Software for animal randomization: A tool for increasing the reproducibility of science.

Poorly designed preclinical studies may compromise human health due to erroneous conclusions regarding treatment effects in addition to contributing to experimental irreproducibility and wasted resources. Randomization is one of the crucial steps to enhance scientific rigor and is a commonly recognized bias-reducing instrument that increases the reliability and reproduction of studies involving animals (even with syngeneic animals). This procedure should be considered when planning a study and reported during data publication. In this context, this work aimed to highlight the importance of adopting quality measures in preclinical trials, with an emphasis on animal randomization. The 'Mouse Randomization' app was developed to help researchers estimate an adequate sample size to obtain significant statistical power, ensuring the ethical use of animals. This app is freely available on the internet to carry out animal randomization and calculate sample sizes for in vivo experiments. We believe that this brief discussion about animal randomization could raise awareness among researchers on how to improve the quality of preclinical research, increasing reproducibility and avoiding animal misuse.

Teaching and learning pharmacology in Brazil before COVID-19 pandemic: a case study in Rio de Janeiro.

BACKGROUND: Knowledge of pharmacology is crucial for physicians to perform rational and safe medicine. Medical professionals are responsible for prescribing drugs and a weak performace of those can result in medication errors leading to disability, hospitalization, and death, among other situations. It occurs worldwide, including in Brazil, so that learning pharmacology impacts on public health service. We aim to investigate the current pharmacology educational practices in medical schools in the state of Rio de Janeiro, Brazil. METHODS: We surveyed 14 of 22 medical schools in Rio de Janeiro. Pharmacology teachers (n=16) and medical students (n=89) answered a semi-structured questionnaire that included questions about the staff characteristics, pharmacology content, teacher's concepts, and common practices and resources that were used in pharmacology classes. RESULTS: Our results revealed that the medical schools had similar overall curriculums. Pharmacology teachers work more than 30hs a week (75%) and conducted both research and teaching (62.5%). We also found that the multimedia projector was the most common resource (71.9%), and passive pedagogical methodologies (e.g., expository classes) remain a current strategy in pharmacology classes (89.9%). In general, medical students are poorly motivated (55%), which may be related to their performance in assessments. In addition, students believe that pharmacology is a complex (52%) or very complex subject (46%) since for its full understanding the student needs concepts from other disciplines, which can have an impact on the performance and motivation of students. As a result, these medical students do not fully understand the integration between pharmacology's basic concepts and their clinical applications. CONCLUSION: These data seem to demonstrate that the adopted teaching and learning pharmacology strategies and methodologies can be improved in Rio de Janeiro.

Magnetic Nanostructures and Stem Cells for Regenerative Medicine, Application in Liver Diseases.

The term "liver disease" refers to any hepatic condition that leads to tissue damage or altered hepatic function and can be induced by virus infections, autoimmunity, inherited genetic mutations, high consumption of alcohol or drugs, fat accumulation, and cancer. Some types of liver diseases are becoming more frequent worldwide. This can be related to increasing rates of obesity in developed countries, diet changes, higher alcohol intake, and even the coronavirus disease 2019 (COVID-19) pandemic was associated with increased liver disease-related deaths. Although the liver can regenerate, in cases of chronic damage or extensive fibrosis, the recovery of tissue mass is impossible, and a liver transplant is indicated. Because of reduced organ availability, it is necessary to search for alternative bioengineered solutions aiming for a cure or increased life expectancy while a transplant is not possible. Therefore, several groups were studying the possibility of stem cells transplantation as a therapeutic alternative since it is a promising strategy in regenerative medicine for treating various diseases. At the same time, nanotechnological advances can contribute to specifically targeting transplanted cells to injured sites using magnetic nanoparticles. In this review, we summarize multiple magnetic nanostructure-based strategies that are promising for treating liver diseases.

Development and implementation of a significantly low-cost 3D bioprinter using recycled scrap material.

The field of 3D bioengineering proposes to effectively contribute to the manufacture of artificial multicellular organ/tissues and the understanding of complex cellular mechanisms. In this regard, 3D cell cultures comprise a promising bioengineering possibility for the alternative treatment of organ function loss, potentially improving patient life expectancies. Patients with end-stage disease, for example, could benefit from treatment until organ transplantation or even undergo organ function restoration. Currently, 3D bioprinters can produce tissues such as trachea cartilage or artificial skin. Most low-cost 3D bioprinters are built from fused deposition modeling 3D printer frames modified for the deposition of biologically compatible material, ranging between $13.000,00 and $300.000,00. Furthermore, the cost of consumables should also be considered as they, can range from $3,85 and $100.000,00 per gram, making biomaterials expensive, hindering bioprinting access. In this context, our report describes the first prototype of a significantly low-cost 3D bioprinter built from recycled scrap metal and off-the-shelf electronics. We demonstrate the functionalized process and methodology proof of concept and aim to test it in different biological tissue scaffolds in the future, using affordable materials and open-source methodologies, thus democratizing the state of the art of this technology.

Physiologic roles of P2 receptors in leukocytes.

Since their discovery in the 1970s, purinergic receptors have been shown to play key roles in a wide variety of biologic systems and cell types. In the immune system, purinergic receptors participate in innate immunity and in the modulation of the adaptive immune response. In particular, P2 receptors, which respond to extracellular nucleotides, are widely expressed on leukocytes, causing the release of cytokines and chemokines and the formation of inflammatory mediators, and inducing phagocytosis, degranulation, and cell death. The activity of these receptors is regulated by ectonucleotidases-expressed in these same cell types-which regulate the availability of nucleotides in the extracellular environment. In this article, we review the characteristics of the main purinergic receptor subtypes present in the immune system, focusing on the P2 family. In addition, we describe the physiologic roles of the P2 receptors already identified in leukocytes and how they can positively or negatively modulate the development of infectious diseases, inflammation, and pain.

Natural Biopolymers as Additional Tools for Cell Microencapsulation Applied to Cellular Therapy.

One of the limitations in organ, tissue or cellular transplantations is graft rejection. To minimize or prevent this, recipients must make use of immunosuppressive drugs (IS) throughout their entire lives. However, its continuous use generally causes several side effects. Although some IS dose reductions and withdrawal strategies have been employed, many patients do not adapt to these protocols and must return to conventional IS use. Therefore, many studies have been carried out to offer treatments that may avoid IS administration in the long term. A promising strategy is cellular microencapsulation. The possibility of microencapsulating cells originates from the opportunity to use biomaterials that mimic the extracellular matrix. This matrix acts as a support for cell adhesion and the syntheses of new extracellular matrix self-components followed by cell growth and survival. Furthermore, by involving the cells in a polymeric matrix, the matrix acts as an immunoprotective barrier, protecting cells against the recipient's immune system while still allowing essential cell survival molecules to diffuse bilaterally through the polymer matrix pores. In addition, this matrix can be associated with IS, thus diminishing systemic side effects. In this context, this review will address the natural biomaterials currently in use and their importance in cell therapy.

Rational design of large flat nitrogen-doped graphene oxide quantum dots with green-luminescence suitable for biomedical applications.

Rational synthesis and simple methodology for the purification of large (35-45 nm in lateral size) and flat (1.0-1.5 nm of height) nitrogen-doped graphene oxide quantum dots (GOQDs) are presented. The methodology allows robust metal-free and acid-free preparation of N-GOQDs with a yield of about 100% and includes hydrothermal treatment of graphene oxide with hydrogen peroxide and ammonia. It was demonstrated that macroscopic impurities can be separated from N-GOQD suspension by their coagulation with 0.9% NaCl solution. Redispersible in water and saline solutions, particles of N-GOQDs were characterized using tip-enhanced Raman spectroscopy (TERS), photoluminescent, XPS, and UV-VIS spectroscopies. The size and morphology of N-GOQDs were studied by dynamic light scattering, AFM, SEM, and TEM. The procedure proposed allows nitrogen-doped GOQDs to be obtained, having 60-51% of carbon, 34-45% of oxygen, and up to 7.2% of nitrogen. The N-GOQD particles obtained in two hours of synthesis contain only pyrrolic defects of the graphene core. The fraction of pyridine moieties grows with the time of synthesis, while the fraction of quaternary nitrogen declines. Application of TERS allows demonstration that the N-GOQDs consist of a graphene core with an average crystallite size of 9 nm and an average distance between nearest defects smaller than 3 nm. The cytotoxicity tests reveal high viability of the monkey epithelial kidney cells Vero in the presence of N-GOQDs in a concentration below 60 mg L-1. The N-GOQDs demonstrate green luminescence with an emission maximum at 505 nm and sedimentation stability in the cell culture medium.

The scientific publication of the Memórias do Instituto Oswaldo Cruz (1909-2020): a history of contribution to the biomedical sciences.

BACKGROUND: The Memórias do Instituto Oswaldo Cruz (MIOC) is one of the first scientific journals created in Brazil and currently one of the most important biomedical journals in South America. Knowledge of the main themes disseminated over time and its main contributors can contribute towards a better understanding of its trajectory and future. OBJECTIVES: Map the journal's scientific publication between 1909 and 2020. METHODS: Data from three scientific databases was combined, alongside bibliometrics and network analysis to analyse publication records between 1909 and 2020. FINDINGS: Publications increased substantially since the 1980s. The main publishing organisations are Brazilian. Excluding Brazil, the main publishing countries are the USA, Argentina, and Colombia. During the entire investigated period, the main themes refer to Chagas disease, schistosomiasis, and Leishmaniasis. During some periods, publications followed disease outbreaks in Brazil (e.g., dengue fever and yellow fever). MAIN CONCLUSIONS: Since its foundation in 1909, the MIOC has focused on infectious and parasitic diseases. The editorial changes implemented from the 1980s onwards led MIOC to a relevant growth concerning annual publications and its transformation into an important communication vehicle for researchers from several Brazilian organisations besides Fiocruz, as well as organisations from other countries, especially within Latin America.

Animal models applied to acute-on-chronic liver failure: Are new models required to understand the human condition?

The liver is a multifaceted organ; its location and detoxifying function expose this organ to countless injuries. Acute-on-chronic failure liver (ACLF) is a severe syndrome that affects the liver due to acute decompensation in patients with chronic liver disease. An infection environment, ascites, increased liver enzymes and prothrombin time, encephalopathy and fast-evolving multiorgan failure, leading to death, usually accompany this. The pathophysiology remains poorly understand. In this context, animal models become a very useful tool in this regard, as understanding; the disease may be helpful in developing novel therapeutic methodologies for ACLF. However, although animal models display several similarities to the human condition, they do not represent all ACLF manifestations, resulting in significant challenges. An initial liver cirrhosis framework followed by the induction of an acute decompensation by administering lipopolysaccharide and D-GaIN, potentiating liver damage supports the methodologies applied to induce experimental ACLF. The entire methodology has been described mostly for rats. Nevertheless, a quick PubMed database search indicates about 30 studies concerning ACFL models and over 1000 regarding acute liver failure models. These findings demonstrate the clear need to establish easily reproducible ACFL models to elucidate questions about this quickly established and often fatal syndrome.

Virtual immunology: an educational software to encourage antigen-antibody interaction learning.

Immunology is a knowledge area of paramount importance in life sciences and health care professional education with diverse applications, as well as for a general public understanding of issues related to vaccination. However, many concepts are complex and difficult to understand based only on conventional classes or static images. The use of tools, such as educational software, may enhance the learning of dynamic molecular phenomena that occur in our bodies. Virtual Immunology is a software that aims to facilitate the learning of certain complex immunology concepts. Herein, we present the "Antigen-antibody interactions" module that was used and evaluated by 127 students and 3 teachers from medical schools from 2 universities, 1 public and 1 private, both in the state of Rio de Janeiro, Brazil. The pretest/posttest research design was used to assess student learning in a randomized sample. To evaluate user perceptions concerning software quality, 14 statements were analyzed using a Likert scale. Results indicate suitable evaluations from both students and teachers concerning the "Antigen-antibody module" as an auxiliary tool in immunology teaching. The software was well rated as an educational resource since it allows dynamically viewing immunological phenomena. In addition, its ease of use and immunological process visualization were the best-evaluated parameters by the students, who recommended this software module as an auxiliary learning tool. The use of the evaluated software may motivate students and aid in the understanding of immunology-related concepts, becoming a complementary tool that may enhance the teaching-learning process.

The scientific publication of the Memórias do Instituto Oswaldo Cruz (1909-2020): a history of contribution to the biomedical sciences

BACKGROUND The Memórias do Instituto Oswaldo Cruz (MIOC) is one of the first scientific journals created in Brazil and currently one of the most important biomedical journals in South America. Knowledge of the main themes disseminated over time and its main contributors can contribute towards a better understanding of its trajectory and future. OBJECTIVES Map the journal's scientific publication between 1909 and 2020. METHODS Data from three scientific databases was combined, alongside bibliometrics and network analysis to analyse publication records between 1909 and 2020. FINDINGS Publications increased substantially since the 1980s. The main publishing organisations are Brazilian. Excluding Brazil, the main publishing countries are the USA, Argentina, and Colombia. During the entire investigated period, the main themes refer to Chagas disease, schistosomiasis, and Leishmaniasis. During some periods, publications followed disease outbreaks in Brazil (e.g., dengue fever and yellow fever). MAIN CONCLUSIONS Since its foundation in 1909, the MIOC has focused on infectious and parasitic diseases. The editorial changes implemented from the 1980s onwards led MIOC to a relevant growth concerning annual publications and its transformation into an important communication vehicle for researchers from several Brazilian organisations besides Fiocruz, as well as organisations from other countries, especially within Latin America.

A processual view on the use of problem-based learning in high school physiology teaching.

In problem-based learning (PBL), the steps and processes present in the PBL tutorial cycle are essential for constructive, self-directed, collaborative, and contextual student learning. This article presents a procedural study of a PBL tutorial cycle with high school students new to the method regarding human respiration and circulation physiology. We observed group dynamics and the learning process that occurred throughout the PBL tutorial cycle. The results indicate that conceptual changes were close to the planned learning objectives and that students enjoyed studying applying PBL. Moreover, a positive correlation was observed between group dynamics, self-directed learning and learning outcomes. Our results provide grounds for restructuring the tutorial cycle, especially important for novice PBL students, such as problem reformulation and the development and diversification of applied learning scaffolds. We conclude that the qualitative analysis performed herein can yield a deeper understanding of the PBL tutorial cycle and may be used to foster PBL implementation in institutions with little experience with the method and monitor its outcomes in organizations with mature PBL use.

Use of an evidence-based health portal to improve teaching and learning in primary care: a mixed methods evaluation.

BACKGROUND: Worldwide, primary care is for most people the gateway into many health systems. Offering solutions to the demands of the communities served requires the constant preparation of professionals, especially doctors and medical undergraduate students. We analyze and propose ways to improve the teaching and learning processes facilitated by the Basic Family Health Units (BFHUs) based on the use of electronic portals with evidence-based medicine criteria. METHOD: First phase: The authors conducted a qualitative-quantitative study on students and instructors of primary care (PC) medicine by administering a survey of open- and closed-ended questions at medical schools. The closed-ended questions were studied with descriptive statistics, and open-ended questions were analyzed via the creation of categories. Perceptions of major teaching and learning problems were then identified. Second phase: Meetings were held with students and their instructors for 6 months and involved the use of electronic portals and the application of new questionnaires using a Likert scale for pre- and postevaluation. RESULTS: In the first phase, 40% of the students considered local instructor training levels a problem. A similar result was found regarding teachers' lectures, revealing a lack of adequate PC training and performance. Building on our results, we focused on BFHUs to apply new strategies for teaching and learning, such as the use of the Evidence-Based Health (SBE) Portal, which includes several databases with clinical evidence criteria. In the second phase, the authors identified an improvement in the quality of learning among instructors and students. This outcome improved safety in daily clinical practice in PC, possibly with better results for its users. CONCLUSIONS: The use of electronic portals can facilitate BFHU teaching and learning and promote the health of users.

Graph Neural Networks as a Potential Tool in Improving Virtual Screening Programs.

Despite the increasing number of pharmaceutical companies, university laboratories and funding, less than one percent of initially researched drugs enter the commercial market. In this context, virtual screening (VS) has gained much attention due to several advantages, including timesaving, reduced reagent and consumable costs and the performance of selective analyses regarding the affinity between test molecules and pharmacological targets. Currently, VS is based mainly on algorithms that apply physical and chemistry principles and quantum mechanics to estimate molecule affinities and conformations, among others. Nevertheless, VS has not reached the expected results concerning the improvement of market-approved drugs, comprising less than twenty drugs that have reached this goal to date. In this context, graph neural networks (GNN), a recent deep-learning subtype, may comprise a powerful tool to improve VS results concerning natural products that may be used both simultaneously with standard algorithms or isolated. This review discusses the pros and cons of GNN applied to VS and the future perspectives of this learnable algorithm, which may revolutionize drug discovery if certain obstacles concerning spatial coordinates and adequate datasets, among others, can be overcome.

A Low-Cost Open Source Device for Cell Microencapsulation.

Microencapsulation is a widely studied cell therapy and tissue bioengineering technique, since it is capable of creating an immune-privileged site, protecting encapsulated cells from the host immune system. Several polymers have been tested, but sodium alginate is in widespread use for cell encapsulation applications, due to its low toxicity and easy manipulation. Different cell encapsulation methods have been described in the literature using pressure differences or electrostatic changes with high cost commercial devices (about 30,000 US dollars). Herein, a low-cost device (about 100 US dollars) that can be created by commercial syringes or 3D printer devices has been developed. The capsules, whose diameter is around 500 µm and can decrease or increase according to the pressure applied to the system, is able to maintain cells viable and functional. The hydrogel porosity of the capsule indicates that the immune system is not capable of destroying host cells, demonstrating that new studies can be developed for cell therapy at low cost with microencapsulation production. This device may aid pre-clinical and clinical projects in low- and middle-income countries and is lined up with open source equipment devices.

Molecular Modeling Applied to the Discovery of New Lead Compounds for P2 Receptors Based on Natural Sources.

P2 receptors are a family of transmembrane receptors activated by nucleotides and nucleosides. Two classes have been described in mammals, P2X and P2Y, which are implicated in various diseases. Currently, only P2Y12 has medicines approved for clinical use as antiplatelet agents and natural products have emerged as a source of new drugs with action on P2 receptors due to the diversity of chemical structures. In drug discovery, in silico virtual screening (VS) techniques have become popular because they have numerous advantages, which include the evaluation of thousands of molecules against a target, usually proteins, faster and cheaper than classical high throughput screening (HTS). The number of studies using VS techniques has been growing in recent years and has led to the discovery of new molecules of natural origin with action on different P2X and P2Y receptors. Using different algorithms it is possible to obtain information on absorption, distribution, metabolism, toxicity, as well as predictions on biological activity and the lead-likeness of the selected hits. Selected biomolecules may then be tested by molecular dynamics and, if necessary, rationally designed or modified to improve their interaction for the target. The algorithms of these in silico tools are being improved to permit the precision development of new drugs and, in the future, this process will take the front of drug development against some central nervous system (CNS) disorders. Therefore, this review discusses the methodologies of in silico tools concerning P2 receptors, as well as future perspectives and discoveries, such as the employment of artificial intelligence in drug discovery.

A new insight into purinergic pharmacology: Three fungal species as natural P2X7R antagonists.

P2X7 is a purinergic receptor involved in important physiological functions and pathological processes, such as inflammation, neurodegeneration, and pain. Despite its relevance, there is no selective antagonist useful in the treatment of diseases related to this receptor. In this context, research for a selective, safe, and potent antagonist compound that can be used in clinical therapy has been growing. In this work, we evaluated the potential antagonistic activity of three fungal extracts, namely, Vishniacozyma victoriae, Metschnikowia australis, and Ascomycota sp., which were discovered in a high-throughput screening campaign to search for new antagonists for P2X7R from natural products. First, the IC50 values of these fungal extracts were determined in J774.G8 (murine macrophage cell line) and U937 (human monocyte cell line) cells through dye uptake assays. The IC50 values of V. victoriae were 2.6 and 0.92 µg/mL, M. australis has IC50 values of 3.8 and 1.5 µg/mL, and Ascomycota sp. showed values of 2.1 and 0.67 µg/mL in J774.G8 and U937 cells, respectively. These extracts also significantly inhibited propidium iodide and Lucifer yellow uptake via P2X7R pore, P2X7R currents in electrophysiology, IL-1ß release, and the production of oxide nitric and reactive oxygen species. The extracts did not cause cytotoxicity within a period of 24 h. The results showed the promising antagonistic activity of these extracts toward P2X7R, thereby indicating that they can be future candidates for phytomedicines with potential clinical applicability.

Open educational resources in immunology education.

The use of computers as a pedagogical resource is currently on the rise. In the case of immunology, students present difficulties in visualizing molecular phenomena. Thus the use of animations and simulations available on the internet might facilitate the learning of complex immunological concepts. In this context, it is important to map and assess the currently available resources that may be used for educational purposes. This study comprises the search and analysis of educational immunology software freely available on the internet, which can aid students and health professionals in effective learning and continuing education scenarios. A detailed search in English on the existence of free software was carried out on websites and scientific databases. The results clearly indicate a lack of freely available and scientifically validated immunology educational software, despite the existence of several software programs that could be used as auxiliary teaching tools.

Assessment of the knowledge and perceptions of Brazilian medical residents on transfusion medicine

Abstract Background Medical education has a major social impact because it ultimately influences the quality and safety of the health service offered to the population. Several studies have acknowledged the relationship between medical knowledge on transfusion medicine and the proper use of this therapy. The rational use of blood has become a worldwide concern. In this context, the aim of the present study was to evaluate medical residents' knowledge on transfusion medicine in hospitals located in Rio de Janeiro, Brazil, and their training during their medical education. Methods One hundred and six residents from eight medical specialties of four hospitals participated. A questionnaire developed by the Biomedical Excellence for Safer Transfusion (BEST) group was applied to evaluate the participants' medical knowledge. Another questionnaire was also applied to evaluate participant profiles regarding frequency of transfusion prescriptions, self-perceived knowledge and relevance of the subject. Results The mean number of correct answers to the questionnaire on knowledge about transfusion practices was 43.5% (range: 15-80%). A relationship between training during medical residency and the obtained result was observed (p-value = 0.0007). Most residents (73%) did not receive training in transfusion medicine during their graduation or residency and 93% would like to receive additional training. Conclusion A clear deficit in the knowledge of transfusion medicine was verified, indicating the need for change in the teaching of this specialty. This result is similar to some developed countries.

Assessment of the knowledge and perceptions of Brazilian medical residents on transfusion medicine.

BACKGROUND: Medical education has a major social impact because it ultimately influences the quality and safety of the health service offered to the population. Several studies have acknowledged the relationship between medical knowledge on transfusion medicine and the proper use of this therapy. The rational use of blood has become a worldwide concern. In this context, the aim of the present study was to evaluate medical residents' knowledge on transfusion medicine in hospitals located in Rio de Janeiro, Brazil, and their training during their medical education. METHODS: One hundred and six residents from eight medical specialties of four hospitals participated. A questionnaire developed by the Biomedical Excellence for Safer Transfusion (BEST) group was applied to evaluate the participants' medical knowledge. Another questionnaire was also applied to evaluate participant profiles regarding frequency of transfusion prescriptions, self-perceived knowledge and relevance of the subject. RESULTS: The mean number of correct answers to the questionnaire on knowledge about transfusion practices was 43.5% (range: 15-80%). A relationship between training during medical residency and the obtained result was observed (p-value = 0.0007). Most residents (73%) did not receive training in transfusion medicine during their graduation or residency and 93% would like to receive additional training. CONCLUSION: A clear deficit in the knowledge of transfusion medicine was verified, indicating the need for change in the teaching of this specialty. This result is similar to some developed countries.