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Sexual dimorphism of visceral pain has been documented in clinics and experimental animal models. Aside from hormones, emerging evidence suggests the sex-differential intrinsic neural regulation of pain generation and maintenance. According to the International Association for the Study of Pain (IASP) and the American College of Gastroenterology (ACG), up to 25% of the population have visceral pain at any one time, and in the United States 10–15 percent of adults suffer from irritable bowel syndrome (IBS). Here we examine the preclinical and clinical evidence of sex differences in visceral pain focusing on IBS, other forms of bowel dysfunction and IBS-associated comorbidities. We summarize preclinical animal models that provide a means to investigate the underlying molecular mechanisms in the sexual dimorphism of visceral pain. Neurons and nonneuronal cells (glia and immune cells) in the peripheral and central nervous systems, and the communication of gut microbiota and neural systems all contribute to sex-dependent nociception and nociplasticity in visceral painful signal processing. Emotion is another factor in pain perception and appears to have sexual dimorphism. [ABSTRACT FROM AUTHOR]

Background: The concept of reserve was established to account for the observation that a given degree of neurodegenerative pathology may result in varying degrees of symptoms in different individuals. There is a large amount of evidence on epidemiological risk and protective factors for neurodegenerative diseases and dementia, yet the biological mechanisms that underpin the protective effects of certain lifestyle and physiological variables remain poorly understood, limiting the development of more effective preventive and treatment strategies. Additionally, different definitions and concepts of reserve exist, which hampers the coordination of research and comparison of results across studies.Discussion: This paper represents the consensus of a multidisciplinary group of experts from different areas of research related to reserve, including clinical, epidemiological and basic sciences. The consensus was developed during meetings of the working groups of the first International Conference on Cognitive Reserve in the Dementias (24-25 November 2017, Munich, Germany) and the Alzheimer's Association Reserve and Resilience Professional Interest Area (25 July 2018, Chicago, USA). The main objective of the present paper is to develop a translational perspective on putative mechanisms underlying reserve against neurodegenerative disease, combining evidence from epidemiological and clinical studies with knowledge from animal and basic research. The potential brain functional and structural basis of reserve in Alzheimer's disease and other brain disorders are discussed, as well as relevant lifestyle and genetic factors assessed in both humans and animal models.Conclusion: There is an urgent need to advance our concept of reserve from a hypothetical model to a more concrete approach that can be used to improve the development of effective interventions aimed at preventing dementia. Our group recommends agreement on a common dictionary of terms referring to different aspects of reserve, the improvement of opportunities for data sharing across individual cohorts, harmonising research approaches across laboratories and groups to reduce heterogeneity associated with human data, global coordination of clinical trials to more effectively explore whether reducing epidemiological risk factors leads to a reduced burden of neurodegenerative diseases in the population, and an increase in our understanding of the appropriateness of animal models for reserve research. [ABSTRACT FROM AUTHOR]

Food allergy is an emerging epidemic that affects all age groups, with the highest prevalence rates being reported amongst Western countries such as the United States (US), United Kingdom (UK), and Australia. The development of animal models to test various food allergies has been beneficial in allowing more rapid and extensive investigations into the mechanisms involved in the allergic pathway, such as predicting possible triggers as well as the testing of novel treatments for food allergy. Traditionally, small animal models have been used to characterise immunological pathways, providing the foundation for the development of numerous allergy models. Larger animals also merit consideration as models for food allergy as they are thought to more closely reflect the human allergic state due to their physiology and outbred nature. This paper will discuss the use of animal models for the investigation of the major food allergens; cow's milk, hen's egg, and peanut/other tree nuts, highlight the distinguishing features of each of these models, and provide an overview of how the results from these trials have improved our understanding of these specific allergens and food allergy in general. [ABSTRACT FROM AUTHOR]

In recent years scientists have created genetically modified pigs for the purpose of xenotransplantations. These are transplants of animal organs into human patients. But xenotransplantation has a long history. Since the early twentieth century, many surgeons tried to insert animal organs into human and non-human bodies. This paper examines the controversies that these innovations have caused in the United States and France, including the notion of the objectification of animals. Three phases are described. The historical review shows that far from the choice of pigs being "natural" it turns out to be recent and to follow controversies surrounding the possible use of primates. During the last phase, the scientists have internalized the "animal issue" in their practice: the official donor is now the pig, and the animals are treated respectfully during all the lab manipulations. Since pigs are different from humans they can be objectified and thus absorbed. This objective distance is, however, threatened by new discourses on animal rights, by genetic manipulations that "humanise" pigs, and by scientific practice itself that recognizes a moral proximity between pigs and men. [ABSTRACT FROM AUTHOR]

Background: Translational science supports successful transition of early biomedical research into human applications. In 2009 a translatability score to assess risk and identify strengths and weaknesses of a given project has been designed and successfully tested in case studies. The score elements, in particular the contributing weight factors, are heterogeneous for different disease areas; therefore, the score was individualized for six areas (cardiovascular, oncology, psychiatric, anti-viral, anti-bacterial/fungal and monogenetic diseases).Results: FDA reviews and related literature were used for modifications of the score with emphasis on biomarkers, personalized medicine and animal models. 113 new medical entities approved by FDA from 2012 through 2016 were evaluated and metrics obtained for companion diagnostics and animal models as starting points for author-based individualization of the score. Most drugs approved in this period were related to oncology (46%), while the approvals were lowest for psychiatrics (4%). The evaluation of the FDA package inserts revealed that companion diagnostics play an important role in every field except psychiatrics. Further the analysis of the FDA reviews showed the weakness of animal models in psychiatrics and anti-virals, while useful animal models were present for all other fields. Consequently the scoring system was adapted to the different fields, resulting in increased weights for animal models, biomarker and personalized medicine in oncology. For psychiatrics the weights for animal models, biomarker and personalized medicine were decreased, while the weight for model compounds, clinical trials and surrogate or endpoint strategy were increased. For anti-viral drugs weights for in vitro data and personalized medicine were increased, while the weight for animal models was decreased. Further, for anti-bacterial/fungal drugs weights for animal models and personalized medicine were increased. Weights were increased for genetics and personalized medicine and decreased for model compounds for monogenetic orphans.Conclusions: Adaptation of the score to different disease areas should help to support a structured and diverse approach to translation and encourage researchers in the private or public sectors to further customize the score. [ABSTRACT FROM AUTHOR]

The recently implemented National Institutes of Health policy requiring that grant applicants consider sex as a biological variable in the design of basic and preclinical animal research studies has prompted considerable discussion within the neuroscience community. Here, we present reasons to be optimistic that this new policy will be valuable for neuroscience, and we suggest some ways for neuroscientists to think about incorporating sex as a variable in their research. [ABSTRACT FROM AUTHOR]

The article focuses on the use of rabbits for testing the potential of dangerous chemicals by the U.S. Department of Transportation (DOT). According to People for the Ethical Treatment of Animals (PETA), animal rights organization, thousands of rabbits are used before the corrosive substances are assigned the U.S. shipping labels. PETA also claims that even when alternate methods like the Corrositex test is available for testing the hazardous materials, this practice is encouraged by DOT.

The Guide for the Care and Use of Laboratory Animals (NRC 2011) serves as the principal reference for the oversight of most vertebrate use in research and teaching in the United States. The Guide was developed as a reference for biomedical research. Beyond guiding ethical principles, the Guide contains little information useful for the oversight of research involving wild taxa. To fill this breach, and at the behest of the National Science Foundation, taxon-specific societies in the United States developed independent guidelines that held to the principles of ethical use of animals in research and that were specific to wildlife. Recognition of these taxon-specific guidelines by federal grantmaking agencies and the animal welfare community as appropriate standards for wildlife research will facilitate the required oversight of research involving wild taxa and the ethical use of wild animals in research and teaching. [ABSTRACT FROM AUTHOR]

Though better recognized for its immediate endeavors in human embryo research, the Carnegie Department of Embryology also employed a breeding colony of rhesus macaques for the purposes of studying human reproduction. This essay follows the course of the first enterprise in maintaining a primate colony for laboratory research and the overlapping scientific, social, and political circumstances that tolerated and cultivated the colony's continued operation from 1925 until 1971. Despite a new-found priority for reproductive sciences in the United States, by the early 1920s an unfertilized human ovum had not yet been seen and even the timing of ovulation remained unresolved. Progress would require an organized research approach that could extend beyond the limitations of working with scant and inherently restrictive human subjects or with common lab mammals like mice. In response, the Department of Embryology, under the Carnegie Institution of Washington (CIW), instituted a novel methodology using a particular primate species as a surrogate in studying normal human reproductive physiology. Over more than 40 years the monkey colony followed an unpremeditated trajectory that would contribute fundamentally to discoveries in human reproduction, early embryo development, reliable birth control methods, and to the establishment of the rhesus macaque as a common model organism. [ABSTRACT FROM AUTHOR]

The article presents information regarding the rights and legal protections of animals with special emphasis on primates which are mostly used for research purposes, under the U.S. Animal Welfare Act and evaluates the Act in terms of legislation inadequacies. It concludes that existing protective law for animals is human-focused and inadequate. It suggests that animal laboratory research necessitates the need to rebuilt speciesist ideology that legalizes the use of animals in research.

The article focuses on the U.S. National Research Council (NRC)'s report entitled "Toxicity Testing in the 21st Century: A Vision and a Strategy," called for moving away from traditional high-dose animal studies to an approach based on perturbation of cellular responses using well-designed in vitro assays. The approaches for assessing the health risks of chemical exposure rely on conservative extrapolations to relate animal studies to much lower-dose human exposures.

Research that includes non-human animal experimentation is fundamentally a dilemmatic enterprise. Humans use other animals in research to improve life for their own species. Ethical principles are established to deal with this dilemma. But despite this ethical apparatus, people who in one way or another work with animal experimentation have to interpret and understand the principles from their individual points of view. In interviews with members of Swedish animal ethics committees, different views on what the term ethics really means were articulated. For one member, the difficult ethical dilemma of animal experimentation is the lack of enriched cages for mice. For another, the ethical problem lies in regulations restraining research. A third member talks about animals' right not to be used for human interests. These different views on "ethics" intersect once a month in the animal ethics committee meetings. There is no consensus on what constitutes the ethical problem that the members should be discussing. Therefore, personal views on what ethics means, and hierarchies among committee members, characterise the meetings. But committee traditions and priorities of interpretation as well are important to the decisions. The author discusses how "ethics" becomes situated and what implications this may have for committees' decisions. [ABSTRACT FROM AUTHOR]

The article mentions animal studies on the health effects of perfluoroalkyl acids (PFAA), which are ubiquitous in the environment and can take months for the monkey to eliminate from its body. The compounds perfluorooctanoic acid (PFOA) and perfluorooctanyl sulfonate (PFOS) have been linked to adult obesity in mice and immunotoxicity in dolphins. Toxicological studies conducted by the U.S. Environmental Protection Agency, the Centers for Disease Control and Prevention, and Johns Hopkins University are discussed. Two hypotheses are mentioned: that PFOA increases fatty acid metabolism in utero and contributes to fetal undernourishment; and that fetal programming syndrome is a factor in human weight problems.

The author reflects on the therapeutic cloning and regenerative research in animal models. Despite the therapeutic potential of cloning in human being, the U.S. government calls for a total ban to any form of cloning research in human. As a result, the author and his fellows are concentrating on animals as their model for cloning studies. He offers several reviews which explore the beneficial effects of cloning, including a review on issues surrounding the genetic age of clones.

The article presents information on the discussion that took place at a two day symposium titled "The Future of Animals, Cells, Models, and Systems in Research, Development, Education, and Testing," held at the U.S. National Academy of Sciences. The symposium focused on the need of animals as research tools and the possibility of replacing them with organ culture or computer technology. Several academicians participated in the symposium, including Kurt Benirschke, Sol Kramer, and Mary Dawson. INSET: Computer Techniques.

Reports on the study results about health effects of diesel exhaust particles (DEP) in the U.S. Total hydrogen-ion concentration of DEP; Comparison of the pulmonary and genotoxic effects of DEP in mice and Salmonella; Need for evaluation of a wide range of DEP samples.