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Tafenoquine (TQ) is a new 8-aminoquinoline antimalarial drug developed by the US Army for Plasmodium vivax malaria treatment. Modeling and simulation are essential tools for drug development and improving rationality in pharmacotherapy, and different modeling approaches are used. This study aims to summarize and explore the pharmacokinetic (PK) models available for tafenoquine in the literature. An integrative methodology was used to collect and review published data. Fifteen articles were identified using three modeling approaches: non-compartmental analysis (NCA), population pharmacokinetic analysis (popPK), and pharmacokinetic/pharmacodynamic analysis (PK/PD). An NCA was mainly used to describe the PK profile of TQ and to compare its PK profile alone to those obtained in association with other drugs. PopPK was used to assess TQ population PK parameters, covariates' impact, and dose selection. PK/PD helped understand the relationship between TQ concentrations, some adverse events common for 8-aminoquilones, and the efficacy assessment for Plasmodium falciparum. In summary, pharmacokinetic models were widely used during TQ development. However, there is still a need for different modeling approaches to support further therapeutic questions, such as treatment for special populations and potential drug-drug interactions.

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Yellow fever vaccine (YFV) is a live attenuated vaccine that can cause a mild infection in immunocompetent patients. However, it may not be self-limiting in patients with inborn errors of immunity (IEI) and may be the first and most severe presentation in these patients. A 10-month-old female infant sought emergency care presenting fever for three days and diffuse exanthema. She was a previous healthy child of consanguineous parents. The child had received YFV 28 days before the onset of symptoms. Upon hospital admission, petechial rash on the limbs and hepatosplenomegaly were noted on physical exam. Laboratory tests showed thrombocytopenia, increased serum aminotransferases and elevated gamma-glutamyl transferase (GGT) and alkaline phosphatase levels. During hospitalization she developed hypoactivity, drowsiness, and hypotonia. The possibility of viscerotropic and neurotropic vaccine associated disease was suspected and a possible primary immunodeficiency disease considered. The patient was tested for antibodies against the yellow fever virus (MAC ELISA) on serum and cerebrospinal fluid (CSF) samples, showing positive IgM results. Immunophenotyping showed low levels of lymphocytes and absence of T-cell receptor excision circles (TREC), leading to diagnose of severe combined immunodeficiency disease (SCID). Despite treatment, after 35 days of hospitalization, she evolved to cardiorespiratory arrest and death. Serious adverse events after administration of the YFV are rare and associated with neurological or visceral involvement in most cases. The unfavorable outcome highlights the importance of neonatal screening for SCID and the clinical suspicion of primary immunodeficiencies in infants who have serious adverse events to live virus vaccines.

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α-Bisabolol (α-BIS) is a sesquiterpene alcohol present in chamomile essential oil [Chamomilla recutita (L.) Rauschert]. Despite its numerous pharmacological effects, its pharmacokinetics remain understudied. An analytical method capable of quantifying α-BIS in plasma is crucial to enable pharmacokinetic analysis. Presently, only one study has quantified it using mass spectrometry. Administering α-BIS requires a nanoemulsion for intravenous injection. This study aimed to develop and validate a bioanalytical method using high-performance liquid chromatography with an ultraviolet detector to quantify α-BIS in rat plasma. The method employed acetonitrile and ultrapure water (80:20, v/v) as the mobile phase, with a flow rate of 1 ml/min and concentrations ranging from 465 to 29.625 µg/ml. All US Food and Drug Administration-designated assays were successful, indicating the method's precision, accuracy, sensitivity and linearity in determining α-BIS in rat plasma. The developed nanoemulsion, assessed through dynamic light scattering analysis, the ensemble collection of particles and polydispersity index evaluation, proved safe and effective for intravenous administration. The pharmacokinetic parameters such as volume of distribution, clearance and half-life indicated that α-BIS tends to persist in the body. This study provides a foundation for further research to explore α-BIS's potential pharmaceutical applications in the future.

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Phospholipases A2 (PLA2s) from snake venom possess antitumor and antiangiogenic properties. In this study, we evaluated the antimetastatic and antiangiogenic effects of MjTX-II, a Lys49 PLA2 isolated from Bothrops moojeni venom, on lung cancer and endothelial cells. Using in vitro and ex vivo approaches, we demonstrated that MjTX-II reduced cell proliferation and inhibited fundamental processes for lung cancer cells (A549) growth and metastasis, such as adhesion, migration, invasion, and actin cytoskeleton decrease, without significantly interfering with non-tumorigenic lung cells (BEAS-2B). Furthermore, MjTX-II caused cell cycle alterations, increased reactive oxygen species production, modulated the expression of pro- and antiangiogenic genes, and decreased vascular endothelial growth factor (VEGF) expression in HUVECs. Finally, MjTX-II inhibited ex vivo angiogenesis processes in an aortic ring model. Therefore, we conclude that MjTX-II exhibits antimetastatic and antiangiogenic effects in vitro and ex vivo and represents a molecule that hold promise as a pharmacological model for antitumor therapy.

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BACKGROUND: Eco-anxiety is increasingly recognized as a shared experience by many people internationally, encompassing fear of environmental catastrophe and anxiety about ecological crises. Despite its importance in the context of the changing climate, measures for this construct are still being developed in languages other than English. METHODS: To contribute to global eco-anxiety research, we translated the Hogg Eco-Anxiety Scale (HEAS) into Spanish, creating the HEAS-SP. We validated this measure in samples from both Argentina (n = 990) and Spain (n = 548), performing measurement invariance and confirmatory factor analyses. Internal consistency of the scale and score stability over time were investigated through reliability analyses. Differences in eco-anxiety across sociodemographic variables were explored through Student's t-tests and Pearson's r tests. RESULTS: The four-factor model of the HEAS-SP comprising affective and behavioural symptoms, rumination, and anxiety about personal impact demonstrated excellent model fit. We found good internal consistency for each subscale, and established measurement invariance between Spanish and Argentine samples, as well as across genders and participants' age. Spanish participants reported higher scores on the affective symptoms and personal impact anxiety factors compared to the Argentinian sample. Also, men reported lower levels than women on the subscales of affective symptoms, rumination, and personal impact anxiety. It was found that the relationship between both age and personal impact anxiety and age and affective symptoms varies significantly depending on the gender of the individuals. Younger participants tended to report higher scores on most dimensions of eco-anxiety. CONCLUSIONS: These findings enhance the global initiative to investigate, explore and therefore comprehend eco-anxiety by introducing the first valid and reliable Spanish-language version of this psychometric instrument for its use within Spanish and Argentinian populations. This study augments the body of evidence supporting the robust psychometric properties of the HEAS, as demonstrated in prior validations for Australian, Turkish, Portuguese, German, French, and Italian populations.

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OBJECTIVE: To evaluate the association between Doppler patterns in fetuses with Down syndrome (DS) and their placental histopathologic findings. METHODS: A retrospective cross-sectional study was performed by collecting data from medical records of singleton pregnancies between January 2014 and January 2022, whose fetuses had a confirmed diagnosis of DS either prenatally or postnatally. Placental histopathology, maternal characteristics, and prenatal ultrasound (biometric parameters and umbilical artery [UA] Doppler) were evaluated. RESULTS: Of 69 eligible pregnant women, 61 met the inclusion and exclusion criteria. In the sample, 15 fetuses had an estimated fetal weight < 10th percentile for gestational age (GA) and were considered small for gestational age (SGA). Thirty-eight fetuses had increased resistance on the UA Doppler. Histologic changes were detected in 100% of the placentas, the most common being delayed villous maturation, alterations associated with poor fetal vascular perfusion, and villous dysmorphism. More than 50% of the placentas showed alterations related to placental insufficiency. We did not observe a statistically significant association between UA Doppler examination and placental alterations. All placentas analyzed in the SGA subgroup showed findings compatible with placental insufficiency. CONCLUSION: We found no statistically significant association between placental histopathologic findings and UA Doppler abnormalities in fetuses with DS. The placental alterations identified were delayed villous maturation, alterations associated with poor fetal vascular perfusion, and villous dysmorphism.

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INTRODUÇÃO: A reoperação para tratamento de Insuficiência Tricúspide (IT) importante funcional isolada está associada à alta morbimortalidade. Considerando este cenário, esforços são direcionados para pesquisas envolvendo tratamento por via percutânea da valva tricúspide em pacientes de alto risco cirúrgico. Uma das soluções propostas é o TricValve®, dispositivo composto por valvas autoexpansíveis implantadas na veia cava superior e inferior, com o objetivo de reduzir a congestão venosa sistêmica e melhorar a qualidade de vida. MATERIAL E MÉTODO: Estudo prospectivo, observacional, unicêntrico, realizado entre 2022 e 2024. Critérios de inclusão: pacientes com IT importante, funcional, com insuficiência cardíaca direita refratária ao tratamento medicamentoso otimizado e sem indicação de intervenção do lado esquerdo do coração. CRITÉRIOS DE EXCLUSÃO: disfunção grave do ventrículo direito (VD) e pressão de artéria pulmonar ≥ 65mmHg. Os pacientes foram avaliados com ecocardiograma transtorácico e tomografia computadorizada. O implante do TricValve® foi realizado por veia femoral, com o dispositivo implantado nas veias cava inferior e superior, sob anestesia geral e monitorização com ecocardiograma transesofágico e fluoroscopia. RESULTADOS: Foram incluídos cinco pacientes, três mulheres e dois homens, com idade entre 59 e 79 anos, um deles com prótese mitral, dois mitroaórticos e dois transplantados do coração. Ocorreu uma complicação imediata: paralisia do nervo frênico direito confirmado por exame de imagem. Não houve mortalidade hospitalar. No seguimento médio de 15 meses (8 a 20 meses) todos os pacientes estão vivos e em quatro deles (80%) houve melhora importante da classe funcional (NYHA de III para I). O grau da IT manteve-se importante em todos os casos, houve melhora da função ventricular direita em dois pacientes (FAC de 29% para 37% e de 31% para 35%) e remodelamento do átrio direito em um paciente. CONCLUSÃO: Em um seguimento médio de 15 meses, o implante de TricValve® dedicado à IT funcional grave foi seguro e efetivo em melhorar a classe funcional dos pacientes. A melhora da função ventricular direita foi observada em metade dos casos.

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Angiogenesis is a process that is controlled by a delicate combination of proangiogenic and antiangiogenic molecules and can be disrupted in various illnesses, including cancer. Non-cancerous diseases can also have an abnormal or insufficient vascular growth, inflammation and hypoxia, which exacerbate angiogenesis. These conditions include atherosclerosis, psoriasis, endometriosis, asthma, obesity and AIDS. Based on that, the present work assessed the in vitro and ex vivo antiangiogenic properties stemming from BthMP, a P-I metalloproteinase from Bothrops moojeni snake venom, via the VEGF pathway. BthMP at a concentration of 5 and 40 µg/mL showed no toxicity to endothelial cells (HUVEC) in the MTT assay and was not able to induce necrosis and colony proliferation. Interestingly, BthMP inhibited adhesion, migration and invasion of HUVECs in Matrigel and arrested in vitro angiogenesis by reducing the average number of nodules in toxin-treated cells by 9.6 and 17.32 at 5 and 40 µg/mL, respectively, and the number of tubules by 15.9 at 5 µg/mL and 21.6 at 40 µg/mL in a VEGF-dependent way, an essential proangiogenic property. Furthermore, BthMP inhibited the occurrence of the angiogenic process in an ex vivo aortic ring test by decreasing new vessel formation by 52% at 5 µg/mL and by 66% at 40 µg/mL and by increasing the expression of an antiangiogenic gene, SFLT-1, and decreasing the expression of the proangiogenic genes VEGFA and ANGPT-1. Finally, this toxin reduces the production of nitric oxide, a marker that promotes angiogenesis and VEGF modulation, and decreases the protein expression of VEGFA in the supernatant of the HUVEC culture by about 30 %. These results suggest that BthMP has a promising antiangiogenic property and proves to be a biotechnological mechanism for understanding the antiangiogenic responses induced by snake venom metalloproteinases, which could be applied to a variety of diseases that exhibit an imbalance of angiogenesis mechanisms.

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ABSTRACT Yellow fever vaccine (YFV) is a live attenuated vaccine that can cause a mild infection in immunocompetent patients. However, it may not be self-limiting in patients with inborn errors of immunity (IEI) and may be the first and most severe presentation in these patients. A 10-month-old female infant sought emergency care presenting fever for three days and diffuse exanthema. She was a previous healthy child of consanguineous parents. The child had received YFV 28 days before the onset of symptoms. Upon hospital admission, petechial rash on the limbs and hepatosplenomegaly were noted on physical exam. Laboratory tests showed thrombocytopenia, increased serum aminotransferases and elevated gamma-glutamyl transferase (GGT) and alkaline phosphatase levels. During hospitalization she developed hypoactivity, drowsiness, and hypotonia. The possibility of viscerotropic and neurotropic vaccine associated disease was suspected and a possible primary immunodeficiency disease considered. The patient was tested for antibodies against the yellow fever virus (MAC ELISA) on serum and cerebrospinal fluid (CSF) samples, showing positive IgM results. Immunophenotyping showed low levels of lymphocytes and absence of T-cell receptor excision circles (TREC), leading to diagnose of severe combined immunodeficiency disease (SCID). Despite treatment, after 35 days of hospitalization, she evolved to cardiorespiratory arrest and death. Serious adverse events after administration of the YFV are rare and associated with neurological or visceral involvement in most cases. The unfavorable outcome highlights the importance of neonatal screening for SCID and the clinical suspicion of primary immunodeficiencies in infants who have serious adverse events to live virus vaccines.

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Phospholipases A2 (PLA2s) from snake venom possess antitumor and antiangiogenic properties. In this study, we evaluated the antimetastatic and antiangiogenic effects of MjTX-II, a Lys49 PLA2 isolated from Bothrops moojeni venom, on lung cancer and endothelial cells. Using in vitro and ex vivo approaches, we demonstrated that MjTX-II reduced cell proliferation and inhibited fundamental processes for lung cancer cells (A549) growth and metastasis, such as adhesion, migration, invasion, and actin cytoskeleton decrease, without significantly interfering with non-tumorigenic lung cells (BEAS-2B). Furthermore, MjTX-II caused cell cycle alterations, increased reactive oxygen species production, modulated the expression of pro- and antiangiogenic genes, and decreased vascular endothelial growth factor (VEGF) expression in HUVECs. Finally, MjTX-II inhibited ex vivo angiogenesis processes in an aortic ring model. Therefore, we conclude that MjTX-II exhibits antimetastatic and antiangiogenic effects in vitro and ex vivo and represents a molecule that hold promise as a pharmacological model for antitumor therapy.

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Angiogenesis is a process that is controlled by a delicate combination of proangiogenic and antiangiogenic molecules and can be disrupted in various illnesses, including cancer. Non-cancerous diseases can also have an abnormal or insufficient vascular growth, inflammation and hypoxia, which exacerbate angiogenesis. These conditions include atherosclerosis, psoriasis, endometriosis, asthma, obesity and AIDS. Based on that, the present work assessed the in vitro and ex vivo antiangiogenic properties stemming from BthMP, a P–I metalloproteinase from Bothrops moojeni snake venom, via the VEGF pathway. BthMP at a concentration of 5 and 40 μg/mL showed no toxicity to endothelial cells (HUVEC) in the MTT assay and was not able to induce necrosis and colony proliferation. Interestingly, BthMP inhibited adhesion, migration and invasion of HUVECs in Matrigel and arrested in vitro angiogenesis by reducing the average number of nodules in toxin-treated cells by 9.6 and 17.32 at 5 and 40 μg/mL, respectively, and the number of tubules by 15.9 at 5 μg/mL and 21.6 at 40 μg/mL in a VEGF-dependent way, an essential proangiogenic property. Furthermore, BthMP inhibited the occurrence of the angiogenic process in an ex vivo aortic ring test by decreasing new vessel formation by 52% at 5 μg/mL and by 66% at 40 μg/mL and by increasing the expression of an antiangiogenic gene, SFLT-1, and decreasing the expression of the proangiogenic genes VEGFA and ANGPT-1. Finally, this toxin reduces the production of nitric oxide, a marker that promotes angiogenesis and VEGF modulation, and decreases the protein expression of VEGFA in the supernatant of the HUVEC culture by about 30 %. These results suggest that BthMP has a promising antiangiogenic property and proves to be a biotechnological mechanism for understanding the antiangiogenic responses induced by snake venom metalloproteinases, which could be applied to a variety of diseases that exhibit an imbalance of angiogenesis mechanisms.

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Abstract: The COVID-19 pandemic significantly affected the quality of life of older Brazilian adults. This study aimed to investigate the level of loneliness and social support of older adults during the COVID-19 pandemic and its relation with cognitive reserve, sociodemographic data, daily habits, and perceived health. An online cross-sectional study was conducted. The final sample consisted of 116 Brazilians aged over 60 years. The following instruments were used: sociodemographic questionnaire, questionnaire on the everyday habits during the pandemic, CRIq, Revised UCLA Loneliness Scale and MOS-SSS. The results showed a significant association between loneliness and social support. The regression models demonstrate the influence of perceived health and different forms of social contact in predicting social support and loneliness. These results evince the importance of the evaluation of factors related to the quality of life of older Brazilian adults during and after the COVID-19 pandemic.

Resumo: A pandemia da COVID-19 afetou significativamente a qualidade de vida das pessoas idosas brasileiras. O objetivo deste estudo foi analisar o nível de apoio social e de solidão de pessoas idosas durante a pandemia do COVID-19 e sua relação com variáveis como a reserva cognitiva, dados sociodemográficos, hábitos diários e a saúde percebida. Foi conduzido um estudo transversal, online, com uma amostra de 116 brasileiros com mais de 60 anos. Os seguintes instrumentos foram aplicados: Questionário sociodemográfico, Questionário sobre hábitos na pandemia, CRIq, Revised UCLA Loneliness Scale e MOS-SSS . Foi observada uma associação significativa entre a solidão e o apoio social. Os modelos de regressão demonstram a influência da percepção da saúde, e de diferentes meios de comunicação na predição do apoio social e da solidão. Os resultados apresentados demonstram a importância de avaliar fatores psicossociais relacionados à qualidade de vida das pessoas idosas brasileiras durante e após a pandemia de COVID-19.

Resumen: La pandemia del COVID-19 ha afectado significativamente a la calidad de vida de los adultos mayores brasileños. El objetivo de este estudio fue investigar el nivel de apoyo social y la soledad en los adultos mayores durante la pandemia del covid-19 y su relación con las variables como reserva cognitiva, datos sociodemográficos, hábitos diarios y salud percibida. Se realizó un estudio transversal en línea con una muestra de 116 participantes con más de 60 años de edad. Se utilizaron los instrumentos: Cuestionario sociodemográfico, cuestionario sobre hábitos en la pandemia, CRIq , Revised UCLA Loneliness Scale y MOS-SSS . Se encontró una correlación significativa entre la soledad y el apoyo social. Los modelos de regresión encontrados demuestran la influencia de la percepción del estado de salud y de diferentes medios en la predicción del apoyo social y la soledad. Los resultados presentados muestran la importancia de evaluar los factores psicosociales relacionados con la calidad de vida de los adultos mayores brasileños durante y después de la pandemia del COVID-19.

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BACKGROUND: Leishmaniasis, a neglected disease caused by the parasite Leishmania, is treated with drugs associated with high toxicity and limited efficacy, in addition to constant reports of the emergence of resistant parasites. In this context, snake serums emerge as good candidates since they are natural sources with the potential to yield novel drugs. OBJECTIVES: We aimed to show the antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, against Leishmania (Leishmania) amazonensis. METHODS: Promastigotes forms were exposed to γCdcPLI, and we assessed the parasite viability and cell cycle, as well as invasion and proliferation assays. FINDINGS: Despite the low cytotoxicity effect on macrophages, our data indicate that γCdcPLI has a direct effect on parasites promoting an arrest in the G1 phase and reduction in the G2/M phase at the highest dose tested. Moreover, this PLA2 inhibitor reduced the parasite infectivity when promastigotes were pre-treated. Also, we demonstrated that the γCdcPLI treatment modulated the host cell environment impairing early and late steps of the parasitism. MAIN CONCLUSIONS: γCdcPLI is an interesting tool for the discovery of new essential targets on the parasite, as well as an alternative compound to improve the effectiveness of the leishmaniasis treatment.

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BACKGROUND: Shift work is related to several negative impacts on the health of workers. This study aimed to evaluate the association between vitamin D deficiency (VDD) and hyperglycemia in shift workers. METHODOLOGY: This cross-sectional study included male rotating shift workers in an iron ore extraction company. Participants were classified as VDD when 25(OH)D < 20 ng/mL for a healthy population and 25(OH)D < 30 ng/mL for groups at risk for VDD. Hyperglycemia was classified when fasting glucose ≥100 mg/dL or HbA1c ≥ 5.7%. Data were compared using chi-square analysis with Cramer's V as effect size, and Bonferroni correction. Multivariate logistic regression, from a model of determination, was performed to investigate whether VDD was associated with hyperglycemia. RESULTS: The study evaluated 1411 workers, most workers were aged 30-39 years (53.2%), and 77.5% self-declared as black, brown, with up to complete high school (71.4%) and working alternate shifts for more than 5 years (76.1%). Regarding glucose and vitamin D, 32.0% and 29.1% of the workers had hyperglycemia and VDD, respectively. In multivariate analysis, controlled for confounding factors, workers with VDD had a 119% increased chance of hyperglycemia (OR: 2.19; IC95%: 1.56-3.08). Furthermore, vitamin D levels in distribution quintiles showed a dose-response gradient in relation to hyperglycemia, where increased vitamin D values were associated with a reduction in the occurrence of hyperglycemia. CONCLUSION: Rotating shift workers with vitamin D deficiency are more likely to have hyperglycemia.

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A pioneering study regarding the isolation, biochemical evaluation, functional assays and first PEGylation report of a novel vascular endothelial growth factor from Crotalus durissus terrificus venom (CdtVEGF and PEG-CdtVEGF). CdtVEGF was isolated from crude venom using two different chromatographic steps, representing 2% of soluble venom proteins. Its primary sequence was determined using mass spectrometry analysis, and the molecule demonstrated no affinity to heparin. The Brazilian crotalid antivenom recognized CdtVEGF. Both native and PEGylated CdtVEGF were able to induce new vessel formation and migration, and to increase the metabolic activity of human umbilical endothelial vascular cells (HUVEC), resulting in better wound closure (~50% within 12 h) using the native form. CdtVEGF induced leukocyte recruitment to the peritoneal cavity in mice, with a predominance of neutrophil influx followed by lymphocytes, demonstrating the ability to activate the immune system. The molecule also induced a dose-dependent increase in vascular permeability, and PEG-CdtVEGF showed less in vivo inflammatory activity than CdtVEGF. By unraveling the intricate properties of minor components of snake venom like svVEGF, this study illuminates the indispensable significance of exploring these molecular tools to unveil physiological and pathological processes, elucidates the mechanisms of snakebite envenomings, and could possibly be used to design a therapeutic drug.

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OBJECTIVE: To identify and describe the mental health training programs for non-health professionals and volunteers who work, have worked, or would work with asylum seekers and/or refugees. METHOD: Scoping review following JBI methodology. Search carried out in MEDLINE, CINAHL, ERIC, SCOPUS, PsycINFO, Psychology & Behavioral Sciences Collection, RCAAP, ProQuest, and websites of Clinical Trials, UNHCR, International Organization for Migration, WHO, Save the Children, International Migration, Integration and Social Cohesion in Europe, and International Federation of Red Cross and Red Crescent Societies. Studies written in English, Portuguese, French, Spanish and Swedish. RESULTS: Of the 8954 articles identified, 16 were included reporting on 11 training programs: Mind-Spring, PM+, MHFA, Cognitive-Behavioral Training for Community and Religious Leaders, EmpaTeach, Suicide Prevention Education Program, Teaching Recovery Techniques, Handbook for Teachers of Vietnamese Refugee Students, PFA, Psychosocial support of volunteers and CBP&MHPSS. CONCLUSION: Training programs from scientific literature focus on mental health disorders, while non-governmental organizations' documents focus on resilience and self-care. The current mental health training programs might be insufficient.

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ABSTRACT Objective: To identify and describe the mental health training programs for non-health professionals and volunteers who work, have worked, or would work with asylum seekers and/or refugees. Method: Scoping review following JBI methodology. Search carried out in MEDLINE, CINAHL, ERIC, SCOPUS, PsycINFO, Psychology & Behavioral Sciences Collection, RCAAP, ProQuest, and websites of Clinical Trials, UNHCR, International Organization for Migration, WHO, Save the Children, International Migration, Integration and Social Cohesion in Europe, and International Federation of Red Cross and Red Crescent Societies. Studies written in English, Portuguese, French, Spanish and Swedish. Results: Of the 8954 articles identified, 16 were included reporting on 11 training programs: Mind-Spring, PM+, MHFA, Cognitive-Behavioral Training for Community and Religious Leaders, EmpaTeach, Suicide Prevention Education Program, Teaching Recovery Techniques, Handbook for Teachers of Vietnamese Refugee Students, PFA, Psychosocial support of volunteers and CBP&MHPSS. Conclusion: Training programs from scientific literature focus on mental health disorders, while non-governmental organizations' documents focus on resilience and self-care. The current mental health training programs might be insufficient.

RESUMEN Objetivo: Identificar y describir los programas de formación en salud mental para profesionales no sanitarios y voluntarios que trabajan, han trabajado o gustarían de trabajar con solicitantes de asilo y/o refugiados. Método: Revisión de alcance según la metodología JBI. Búsqueda realizada en MEDLINE, CINAHL, ERIC, SCOPUS, PsycINFO, Psychology & Behavioral Sciences Collection, RCAAP, ProQuest, y sitios web de ClinicalTrials, ACNUR, Organización Internacional para las Migraciones, OMS, Save the Children, Migración Internacional, Integración y Cohesión Social en Europa, y Federación Internacional de Sociedades de la Cruz Roja y de la Media Luna Roja. Estudios escritos en inglés, portugués, francés, español y sueco. Resultados: De los 8954 artículos identificados, se incluyeron 16 que informan sobre 11 programas de capacitación: Mind-Spring, PM+, MHFA, Capacitación cognitiva conductual para líderes comunitarios y religiosos, EmpaTeach, Programa de educación para la prevención del suicidio, Enseñanza de técnicas de recuperación, Manual para maestros de Estudiantes refugiados vietnamitas, PFA, apoyo psicosocial de voluntarios y CBP&MHPSS. Conclusión: Los programas de formación en la literatura científica se centran en los trastornos de salud mental, mientras que los documentos de las organizaciones no gubernamentales se centran en la resiliencia y el autocuidado. Los actuales programas de formación en salud mental pueden ser insuficientes.

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BACKGROUND Leishmaniasis, a neglected disease caused by the parasite Leishmania, is treated with drugs associated with high toxicity and limited efficacy, in addition to constant reports of the emergence of resistant parasites. In this context, snake serums emerge as good candidates since they are natural sources with the potential to yield novel drugs. OBJECTIVES We aimed to show the antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, against Leishmania (Leishmania) amazonensis. METHODS Promastigotes forms were exposed to γCdcPLI, and we assessed the parasite viability and cell cycle, as well as invasion and proliferation assays. FINDINGS Despite the low cytotoxicity effect on macrophages, our data indicate that γCdcPLI has a direct effect on parasites promoting an arrest in the G1 phase and reduction in the G2/M phase at the highest dose tested. Moreover, this PLA2 inhibitor reduced the parasite infectivity when promastigotes were pre-treated. Also, we demonstrated that the γCdcPLI treatment modulated the host cell environment impairing early and late steps of the parasitism. MAIN CONCLUSIONS γCdcPLI is an interesting tool for the discovery of new essential targets on the parasite, as well as an alternative compound to improve the effectiveness of the leishmaniasis treatment.

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BACKGROUND & AIM: Liver transplantation (LT) selection models for hepatocellular carcinoma (HCC) have not been proposed to predict waitlist dropout because of tumour progression. The aim of this study was to compare the alpha-foetoprotein (AFP) model and other pre-LT models in their prediction of HCC dropout. METHODS: A multicentre cohort study was conducted in 20 Latin American transplant centres, including 994 listed patients for LT with HCC from 2012 to 2018. Longitudinal tumour characteristics, and patterns of progression were recorded at time of listing, after treatments and at last follow-up over the waitlist period. Competing risk regression models were performed, and model's discrimination was compared estimating Harrell's adapted c-statistics. RESULTS: HCC dropout rate was significantly higher in patients beyond (24% [95% CI 16-28]) compared to those within Milan criteria (8% [95% IC 5%-12%]; p < .0001), with a SHR of 3.01 [95% CI 2.03-4.47]), adjusted for waiting list time and bridging therapies (c-index 0.63 [95% CI 0.57; 0.69). HCC dropout rates were higher in patients with AFP scores >2 (adjusted SHR of 3.17 [CI 2.13-4.71]), c-index of 0.71 (95% CI 0.65-0.77; p = .09 vs Milan). Similar discrimination power for HCC dropout was observed between the AFP score and the Metroticket 2.0 model. In patients within Milan, an AFP score >2 points discriminated two populations with a higher risk of HCC dropout (SHR 1.68 [95% CI 1.08-2.61]). CONCLUSIONS: Pre-transplant selection models similarly predicted HCC dropout. However, the AFP model can discriminate a higher risk of dropout among patients within Milan criteria.

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RESUMO Objetivo analisar a assistência de Enfermagem ao usuário de substâncias psicoativas na Estratégia Saúde da Família. Método estudo descritivo e qualitativo realizado com sete enfermeiros da Estratégia Saúde da Família de Juiz de Fora, Minas Gerais. Os dados foram obtidos por meio de entrevistas guiadas por um roteiro semiestruturado e a Análise Temática de Conteúdo foi utilizada para o seu tratamento. Resultados a assistência prestada pelos entrevistados é pautada na demanda espontânea, sem estratégias de busca ativa, com a valorização de práticas orientadas pela medicalização da pessoa e o encaminhamento aos serviços especializados. A inclusão da família no processo de reabilitação, o atendimento imediato e o exercício da escuta terapêutica foram mencionados como estratégias que podem ser adotadas para uma assistência integral. Os desafios mencionados referiram-se à falta de formação em saúde mental, à fragmentação do conhecimento acerca da especialidade, à ausência de capacitações e ao desejo do paciente em participar do tratamento. Considerações finais e implicações para a prática os enfermeiros referiram um cuidado insuficiente para a garantia da integralidade da assistência permeado pela falta de conhecimentos e habilidades para lidar com esse público, o que leva ao encaminhamento para serviços especializados como principal intervenção, reforçando a necessidade de capacitação desses profissionais.

RESUMEN Objetivo analizar la atención de Enfermería a usuarios de sustancias psicoactivas en la Estrategia Salud de la Familia. Método estudio descriptivo y cualitativo realizado con siete enfermeros de la Estrategia Salud de la Familia en Juiz de Fora, Minas Gerais. Los datos fueron obtenidos a través de entrevistas guiadas por un guion semiestructurado y se utilizó el Análisis de Contenido Temático para su tratamiento. Resultados la asistencia proporcionada por los entrevistados se basa en la demanda espontánea, sin estrategias de búsqueda activa, con la valoración de prácticas guiadas por la medicalización de la persona y la derivación a servicios especializados. La inclusión de la familia en el proceso de rehabilitación, la atención inmediata y el ejercicio de la escucha terapéutica fueron mencionadas como estrategias que pueden ser adoptadas para la atención integral. Los desafíos mencionados se refirieron a la falta de formación en salud mental, la fragmentación del conocimiento sobre la especialidad, la falta de formación y el deseo del paciente de participar en el tratamiento. Consideraciones finales e implicaciones para la práctica los enfermeros mencionaron cuidados insuficientes para garantizar una atención integral permeada por la falta de conocimientos y habilidades para el trato con este público, lo que lleva a la derivación a servicios especializados como principal intervención, reforzando la necesidad de formación de estos profesionales.

ABSTRACT Objective to analyze the nursing care provided to users of psychoactive substances in the Family Health Strategy. Method a descriptive and qualitative study carried out with seven nurses from the Family Health Strategy of Juiz de Fora, Minas Gerais. Data was obtained through interviews guided by a semi-structured script and the Thematic Content Analysis was used for its treatment. Results the care provided by the interviewees is based on spontaneous demand, without active search strategies, with the valorization of practices guided by the medicalization of the person and the referral to specialized services. The inclusion of the family in the rehabilitation process, immediate care, and therapeutic listening were mentioned as strategies that can be adopted for an integral assistance. The challenges mentioned referred to the lack of training in mental health, the fragmentation of knowledge about the specialty, the absence of training, and the patient's desire to participate in the treatment. Final considerations and implications for the practice the nurses reported insufficient care to ensure comprehensive care permeated by a lack of knowledge and skills to deal with this public, which leads to referral to specialized services as the main intervention, reinforcing the need to train these professionals.

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