool and the clarity of its content as excellent. The modules considered most relevant were those related to solving problems with future implications. The students considered the advice very applicable to everyday life and a good correspondence between problem situations and real life. Conclusion: This type of intervention is configured as one more option in the list of strategies to promote nursing students' mental health, although it does not replace face-to-face care.

RESUMEN Objetivo: Evaluar un software de promoción de la salud mental dirigido a estudiantes de los primeros años de graduación en enfermería. Método: Estudio descriptivo desarrollado con 41 estudiantes de graduación de una institución de enseñanza superior privada del interior del estado de São Paulo, aprobado por el Comité de Ética en Investigación. La recolección de datos se realizó de forma remota de abril a octubre de 2021, utilizando un cuestionario de caracterización sociodemográfica y evaluación de los estudiantes del programa. Los resultados fueron analizados por estadística descriptiva. Resultados: La mayoría de los encuestados calificaron la herramienta y la claridad de su contenido como excelentes. Los módulos considerados más relevantes fueron los relacionados con la resolución de problemas con implicaciones futuras. Los alumnos consideraron los consejos muy aplicables a la vida cotidiana y una buena correspondencia entre las situaciones-problema y la vida real. Conclusión: Este tipo de intervención es una opción más en la lista de estrategias para promover la salud mental de los estudiantes de enfermería, aunque no reemplaza la atención presencial.

RESUMO Objetivo: Avaliar um software de promoção da saúde mental destinado a estudantes dos anos iniciais da graduação em enfermagem. Método: Estudo descritivo desenvolvido com 41 graduandos de uma instituição privada de ensino superior do interior do estado de São Paulo, aprovado pelo Comitê de Ética em Pesquisa. A coleta de dados foi realizada de forma remota de abril a outubro de 2021, usando um questionário de caracterização sociodemográfica e avaliação dos estudantes acerca do programa. Os resultados foram analisados por estatística descritiva. Resultados: A maioria dos participantes classificou a ferramenta e a clareza de seu conteúdo como excelentes. Os módulos considerados mais relevantes foram aqueles relacionados à resolução de problemas com implicações futuras. Os estudantes consideraram os aconselhamentos muito aplicáveis ao cotidiano e uma boa correspondência das situações-problema com a vida real. Conclusão Essa modalidade de intervenção configura-se como mais uma opção no rol de estratégias de promoção da saúde mental de graduandos de enfermagem, ainda que não substitua o cuidado face-a-face.

Experience of Vulnerable Women Narrated through the Body-Mapping Technique.

Vulnerable women are considered a priority in public policies and research agendas. It is necessary to understand better the specificities of their daily lives and the meanings they attribute to their experiences, as this undoubtedly contributes to more grounded and culturally appropriate practices. Additionally, innovative techniques in qualitative research are demanded in academia. This narrative research study was carried out with fourteen women from a Brazilian socioeconomically vulnerable neighborhood. We used the body-mapping technique to investigate the experiences of women with mental health disorders or psychosocial distress. The aim was to analyze the self-perception about daily stressors and discuss the feasibility of this technique to facilitate this group's storytelling. Data collection was performed through focus groups, guided by the body-mapping technique steps, and supplemented with individual interviews. Interpersonal conflicts and violence were the main stressors. These strongly impacted the well-being of these women and their children. Some important personal qualities and resilience were identified. Body-mapping played a fundamental role in facilitating storytelling. It amplified the linguistic possibilities for participants to express their feelings and promoted reflections about the present, past, and glimpses into the future.

Role of sociodemographic factors and self-efficacy in the perception of social support of nursing students.

OBJECTIVE: To analyze the role of sociodemographic factors and self-efficacy in the perception of social support by nursing students of the first years of nursing school. METHOD: This is a quantitative cross-sectional research, developed with 121 undergraduate students from the early years of the course. A sociodemographic questionnaire, the Higher Education Self-Efficacy Scale and the abbreviated version of the Social Support Questionnaire were used. Spearman and Mann-Whitney correlation tests were performed using software for statistical analysis. RESULTS: It was identified that students with better self-efficacy and who are self-declared black or brown reported, respectively, greater satisfaction with the support and a smaller number of supporters. CONCLUSION: Considering that the race/color factor had a negative influence and self-efficacy a positive influence in the perception of social support, it is recommended that mental health promotion strategies be conducted that permeate both affirmative action policies and improvements in the teaching-learning process, especially in the first years of the nursing course.

The influence of work environment relationships on mental health of Brazilian seamstresses.

BACKGROUND: The work environment is a place in which different kinds of interpersonal relationships are developed and can contribute positively or negatively to productivity and to workers' well-being. Discussion on this topic may contribute to building more coping strategies to fight against gender inequality and the emotional repercussions of these conditions. OBJECTIVE: This is a cross-sectional study that investigated the possible influence of work environment relationships on the mental health of Brazilian seamstresses. METHODS: The participants were seamstresses from four clothing factories in a city in the southwest of Brazil. For data collection, we used the Social Support Perception at Work Scale; Self-Report Questionnaire; Alcohol, Smoking and Substance Involvement Screening Test; and a focus group. The quantitative data were statistically analyzed, and data from the focus groups were analyzed using content analysis. RESULTS: Interpersonal relationships at work were mentioned as sources of conflict and stress but also as emotional and material social support providers. In the sample studied, these relationships did not influence directly the development of mental health disorders. CONCLUSIONS: Study results suggest that a low level of education is an important factor that increases the vulnerability of these women to the precariousness of work, and, consequently to developing mental health symptoms or aggravating previous mental health distress. However, emotional and material support from peers likely protects these workers' mental health.

Oral treatment with a chemically characterized parsley (Petroselinum crispum var. neapolitanum Danert) aqueous extract reduces thrombi formation in rats.

Petroselinum crispum var. neapolitanum Danert (Apiaceae) (PC), popularly known as parsley, is an herb native to the Mediterranean region widely cultivated around the world for culinary and ethnomedicinal purposes. The herb is traditionally used in various parts of the world to treat arterial hypertension, hemorrhoid, nose bleeding, hyperlipidemia, and pain, among other indications. The aim of this study was to evaluate the antithrombotic activity of an aqueous extract PC in rats. Aerial parts of a flat-leaf variety of parsley were extracted by decoction. In vivo thrombosis in rat models as well as ex vivo assays were used in the evaluation of PC antithrombotic effects. Intravenous administration of PC (25 mg/kg.b.w), 5 min before thrombosis induction, reduced the venous thrombus formation by 98.2%, while oral administration (125 mg/kg.b.w) impaired it by 76.2%. In the arterial thrombosis model, the oral administration of PC at 15 or 25 mg/kg.b.w, 60 min before thrombosis induction, increased the carotid artery occlusion time by 150% (37.0 ± 6.44 min) and 240% (more than 60 min), respectively. A HPLC-DAD-MS/MS profile of PC extract used in this study was provided. Apiin showed to be the most abundant phenolic compound in the extract. It also revealed the presence of many coumaric acid derivatives. Our results indicate that PC is a potential candidate for the development of a phytotherapeutic drug in the treatment of thromboembolic diseases and provide a detailed chemical profile useful for controlling PC extract production in view of phytotherapy.

Eremantholide C from aerial parts of Lychnophora trichocarpha, as drug candidate: fraction absorbed prediction in humans and BCS permeability class determination.

BACKGROUND: Lychnophora trichocarpha (Spreng.) Spreng. ex Sch.Bip has been used in folk medicine to treat pain, inflammation, rheumatism and bruises. Eremantholide C, a sesquiterpene lactone, is one of the substances responsible for the anti-inflammatory and anti-hyperuricemic effects of L. trichocarpha. OBJECTIVES: Considering the potential to become a drug for the treatment of inflammation and gouty arthritis, this study evaluated the permeability of eremantholide C using in situ intestinal perfusion in rats. From the permeability data, it was possible to predict the fraction absorbed of eremantholide C in humans and elucidate its oral absorption process. METHODS: In situ intestinal perfusion studies were performed in the complete small intestine of rats using different concentrations of eremantholide C: 960 µg/ml, 96 µg/ml and 9.6 µg/ml (with and without sodium azide), in order to verify the lack of dependence on the measured permeability as a function of the substance concentration in the perfusion solutions. RESULTS: Eremantholide C showed Peff values, in rats, greater than 5 × 10-5 cm/s and fraction absorbed predicted for humans greater than 85%. These results indicated the high permeability for eremantholide C. Moreover, its permeation process occurs only by passive route, because there were no statistically significant differences between the Peff values for eremantholide C. CONCLUSION: The high permeability, in addition to the low solubility, indicated that eremantholide C is a biologically active substance BCS class II. The pharmacological activities, low toxicity and biopharmaceutics parameters demonstrate that eremantholide C has the necessary requirements for the development of a drug product, to be administered orally, with action on inflammation, hyperuricemia and gout.

Novel Insights to Enhance Therapeutics With Acyclovir in the Management of Herpes Simplex Encephalitis.

Acyclovir is an antiviral drug poorly absorbed in the gastrointestinal tract due to its hydrophilicity, with low oral bioavailability (~20%). Although acyclovir is prescribed in the management of herpes simplex encephalitis (HSE), the disease has a poor prognosis, particularly if the treatment is delayed, reaching mortality rates of 70% if left untreated. Thus, high acyclovir doses are administered by intravenous (IV) infusion, usually at a dosage of 10 mg kg-1 8-hourly in adults with normal renal function. However, the mortality related to HSE treated with acyclovir remains high (~20%) and permanent sequelae are commonly reported after 1 year (~50%). This review analyzed clinical trials following IV acyclovir administration. Novel insights aiming to improve drug bioavailability were reviewed, including acyclovir or its prodrugs, leading to the systemic distribution of the drug or drug targeting. Much research effort has been made to improve antiviral therapy, searching for delivery systems increasing acyclovir bioavailability by non-invasive pathways, such as oral and nasal pathways, or parenterally administered nanotechnology-based systems leading to drug targeting. Nanocarriers administered by non-invasive pathways represent feasible alternatives to treat HSE, even though not be industrially manufactured yet.

Machine learning and statistics to qualify environments through multi-traits in Coffea arabica.

Several factors such as genotype, environment, and post-harvest processing can affect the responses of important traits in the coffee production chain. Determining the influence of these factors is of great relevance, as they can be indicators of the characteristics of the coffee produced. The most efficient models choice to be applied should take into account the variety of information and the particularities of each biological material. This study was developed to evaluate statistical and machine learning models that would better discriminate environments through multi-traits of coffee genotypes and identify the main agronomic and beverage quality traits responsible for the variation of the environments. For that, 31 morpho-agronomic and post-harvest traits were evaluated, from field experiments installed in three municipalities in the Matas de Minas region, in the State of Minas Gerais, Brazil. Two types of post-harvest processing were evaluated: natural and pulped. The apparent error rate was estimated for each method. The Multilayer Perceptron and Radial Basis Function networks were able to discriminate the coffee samples in multi-environment more efficiently than the other methods, identifying differences in multi-traits responses according to the production sites and type of post-harvest processing. The local factors did not present specific traits that favored the severity of diseases and differentiated vegetative vigor. Sensory traits acidity and fragrance/aroma score also made little contribution to the discrimination process, indicating that acidity and fragrance/aroma are characteristic of coffee produced and all coffee samples evaluated are of the special type in the Mata of Minas region. The main traits responsible for the differentiation of production sites are plant height, fruit size, and bean production. The sensory trait "Body" is the main one to discriminate the form of post-harvest processing.

Biopharmaceutics considerations for direct oral anticoagulants.

Vitamin K antagonists (VKA) and direct oral anticoagulants (DOACs) have been clinically used in the treatment of coagulation disorders. There are four DOACs approved since 2010 (dabigatran etexilate, rivaroxaban, apixaban, and edoxaban), and they were designed to overcome the practical limitations of VKA. This review summarized biopharmaceutics considerations about DOACs, which are critically discussed, applying risk analyses to subside the further classification of these drugs according to the Biopharmaceutics Classification System (BCS). These discussions included data compiled about physicochemical properties, equilibrium solubility, permeability, and drug dissolution of DOACs. From the biopharmaceutics characteristics is possible to identify critical variables related to the absorption process, which can help in the design of new formulations. The data were compared with the criteria recommended by regulatory agencies for the biopharmaceutics classification according to the BCS. From that, these data may be used to discuss the approval of generic medicines by the BCS-based biowaiver, and the clinical risks arising from novel formulations with DOACs. However, although there are indications of biopharmaceutics classifications for DOACs, conclusive information to classify these compounds according to the BCS is lacking, requiring more experimental studies to achieve this aim. Conclusive information is essential for a safe decision about the biowaiver, as well as to guide the development of new formulations containing the DOACs.