A brief history of the animals' scientific research, international rules and Brazilian regulations.

Several countries and non-governmental organizations have discussed the use of animals in industry and biomedical areas. This work shows the progression of animal' rights for scientific purposes in Brazil and how Brazilian Councils have advanced to follow worldwide regulations. Since the first rules about animals' usage in Ireland in 1635, the British Cruelty to Animals Act in 1876, and the Brazilian animal protection rules in 1924 and 1934, most worldwide actions culminated in the Universal Declaration of Animal Rights (1978). In 1979, the Brazilian Law 6.638 displayed directives for didactic-scientific practice of vivisection. In 2008, the Arouca Law 11.794 filled regulatory gaps and created the National Council for the Control of Animal Experimentation (CONCEA). In 2014, the CONCEA incorporated the 3R's philosophy and recognized substitute techniques, but only in 2023 it prohibited vertebrate animals in scientific research, development and control of personal hygiene products, cosmetics and perfumes. It is clear current Brazilian and international rules are unable to cover all aspects of animal wellbeing, even for regulations of commercial issues. Certainly, innovative tools, as organ-on-chip, in vitro techniques and bioinformatical advancements will provide a crucial animal welfare and new laws will minimize animal pain and distress, including for disregarded invertebrates.

Q&A with Daniel Drucker.

Med discusses the history and future of GLP-1 research with Professor Daniel Drucker from the Lunenfeld Tanenbaum Research Institute at Mount Sinai Hospital in Toronto, Canada.

Conceptual Parallels: Microbiome Research and Ancient Medicine.

The concepts currently operating in much medical microbiome research bear a curious resemblance to an ancient tradition of Western medicine. This tradition, humoral medicine, is concerned with the four humors: yellow and black bile, phlegm, blood. Both humoral medicine and medical microbiome research use notions of imbalance and balance for broad explanations of disease and health. Both traditions also hold that the composition of humors or microbiomes determines bodily as well as mental states. Causality in each system is often conceived teleologically, meaning that humors or microbiomes "function for" the maintenance of the whole. And ultimately, each framework situates the humors or microbiomes in a multilevel interactionist theory that conceptualizes individual health within a broader environmental context. As well as critically assessing the parallels between these systems, this article sketches some explanations of how they may have arisen. The authors also evaluate the implications of these similarities for the future of medical microbiome research and suggest ways in which the field might move forward.

National Institute on Aging's 50th Anniversary: Advancing Cognitive Aging Research and the Cognitive Health of Older Adults.

In celebration of the National Institute on Aging's (NIA) 50th anniversary, this paper highlights the significant advances in cognitive aging research and the promotion of cognitive health among older adults. Since its inception in 1974, the NIA has played a pivotal role in understanding cognitive aging, including cognitive epidemiology, interventions, and methods, for measuring cognitive change. Key milestones include the shift toward understanding cognitive impairment and Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD), the development of large-scale longitudinal studies, and the incorporation of AD/ADRD-related biomarkers in cognitive aging cohorts. Additionally, NIA has championed diversifying the scientific workforce through initiatives, such as the Resource Centers for Minority Aging Research and the Butler-Williams Scholars Program. The next 50 years will continue to emphasize the importance of inclusion, innovation, and impactful research to enhance the cognitive health and well-being of older adults.

20 years of herpes simplex virus type 2 (HSV-2) research in low-income and middle-income countries: systematic evaluation of progress made in addressing WHO priorities for research in HSV-2/HIV interactions, HSV-2 control and mathematical modelling.

INTRODUCTION: Reviewing and updating research priorities is essential to assess progress and to ensure optimal allocation of financial and human resources in research. In 2001, WHO held a research priority setting workshop for herpes simplex virus type 2 (HSV-2) research in low-income and middle-income countries (LMICs). This study aimed to describe progress between 2000 and 2020 in three of the five key research priority areas outlined in the workshop: HSV-2/HIV interactions, HSV-2 control measures and HSV-2 mathematical modelling. The remaining priorities are addressed in a companion paper. METHOD: A systematic literature search of MEDLINE, CINAHL, Global Health and Cochrane databases was carried out. Relevant primary research studies based in LMICs, written in English and published on 2000-2020 were included. Papers were screened by two independent reviewers, and suitable variables were selected for manual extraction from study texts. Data were organised into an Excel spreadsheet and analysed using IBM SPSS. RESULTS: In total, 3214 discrete papers were identified, of which 180 were eligible for inclusion (HSV-2/HIV interactions, 98; control measures, 58; mathematical modelling, 24). Most studies were conducted in East Africa. The majority of the 2001 WHO HSV-2 research priorities were addressed at least in part. Overall, despite several studies describing a strong relationship between HSV-2 and the acquisition and transmission of HIV, HSV-2 control repeatedly demonstrated little effect on HIV shedding or transmission. Further, although mathematical modelling predicted that vaccines could significantly impact HSV-2 indicators, HSV-2 vaccine studies were few. Studies of antiviral resistance were also few. CONCLUSION: Since 2000, LMIC HSV-2 research addressing its control, HIV interactions and mathematical modelling has largely addressed the priorities set in the 2001 WHO HSV-2 workshop. However, key knowledge gaps remain in vaccine research, antiviral cost-effectiveness, antiviral resistance and specific geographical areas.

PPARs in Clinical Experimental Medicine after 35 Years of Worldwide Scientific Investigations and Medical Experiments.

This year marks the 35th anniversary of Professor Walter Wahli's discovery of the PPARs (Peroxisome Proliferator-Activated Receptors) family of nuclear hormone receptors. To mark the occasion, the editors of the scientific periodical Biomolecules decided to publish a special issue in his honor. This paper summarizes what is known about PPARs and shows how trends have changed and how research on PPARs has evolved. The article also highlights the importance of PPARs and what role they play in various diseases and ailments. The paper is in a mixed form; essentially it is a review article, but it has been enriched with the results of our experiments. The selection of works was subjective, as there are more than 200,000 publications in the PubMed database alone. First, all papers done on an animal model were discarded at the outset. What remained was still far too large to describe directly. Therefore, only papers that were outstanding, groundbreaking, or simply interesting were described and briefly commented on.

Lessons for Cardiovascular Clinical Investigators: The Tumultuous 2,500-Year Journey of Physicians Who Ignited Our Fire.

Whereas medical practice stems from Hippocrates, cardiovascular science originates with Aristotle. The Hippocratic philosophy was championed by Galen (129-216 CE), whose advocacy of a tripartite soul found favor in the early Christian Church. In contrast, Aristotle's works were banned as heresy by ecclesiastical authority, only to survive and prosper in the Islamic Golden Age (775-1258 CE). Galen theorized that the circulation consisted of separate venous and arterial systems. Blood was produced in the liver and traveled centrifugally through veins. When arriving in the right ventricle, venous blood passed through tiny pores in the ventricular septum into the left ventricle, where it became aerated by air passing from the lungs through the pulmonary veins to the left side of the heart. Following arrival at distal sites, arterial blood disappeared, being consumed by the tissues, requiring that the liver needed to continually synthesize new blood. The heart was viewed as a sucking organ, and the peripheral pulse was deemed to result from changes in arterial tone, rather than cardiac systole. Galen's framework remained undisputed and dominated medical thought for 1,300 years, but the reintroduction of Aristotelian principles from the Islamic world into Europe (through the efforts of the Toledo School of Translators) were nurtured by the academic freedom and iconoclastic environment uniquely cultivated at the University of Padua, made possible by Venetian rebellion against papal authority. At Padua, the work of Andreas Vesalius, Realdo Colombo, Hieronymus Fabricius ab Acquapendente, and William Harvey (1543-1628) methodically destroyed Galen's model, leading to the modern concept of a closed-ended circulation. Yet, due to political forces, Harvey was ridiculed, as was James Lind, who performed the first prospective controlled trial, involving citrus fruits for scurvy (1747); it took nearly 50 years for his work to be accepted. Even the work of William Withering (1785), the father of cardiovascular pharmacology, was tarnished by professional jealously and the marketing campaign of a pharmaceutical company. Today's cardiovascular investigators should understand that major advances are routinely derided by the medical establishment for political or personal reasons; and it may take decades or centuries for important work to be accepted.