Toxicological profile of IQG-607 after single and repeated oral administration in minipigs: An essential step towards phase I clinical trial.

IQG-607 is an anti-tuberculosis drug candidate, with a promising safety and efficacy profile in models of tuberculosis infection both in vitro and in vivo. Here, we evaluated the safety and the possible toxic effects of IQG-607 after acute and 90-day repeated administrations in minipigs. Single oral administration of IQG-607 (220 mg/kg) to female and male minipigs did not result in any morbidity or mortality. No gross lesions were observed in the minipigs at necropsy. Repeated administration of IQG 607 (65, 30, or 15 mg/kg), given orally, for 90 days, in both male and female animals did not cause any mortality and no significant body mass alteration. Diarrhea and alopecia were the clinical signs observed in animals dosed with IQG-607 for 90 days. Long-term treatment with IQG-607 did not induce evident alterations of blood cell counts or any hematological parameters. Importantly, the repeated schedule of administration of IQG-607 resulted in increased cholesterol levels, increased glucose levels, decrease in the globulin levels, and increased creatinine levels over the time. Most necropsy and histopathological alterations of the organs from IQG-607-treated groups were also observed for the untreated group. In addition, pharmacokinetic parameters were evaluated. IQG-607 represents a potential candidate molecule for anti-tuberculosis drug development programs. Its promising in vivo activity and mild to moderate toxic events detected in this study suggest that IQG-607 represents a candidate for clinical development.

Robot-assisted knee arthroplasty: Analyzing the learning curve and initial institutional experience.

Robot-assisted total knee arthroplasty (rTKA) involves a learning curve for orthopedic surgeons. The aim of the present study was to assess the surgical times of rTKA procedures performed by initial stage and proficiency stage surgeons in comparison with times of conventional total knee arthroplasty (cTKA). The results reveal that the learning curve for rTKA varies considerable between surgeons, suggesting that the skill and aptitude of the individual to adapt to the robotic system play key roles in the learning process. Proficiency stage surgeons were able to reduce rTKA surgical times to levels comparable with those of conventional surgeries after performing approximately 30 to 40 robotic procedures. Ongoing research has shown promising outcomes in terms of improved clinical results and reduced complications following the application of advanced robotic technology to total knee arthroplasty.

Histological Alterations in the Internal Organs of Wistar Han Rats (Rattus norvegicus) Euthanized by Five Different Methods.

Selecting a method of euthanasia is an important step in designing research studies that use animals; euthanasia methods must be humane, cause minimal pain and suffering to the animal, and preserve the tissue architecture of the organs of interest. In this study, we evaluated the histomorphology of the internal organs (lung, spleen, heart, kidney, liver, brain, and adrenal gland) of rats submitted to five different methods of euthanasia, with the goal of determining which protocol caused the least alteration of histomorphology. Twenty adult Wistar Han rats (Rattus norvegicus) were divided into 5 groups of 4 rats each (2 females and 2 males) and were euthanized by CO2 or isoflurane inhalation, sodium thiopental or xylazine plus ketamine overdose, or decapitation. All euthanasia was performed in accordance with published guidelines and local legal require- ments. Necropsy was performed immediately after euthanasia. Specific internal organs were removed and placed in formalin and submitted for routine histologic processing. Histomorphological examination of hematoxylin and eosin-stained tissues revealed circulatory alterations in multiple organs, predominantly congestion in multiple tissues, pulmonary hemorrhage, and hepatic degeneration. The euthanasia methods that induced the most severe alterations were exposure to CO2 and anesthetic overdose with xylazine plus ketamine or sodium thiopental. Euthanasia by overexposure to isoflurane caused less damage, and the alterations were of minimal severity. Decapitation resulted in the lowest incidence of lesions in multiple organs but due its traumatic nature, it caused the highest incidence of pulmonary hemorrhage. In selecting a method of euthanasia, factors to consider are the species of animal, the purpose of the research, and the practical ability to perform the procedure to achieve maximal animal welfare without iatrogenic changes that could compromise the outcome and reproducibility of the study.

Nest-building in breeding mice: Impact of macro- and micro-environment.

The housing conditions of laboratory mice must be strictly controlled in order to reduce the impact of pathophysiological changes that affect animal health and welfare, possibly resulting in increased variability within experimental results. One way to improve the activity and survival of laboratory mice is to provide nesting material. The objective of this study was to determine if nest-building quality could be used to detect changes in murine mating behaviour in a rodent facility under controlled conditions. Nesting scores of 847 cages with monogamous pairs from three different genetic backgrounds (129, B6 and BALB/c) of both sexes were correlated with 18 predefined variables. The effects on nest quality were evaluated using descriptive data analysis, correspondence analysis and ordinal logistic model fitting. The results showed a strong relationship between nest quality and nest position. Humidity, genetic background, cage change and the number and age of pups in the cage affected the nest-building scores. The most important indicators were cage change and relative humidity, both of which exerted significant negative effects on nest-building quality. Even though the criteria were well defined, the observer could still influence nest score appraisal. However, in a long-term observational study, observers could improve their assessment by training and acquiring greater experience in score assignment. Nest-building scores are easy to assess in the cage, with little discomfort to the animal. Moreover, the nest score is a valid indicator of the health and well-being of laboratory mice and can provide valuable support in the management of animal facilities.

Scientists of Tomorrow/ Cientistas do Amanhã : a project to inspire, stimulate scientific thinking, and introduce scientific methodology for young students.

The Scientists of Tomorrow/ Cientistas do Amanhã project is an immersive science training program developed by the Program of Post-Graduation in Health Sciences at Hospital Israelita Albert Einstein. This program was conducted in partnership with Volunteering and Escola Municipal de Ensino Fundamental Professor Paulo Freire in Paraisópolis, São Paulo, Brazil. The Scientists of Tomorrow Program comprised a short training period conducted in May 2022 involving 37 students, and a long training period from August to December 2022, which included 15 students. It aimed to popularize science through practical activities; transfer knowledge to young students; sensitize and guide them to pursue academic-scientific careers; reduce stereotypes about scientific work and scientists; and help students understand the social, political, and ethical roles of science within society. All activities were led by postgraduate students and professors from our postgraduate program, physicians, nurses, physiotherapists, biomedicals, and veterinarians from Hospital Israelita Albert Einstein, as well as medical students from Faculdade Israelita de Ciências da Saúde Albert Einstein . Activities in the short training included lectures on cinema and science, strategies to combat fake news, non-violent communication, innovation, design-thinking framework, and developing a scientific project. During the long training period, discussions were focused on nanotechnology, animal research, big data, bioinformatics, meditation, blood and bone marrow donation, telemedicine, sex and sexually-transmitted infections, rehabilitation, career opportunities, and scientific integrity. In addition, practical activities were further expanded using optical and confocal microscopy, cytometry, and basic concepts regarding the structure and function of living cells. The program also included the launching of the open-air outreach Education E-natureza activity, which turned students into ambassadors of nature. In conclusion, the Scientists of Tomorrow Program was innovative and enabled young students to learn that science is a collective activity that can enhance public health. In Brief Rangel et al. enumerated the Scientists of Tomorrow/Cientistas do Amanhã program, an immersive science initiative conducted in collaboration with a public school. The program, which involved 15 students, aimed to promote science, share knowledge, inspire academic paths, and underscore societal impacts. Led by postgraduates, professors, and healthcare experts, the program included diverse lectures and practical laboratory activities. Highlights Every research endeavor commences with a fundamental question. Sharing of findings by researchers and students contributes toward the expansion of knowledge. Teaching scientific methodology is a pivotal step in nurturing critical thinking skills. Science permeates our daily lives and plays a crucial role in addressing societal issues.

Administration of meloxicam to improve the welfare of mice in research: a systematic review (2000 - 2020).

Although laboratory animals experience pain as a necessary component of the objectives of experimental protocols, the level of pain should be minimized through use of an adequate analgesic regimen. The non-steroidal anti-inflammatory drug meloxicam may be beneficial in alleviating post-operative pain in mice, although no regimen has been demonstrated as universally efficacious owing to differences in experimental protocols, strain, sex, and incomplete descriptions of methodology in the literature. The aim of this systematic literature review was to identify potential applications of meloxicam for pain management in experimental mice and to evaluate the general quality of study design. Searches of MEDLINE, Scopus and CAB Direct databases elicited 94 articles published between January 2000 and April 2020 that focused on the analgesic efficacy of meloxicam in the management of momentary or persistent pain in mice. The extracted data showed that most articles were deficient in descriptions of housing, husbandry, group size calculation and humane endpoint criteria, while few described adverse effects of the drug. A wide range of dosages of meloxicam was identified with analgesic efficiencies that varied considerably according to the different models or procedures studied. It was impossible to correlate the extracted data into a single meta-analysis because of the differences in experimental protocols and strains employed, the low representation of female mice in the studies, and incomplete descriptions of the methodology applied. We conclude that meloxicam has potential application for pain management in mice but that the dosage must be adjusted carefully according to the experimental procedures. Moreover, authors must take more care in designing their studies and in describing the methodology employed.

Identification of early biomarkers in saliva in genetically engineered mouse model C(3)1-TAg of breast cancer.

Breast cancer is one of leading causes of death worldwide in the female population. Deaths from breast cancer could be reduced significantly through earlier and more efficient detection of the disease. Saliva, an oral fluid that contains an abundance of protein biomarkers, has been recognized as a promising diagnostic biofluid that is easy to isolate through non-invasive techniques. Assays on saliva can be performed rapidly and are cost-effective. Therefore, our work aimed to identify salivary biomarkers present in the initial stages of breast cancer, where cell alterations are not yet detectable by histopathological analysis. Using state-of-the-art techniques, we employed a transgenic mouse model of mammary cancer to identify molecular changes in precancerous stage breast cancer through protein analysis in saliva. Through corroborative molecular approaches, we established that proteins related to metabolic changes, inflammatory process and cell matrix degradation are detected in saliva at the onset of tumor development. Our work demonstrated that salivary protein profiles can be used to identify cellular changes associated with precancerous stage breast cancer through non-invasive means even prior to biopsy-evident disease.

Minimally invasive swine spine surgery training: technical aspects, benefits, and anatomical limitations.

OBJECTIVE: To describe the technical specificities and feasibility of simulation of minimally invasive spine surgery in live pigs, as well as similarities and differences in comparison to surgery in humans. METHODS: A total of 22 Large White class swine models, weighing between 60 and 80kg, were submitted to surgical simulations, performed during theoretical-practical courses for training surgical techniques (microsurgical and endoscopic lumbar decompression; percutaneous pedicular instrumentation; lateral access to the thoracic spine, and anterior and retroperitoneal to the lumbar spine, and management of complications) by 86 spine surgeons. For each surgical technique, porcine anatomy (similarities and differences in relation to human anatomy), access route, and dimensions of the instruments and implants used were evaluated. Thus, the authors describe the feasibility of each operative simulation, as well as suggestions to optimize training. Study results are descriptive, with figures and drawings. RESULTS: Neural decompression surgeries (microsurgeries and endoscopic) and pedicular instrumentation presented higher similarities to surgery on humans. On the other hand, intradiscal procedures had limitations due to the narrow disc space in swines. We were able to simulate situations of surgical trauma in surgical complication scenarios, such as cerebrospinal fluid fistulas and excessive bleeding, with comparable realism to surgery on humans. CONCLUSION: A porcine model for simulation of minimally invasive spinal surgical techniques had similarities with surgery on humans, and is therefore feasible for surgeon training.

Training in recovery, perfusion and packaging of organs for transplants: profile of professionals and analysis of post-course learning.

OBJECTIVE: To understand the profile of professionals working in organ harvesting, and analyze the learning results of those trained before and after the course on recovery, perfusion and packaging of organs for transplants. METHODS: A retroprospective, quantitative, analytical-descriptive study about the Course on Recovery, Perfusion and Packaging of Liver and Kidney, in the period from 2012 to 2014. Pre- and post-tests, with ten questions were used to assess knowledge about organ harvesting. The association of knowledge with applied content was verified by the McNemar test. RESULTS: Of the total of 334 participants, 187 (56.0%) were physicians, 104 (31.1%) nurses, and 43 (12.9%) scrub nurses. The majority of participants was male (58.4%), mean age of 39.1 years, 50% had graduated 5 to 10 years before, and 50.4% had less than one-year experience in organ harvesting. In knowledge assessment, there was an increase in the weighted mean, from 6.1 in the pre-test to 7.9 in the post-test. A significant increase in learning was observed in the post-test in 50% of scrub nurses, 33.3% in nurses 20% in physicians. CONCLUSION: The professionals were starting work in organ harvesting, and most were from Southeastern, Northeastern and Northern regions. In terms of learning, the course contributed to enhancing knowledge of the multiprofessional health team, and represented better learning standard.

Scientists of Tomorrow/ Cientistas do Amanhã : a project to inspire, stimulate scientific thinking, and introduce scientific methodology for young students

ABSTRACT The Scientists of Tomorrow/ Cientistas do Amanhã project is an immersive science training program developed by the Program of Post-Graduation in Health Sciences at Hospital Israelita Albert Einstein. This program was conducted in partnership with Volunteering and Escola Municipal de Ensino Fundamental Professor Paulo Freire in Paraisópolis, São Paulo, Brazil. The Scientists of Tomorrow Program comprised a short training period conducted in May 2022 involving 37 students, and a long training period from August to December 2022, which included 15 students. It aimed to popularize science through practical activities; transfer knowledge to young students; sensitize and guide them to pursue academic-scientific careers; reduce stereotypes about scientific work and scientists; and help students understand the social, political, and ethical roles of science within society. All activities were led by postgraduate students and professors from our postgraduate program, physicians, nurses, physiotherapists, biomedicals, and veterinarians from Hospital Israelita Albert Einstein, as well as medical students from Faculdade Israelita de Ciências da Saúde Albert Einstein . Activities in the short training included lectures on cinema and science, strategies to combat fake news, non-violent communication, innovation, design-thinking framework, and developing a scientific project. During the long training period, discussions were focused on nanotechnology, animal research, big data, bioinformatics, meditation, blood and bone marrow donation, telemedicine, sex and sexually-transmitted infections, rehabilitation, career opportunities, and scientific integrity. In addition, practical activities were further expanded using optical and confocal microscopy, cytometry, and basic concepts regarding the structure and function of living cells. The program also included the launching of the open-air outreach Education E-natureza activity, which turned students into ambassadors of nature. In conclusion, the Scientists of Tomorrow Program was innovative and enabled young students to learn that science is a collective activity that can enhance public health.

Minimally invasive swine spine surgery training: technical aspects, benefits, and anatomical limitations

ABSTRACT Objective To describe the technical specificities and feasibility of simulation of minimally invasive spine surgery in live pigs, as well as similarities and differences in comparison to surgery in humans. Methods A total of 22 Large White class swine models, weighing between 60 and 80kg, were submitted to surgical simulations, performed during theoretical-practical courses for training surgical techniques (microsurgical and endoscopic lumbar decompression; percutaneous pedicular instrumentation; lateral access to the thoracic spine, and anterior and retroperitoneal to the lumbar spine, and management of complications) by 86 spine surgeons. For each surgical technique, porcine anatomy (similarities and differences in relation to human anatomy), access route, and dimensions of the instruments and implants used were evaluated. Thus, the authors describe the feasibility of each operative simulation, as well as suggestions to optimize training. Study results are descriptive, with figures and drawings. Results Neural decompression surgeries (microsurgeries and endoscopic) and pedicular instrumentation presented higher similarities to surgery on humans. On the other hand, intradiscal procedures had limitations due to the narrow disc space in swines. We were able to simulate situations of surgical trauma in surgical complication scenarios, such as cerebrospinal fluid fistulas and excessive bleeding, with comparable realism to surgery on humans. Conclusion A porcine model for simulation of minimally invasive spinal surgical techniques had similarities with surgery on humans, and is therefore feasible for surgeon training.

Training in recovery, perfusion and packaging of organs for transplants: profile of professionals and analysis of post-course learning / Capacitação em extração, perfusão e acondicionamento de órgãos para transplantes: perfil dos profissionais e análise de aprendizagem pós-curso

ABSTRACT Objective To understand the profile of professionals working in organ harvesting, and analyze the learning results of those trained before and after the course on recovery, perfusion and packaging of organs for transplants. Methods A retroprospective, quantitative, analytical-descriptive study about the Course on Recovery, Perfusion and Packaging of Liver and Kidney, in the period from 2012 to 2014. Pre- and post-tests, with ten questions were used to assess knowledge about organ harvesting. The association of knowledge with applied content was verified by the McNemar test. Results Of the total of 334 participants, 187 (56.0%) were physicians, 104 (31.1%) nurses, and 43 (12.9%) scrub nurses. The majority of participants was male (58.4%), mean age of 39.1 years, 50% had graduated 5 to 10 years before, and 50.4% had less than one-year experience in organ harvesting. In knowledge assessment, there was an increase in the weighted mean, from 6.1 in the pre-test to 7.9 in the post-test. A significant increase in learning was observed in the post-test in 50% of scrub nurses, 33.3% in nurses 20% in physicians. Conclusion The professionals were starting work in organ harvesting, and most were from Southeastern, Northeastern and Northern regions. In terms of learning, the course contributed to enhancing knowledge of the multiprofessional health team, and represented better learning standard.

RESUMO Objetivo Conhecer o perfil dos profissionais que atuam em captação de órgãos e analisar o resultado da aprendizagem daqueles treinados antes e após o curso de extração, perfusão e acondicionamento de órgãos para transplantes. Métodos Estudo retroprospectivo, quantitativo, analítico-descritivo do Curso de Extração, Perfusão e Acondicionamento de Fígado e Rim, no período de 2012 a 2014. Utilizaram-se o pré e o pós-teste estruturado em dez questões, que avaliaram o conhecimento sobre captação de órgãos. A associação do conhecimento com o conteúdo aplicado foi verificada pelo teste McNemar. Resultados Do total de 334 participantes, 187 (56,0%) eram médicos, 104 (31,1%) enfermeiros e 43 (12,9%) instrumentadores. Houve predominância do sexo masculino (58,4%), com média de idade de 39,1 anos. Tinham entre 5 a 10 anos de formados 50% da amostra, e 50,4% tinham menos de 1 ano de experiência na área de captação de órgãos. Na avaliação do conhecimento, houve elevação na média geral ponderada de 6,1, no pré-teste, para 7,9, no pós-teste. Observou-se aumento significativo da aprendizagem no pós-teste em 50% nos instrumentadores, 33,3% nos enfermeiros e 20% nos médicos. Conclusão Os profissionais eram iniciantes na área de captação de órgãos e, em sua maioria, oriundos das Regiões Sudeste, Nordeste e Norte. No quesito de aprendizagem, o curso contribuiu para o aumento do conhecimento da equipe multiprofissional em saúde, representando ganho no padrão de aprendizagem.