Unbalanced relationships: insights into the interaction between gut microbiota, geohelminths, and schistosomiasis

Hosts and their microbiota and parasites have co-evolved in an adaptative relationship since ancient times. The interaction between parasites and intestinal bacteria in terms of the hosts’ health is currently a subject of great research interest. Therapeutic interventions can include manipulations of the structure of the intestinal microbiota, which have immunological interactions important for modulating the host’s immune system and for reducing inflammation. Most helminths are intestinal parasites; the intestinal environment provides complex interactions with other microorganisms in which internal and external factors can influence the composition of the intestinal microbiota. Moreover, helminths and intestinal microorganisms can modulate the host’s immune system either beneficially or harmfully. The immune response can be reduced due to co-infection, and bacteria from the intestinal microbiota can translocate to other organs. In this way, the treatment can be compromised, which, together with drug resistance by the parasites makes healing even more difficult. Thus, this work aimed to understand interactions between the microbiota and parasitic diseases caused by the most important geohelminths and schistosomiasis and the consequences of these associations

First Evidence of Bovine Viral Diarrhea Virus Infection in Wild Boars

Background: The farming of wild boars has growing due to the interest of the human consumption of this exotic meat. Such a development may pose an increased risk of disease transmission between boars and domestic animals. The wild boar population has increased in South America in the last years due the absence of predator causing economic losses due to direct damage to crops and risk of disease transmission. The genus Pestivirus within the family Flaviviridae are composed by four recognized species by the International Committee on the Taxonomy of Viruses (ICTV): classical swine fever virus (CSFV), border disease virus (BDV), bovine viral diarrhea virus type 1 (BVDV-1) and 2 (BVDV-2). Other putative species denoted as atypical pesitiviruses have been reported as ‘HoBi’-like virus, giraffe pestivirus, Bungowannah pestivirus, Pronghorn antelope virus, atypical porcine pestivirus (APPV), Norwegian rat pestivirus (NrPV) and Rhinolophus affinis bat pestivirus (RaPestV-1). CSFV is commonly detected in wild boars, but despite positive serology, bovine viral diarrhea virus (BVDV) was never detected in this animal species. Thereby, the present communication describes the first detection of BVDV in the lungs of captive boars using RT-PCR and DNA sequencing.Materials, Methods & Results: Forty lung samples from farmed wild boars were collected after slaughter in a commercial abattoir. The organs were crushed separately, centrifuged, and the supernatant was stored for further analysis. The total RNA was isolated using a phenol-based protocol and RT-PCR protocol that amplified 118 bp of 5’ untranslated region (5’UTR) was carried out. One out 40 samples resulted positive. The positive sample had partial fragments of 5’UTR and N terminal autoprotease (Npro) sequenced and analyzed. The strain LV Java/2012 presented 99% of identity in 5’UTR and 98% in Npro region with a BVDV-2 previously reported in bovines in Southern Brazil. In both 5’UTR and Npro phylogenetic analysis, the strain LV Java/2015 clustered with BVDV-2 strains and was most closely related to subtype 2b identified in bovines in Southern Brazil grouping in the same terminal node.Discussion: Wild boars are commonly associated to pathogen transmission to domestic animals. This animal species is considered a reservoir of the pestivirus CSFV and important keys in CSFV control and eradication programs in Europe. Despite indirect presence of BVDV was reported in wild boars by serology tests, the direct detection of the viral agent was never reported. The present study showed the presence of BVDV-2 genomic segments obtained by RT-PCR followed by DNA sequencing in captive wild boars. The reported data suggests a possible importance of this animal species in the epidemiology of ruminant pestiviruses which could interfere in control and eradication programs of these important pathogens for cattle worldwide. The strain LV Java/2012 was closely related to BVDV-2b and presented highest identity with a strain detected in cattle from Southern Brazil. This data suggests that wild boars and bovines could be sharing this pathogen due the similarity of the strains and that both were reported in the same region. It can lead to need of inclusion of wild swines in BVDV control programs since boars can circulate between different regions and carry this pathogen to different cattle herds. The present study reported the first molecular evidence of BVDV in wild boars in the literature. The data generated herein suggests a possible importance of boars in the epidemiology of ruminant pestiviruses

Usefulness of Environmental DNA for Surveillance and Control of Schistosomiasis: Detection and Tracking Schistosoma mansoni and Its Intermediate Host Biomphalaria glabrata in Low Endemic Areas of Minas Gerais, Brazil

Poster Session

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

First Evidence of Bovine Viral Diarrhea Virus Infection in Wild Boars

Background: The farming of wild boars has growing due to the interest of the human consumption of this exotic meat. Such a development may pose an increased risk of disease transmission between boars and domestic animals. The wild boar population has increased in South America in the last years due the absence of predator causing economic losses due to direct damage to crops and risk of disease transmission. The genus Pestivirus within the family Flaviviridae are composed by four recognized species by the International Committee on the Taxonomy of Viruses (ICTV): classical swine fever virus (CSFV), border disease virus (BDV), bovine viral diarrhea virus type 1 (BVDV-1) and 2 (BVDV-2). Other putative species denoted as atypical pesitiviruses have been reported as ‘HoBi’-like virus, giraffe pestivirus, Bungowannah pestivirus, Pronghorn antelope virus, atypical porcine pestivirus (APPV), Norwegian rat pestivirus (NrPV) and Rhinolophus affinis bat pestivirus (RaPestV-1). CSFV is commonly detected in wild boars, but despite positive serology, bovine viral diarrhea virus (BVDV) was never detected in this animal species. Thereby, the present communication describes the first detection of BVDV in the lungs of captive boars using RT-PCR and DNA sequencing.Materials, Methods & Results: Forty lung samples from farmed wild boars were collected after slaughter in a commercial abattoir. The organs were crushed separately, centrifuged, and the supernatant was stored for further analysis. The total RNA was isolated using a phenol-based protocol and RT-PCR protocol that amplified 118 bp of 5’ untranslated region (5’UTR) was carried out. One out 40 samples resulted positive. The positive sample had partial fragments of 5’UTR and N terminal autoprotease (Npro) sequenced and analyzed. The strain LV Java/2012 presented 99% of identity in 5’UTR and 98% in Npro region with a BVDV-2 previously reported in bovines in Southern Brazil. In both 5’UTR and Npro phylogenetic analysis, the strain LV Java/2015 clustered with BVDV-2 strains and was most closely related to subtype 2b identified in bovines in Southern Brazil grouping in the same terminal node.Discussion: Wild boars are commonly associated to pathogen transmission to domestic animals. This animal species is considered a reservoir of the pestivirus CSFV and important keys in CSFV control and eradication programs in Europe. Despite indirect presence of BVDV was reported in wild boars by serology tests, the direct detection of the viral agent was never reported. The present study showed the presence of BVDV-2 genomic segments obtained by RT-PCR followed by DNA sequencing in captive wild boars. The reported data suggests a possible importance of this animal species in the epidemiology of ruminant pestiviruses which could interfere in control and eradication programs of these important pathogens for cattle worldwide. The strain LV Java/2012 was closely related to BVDV-2b and presented highest identity with a strain detected in cattle from Southern Brazil. This data suggests that wild boars and bovines could be sharing this pathogen due the similarity of the strains and that both were reported in the same region. It can lead to need of inclusion of wild swines in BVDV control programs since boars can circulate between different regions and carry this pathogen to different cattle herds. The present study reported the first molecular evidence of BVDV in wild boars in the literature. The data generated herein suggests a possible importance of boars in the epidemiology of ruminant pestiviruses

Bacaba, Pracaxi and Uxi oils for therapeutic purposes: A scoping review

Millena de Sousa Afonsoa*, Luis Phillipe Nagem Lopesb, Matheus Meirelles Ferreirac, Rayssa Arrais da Cruz Ribeiroc, Luana dos Santos Monteiroc, Ana Paula dos Santos Matosd, Mariana Sato de Souza Bustamante Monteiroa, Eduardo Ricci Júniora, Elisabete Pereira dos Santosa, Letícia Coli Louvisse de Abreue, Zaida Maria Faria de Freitasa aGraduate Program in Pharmaceutical Science and Technology, Pharmacy School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. bGraduate Program in Pharmaceutical Sciences, Sorocaba University, São Paulo, Brazil. cPharmacy School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. dInstitute of Technology in Pharmaceuticals, Farmanguinhos, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. eFederal Institute of Education, Science and Technology of Rio de Janeiro, Rio de Janeiro, Brazil Abstract Fruits such as bacaba (Oenocarpus bacaba Mart), pracaxi (Pentaclethra macroloba Kuntze) and uxi (Endopleura uchi (Huber) Cuatrec), from the Amazon rainforest, are potentially interesting for studies of natural products. The current article aims at mapping and characterizing studies on the bacaba, pracaxi and uxi species. This review reports the main bioactive compounds identified in these species and discusses their therapeutic potential. Searches were performed in MEDLINE (Via Pubmed) and Web of Science. Thirty-one studies that described or evaluated the development of formulations aimed at the therapeutic use of the species were included. The findings suggest that species have the potential for the development of pharmaceutical formulations due to their therapeutic properties. However, further studies are required to assess safety and efficacy of these products. Therefore, it is suggested that new research studies propose strategies so that technological development is based on awareness and preservation of the biome. Keywords: Oenocarpus bacaba Mart. Pentaclethra macroloba Kuntze. Endopleura uchi (Huber) Cuatrec. Phytomedications. Technological Innovation. Introduction The Amazon rainforest, belonging to the Brazilian territory, has a diversity of plants and plant species, including native ones little or not at all investigated. Fruits commonly used in the locus, such as bacaba (Oenocarpus bacaba Mart), pracaxi (Pentaclethra macroloba Kuntze) and uxi (Endopleura uchi (Huber) Cuatrec), are potentially relevant for studies of natural products, as vegetable oils are known to have beneficial health effects, in addition to being abundant and readily available renewable resources (Dos Santos Costa et al., 2014). Bacaba one of the most studied species, has valuable nutritional potential, as its oil is rich in unsaturated fatty acids, nonetheless, there is little knowledge about it, mainly about its chemical composition (Santos et al., 2017; Cunha et al., 2019). Pracaxi provides oil with high concentrations of oleic, linoleic and behenic fatty acids, and the oil extracted from the seeds of this plant has been used for therapeutic activities such as wound and cut healing, skin hydration and cell renewal, and other dermatological conditions (Dos Santos Costa et al., 2014; Pires et al., 2022). Like these species, uxizeiro popularly known as “uxi-amarelo” or “uxi-smooth”, presents antioxidant action, its bark is used in the preparation of teas and is indicated as an adjuvant in the treatment of diseases of the female urinary tract, inflammation of the uterus, diabetes and arthritis (Bastos et al., 2020; Oliveira et al., 2020; Pinto et al., 2020; De Oliveira et al., 2021). To date, the published reviews about the fruits from the Amazon biome. A review evaluating the use of nutraceuticals prepared from fruits and seeds from the Amazon did not consider the bacaba, pracaxi and uxi oils (Assmann et al., 2021). These reviews did not perform a systematized mapping of information about the biomes (Albuquerque et al., 2017; Assmann et al., 2021). This scoping review can assist researchers in the development of phytomedications from the Amazon biomes and as well as increase the options of medications in the therapeutic arsenal of the Unified Health System (Sistema Único de Saúde, SUS) (Brazil, 2009). Therefore, the current study aims at mapping and characterizing studies on the bacaba, pracaxi and uxi species, belonging to the Amazon rainforest. Materials and Methods Study design This scoping review followed the methodological guidelines proposed by the Joanna Briggs Institute and was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Extension for Scoping Reviews (PRISMA-ScR) checklist (Tricco et al., 2018; Peters et al., 2020). Protocol and registration A protocol has been previously developed and is available, with open access, in the Open Science Framework repository (Afonso et al., 2023). Eligibility criteria Population Plants of the bacaba, pracaxi and uxi species, regardless of the plant organ. Types of study Primary studies that described or evaluated the development of formulations aimed at the therapeutic use of the bacaba, pracaxi and uxi species were included. Outcome Therapeutic effects of the bacaba, pracaxi and uxi species. Information sources Databases The following databases were consulted: MEDLINE (Via PubMed) and Web of Science. Other information resources 1. The Grey Literature was consulted from the following repositories: Google Scholar to identify potentially eligible studies; 2. A manual check of the references of the studies included was performed; 3. An automatic alert in the databases was monitored until November 2022 to identify eligible studies. Search strategy A previously developed search strategy was used with the following keywords accompanied by Boolean operators: “Bacaba”, “Uxi”, “Pracaxi”, “Oenocarpus bacaba”, “Endopleura uchi”, “Pentaclethra macroloba”, “composition”, “formulation”, “phytochemistry”. The strategy has been adapted for each database as well as for the other information resources and is described in full in appendix additional 2. No restrictions regarding year of publication were applied and only studies in English, Spanish and Portuguese were selected. Eligibility determination The references were managed and screened in the Rayyan software (Qatar Computing Research Institute) and all duplicates were automatically removed. The titles and abstracts were independently evaluated by two reviewers (MSA and LPNL) to verify whether they met the eligibility criteria. Subsequently, a full reading of the studies was performed by the same reviewers (MSA and LPNL), also independently, to confirm eligibility of the guidelines. Any and all discrepancies were resolved by consensus or by a third reviewer (ZMFF), when necessary. Data extraction The information was organized in a Microsoft Excel spreadsheet; the same reviewers (MSA and LPNL) independently extracted the data. Any and all discrepancies were resolved through discussion and consensus, or with the help of a third reviewer (ZMFF). Previously, the reviewers had been calibrated by extracting at least three documents of different quality levels and reaching consensus. This procedure was repeated until the reviewers could extract the data. For this study, the following data were considered: 1) Characteristics of the studies: country, study design, bibliometric information; 2) Characteristics of the plants: Genus, species, main marker, majority components, therapeutic activity and plant organ used, results, limitations and conclusions. Synthesis of the results The data were presented and categorized by plant and descriptively according to guidelines for systematic reviews without meta-analysis (Campbell et al., 2020). Results and Discussion A total of 233 references were identified. Of these, 48 duplicate publications were automatically removed and a total of 185 records were included for initial screening. Based on the reading of titles and abstracts, 39 studies were excluded and 146 were included for full-text review. A detailed analysis of these studies resulted in the inclusion of 31 studies for data synthesis. The process to select the studies is described in Figure 1. Six articles dealing with the bacaba species were identified, as well as 13 articles for pracaxi and 12 for uxi. General characteristics of the studies Bacaba (Oenocarpus bacaba Mart.) All the studies included (n=6) were analytical and Brazilian. Of these, 5 were carried out in the North region of the country. Only one study did not report the plant organ used, the others used the bacaba fruit. No study reported the main markers; however, three cited their major components: oleic and palmitic acids. Only one study identified α-tocopherol, a potent antioxidant, in this species (Table 1). Pracaxi (Pentaclethra macroloba Kuntze) No study on Pracaxi reported the main marker, and only one presented seeds of the species as the plant organ used. However, nine of them classified oleic acid as its major component, followed by behenic acid. As for the design of the studies, ten were analytical and conducted in four Brazilian states (nine of these belonging to the North region); two were experimental; and one referred to clinical research, which is an international study (Table 1). Uxi (Endopleura uchi (Huber) Cuatrec.) Among the studies identified on Uxi (n=12), the majority were Brazilian (n=11). Of these, seven were conducted in the Brazilian North region and the others (n=4) in the states of São Paulo (n=3) and Rio de Janeiro (n=1). Four were analytical studies and eight were related to experimental research. Eight of them used the fruit peel as plant organ, but in different ways: powdered bark, bark extract and stem bark. Two studies used uxi pulp and one employed leaves and branches from this species. Only two reported fatty acids as major components, and eight classified bergenin and its derivatives as main markers (Table 1). Therapeutic applications Bacaba Of the studies included for Bacaba (n=6), some did not report its therapeutic applications (n=3) while others confirmed its use for the treatment of cardiovascular diseases (n=3), and its potent antioxidant activity (n=1). Three studies concluded that bacaba has great potential as a healthy vegetable oil, and only one used this asset for the development of formulations (Table 2). Pracaxi Only three articles reported therapeutic applications for this oil, being considered good for healing due to its antioxidant and anti-inflammatory activities, also assisting in other types of chronic diseases such as cancer, cardiovascular and neurodegenerative diseases. Five studies concluded that it can be used in the pharmaceutical industry, as well as in food and/or cosmetics. Three studies considered pracaxi valuable in the treatment of wounds due to the presence of fatty acids. (Table 2). Uxi The studies agreed that this species has possible anti-inflammatory action (n=4); three mentioned its antioxidant activity, one concluded its great antidiabetic potential and another one considered that this species can be used as a phytotherapeutic product in the treatment of coronary and cardiovascular diseases. Other studies have found that further research is required to encourage use of its extracts in human health applications (n=2). A research study considered the benefits and advantages of uxi, such as functional quality effects due to the majority composition of fatty acids and important plant material with therapeutic potential (n=2) (Table 2). Compilation of results The studies included point to the Brazilian biodiversity, as it has in its territory biomes rich in animal and plant species, such as the Amazon (Ruíz-Méndez et al., 2013; Dobarganes et al., 2013; Roca et al., 2015; Guimarães et al., 2016; Serra et al., 2019; Pereira et al., 2019; Lima et al., 2020; Assmann et al., 2021). Among the plant classes, there is bacaba, pracaxi and uxi. Twenty-one articles included in this review were conducted in northern Brazil. The fruits belong to native trees in this region of the country, which explains the widespread use by the local population (Muniz et al., 2020). Plants have been important sources of constituents with pharmacological activities, especially fatty acids. This justifies the fact that this class was mentioned among the studies on these oils, indicating their potential and nutritional quality (Dobarganes et al., 2013; Pinto et al., 2020; Fonseca et al., 2021). Oleic acid, for example, which was mainly present in all oils, ranging from 30.7% to 72.16%, due to its hypocholesterolemic action, has the advantage of not reducing HDL (High-Density Lipoprotein) cholesterol (Lobato et al., 2006). It is considered promising for pharmaceutical formulations because it has properties that improve wound healing (Alves et al., 2019). Linoleic acid, reported in six studies, when ingested, through the action of the elongase and desaturase enzymes, undergoes an unsaturated reaction and is converted into longer-chain polyunsaturated fatty acids (Perini et al., 2010; Peñuela-Sierra et al., 2015). These compounds are present, for example, in the production of hormones such as Series 3 Prostaglandin (PG), which regulates and protects the body against various effects, such as platelet aggregation (due to its antithrombotic activation) and reduces the risk of cardiovascular diseases (Perini et al., 2010). In addition to the fatty acids found predominantly in all species, some studies (Borges et al., 2011; Silva et al., 2015; Peixoto et al., 2019; Bastos et al., 2020; De Sá Hyacienth et al., 2020a; De Sá Hyacienth et al., 2020b; Muniz et al., 2020; Oliveira et al., 2020) cited another chemical class identified as dominant in uxi: Bergenin, a C-glycoside from 4-O-methyl gallic isolated from several medicinal plants with multiple biological activities. Its antimalarial, antidiabetic, anti-cancer, gastroprotective, antituberculosis, antiarrhythmic, hepatoprotective, antiviral, antiangiogenic, neuroprotective, immunomodulatory, antimicrobial, hypolipidemic, healing, antioxidant, anti-hyperuricemic activity and anti-inflammatory properties stand out (Madaan et al., 2022). This suggests that this plant has great potential to be used as a therapeutic agent for the development of more effective and safer phytomedications (Chen et al., 2020). A number of research studies also cite the presence of phenolic compounds (Ruíz-Méndez et al., 2013; Cunha de Melo et al., 2020) such as α-tocopherol, commonly known as Vitamin E, and considered one of the best natural antioxidants in the bacaba and pracaxi species, and this demonstrates the antioxidant profile and potential therapeutic application against inflammatory diseases of these plants (Ruíz-Méndez et al., 2013; Serra et al., 2019). Inflammation and oxidative stress are related to phenomena involved in pathological conditions such as cardiovascular and phenolic compounds that can contribute to the reduction of inflammatory events (García et al., 2017). Several therapeutic applications were mentioned for the species chosen for this study. Some authors agree on the protection that bacaba confers against cardiovascular diseases (Dobarganes et al., 2013; Ruíz-Méndez et al., 2013; Fonseca et al., 2021). As well as others, which inquired that pracaxi has anti-inflammatory and healing action and prevents chronic diseases such as cancer, cardiovascular and neurodegenerative diseases, respectively (Simmons et al., 2015; Alves et al., 2019; Serra et al., 2019). For uxi, the records indicate analgesic and anti-inflammatory activity to treat arthritis, cholesterol, diabetes, uterine infections and fibroids (Borges et al., 2011; Bento et al., 2014), for example. It also mentioned great antidiabetic potential (Silva et al., 2015), antioxidant activity (Muniz et al., 2020; Oliveira et al., 2020) and the usefulness of this species in the treatment of coronary and cardiovascular diseases (Pinto et al., 2020). Due to the antioxidant knowledge about the bioactive compounds present in these species, some studies have performed phytochemical assays for uxi (Politi et al., 2011; Silva et al., 2015; Peixoto et al., 2019; Lima et al., 2020; Bastos et al., 2020; Muniz et al., 2020). These assays focus on models capable of discovering molecular profiles with high antioxidant power or even evaluating the antioxidant potential of a molecule already known and extracted. The in vitro phytochemistry studies included in this review used extraction methods to obtain a specific molecule or molecular type. Among them, two evaluated antioxidant activity by the DPPH assay, considered a rapid methodology for this objective (Peixoto et al., 2019; Muniz et al., 2020). While one study found positive results for uxi's in vitro antioxidant capacity, another reported low antioxidant activity of this species by this same methodology. The planting modality and place are limiting factors in the cultivation of some species, as it is obvious that plants depend on climate and soil conditions (Alves et al., 2018). This can be highlighted by the findings of the review, which identified different profiles of most of the products in the same species. Although most studies mention these predominant compounds, others did not perform this evaluation. It is of paramount importance to know the profile of these products since, although compounds isolated from plant extracts present biological activity, their crude extracts may not have all the desired characteristics (Simões et al., 2001). Although they are promising natural resources, studies related to the oils of the studied species (bacaba, pracaxi and uxi) have some limitations, such as variation of fatty acid concentrations according to temperature and pressure, which can directly influence quality of the final product formed by these plants and consequent oxidation (Bezerra et al., 2017; Pinto et al., 2018; Fonseca et al., 2021). In addition, when considering the development of formulations that have applicability in the pharmaceutical sector, it is necessary to choose chemically compatible constituents, as some substances may or may not present antioxidant activity when isolated (Alves et al., 2019). The methodologies used by two authors for extracting and obtaining pracaxi oil, respectively, require the use of solvents, which, despite showing positive perspectives, deserve attention regarding toxicity, as its traces can remain in the oil and, therefore, in the case of medicinal products, an adequate choice is needed (Simões et al., 2001; Pereira et al., 2015; Teixeira et al., 2020). Although all studies have cited positive results for uxi, such as antinociceptive effects that inhibit cyclooxygenase (Borges et al., 2011), the antiproliferative effect of this plant against HeLa cells (Bento et al., 2014), inhibiting properties of α-glycosidase, antibacterials and cholinesterases (Silva et al., 2015), substantial antioxidant activity in vitro and in vivo (Peixoto et al., 2019), they showed the need for further research studies on the use of their extracts in therapeutic applications, as their biological activities, as well as their toxicological profile, are not yet elucidated (Peixoto et al., 2019). In addition, few studies have been conducted in humans, and it is necessary to propose clinical trials, especially randomized and controlled, for a safety and efficacy measure. From the statements related to the main bioactive compounds and the therapeutic potential identified in these species, however, some limitations emerge due to the absence of important parameters, such as, absence of clinical trials, heterogeneity of studies, methodological quantitative analysis, difficulties in large-scale exploration, variability extraction methods and others. In view of this, this review maps information from the literature that may help in the development of studies focused on this topic in the future, since more investigations and outcomes are needed for this population. The therapeutic effects reported in the studies included in this review are, for the most part, assumptions that are not based on evidence, since this proof requires the performance of clinical trials that must be approved and monitored by ethical and regulatory authorities to ensure that the ethical conduct and technical aspects of research conform to the required standards (Gouy et al., 2018) It is noted that there is potential in these plants for technological prospecting and investment in more economical, safe and sustainable products for the environment, especially because they meet the SUS epidemiological demands, as cardiovascular diseases, the main therapeutic activity elucidated, represent a significant percentage of expenses and availability of high-complexity services for public health (Oliveira et al., 2022). As they are considered an important source of biologically active natural products, there are some dilemmas regarding the development of medications, as it is necessary to use techniques that allow obtaining a final product with stability, quality and efficacy also for acceptability by the population, as suggested by studies involving the Evaluation of Health Technologies (Calixto et al., 2000; Brazil, 2012). For the pharmaceutical sector, herbal medications can mean an opportunity for development, not only because of the abundance of the country's fauna and flora, but also because of the traditional and scientific knowledge about the biological activity of plants (De Barros et al., 2021). Although many Brazilian studies have shown promising results on bacaba, pracaxi and uxi, none of them proposed strategies for the sustainable use of these plants, nor have they presented any concern regarding environmental preservation in technological innovat

Supplemental_Material_Study_Sites - Efficacy and Safety of a Biosimilar Versus Branded Enoxaparin in the Prevention of Venous Thromboembolism Following Major Abdominal Surgery: A Randomized, Prospective, Single-Blinded, Multicenter Clinical Trial

<p>Supplemental_Material_Study_Sites for Efficacy and Safety of a Biosimilar Versus Branded Enoxaparin in the Prevention of Venous Thromboembolism Following Major Abdominal Surgery: A Randomized, Prospective, Single-Blinded, Multicenter Clinical Trial by Eduardo Ramacciotti, Ubirajara Ferreira, Agenor José Vasconcelos Costa, Selma Regina O. Raymundo, João Antônio Correa, Salvador Gullo Neto, Alessandro Bersch Osvaldt, Leandro Agati, Valéria Cristina Resende Aguiar, Ronaldo Davila, Tania Benevenuto Caltabiano, Flávia Magalhães Magella, Giuliano Giova Volpiani, Valter Castelli, Roberto Augusto Caffaro, Lucas Zeponi DalAcqua, Wagner Eduardo Matheus, Debora Yuri Sato, Gleison Juliano da Silva Russeff, Daniela Garcia de Souza, Lucas Eduardo Pazetto, Tiago Aparecido Maschio de Lima, Eloá Maria da Silva Colnago, Eliane Yumii Fugii, Juliana Sekeres Mussalem, Vanessa Therumi Assao, Odaly Toffoletto, Debora Garcia Rodrigues, Jorge Barros Afiune, and Gilson Roberto Araujo in Clinical and Applied Thrombosis/Hemostasis</p