Advances in Animal Models and Cutting-Edge Research in Alternatives: Proceedings of the Third International Conference on 3Rs Research and Progress, Vishakhapatnam, 2022.

Animal experimentation has been integral to drug discovery and development and safety assessment for many years, since it provides insights into the mechanisms of drug efficacy and toxicity (e.g. pharmacology, pharmacokinetics and pharmacodynamics). However, due to species differences in physiology, metabolism and sensitivity to drugs, the animal models can often fail to replicate the effects of drugs and chemicals in human patients, workers and consumers. Researchers across the globe are increasingly applying the Three Rs principles by employing innovative methods in research and testing. The Three Rs concept focuses on: the replacement of animal models (e.g. with in vitro and in silico models or human studies), on the reduction of the number of animals required to achieve research objectives, and on the refinement of existing experimental practices (e.g. eliminating distress and enhancing animal wellbeing). For the last two years, Oncoseek Bio-Acasta Health, a 3-D cell culture-based cutting-edge translational biotechnology company, has organised an annual International Conference on 3Rs Research and Progress. This series of global conferences aims to bring together researchers with diverse expertise and interests, and provides a platform where they can share and discuss their research to promote practices according to the Three Rs principles. In November 2022, the 3rd international conference, Advances in Animal Models and Cutting-Edge Research in Alternatives, took place at the GITAM University in Vishakhapatnam (AP, India) in a hybrid format (i.e. online and in-person). These conference proceedings provide details of the presentations, which were categorised under five different topic sessions. It also describes a special interactive session on in silico strategies for preclinical research in oncology, which was held at the end of the first day.

Assessment of benthic macroinvertebrates as potential bioindicators of anthropogenic disturbance in southeast Bangladesh coast.

Many human activities can greatly influence and alter the health of aquatic ecosystems. In this regard, the quantitative analysis of macroinvertebrates and their relationships with ecological variables is an effective method in environmental monitoring programs. Here, we used the benthic macroinvertebrate community as bioindicators for assessing anthropogenic impacts on coastal waters in southeast Bangladesh. Sediment samples were collected seasonally from three different sites influenced either by mangrove forests, aquaculture activity or sewage input. The indicator value index (IndVal) analysis revealed 23 species of benthic macroinvertebrates as potential bioindicators namely Enigmonia aenigmatica, Mactra chinensis and Pharella javanica of the class Bivalvia; Tubifex tubifex of the class Clitellata; Lithopoma brevispina, Bullia vittata, Pomacea maculata and Umbonium vestiarium of the class Gastropoda; Gammarus roeselii of the class Malacostraca; and Amphicteis gunneri, Amphitrite ornata, Aricidea simplex, Cirratulus cirratus, Heterospio catalinensis, Hypereteone foliosa, Lopadorrhynchus henseni, Neanthes chingrighattensis, Micronephthys oligobranchia, Nephtys hombergii, Nereis jacksoni, Nereis zonata, Polyodontes maxillosus and Stygocapitella subterranean of the class Polychaeta. Their composition across three sites varied significantly (P < 0.05) due to influence of environmental conditions as inferred from redundancy analysis. Polychaeta, Gastropoda and Malacostraca were susceptible to sewage input, while Bivalvia and Clitellata were susceptible to aquaculture effluent. The results of this baseline study suggest that the identified benthic macroinvertebrate species can potentially be used to monitor anthropogenic disturbances in the marine environment.

Intertidal macroinvertebrate community structure in a subtropical channel is driven by sediment properties across different land-use types.

Macroinvertebrate community in the intertidal setup plays an important role in coastal ecosystem functions and biogeochemical cycle. However, different land use pattern may influence on their community structure, diversity, and composition in the coastal ecosystems. Using Van-Veen grab sampler, 60 sediment samples were seasonally collected from mangroves-dominated, aquaculture-dominated, and anthropogenically affected area in the lower intertidal zone of the Kohelia channel of Bangladesh, the Northern Bay of Bengal. We have tasted the variation in sediment properties across three land-use types in this intertidal habitat. To understand the patterns of benthic macroinvertebrate distribution, a neutral community model was applied. Our results showed that community composition and biodiversity of the benthic macroinvertebrate communities varied significantly between mangrove-dominated area with anthropogenically affected areas among the four seasons. The neutral community model revealed that community assembly of benthic macroinvertebrates in the lower intertidal habitats is structured by stochastic processes while sediment properties have significant influence on species distribution and interactions. Results suggested that land-use changes altered sediment properties and could change the diversity and distribution of the macroinvertebrate communities in the lower intertidal habitats.

Nonhuman Animals, Public Health, and Ethics: A First Step, But .

In December 2015, the Johns Hopkins Bloomberg School of Public Health held the first-ever summit on the intersection between nonhuman animal ethics and human health. The conference covered a variety of issues where animal health intersects with human health, including the wildlife trade, animal agriculture, and animal experimentation. This article provides a brief overview and critique of the summit.

The flaws and human harms of animal experimentation.

Nonhuman animal ("animal") experimentation is typically defended by arguments that it is reliable, that animals provide sufficiently good models of human biology and diseases to yield relevant information, and that, consequently, its use provides major human health benefits. I demonstrate that a growing body of scientific literature critically assessing the validity of animal experimentation generally (and animal modeling specifically) raises important concerns about its reliability and predictive value for human outcomes and for understanding human physiology. The unreliability of animal experimentation across a wide range of areas undermines scientific arguments in favor of the practice. Additionally, I show how animal experimentation often significantly harms humans through misleading safety studies, potential abandonment of effective therapeutics, and direction of resources away from more effective testing methods. The resulting evidence suggests that the collective harms and costs to humans from animal experimentation outweigh potential benefits and that resources would be better invested in developing human-based testing methods.

The need to include animal protection in public health policies.

Many critical public health issues require non-traditional approaches. Although many novel strategies are used, one approach not widely applied involves improving the treatment of animals. Emerging infectious diseases are pressing public health challenges that could benefit from improving the treatment of animals. Other human health issues, that overlap with animal treatment issues, and that warrant further exploration, are medical research and domestic violence. The diverse nature of these health issues and their connection with animal treatment suggest that there may be other similar intersections. Public health would benefit by including the treatment of animals as a topic of study and policy development.

The risk of immune thrombocytopenic purpura after vaccination in children and adolescents.

BACKGROUND: The risk of immune thrombocytopenic purpura (ITP) after childhood vaccines other than measles-mumps-rubella vaccine (MMR) is unknown. METHODS: Using data from 5 managed care organizations for 2000 to 2009, we identified a cohort of 1.8 million children ages 6 weeks to 17 years. Potential ITP cases were identified by using diagnostic codes and platelet counts. All cases were verified by chart review. Incidence rate ratios were calculated comparing the risk of ITP in risk (1 to 42 days after vaccination) and control periods. RESULTS: There were 197 chart-confirmed ITP cases out of 1.8 million children in the cohort. There was no elevated risk of ITP after any vaccine in early childhood other than MMR in the 12- to 19-month age group. There was a significantly elevated risk of ITP after hepatitis A vaccine at 7 to 17 years of age, and for varicella vaccine and tetanus-diphtheria-acellular pertussis vaccine at 11 to 17 years of age. For hepatitis A, varicella, and tetanus-diphtheria-acellular pertussis vaccines, elevated risks were based on one to two vaccine-exposed cases. Most cases were acute and mild with no long-term sequelae. CONCLUSIONS: ITP is unlikely after early childhood vaccines other than MMR. Because of the small number of exposed cases and potential confounding, the possible association of ITP with hepatitis A, varicella, and tetanus-diphtheria-acellular pertussis vaccines in older children requires further investigation.

Immunization-safety monitoring systems for the 2009 H1N1 monovalent influenza vaccination program.

The effort to vaccinate the US population against the 2009 H1N1 influenza virus hinged, in part, on public confidence in vaccine safety. Early in the vaccine program, >20% of parents reported that they would not vaccinate their children. Concerns about the safety of the vaccines were reported by many parents as a factor that contributed to their intention to forgo vaccination (see www.hsph.harvard.edu/news/press-releases/2009-releases/survey-40-adults-absolutely-certain-h1n1-vaccine.html and www.med.umich.edu/mott/npch/reports/h1n1.htm). The safety profiles of 2009 H1N1 monovalent influenza vaccines were anticipated to be (and have been) similar to those of seasonal influenza vaccines, for which an excellent safety profile has been demonstrated. Here we describe steps taken by the US government to (1) assess the key federal systems in place before 2009 for monitoring the safety of vaccines and (2) integrate and upgrade those systems for optimal vaccine-safety monitoring during the 2009 H1N1 monovalent influenza vaccination program. These efforts improved monitoring of 2009 H1N1 vaccine safety, hold promise for enhancing future national monitoring of vaccine safety, and may ultimately help improve public confidence in vaccines.

Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines.

Because of the advent of a new influenza A H1N1 strain, many countries have begun mass immunisation programmes. Awareness of the background rates of possible adverse events will be a crucial part of assessment of possible vaccine safety concerns and will help to separate legitimate safety concerns from events that are temporally associated with but not caused by vaccination. We identified background rates of selected medical events for several countries. Rates of disease events varied by age, sex, method of ascertainment, and geography. Highly visible health conditions, such as Guillain-Barré syndrome, spontaneous abortion, or even death, will occur in coincident temporal association with novel influenza vaccination. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, 21.5 cases of Guillain-Barré syndrome and 5.75 cases of sudden death would be expected to occur within 6 weeks of vaccination as coincident background cases. In female vaccinees in the USA, 86.3 cases of optic neuritis per 10 million population would be expected within 6 weeks of vaccination. 397 per 1 million vaccinated pregnant women would be predicted to have a spontaneous abortion within 1 day of vaccination.

Animal studies in spinal cord injury: a systematic review of methylprednisolone.

The objective of this study was to examine whether animal studies can reliably be used to determine the usefulness of methylprednisolone (MP) and other treatments for acute spinal cord injury (SCI) in humans. This was achieved by performing a systematic review of animal studies on the effects of MP administration on the functional outcome of acute SCI. Data were extracted from the published articles relating to: outcome; MP dosing regimen; species/strain; number of animals; methodological quality; type of injury induction; use of anaesthesia; functional scale used; and duration of follow-up. Subgroup analyses were performed, based on species or strain, injury method, MP dosing regimen, functional outcome measured, and methodological quality. Sixty-two studies were included, which involved a wide variety of animal species and strains. Overall, beneficial effects of MP administration were obtained in 34% of the studies, no effects in 58%, and mixed results in 8%. The results were inconsistent both among and within species, even when attempts were made to detect any patterns in the results through subgroup analyses. The results of this study demonstrate the barriers to the accurate prediction from animal studies of the effectiveness of MP in the treatment of acute SCI in humans. This underscores the need for the development and implementation of validated testing methods.

Health professionals' roles in animal agriculture, climate change, and human health.

What we eat is rapidly becoming an issue of global concern. With food shortages, the rise in chronic disease, and global warming, the impact of our dietary choices seems more relevant today than ever. Globally, a transition is taking place toward greater consumption of foods of animal origin, in lieu of plant-based diets. With this transition comes intensification of animal agriculture that in turn is associated with the emergence of zoonotic infectious diseases, environmental degradation, and the epidemics of chronic disease and obesity. Health professionals should be aware of these trends and consider them as they promote healthier and more environmentally-sustainable diets.

Animal models in spinal cord injury: a review.

Multiple neuroprotective agents have shown benefit for the treatment of acute spinal cord injury (SCI) in animal studies. However, clinical trials have, thus far, been uniformly disappointing. This review explores reasons for discrepancies between promising animal studies and disappointing clinical trials and potential barriers to extrapolation of research results from animals to humans. The three major barriers disclosed are: differences in injury type between laboratory-induced SCI and clinical SCI, difficulties in interpreting functional outcome in animals, and inter-species and interstrain differences in pathophysiology of SCI. These barriers can impair the effectiveness of animal models of SCI to predict human outcomes. While some of these barriers can be overcome, others are inherent to the animal models.

A morphological and morphometric study of extra hepatic biliary duct of autopsied population of Bangladesh.

The study was carried out in 20 humans to observe the mean length, external and luminal diameters of different parts of the extra-hepatic bile duct. The largest mean length and diameters were found in common bile duct.