Gutierrez, Eric; Quinn, Daniel B; Chin, Diana D; Lentink, David
There are three common methods for calculating the lift generated by a flying animal based on the measured airflow in the wake. However, these methods might not be accurate according to computational and robot-based studies of flapping wings. Here we test this hypothesis for the first time for a slowly flying Pacific parrotlet in still air using stereo particle image velocimetry recorded at 1000 Hz. The bird was trained to fly between two perches through a laser sheet wearing laser safety goggles. We found that the wingtip vortices generated during mid-downstroke advected down and broke up quickly, contradicting the frozen turbulence hypothesis typically assumed in animal flight experiments. The quasi-steady lift at mid-downstroke was estimated based on the velocity field by applying the widely used Kutta-Joukowski theorem, vortex ring model, and actuator disk model. The calculated lift was found to be sensitive to the applied model and its different parameters, including vortex span and distance between the bird and laser sheet-rendering these three accepted ways of calculating weight support inconsistent. The three models predict different aerodynamic force values mid-downstroke compared to independent direct measurements with an aerodynamic force platform that we had available for the same species flying over a similar distance. Whereas the lift predictions of the Kutta-Joukowski theorem and the vortex ring model stayed relatively constant despite vortex breakdown, their values were too low. In contrast, the actuator disk model predicted lift reasonably accurately before vortex breakdown, but predicted almost no lift during and after vortex breakdown. Some of these limitations might be better understood, and partially reconciled, if future animal flight studies report lift calculations based on all three quasi-steady lift models instead. This would also enable much needed meta studies of animal flight to derive bioinspired design principles for quasi-steady lift
protection against MDRO in an rabbit model. Year 1. Establishing the mono-organisms rabbit osteomyelitis war wound model KEY RESEARCH...purified, and will be used as vaccine candidates to test for protection against challenge since they match the criteria discussed below: While the...protein and a dipeptide transporter. These antigens will be used in subsequent experiments to show the potential to provide protection against
Hu, Yijie; Yibrehu, Betel; Zabini, Diana; Kuebler, Wolfgang M
Sarcoidosis is a debilitating, inflammatory, multiorgan, granulomatous disease of unknown cause, commonly affecting the lung. In contrast to other chronic lung diseases such as interstitial pulmonary fibrosis or pulmonary arterial hypertension, there is so far no widely accepted or implemented animal model for this disease. This has hampered our insights into the etiology of sarcoidosis, the mechanisms of its pathogenesis, the identification of new biomarkers and diagnostic tools and, last not least, the development and implementation of novel treatment strategies. Over past years, however, a number of new animal models have been described that may provide useful tools to fill these critical knowledge gaps. In this review, we therefore outline the present status quo for animal models of sarcoidosis, comparing their pros and cons with respect to their ability to mimic the etiological, clinical and histological hallmarks of human disease and discuss their applicability for future research. Overall, the recent surge in animal models has markedly expanded our options for translational research; however, given the relative early stage of most animal models for sarcoidosis, appropriate replication of etiological and histological features of clinical disease, reproducibility and usefulness in terms of identification of new therapeutic targets and biomarkers, and testing of new treatments should be prioritized when considering the refinement of existing or the development of new models.
There has been extensive research on how new ideas and technologies are accepted in society. This has resulted in the creation of many models that are used to discover and assess the contributing factors. The Technology Acceptance Model (TAM) is one that is a widely accepted model. This model examines people's acceptance of new technologies based on variables that directly correlate to how the end user views the product. This paper introduces the Policy Acceptance Model (PAM), an expansion of TAM, which is designed for the analysis and evaluation of acceptance of new policy implementation. PAM includes the traditional constructs of TAM and adds the variables of age, ethnicity, and family. The model is demonstrated using a survey of people's attitude toward the upcoming healthcare reform in the United States (US) from 72 survey respondents. The aim is that the theory behind this model can be used as a framework that will be applicable to studies looking at the introduction of any new or modified policies.
Dybiec, Bartlomiej; Mitarai, Namiko; Sneppen, Kim
Agents building social systems are characterized by complex states, and interactions among individuals can align their opinions. The Axelrod model describes how local interactions can result in emergence of cultural domains. We propose two variants of the Axelrod model where local consensus is reached either by listening and accepting one of neighbors' opinion or two agents discuss their opinion and achieve an agreement with mixed opinions. We show that the local agreement rule affects the character of the transition between the single culture and the multiculture regimes.
Sauer, Ursula G; Hill, Erin H; Curren, Rodger D; Raabe, Hans A; Kolle, Susanne N; Teubner, Wera; Mehling, Annette; Landsiedel, Robert
In general, no single non-animal method can cover the complexity of any given animal test. Therefore, fixed sets of in vitro (and in chemico) methods have been combined into testing strategies for skin and eye irritation and skin sensitisation testing, with pre-defined prediction models for substance classification. Many of these methods have been adopted as OECD test guidelines. Various testing strategies have been successfully validated in extensive in-house and inter-laboratory studies, but they have not yet received formal acceptance for substance classification. Therefore, under the European REACH Regulation, data from testing strategies can, in general, only be used in so-called weight-of-evidence approaches. While animal testing data generated under the specific REACH information requirements are per se sufficient, the sufficiency of weight-of-evidence approaches can be questioned under the REACH system, and further animal testing can be required. This constitutes an imbalance between the regulatory acceptance of data from approved non-animal methods and animal tests that is not justified on scientific grounds. To ensure that testing strategies for local tolerance testing truly serve to replace animal testing for the REACH registration 2018 deadline (when the majority of existing chemicals have to be registered), clarity on their regulatory acceptance as complete replacements is urgently required.
Shimamura, Tsuyoshi; Kubota, Nobuo; Shibuya, Kazutoshi
Dermatophytosis is superficial fungal infection caused by dermatophytes that invade the keratinized tissue of humans and animals. Lesions from dermatophytosis exhibit an inflammatory reaction induced to eliminate the invading fungi by using the host's normal immune function. Many scientists have attempted to establish an experimental animal model to elucidate the pathogenesis of human dermatophytosis and evaluate drug efficacy. However, current animal models have several issues. In the present paper, we surveyed reports about the methodology of the dermatophytosis animal model for tinea corporis, tinea pedis, and tinea unguium and discussed future prospects. PMID:22619489
Collins, Lisa M.; Part, Chérie E.
Simple Summary In this review paper we discuss the different modeling techniques that have been used in animal welfare research to date. We look at what questions they have been used to answer, the advantages and pitfalls of the methods, and how future research can best use these approaches to answer some of the most important upcoming questions in farm animal welfare. Abstract The use of models in the life sciences has greatly expanded in scope and advanced in technique in recent decades. However, the range, type and complexity of models used in farm animal welfare is comparatively poor, despite the great scope for use of modeling in this field of research. In this paper, we review the different modeling approaches used in farm animal welfare science to date, discussing the types of questions they have been used to answer, the merits and problems associated with the method, and possible future applications of each technique. We find that the most frequently published types of model used in farm animal welfare are conceptual and assessment models; two types of model that are frequently (though not exclusively) based on expert opinion. Simulation, optimization, scenario, and systems modeling approaches are rarer in animal welfare, despite being commonly used in other related fields. Finally, common issues such as a lack of quantitative data to parameterize models, and model selection and validation are discussed throughout the review, with possible solutions and alternative approaches suggested. PMID:26487411
Bobyn, Justin D; Little, David G; Gray, Randolph; Schindeler, Aaron
Multiple techniques designed to induce scoliotic deformity have been applied across many animal species. We have undertaken a review of the literature regarding experimental models of scoliosis in animals to discuss their utility in comprehending disease aetiology and treatment. Models of scoliosis in animals can be broadly divided into quadrupedal and bipedal experiments. Quadrupedal models, in the absence of axial gravitation force, depend upon development of a mechanical asymmetry along the spine to initiate a scoliotic deformity. Bipedal models more accurately mimic human posture and consequently are subject to similar forces due to gravity, which have been long appreciated to be a contributing factor to the development of scoliosis. Many effective models of scoliosis in smaller animals have not been successfully translated to primates and humans. Though these models may not clarify the aetiology of human scoliosis, by providing a reliable and reproducible deformity in the spine they are a useful means with which to test interventions designed to correct and prevent deformity.
Turner, R. T.; Maran, A.; Lotinun, S.; Hefferan, T.; Evans, G. L.; Zhang, M.; Sibonga, J. D.
Animal models will continue to be important tools in the quest to understand the contribution of specific genes to establishment of peak bone mass and optimal bone architecture, as well as the genetic basis for a predisposition toward accelerated bone loss in the presence of co-morbidity factors such as estrogen deficiency. Existing animal models will continue to be useful for modeling changes in bone metabolism and architecture induced by well-defined local and systemic factors. However, there is a critical unfulfilled need to develop and validate better animal models to allow fruitful investigation of the interaction of the multitude of factors which precipitate senile osteoporosis. Well characterized and validated animal models that can be recommended for investigation of the etiology, prevention and treatment of several forms of osteoporosis have been listed in Table 1. Also listed are models which are provisionally recommended. These latter models have potential but are inadequately characterized, deviate significantly from the human response, require careful choice of strain or age, or are not practical for most investigators to adopt. It cannot be stressed strongly enough that the enormous potential of laboratory animals as models for osteoporosis can only be realized if great care is taken in the choice of an appropriate species, age, experimental design, and measurements. Poor choices will results in misinterpretation of results which ultimately can bring harm to patients who suffer from osteoporosis by delaying advancement of knowledge.
Brozoski, Thomas J; Bauer, Carol A
Presented is a thematic review of animal tinnitus models from a functional perspective. Chronic tinnitus is a persistent subjective sound sensation, emergent typically after hearing loss. Although the sensation is experientially simple, it appears to have central a nervous system substrate of unexpected complexity that includes areas outside of those classically defined as auditory. Over the past 27 years animal models have significantly contributed to understanding tinnitus' complex neurophysiology. In that time, a diversity of models have been developed, each with its own strengths and limitations. None has clearly become a standard. Animal models trace their origin to the 1988 experiments of Jastreboff and colleagues. All subsequent models derive some of their features from those experiments. Common features include behavior-dependent psychophysical determination, acoustic conditions that contrast objective sound and silence, and inclusion of at least one normal-hearing control group. In the present review, animal models have been categorized as either interrogative or reflexive. Interrogative models use emitted behavior under voluntary control to indicate hearing. An example would be pressing a lever to obtain food in the presence of a particular sound. In this type of model animals are interrogated about their auditory sensations, analogous to asking a patient, "What do you hear?" These models require at least some training and motivation management, and reflect the perception of tinnitus. Reflexive models, in contrast, employ acoustic modulation of an auditory reflex, such as the acoustic startle response. An unexpected loud sound will elicit a reflexive motor response from many species, including humans. Although involuntary, acoustic startle can be modified by a lower-level preceding event, including a silent sound gap. Sound-gap modulation of acoustic startle appears to discriminate tinnitus in animals as well as humans, and requires no training or
Organ transplantation has become a successful and acceptable treatment for end-stage organ failure. Such success has allowed transplant patients to resume a normal lifestyle. The demands for transplantation have been steadily increasing, as more patients and new diseases are being deemed eligible for treatment via transplantation. However, it is clear that human organs will never meet the increasing demand of transplantation. Therefore, scientists must continue to pursue alternative therapies and explore new treatments to meet the growing demand for the limited number of organs available. Transplanting organs from animals into humans (xenotransplantation) is one such therapy. The observed enthusiasm for xenotransplantation, irrespective of the severe shortage of human organs and tissues available for transplantation, can be said to stem from at least two factors. First, there is the possibility that animal organs and tissues might be less susceptible than those of humans to the recurrence of disease processes. Second, a xenograft might be used as a vehicle for introducing novel genes or biochemical processes which could be of therapeutic value for the transplant recipient.To date, millions of lives have been saved by organ transplantation. These remarkable achievements would have been impossible without experimental transplantation research in animal models. Presently, more than 95% of organ transplantation research projects are carried out using rodents, such as rats and mice. The key factor to ensure the success of these experiments lies in state-of-the art experimental surgery. Small animal models offer unique advantages for the mechanistic study of xenotransplantation rejection. Currently, multiple models have been developed for investigating the different stages of immunological barriers in xenotransplantation. In this chapter, we describe six valuable small animal models that have been used in xenotransplantation research. The methodology for the small animal
The major types of osteoporosis in humans are postmenopausal osteoporosis, disuse osteoporosis, and glucocorticoid-induced osteoporosis. Animal models for postmenopausal osteoporosis are generated by ovariectomy. Bone loss occurs in estrogen deficiency due to enhanced bone resorption and impaired osteoblast function. Estrogen receptor α induces osteoclast apoptosis, but the mechanism for impaired osteoblast function remains to be clarified. Animal models for unloading are generated by tail suspension or hind limb immobilization by sciatic neurectomy, tenotomy, or using plaster cast. Unloading inhibits bone formation and enhances bone resorption, and the involvement of the sympathetic nervous system in it needs to be further investigated. The osteocyte network regulates bone mass by responding to mechanical stress. Osteoblast-specific BCL2 transgenic mice, in which the osteocyte network is completely disrupted, can be a mouse model for the evaluation of osteocyte functions. Glucocorticoid treatment inhibits bone formation and enhances bone resorption, and markedly reduces cancellous bone in humans and large animals, but not consistently in rodents.
SEP 2015 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Complexity and animal models 5a. CONTRACT NUMBER 5b. GRANT NUMBER...decrease W/Wmax, thereby maintaining the relationship between variability and W/Wmax. doi:10.1016/j.jcrc.2010.05.012 Complexity and animal models...may not be possible during mass casualty and natural disaster situations or may need to be postponed during combat to avoid danger to the medic’s life
Jones, J.B.; Lange, R.D.
The four existing animal models of cyclic hematopoiesis are briefly described. The unusual erythropoietin (Ep) responses of the W/Wv mouse, the Sl/Sld mouse, and cyclic hematopoietic dog are reviewed. The facts reviewed indicate that the bone marrow itself is capable of influencing regulatory events of hematopoiesis.
Jones, CA; Watson, DJG; Fone, KCF
Developing reliable, predictive animal models for complex psychiatric disorders, such as schizophrenia, is essential to increase our understanding of the neurobiological basis of the disorder and for the development of novel drugs with improved therapeutic efficacy. All available animal models of schizophrenia fit into four different induction categories: developmental, drug-induced, lesion or genetic manipulation, and the best characterized examples of each type are reviewed herein. Most rodent models have behavioural phenotype changes that resemble ‘positive-like’ symptoms of schizophrenia, probably reflecting altered mesolimbic dopamine function, but fewer models also show altered social interaction, and learning and memory impairment, analogous to negative and cognitive symptoms of schizophrenia respectively. The negative and cognitive impairments in schizophrenia are resistant to treatment with current antipsychotics, even after remission of the psychosis, which limits their therapeutic efficacy. The MATRICS initiative developed a consensus on the core cognitive deficits of schizophrenic patients, and recommended a standardized test battery to evaluate them. More recently, work has begun to identify specific rodent behavioural tasks with translational relevance to specific cognitive domains affected in schizophrenia, and where available this review focuses on reporting the effect of current and potential antipsychotics on these tasks. The review also highlights the need to develop more comprehensive animal models that more adequately replicate deficits in negative and cognitive symptoms. Increasing information on the neurochemical and structural CNS changes accompanying each model will also help assess treatments that prevent the development of schizophrenia rather than treating the symptoms, another pivotal change required to enable new more effective therapeutic strategies to be developed. LINKED ARTICLES This article is part of a themed issue on
Ramadiani; Rodziah, A.; Hasan, S. M.; Rusli, A.; Noraini, C.
E-learning is not going to work if the system is not used in accordance with user needs. User Interface is very important to encourage using the application. Many theories had discuss about user interface usability evaluation and technology acceptance separately, actually why we do not make it correlation between interface usability evaluation and user acceptance to enhance e-learning process. Therefore, the evaluation model for e-learning interface acceptance is considered important to investigate. The aim of this study is to propose the integrated e-learning user interface acceptance evaluation model. This model was combined some theories of e-learning interface measurement such as, user learning style, usability evaluation, and the user benefit. We formulated in constructive questionnaires which were shared at 125 English Language School (ELS) students. This research statistics used Structural Equation Model using LISREL v8.80 and MANOVA analysis.
Jacobson, I. D.
A technique developed to evaluate the passenger response to a transportation system environment is described. Reactions to motion, noise, temperature, seating, ventilation, sudden jolts and descents are modeled. Statistics are presented for the age, sex, occupation, and income distributions of the candidates analyzed. Values are noted for the relative importance of system variables such as time savings, on-time arrival, convenience, comfort, safety, the ability to read and write, and onboard services.
Chen, Lichao; Brown, Ritchie E; McKenna, James T; McCarley, Robert W
Narcolepsy is a debilitating sleep disorder with excessive daytime sleepiness and cataplexy as its two major symptoms. Although this disease was first described about one century ago, an animal model was not available until the 1970s. With the establishment of the Stanford canine narcolepsy colony, researchers were able to conduct multiple neurochemical studies to explore the pathophysiology of this disease. It was concluded that there was an imbalance between monoaminergic and cholinergic systems in canine narcolepsy. In 1999, two independent studies revealed that orexin neurotransmission deficiency was pivotal to the development of narcolepsy with cataplexy. This scientific leap fueled the generation of several genetically engineered mouse and rat models of narcolepsy. To facilitate further research, it is imperative that researchers reach a consensus concerning the evaluation of narcoleptic behavioral and EEG phenomenology in these models.
Current trends and issues in the development of alternatives to the use of animals in biomedical experimentation are discussed in this position paper. Eight topics are considered and include refinement of acute toxicity assays; eye corrosion/irritation alternatives; skin corrosion/irritation alternatives; contact sensitization alternatives; developmental/reproductive testing alternatives; genetic engineering (transgenic) assays; toxicogenomics; and validation of alternative methods. The discussion of refinement of acute toxicity assays is focused primarily on developments with regard to reduction of the number of animals used in the LD(50) assay. However, the substitution of humane endpoints such as clinical signs of toxicity for lethality in these assays is also evaluated. Alternative assays for eye corrosion/irritation as well as those for skin corrosion/irritation are described with particular attention paid to the outcomes, both successful and unsuccessful, of several validation efforts. Alternative assays for contact sensitization and developmental/reproductive toxicity are presented as examples of methods designed for the examination of interactions between toxins and somewhat more complex physiological systems. Moreover, genetic engineering and toxicogenomics are discussed with an eye toward the future of biological experimentation in general. The implications of gene manipulation for research animals, specifically, are also examined. Finally, validation methods are investigated as to their effectiveness, or lack thereof, and suggestions for their standardization and improvement, as well as implementation are reviewed.
Hanna, Steven; Chang, Joseph
The authors suggested acceptance criteria for rural dispersion models' performance measures in this journal in 2004. The current paper suggests modified values of acceptance criteria for urban applications and tests them with tracer data from four urban field experiments. For the arc-maximum concentrations, the fractional bias should have a magnitude <0.67 (i.e., the relative mean bias is less than a factor of 2); the normalized mean-square error should be <6 (i.e., the random scatter is less than about 2.4 times the mean); and the fraction of predictions that are within a factor of two of the observations (FAC2) should be >0.3. For all data paired in space, for which a threshold concentration must always be defined, the normalized absolute difference should be <0.50, when the threshold is three times the instrument's limit of quantification (LOQ). An overall criterion is then applied that the total set of acceptance criteria should be satisfied in at least half of the field experiments. These acceptance criteria are applied to evaluations of the US Department of Defense's Joint Effects Model (JEM) with tracer data from US urban field experiments in Salt Lake City (U2000), Oklahoma City (JU2003), and Manhattan (MSG05 and MID05). JEM includes the SCIPUFF dispersion model with the urban canopy option and the urban dispersion model (UDM) option. In each set of evaluations, three or four likely options are tested for meteorological inputs (e.g., a local building top wind speed, the closest National Weather Service airport observations, or outputs from numerical weather prediction models). It is found that, due to large natural variability in the urban data, there is not a large difference between the performance measures for the two model options and the three or four meteorological input options. The more detailed UDM and the state-of-the-art numerical weather models do provide a slight improvement over the other options. The proposed urban dispersion model acceptance
Greater susceptibility to infection is a hallmark of compromised immune function in humans and animals, and is often considered the benchmark against which the predictive value of immune function tests are compared. This focus of this paper is resistance to infection with the pa...
Boehncke, W H
Co-existing inflammation and epidermal hyperproliferation characteristic for psoriasis have been shown to be reproducible in several animal models utilizing a variety of different strategies. These models highlight some points of the multicausal pathogenesis of psoriasis. Based on observations made in the animal models, a hypothesis is proposed for the pathogenesis of psoriasis, the elements of which can be tested in a recently established xenogeneic transplantation model.
Kapoor, Mandeep Singh; Khan, Samsroz Ahmad; Gupta, Sanjay Kumar; Choudhary, Rajesh; Bodakhe, Surendra H
Erectile dysfunction (ED) is a prevalent male sexual dysfunction with profound adverse effects on the physical and the psychosocial health of men and, subsequently, on their partners. The expanded use of various types of rodent models has produced some advances in the study of ED, and neurophysiological studies using various animal models have provided important insights into human sexual dysfunction. At present, animal models play a key role in exploring and screening novel drugs designed to treat ED.
Zelia, O P
A comparative efficiency of different regimes for infecting laboratory animals has been determined in order to find out optimal conditions under which an experimental model of intestinal schistosomiasis (infection with Schistosoma mansoni) can be maintained. When evaluating the results of laboratory definitive hosts infection we took into account the character of Schistosoma distribution in animals, which with high probability rate was modelled by means of negative binomial distribution. The main parameters of this distribution were used for determination of effective doses and methods of animals infection alongside with generally accepted indices of infection rate and intensiveness. Analysis of the data obtained has shown that the infection of 150 cercarians per mouse and 200 cercarians per golden and striped hairy-footed hamster by their subcutaneous administration creates optimal density of parasites in the host. Results of investigations have shown that striped hairy-footed hamsters can be used as definitive hosts of Schistosoma.
Khodanovich, M. Yu.; Kisel, A. A.
Cerebral ischemia remains one of the most frequent causes of death and disability worldwide. Animal models are necessary to understand complex molecular mechanisms of brain damage as well as for the development of new therapies for stroke. This review considers a certain range of animal models of cerebral ischemia, including several types of focal and global ischemia. Since animal models vary in specificity for the human disease which they reproduce, the complexity of surgery, infarct size, reliability of reproduction for statistical analysis, and adequate models need to be chosen according to the aim of a study. The reproduction of a particular animal model needs to be evaluated using appropriate tools, including the behavioral assessment of injury and non-invasive and post-mortem control of brain damage. These problems also have been summarized in the review.
Abdullahi, A.; Amini-Nik, S.; Jeschke, M.G
Burn injury is a severe form of trauma affecting more than two million people in North America each year. Burn trauma is not a single pathophysiological event but a devastating injury that causes structural and functional deficits in numerous organ systems. Due to its complexity and the involvement of multiple organs, in vitro experiments cannot capture this complexity nor address the pathophysiology. In the past two decades, a number of burn animal models have been developed to replicate the various aspects of burn injury; to elucidate the pathophysiology and explore potential treatment interventions. Understanding the advantages and limitations of these animal models is essential for the design and development of treatments that are clinically relevant to humans. This review paper aims to highlight the common animal models of burn injury in order to provide investigators with a better understanding of the benefits and limitations of these models for translational applications. While many animal models of burn exist, we limit our discussion to the skin healing of mouse, rat, and pig. Additionally, we briefly explain hypermetabolic characteristics of burn injury and the animal model utilized to study this phenomena. Finally, we discuss the economic costs associated with each of these models in order to guide decisions of choosing the appropriate animal model for burn research. PMID:24714880
Conti, Heather R.; Huppler, Anna R.; Whibley, Natasha; Gaffen, Sarah L.
Multiple forms of candidiasis are clinically important in humans. Established murine models of disseminated, oropharyngeal, vaginal, and cutaneous candidiasis caused by Candida albicans are described in this unit. Detailed materials and methods for C. albicans growth and detection are also described. PMID:24700323
Marquart, Mary E.
Bacterial keratitis is a disease of the cornea characterized by pain, redness, inflammation, and opacity. Common causes of this disease are Pseudomonas aeruginosa and Staphylococcus aureus. Animal models of keratitis have been used to elucidate both the bacterial factors and the host inflammatory response involved in the disease. Reviewed herein are animal models of bacterial keratitis and some of the key findings in the last several decades. PMID:21274270
Wang, Yanling; Xiao, Qian; Sun, Liu; Wu, Ying
This study explores Chinese nurses' acceptance of PDA, using a questionnaire based on the framework of Technology Acceptance Model (TAM). 357 nurses were involved in the study. The results reveal the scores of the nurses' acceptance of PDA were means 3.18~3.36 in four dimensions. The younger of nurses, the higher nurses' title, the longer previous usage time, the more experienced using PDA, and the more acceptance of PDA. Therefore, the hospital administrators may change strategies to enhance nurses' acceptance of PDA, and promote the wide application of PDA.
Storer, Robin James; Supronsinchai, Weera; Srikiatkhachorn, Anan
Many animal models of migraine have been described. Some of them have been useful in the development of new therapies. All of them have their shortcomings. Animal models of chronic migraine have been relatively less frequently described. Whether a rigid distinction between episodic and chronic migraine is useful when their underlying pathophysiology is likely to be the same and that migraine frequency probably depends on complex polygenic influences remains to be determined. Any model of chronic migraine must reflect the chronicity of the disorder and be reliable and validated with pharmacological interventions. Future animal models of chronic migraine are likely to involve recurrent activation of the trigeminal nociceptive system. Valid models would provide a means for investigating pathophysiological mechanism of the transformation from episodic to chronic migraine and may also be used to test the efficacy of potential preventive medications.
Simmons, J. K.; Hildreth, B. E.; Supsavhad, W.; Elshafae, S. M.; Hassan, B. B.; Dirksen, W. P.; Toribio, R. E.; Rosol, T. J.
Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone. PMID:26021553
The aim of this study is to investigate technology acceptance of prospective English teachers by using Technology Acceptance Model (TAM) in Turkish context. The study is based on Structural Equation Model (SEM). The participants of the study from English Language Teaching Departments of Hacettepe, Gazi and Baskent Universities. The participants…
Sekimizu, N; Paudel, A; Hamamoto, H
Sacrificing model animals is required for developing effective drugs before being used in human beings. In Japan today, at least 4,210,000 mice and other mammals are sacrificed to a total of 6,140,000 per year for the purpose of medical studies. All the animals treated in Japan, including test animals, are managed under control of "Act on Welfare and Management of Animals". Under the principle of this Act, no person shall kill, injure, or inflict cruelty on animals without due cause. "Animal" addressed in the Act can be defined as a "vertebrate animal". If we can make use of invertebrate animals in testing instead of vertebrate ones, that would be a remarkable solution for the issue of animal welfare. Furthermore, there are numerous advantages of using invertebrate animal models: less space and small equipment are enough for taking care of a large number of animals and thus are cost-effective, they can be easily handled, and many biological processes and genes are conserved between mammals and invertebrates. Today, many invertebrates have been used as animal models, but silkworms have many beneficial traits compared to mammals as well as other insects. In a Genome Pharmaceutical Institute's study, we were able to achieve a lot making use of silkworms as model animals. We would like to suggest that pharmaceutical companies and institutes consider the use of the silkworm as a model animal which is efficacious both for financial value by cost cutting and ethical aspects in animals' welfare.
Lines, K.E.; Stevenson, M.; Thakker, R.V.
Pituitary neoplasias can occur as part of a complex inherited disorder, or more commonly as sporadic (non-familial) disease. Studies of the molecular and genetic mechanisms causing such pituitary tumours have identified dysregulation of >35 genes, with many revealed by studies in mice, rats and zebrafish. Strategies used to generate these animal models have included gene knockout, gene knockin and transgenic over-expression, as well as chemical mutagenesis and drug induction. These animal models provide an important resource for investigation of tissue-specific tumourigenic mechanisms, and evaluations of novel therapies, illustrated by studies into multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome in which ∼30% of patients develop pituitary adenomas. This review describes animal models of pituitary neoplasia that have been generated, together with some recent advances in gene editing technologies, and an illustration of the use of the Men1 mouse as a pre clinical model for evaluating novel therapies. PMID:26320859
Tarhini, Ali; Elyas, Tariq; Akour, Mohammad Ali; Al-Salti, Zahran
The main aim of this paper is to develop an amalgamated conceptual model of technology acceptance that explains how individual, social, cultural and organizational factors affect the students' acceptance and usage behaviour of the Web-based learning systems. More specifically, the proposed model extends the Technology Acceptance Model (TAM) to…
Smouse, Peter E.; Focardi, Stefano; Moorcroft, Paul R.; Kie, John G.; Forester, James D.; Morales, Juan M.
Modern animal movement modelling derives from two traditions. Lagrangian models, based on random walk behaviour, are useful for multi-step trajectories of single animals. Continuous Eulerian models describe expected behaviour, averaged over stochastic realizations, and are usefully applied to ensembles of individuals. We illustrate three modern research arenas. (i) Models of home-range formation describe the process of an animal ‘settling down’, accomplished by including one or more focal points that attract the animal's movements. (ii) Memory-based models are used to predict how accumulated experience translates into biased movement choices, employing reinforced random walk behaviour, with previous visitation increasing or decreasing the probability of repetition. (iii) Lévy movement involves a step-length distribution that is over-dispersed, relative to standard probability distributions, and adaptive in exploring new environments or searching for rare targets. Each of these modelling arenas implies more detail in the movement pattern than general models of movement can accommodate, but realistic empiric evaluation of their predictions requires dense locational data, both in time and space, only available with modern GPS telemetry. PMID:20566497
LaFerla, Frank M; Green, Kim N
Significant insights into the function of genes associated with Alzheimer disease and related dementias have occurred through studying genetically modified animals. Although none of the existing models fully reproduces the complete spectrum of this insidious human disease, critical aspects of Alzheimer pathology and disease processes can be experimentally recapitulated. Genetically modified animal models have helped advance our understanding of the underlying mechanisms of disease and have proven to be invaluable in the preclinical evaluation of potential therapeutic interventions. Continuing refinement and evolution to yield the next generation of animal models will facilitate successes in producing greater translational concordance between preclinical studies and human clinical trials and eventually lead to the introduction of novel therapies into clinical practice.
Zaragoza, Carlos; Gomez-Guerrero, Carmen; Martin-Ventura, Jose Luis; Blanco-Colio, Luis; Lavin, Begoña; Mallavia, Beñat; Tarin, Carlos; Mas, Sebastian; Ortiz, Alberto; Egido, Jesus
Cardiovascular diseases are the first leading cause of death and morbidity in developed countries. The use of animal models have contributed to increase our knowledge, providing new approaches focused to improve the diagnostic and the treatment of these pathologies. Several models have been developed to address cardiovascular complications, including atherothrombotic and cardiac diseases, and the same pathology have been successfully recreated in different species, including small and big animal models of disease. However, genetic and environmental factors play a significant role in cardiovascular pathophysiology, making difficult to match a particular disease, with a single experimental model. Therefore, no exclusive method perfectly recreates the human complication, and depending on the model, additional considerations of cost, infrastructure, and the requirement for specialized personnel, should also have in mind. Considering all these facts, and depending on the budgets available, models should be selected that best reproduce the disease being investigated. Here we will describe models of atherothrombotic diseases, including expanding and occlusive animal models, as well as models of heart failure. Given the wide range of models available, today it is possible to devise the best strategy, which may help us to find more efficient and reliable solutions against human cardiovascular diseases.
P Bradley And Claude M Nagamine, Michael
Zika virus has garnered great attention over the last several years, as outbreaks of the disease have emerged throughout the Western Hemisphere. Until quite recently Zika virus was considered a fairly benign virus, with limited clinical severity in both people and animals. The size and scope of the outbreak in the Western Hemisphere has allowed for the identification of severe clinical disease that is associated with Zika virus infection, most notably microcephaly among newborns, and an association with Guillian-Barré syndrome in adults. This recent association with severe clinical disease, of which further analysis strongly suggested causation by Zika virus, has resulted in a massive increase in the amount of both basic and applied research of this virus. Both small and large animal models are being used to uncover the pathogenesis of this emerging disease and to develop vaccine and therapeutic strategies. Here we review the animal-model-based Zika virus research that has been performed to date.
Itatani, Naoya; Klump, Georg M
Sounds in the natural environment need to be assigned to acoustic sources to evaluate complex auditory scenes. Separating sources will affect the analysis of auditory features of sounds. As the benefits of assigning sounds to specific sources accrue to all species communicating acoustically, the ability for auditory scene analysis is widespread among different animals. Animal studies allow for a deeper insight into the neuronal mechanisms underlying auditory scene analysis. Here, we will review the paradigms applied in the study of auditory scene analysis and streaming of sequential sounds in animal models. We will compare the psychophysical results from the animal studies to the evidence obtained in human psychophysics of auditory streaming, i.e. in a task commonly used for measuring the capability for auditory scene analysis. Furthermore, the neuronal correlates of auditory streaming will be reviewed in different animal models and the observations of the neurons' response measures will be related to perception. The across-species comparison will reveal whether similar demands in the analysis of acoustic scenes have resulted in similar perceptual and neuronal processing mechanisms in the wide range of species being capable of auditory scene analysis.This article is part of the themed issue 'Auditory and visual scene analysis'.
Hraiech, Sami; Papazian, Laurent; Rolain, Jean-Marc; Bregeon, Fabienne
Pneumonia is one of the leading causes of severe and occasionally life-threatening infections. The physiopathology of pneumonia has been extensively studied, providing information for the development of new treatments for this condition. In addition to in vitro research, animal models have been largely used in the field of pneumonia. Several models have been described and have provided a better understanding of pneumonia under different settings and with various pathogens. However, the concept of one pathogen leading to one infection has been challenged, and recent flu epidemics suggest that some pathogens exhibit highly virulent potential. Although “two hits” animal models have been used to study infectious diseases, few of these models have been described in pneumonia. Therefore the aims of this review were to provide an overview of the available literature in this field, to describe well-studied and uncommon pathogen associations, and to summarize the major insights obtained from this information. PMID:26170617
Campo, M Saveria
Tumorigenesis due to papillomavirus (PV) infection was first demonstrated in rabbits and cattle early last century. Despite the evidence obtained in animals, the role of viruses in human cancer was dismissed as irrelevant. It took a paradigm shift in the late 1970s for some viruses to be recognised as 'tumour viruses' in humans, and in 1995, more than 60 years after Rous's first demonstration of CRPV oncogenicity, WHO officially declared that 'HPV-16 and HPV-18 are carcinogenic to humans'. Experimental studies with animal PVs have been a determining factor in this decision. Animal PVs have been studied both as agents of disease in animals and as models of human PV infection. In addition to the study of PV infection in whole animals, in vitro studies with animal PV proteins have contributed greatly to the understanding of the mechanisms of cell transformation. Animal PVs cause distressing diseases in both farm and companion animals, such as teat papillomatosis in cattle, equine sarcoids and canine oral papillomatosis and there is an urgent need to understand the pathogenesis of these problematic infections. Persistent and florid teat papillomatosis in cows can lead to mastitis, prevent the suckling of calves and make milking impossible; heavily affected animals are culled and so occasionally are whole herds. Equine sarcoids are often recurrent and untreatable and lead to loss of valuable animals. Canine oral papillomatosis can be very extensive and persistent and lead to great distress. Thus the continuing research in the biology of animal PVs is amply justified. BPVs and CRPV have been for many years the model systems with which to study the biology of HPV. Induction of papillomas and their neoplastic progression has been experimentally demonstrated and reproduced in cattle and rabbits, and virus-cofactor interactions have been elucidated in these systems. With the advancements in molecular and cell culture techniques, the direct study of HPV has become less
Crystal, Jonathon D
Source memory is the aspect of episodic memory that encodes the origin (i.e., source) of information acquired in the past. Episodic memory (i.e., our memories for unique personal past events) typically involves source memory because those memories focus on the origin of previous events. Source memory is at work when, for example, someone tells a favorite joke to a person while avoiding retelling the joke to the friend who originally shared the joke. Importantly, source memory permits differentiation of one episodic memory from another because source memory includes features that were present when the different memories were formed. This article reviews recent efforts to develop an animal model of source memory using rats. Experiments are reviewed which suggest that source memory is dissociated from other forms of memory. The review highlights strengths and weaknesses of a number of animal models of episodic memory. Animal models of source memory may be used to probe the biological bases of memory. Moreover, these models can be combined with genetic models of Alzheimer's disease to evaluate pharmacotherapies that ultimately have the potential to improve memory.
García Pardo, María Pilar; Roger Sánchez, Concepción; De la Rubia Ortí, José Enrique; Aguilar Calpe, María Asunción
The development of animal models of drug reward and addiction is an essential factor for progress in understanding the biological basis of this disorder and for the identification of new therapeutic targets. Depending on the component of reward to be studied, one type of animal model or another may be used. There are models of reinforcement based on the primary hedonic effect produced by the consumption of the addictive substance, such as the self-administration (SA) and intracranial self-stimulation (ICSS) paradigms, and there are models based on the component of reward related to associative learning and cognitive ability to make predictions about obtaining reward in the future, such as the conditioned place preference (CPP) paradigm. In recent years these models have incorporated methodological modifications to study extinction, reinstatement and reconsolidation processes, or to model specific aspects of addictive behavior such as motivation to consume drugs, compulsive consumption or drug seeking under punishment situations. There are also models that link different reinforcement components or model voluntary motivation to consume (two-bottle choice, or drinking in the dark tests). In short, innovations in these models allow progress in scientific knowledge regarding the different aspects that lead individuals to consume a drug and develop compulsive consumption, providing a target for future treatments of addiction.
Tayebati, Seyed Khosrow
The increased life expectancy in industrialised countries in the last half century has also brought to a greater incidence of neurological disorders, including neurodegenerative diseases and developing in a rather long time. In this respect, Alzheimer's disease (AD), for the large incidence, and the dramatic loss of autonomy caused by its cognitive and behavioural symptoms represents one of the main challenges of modern medicine. Although AD is a typical human disease and probably includes several nosographic entities, the use of animal models may contribute to understand specific aspects of pathophysiology of the disease. The most widely used animal models are rodents and non-human primates. In this review different animal models characterised by impaired cognitive functions are analysed. None of the models available mimics exactly cognitive, behavioural, biochemical and histopathological abnormalities observed in neurological disorders characterised by cognitive impairment. However, partial reproduction of neuropathology and/or cognitive deficits of Alzheimer's disease (AD), vascular dementia and dementia occurring in Huntington's and Parkinson's diseases, or in other neurodegenerative disorders may represent a basis for understanding pathophysiological traits of these diseases and for contributing to their treatments.
... 49 Transportation 1 2010-10-01 2010-10-01 false Acceptable model codes. 41.120 Section 41.120 Transportation Office of the Secretary of Transportation SEISMIC SAFETY § 41.120 Acceptable model codes. (a) This... of this part. (b)(1) The following are model codes which have been found to provide a level...
Chen, Ke; Chan, Alan Hoi Shou
The purpose of this study was to develop and test a senior technology acceptance model (STAM) aimed at understanding the acceptance of gerontechnology by older Hong Kong Chinese people. The proposed STAM extended previous technology acceptance models and theories by adding age-related health and ability characteristics of older people. The proposed STAM was empirically tested using a cross-sectional questionnaire survey with a sample of 1012 seniors aged 55 and over in Hong Kong. The result showed that STAM was strongly supported and could explain 68% of the variance in the use of gerontechnology. For older Hong Kong Chinese, individual attributes, which include age, gender, education, gerontechnology self-efficacy and anxiety, and health and ability characteristics, as well as facilitating conditions explicitly and directly affected technology acceptance. These were better predictors of gerontechnology usage behaviour (UB) than the conventionally used attitudinal factors (usefulness and ease of use).
Dutle, Aaron M.; Munoz, Cesar A.; Narkawicz, Anthony J.; Butler, Ricky W.
This paper explores a new approach to validating software implementations that have been produced from formally-verified algorithms. Although visual inspection gives some confidence that the implementations faithfully reflect the formal models, it does not provide complete assurance that the software is correct. The proposed approach, which is based on animation of formal specifications, compares the outputs computed by the software implementations on a given suite of input values to the outputs computed by the formal models on the same inputs, and determines if they are equal up to a given tolerance. The approach is illustrated on a prototype air traffic management system that computes simple kinematic trajectories for aircraft. Proofs for the mathematical models of the system's algorithms are carried out in the Prototype Verification System (PVS). The animation tool PVSio is used to evaluate the formal models on a set of randomly generated test cases. Output values computed by PVSio are compared against output values computed by the actual software. This comparison improves the assurance that the translation from formal models to code is faithful and that, for example, floating point errors do not greatly affect correctness and safety properties.
Morgan, Drake; Sizemore, Glen M
The concept of "food addiction" is gaining acceptance among the scientific community, and much is known about the influence of various components of food (e.g. high-fat, sugar, carbohydrate, salt) on behavior and physiology. Most of the studies to date have studied these consequences following relatively long-term diet manipulations and/or relatively free access to the food of interest. It is suggested that these types of studies are primarily tapping into the energy regulation and homeostatic processes that govern food intake and consumption. More recently, the overlap between the neurobiology of "reward-related" or hedonic effects of food ingestion and other reinforcers such as drugs of abuse has been highlighted, contributing to the notion that "food addiction" exists and that various components of food may be the substance of abuse. Based on preclinical animal models of drug addiction, a new direction for this field is using self-administration procedures and identifying an addiction-like behavioral phenotype in animals following various environmental, genetic, pharmacological, and neurobiological manipulations. Here we provide examples from this research area, with a focus on fat and sugar self-administration, and how the sophisticated animal models of drug addiction can be used to study the determinants and consequences of food addiction.
Chorro, Francisco J; Such-Belenguer, Luis; López-Merino, Vicente
The use of animal models to study cardiovascular disease has made a substantial contribution to increasing our understanding of disease pathogenesis, has led to the development of diagnostic techniques, and has made it possible to verify the effectiveness of different preventative and therapeutic approaches, whether pharmacological or interventional. The main limitations stem from differences between human and experimentally induced pathology, in terms of both genetic regulatory mechanisms and factors that influence cardiovascular function. The experimental models and preparations used in cardiovascular research include those based on isolated cells or tissues or structures immersed in organ baths. The Langendorff system enables isolated perfused hearts to be studied directly under conditions of either no load or controlled loading. In small mammals, a number of models have been developed of cardiovascular conditions that result from spontaneous genetic mutations or, alternatively, that may be induced by specific genomic modification. One of the techniques employed is gene transfer, which can involve the controlled induction of mutations that result in the expression of abnormalities associated with the development of a broad range of different types of cardiovascular disease. Larger animals are used in experimental models in which it is important that physiological regulatory and homeostatic mechanisms are present.
Allen, Richard P; Donelson, Nathan C; Jones, Byron C; Li, Yuqing; Manconi, Mauro; Rye, David B; Sanyal, Subhabrata; Winkelmann, Juliane
Restless legs syndrome (RLS) is a complex disorder that involves sensory and motor systems. The major pathophysiology of RLS is low iron concentration in the substantia nigra containing the cell bodies of dopamine neurons that project to the striatum, an area that is crucial for modulating movement. People who have RLS often present with normal iron values outside the brain; recent studies implicate several genes are involved in the syndrome. Like most complex diseases, animal models usually do not faithfully capture the full phenotypic spectrum of "disease," which is a uniquely human construct. Nonetheless, animal models have proven useful in helping to unravel the complex pathophysiology of diseases such as RLS and suggesting novel treatment paradigms. For example, hypothesis-independent genome-wide association studies (GWAS) have identified several genes as increasing the risk for RLS, including BTBD9. Independently, the murine homolog Btbd9 was identified as a candidate gene for iron regulation in the midbrain in mice. The relevance of the phenotype of another of the GWAS identified genes, MEIS1, has also been explored. The role of Btbd9 in iron regulation and RLS-like behaviors has been further evaluated in mice carrying a null mutation of the gene and in fruit flies when the BTBD9 protein is degraded. The BTBD9 and MEIS1 stories originate from human GWAS research, supported by work in a genetic reference population of mice (forward genetics) and further verified in mice, fish flies, and worms. Finally, the role of genetics is further supported by an inbred mouse strain that displays many of the phenotypic characteristics of RLS. The role of animal models of RLS phenotypes is also extended to include periodic limb movements.
Beuschlein, Felix; Galac, Sara; Wilson, David B.
Over the past decade, research on human adrenocortical neoplasia has been dominated by gene expression profiling of tumor specimens and by analysis of genetic disorders associated with a predisposition to these tumors. Although these studies have identified key genes and associated signaling pathways that are dysregulated in adrenocortical neoplasms, the molecular events accounting for the frequent occurrence of benign tumors and low rate of malignant transformation remain unknown. Moreover, the prognosis for patients with adrenocortical carcinoma remains poor, so new medical treatments are needed. Naturally occurring and genetically engineered animal models afford a means to investigate adrenocortical tumorigenesis and to develop novel therapeutics. This comparative review highlights adrenocortical tumor models useful for either mechanistic studies or preclinical testing. Three model species – mouse, ferret, and dog – are reviewed, and their relevance to adrenocortical tumors in humans is discussed. PMID:22100615
The peripheral nervous system (PNS) comprises the cranial nerves, the spinal nerves with their roots and rami, dorsal root ganglia neurons, the peripheral nerves, and peripheral components of the autonomic nervous system. Cell-mediated or antibody-mediated immune attack on the PNS results in distinct clinical syndromes, which are classified based on the tempo of illness, PNS component(s) involved, and the culprit antigen(s) identified. Insights into the pathogenesis of autoimmune neuropathy have been provided by ex vivo immunologic studies, biopsy materials, electrophysiologic studies, and experimental models. This review article summarizes earlier seminal observations and highlights the recent progress in our understanding of immunopathogenesis of autoimmune neuropathies based on data from animal models. PMID:24615441
Background The concept of conserved processes presents unique opportunities for using nonhuman animal models in biomedical research. However, the concept must be examined in the context that humans and nonhuman animals are evolved, complex, adaptive systems. Given that nonhuman animals are examples of living systems that are differently complex from humans, what does the existence of a conserved gene or process imply for inter-species extrapolation? Methods We surveyed the literature including philosophy of science, biological complexity, conserved processes, evolutionary biology, comparative medicine, anti-neoplastic agents, inhalational anesthetics, and drug development journals in order to determine the value of nonhuman animal models when studying conserved processes. Results Evolution through natural selection has employed components and processes both to produce the same outcomes among species but also to generate different functions and traits. Many genes and processes are conserved, but new combinations of these processes or different regulation of the genes involved in these processes have resulted in unique organisms. Further, there is a hierarchy of organization in complex living systems. At some levels, the components are simple systems that can be analyzed by mathematics or the physical sciences, while at other levels the system cannot be fully analyzed by reducing it to a physical system. The study of complex living systems must alternate between focusing on the parts and examining the intact whole organism while taking into account the connections between the two. Systems biology aims for this holism. We examined the actions of inhalational anesthetic agents and anti-neoplastic agents in order to address what the characteristics of complex living systems imply for inter-species extrapolation of traits and responses related to conserved processes. Conclusion We conclude that even the presence of conserved processes is insufficient for inter
Yousif, Wael K.
This causal and correlational study was designed to extend the Technology Acceptance Model (TAM) and to test its applicability to Valencia Community College (VCC) Engineering and Technology students as the target user group when investigating the factors influencing their decision to adopt and to utilize VMware as the target technology. In…
Lee, Doo Young; Lehto, Mark R.
The present study was framed using the Technology Acceptance Model (TAM) to identify determinants affecting behavioral intention to use YouTube. Most importantly, this research emphasizes the motives for using YouTube, which is notable given its extrinsic task goal of being used for procedural learning tasks. Our conceptual framework included two…
Park, Eunil; Kim, Ki Joon
Purpose: The aim of this paper is to propose an integrated path model in order to explore user acceptance of long-term evolution (LTE) services by examining potential causal relationships between key psychological factors and user intention to use the services. Design/methodology/approach: Online survey data collected from 1,344 users are analysed…
Kato, T; Kasahara, T; Kubota-Sakashita, M; Kato, T M; Nakajima, K
Animal models of mental disorders should ideally have construct, face, and predictive validity, but current animal models do not always satisfy these validity criteria. Additionally, animal models of depression rely mainly on stress-induced behavioral changes. These stress-induced models have limited validity, because stress is not a risk factor specific to depression, and the models do not recapitulate the recurrent and spontaneous nature of depressive episodes. Although animal models exhibiting recurrent depressive episodes or bipolar depression have not yet been established, several researchers are trying to generate such animals by modeling clinical risk factors as well as by manipulating a specific neural circuit using emerging techniques.
Gootenberg, D B; Turnbaugh, P J
Humans and other mammals are colonized by trillions of microorganisms, most of which reside in the gastrointestinal tract, that provide key metabolic capabilities, such as the biosynthesis of vitamins and AA, the degradation of dietary plant polysaccharides, and the metabolism of orally administered therapeutics. Although much progress has been made by studying the human microbiome directly, comparing the human microbiome with that of other animals, and constructing in vitro models of the human gut, there remains a need to develop in vivo models where host, microbial, and environmental parameters can be manipulated. Here, we discuss some of the initial results from a promising method that enables the direct manipulation of microbial community structure, environmental exposures, host genotype, and other factors: the colonization of germ-free animals with complex microbial communities, including those from humans or other animal donors. Analyses of these resulting "humanized" gut microbiomes have begun to reveal 1) that key microbial activities can be transferred from the donor to the recipient animal (e.g., microbial reduction of cholesterol and production of equol), 2) that dietary shifts can affect the composition, gene abundance, and gene expression of the gut microbiome, 3) the succession of the microbial community in infants and ex-germ-free adult animals, and 4) the biogeography of these microbes across the length of gastrointestinal tract. Continued studies of humanized and other intentionally colonized animal models stand to provide new insight into not only the human microbiome, but also the microbiomes of our animal companions.
Stress urinary incontinence (SUI) is a common health problem significantly affecting the quality of life of women worldwide. Animal models that simulate SUI enable the assessment of the mechanism of risk factors for SUI in a controlled fashion, including childbirth injuries, and enable preclinical testing of new treatments and therapies for SUI. Animal models that simulate childbirth are presently being utilized to determine the mechanisms of the maternal injuries of childbirth that lead to SUI with the goal of developing prophylactic treatments. Methods of assessing SUI in animals that mimic diagnostic methods used clinically have been developed to evaluate the animal models. Use of these animal models to test innovative treatment strategies has the potential to improve clinical management of SUI. This chapter provides a review of the available animal models of SUI, as well as a review of the methods of assessing SUI in animal models, and potential treatments that have been tested on these models. PMID:21290221
Ozaki, Shigeru; Hisano, Setsuji; Iwamoto, Yoshiki
Various species of animals have been used as animal models for neuroscience and provided critical information about the brain functions. Although it seems difficult to elucidate a highly advanced function of the human brain, animal models have potency to clarify the fundamental mechanisms of emotion, decision-making and social behavior. In this review, we will pick up common animal models and point to both the merits and demerits caused by the characteristics. We will also mention that wide-ranging approaches from animal models are advantageous to understand KANSEI as well as mind in humans.
Hayes, Sarah H.; Radziwon, Kelly E.; Stolzberg, Daniel J.; Salvi, Richard J.
The phantom perception of tinnitus and reduced sound-level tolerance associated with hyperacusis have a high comorbidity and can be debilitating conditions for which there are no widely accepted treatments. One factor limiting the development of treatments for tinnitus and hyperacusis is the lack of reliable animal behavioral models of these disorders. Therefore, the purpose of this review is to highlight the current animal models of tinnitus and hyperacusis, and to detail the advantages and disadvantages of each paradigm. To date, this is the first review to include models of both tinnitus and hyperacusis. PMID:25278931
Rosenwasser, Alan M
Clinical and epidemiological observations have revealed that alcohol abuse and alcoholism are associated with widespread disruptions in sleep and other circadian biological rhythms. As with other psychiatric disorders, animal models have been very useful in efforts to better understand the cause and effect relationships underlying the largely correlative human data. This review summarizes the experimental findings indicating bidirectional interactions between alcohol (ethanol) consumption and the circadian timing system, emphasizing behavioral studies conducted in the author's laboratory. Together with convergent evidence from multiple laboratories, the work summarized here establishes that ethanol intake (or administration) alters fundamental properties of the underlying circadian pacemaker. In turn, circadian disruption induced by either environmental or genetic manipulations can alter voluntary ethanol intake. These reciprocal interactions may create a vicious cycle that contributes to the downward spiral of alcohol and drug addiction. In the future, such studies may lead to the development of chronobiologically based interventions to prevent relapse and effectively mitigate some of the societal burden associated with such disorders.
Pendley, Rex D.; Noonan, Caroline H.; Hall, Kenneth R.
The process of acceptance testing large software systems for NASA has been analyzed, and an empirical planning model of the process constructed. This model gives managers accurate predictions of the staffing needed, the productivity of a test team, and the rate at which the system will pass. Applying the model to a new system shows a high level of agreement between the model and actual performance. The model also gives managers an objective measure of process improvement.
In four investigations using Likert-scale questionnaires and think-aloud protocols with 173 university students in total, the willingness to accept evolutionary explanations regarding plant, animal, and human characteristics was examined. Participants were presented with evolutionary explanations for features and behaviors and were asked to rate how much they agreed with evolution as an explanation for each scenario. Some were also asked to explain their reasoning in think-aloud protocols or to discuss item ratings with one another. Overall, participants thought evolutionary explanations appropriate, with median ratings in the upper quarter of the rating scale. They were slightly more willing to ascribe evolutionary explanations to plant than to human phenomena; however, this general effect was mediated by more specific aspects of the evolutionary scenarios in question. Participants who were generally negative regarding evolution were particularly negative towards human evolution. Those who were positive or neutral towards evolution in general were more willing to accept human evolution, but were more likely to use evolution to explain similarities between humans and other species than to explain particular human adaptations. For example, they were more likely to agree that evolution is responsible for the DNA similarities between humans and chimpanzees than that evolution is responsible for human behavioral characteristics, such as the fight or flight response. Think-aloud protocols suggest that, while people are more familiar with human evolutionary relationships than plant evolutionary relationships, they may be less likely to see human characteristics as adaptively valuable. One plausible explanation for these patterns is that an evolutionary explanation is judged jointly by its availability in an individual's memory and its plausibility (i.e., its congruence with the individual's worldview). Popular media coverage, with its focus on controversy and litigation
Chang, Jui-Ling; Lieu, Pang-Tien; Liang, Jung-Hui; Liu, Hsiang-Te; Wong, Seng-lee
This study proposes a causal model for investigating teacher acceptance of technology. We received 258 effective replies from teachers at public and private universities in Taiwan. A questionnaire survey was utilized to test the proposed model. The Lisrel was applied to test the proposed hypotheses. The result shows that computer self-efficacy has…
Piel, Margaret J; Kroin, Jeffrey S; van Wijnen, Andre J; Kc, Ranjan; Im, Hee-Jeong
Assessment of pain in animal models of osteoarthritis is integral to interpretation of a model's utility in representing the clinical condition, and enabling accurate translational medicine. Here we describe behavioral pain assessments available for small and large experimental osteoarthritic pain animal models.
Mizuno, Hiroshi; Akutsu, Hidenori; Kato, Kazuto
Human-animal chimeric embryos are embryos obtained by introducing human cells into a non-human animal embryo. It is envisaged that the application of human-animal chimeric embryos may make possible many useful research projects including producing three-dimensional human organs in animals and verification of the pluripotency of human ES cells or iPS cells in vivo. The use of human-animal chimeric embryos, however, raises several ethical and moral concerns. The most fundamental one is that human-animal chimeric embryos possess the potential to develop into organisms containing human-derived tissue, which may lead to infringing upon the identity of the human species, and thus impairing human dignity. The Japanese Expert Panel on Bioethics in the Cabinet Office carefully considered the scientific significance and ethical acceptability of the issue and released its "Opinions regarding the handling of research using human-animal chimeric embryos". The Panel proposed a framework of case-by-case review, and suggested that the following points must be carefully reviewed from the perspective of ethical acceptability: (a) Types of animal embryos and types of animals receiving embryo transfers, particularly in dealing with non-human primates; (b) Types of human cells and organs intended for production, particularly in dealing with human nerve or germ cells; and (c) Extent of the period required for post-transfer studies. The scientific knowledge that can be gained from transfer into an animal uterus and from the production of an individual must be clarified to avoid unnecessary generation of chimeric animals. The time is ripe for the scientific community and governments to start discussing the ethical issues for establishing a global consensus.
Zhang, Ning; Fang, Marong; Chen, Haohao; Gou, Fangming; Ding, Mingxing
Because there is no curative treatment for spinal cord injury, establishing an ideal animal model is important to identify injury mechanisms and develop therapies for individuals suffering from spinal cord injuries. In this article, we systematically review and analyze various kinds of animal models of spinal cord injury and assess their advantages and disadvantages for further studies. PMID:25598784
Animal models are formidable tools to investigate the etiology, the course and the potential treatment of an illness. No convincing animal model of suicide has been produced to date, and despite the intensive study of thousands of animal species naturalists have not identified suicide in nonhuman species in field situations. When modeling suicidal behavior in the animal, the greatest challenge is reproducing the role of will and intention in suicide mechanics. To overcome this limitation, current investigations on animals focus on every single step leading to suicide in humans. The most promising endophenotypes worth investigating in animals are the cortisol social-stress response and the aggression/impulsivity trait, involving the serotonergic system. Astroglia, neurotrophic factors and neurotrophins are implied in suicide, too. The prevention of suicide rests on the identification and treatment of every element increasing the risk.
Basak, Ecem; Gumussoy, Cigdem Altin; Calisir, Fethi
This study aims at identifying the factors affecting the intention to use personal digital assistant (PDA) technology among physicians in Turkey using an extended Technology Acceptance Model (TAM). A structural equation-modeling approach was used to identify the variables that significantly affect the intention to use PDA technology. The data were collected from 339 physicians in Turkey. Results indicated that 71% of the physicians' intention to use PDA technology is explained by perceived usefulness and perceived ease of use. On comparing both, the perceived ease of use has the strongest effect, whereas the effect of perceived enjoyment on behavioral intention to use is found to be insignificant. This study concludes with the recommendations for managers and possible future research.
... Transportation Office of the Secretary of Transportation SEISMIC SAFETY § 41.120 Acceptable model codes. (a) This section describes the standards that must be used to meet the seismic design and construction requirements... seismic safety substantially equivalent to that provided by use of the 1988 National Earthquake...
... Transportation Office of the Secretary of Transportation SEISMIC SAFETY § 41.120 Acceptable model codes. (a) This section describes the standards that must be used to meet the seismic design and construction requirements... seismic safety substantially equivalent to that provided by use of the 1988 National Earthquake...
... Transportation Office of the Secretary of Transportation SEISMIC SAFETY § 41.120 Acceptable model codes. (a) This section describes the standards that must be used to meet the seismic design and construction requirements... seismic safety substantially equivalent to that provided by use of the 1988 National Earthquake...
Warden, S J
Tendinopathy is a common and significant clinical problem characterised by activity-related pain, focal tendon tenderness and intratendinous imaging changes. Recent histopathological studies have indicated the underlying pathology to be one of tendinosis (degeneration) as opposed to tendinitis (inflammation). Relatively little is known about tendinosis and its pathogenesis. Contributing to this is an absence of validated animal models of the pathology. Animal models of tendinosis represent potential efficient and effective means of furthering our understanding of human tendinopathy and its underlying pathology. By selecting an appropriate species and introducing known risk factors for tendinopathy in humans, it is possible to develop tendon changes in animal models that are consistent with the human condition. This paper overviews the role of animal models in tendinopathy research by discussing the benefits and development of animal models of tendinosis, highlighting potential outcome measures that may be used in animal tendon research, and reviewing current animal models of tendinosis. It is hoped that with further development of animal models of tendinosis, new strategies for the prevention and treatment of tendinopathy in humans will be generated.
Behçet's disease is a chronic, recurrent, multisystemic, inflammatory disorder affecting mainly the oral and urogenital mucosa and the uveal tract. Although the etiology and pathogenesis of Behçet's disease are unknown, numerous etiologies have been proposed, including environmental, infectious, and immunological factors; an autoimmune basis, characterized by circulating immune complexes and complement activation, has gained increasing acceptance. To test and understand immunopathogenesis of Behçet's disease, animal models were developed based on enviromental pollutants, bacterial and human heat shock protein derived peptides, and virus injections. Using these animal models separately and/or concurrently allows for a more effective investigation into Behçet's disease. Animal models developed in the last 10 years aim at the development of efficient and safe treatment options.
Cheung, Ronnie; Vogel, Doug
Collaborative technologies support group work in project-based environments. In this study, we enhance the technology acceptance model to explain the factors that influence the acceptance of Google Applications for collaborative learning. The enhanced model was empirically evaluated using survey data collected from 136 students enrolled in a…
Xu, Ming; Xu, Hongzhi; Qin, Zhiyong
Brain arteriovenous malformation (AVM) is an important cause of hemorrhagic stroke. The etiology is largely unknown and the therapeutics are controversial. A review of AVM-associated animal models may be helpful in order to understand the up-to-date knowledge and promote further research about the disease. We searched PubMed till December 31, 2014, with the term "arteriovenous malformation," limiting results to animals and English language. Publications that described creations of AVM animal models or investigated AVM-related mechanisms and treatments using these models were reviewed. More than 100 articles fulfilling our inclusion criteria were identified, and from them eight different types of the original models were summarized. The backgrounds and procedures of these models, their applications, and research findings were demonstrated. Animal models are useful in studying the pathogenesis of AVM formation, growth, and rupture, as well as in developing and testing new treatments. Creations of preferable models are expected.
Xu, Ming; Xu, Hongzhi; Qin, Zhiyong
Brain arteriovenous malformation (AVM) is an important cause of hemorrhagic stroke. The etiology is largely unknown and the therapeutics are controversial. A review of AVM-associated animal models may be helpful in order to understand the up-to-date knowledge and promote further research about the disease. We searched PubMed till December 31, 2014, with the term “arteriovenous malformation,” limiting results to animals and English language. Publications that described creations of AVM animal models or investigated AVM-related mechanisms and treatments using these models were reviewed. More than 100 articles fulfilling our inclusion criteria were identified, and from them eight different types of the original models were summarized. The backgrounds and procedures of these models, their applications, and research findings were demonstrated. Animal models are useful in studying the pathogenesis of AVM formation, growth, and rupture, as well as in developing and testing new treatments. Creations of preferable models are expected. PMID:26649296
Ketikidis, Panayiotis; Dimitrovski, Tomislav; Lazuras, Lambros; Bath, Peter A
The response of health professionals to the use of health information technology (HIT) is an important research topic that can partly explain the success or failure of any HIT application. The present study applied a modified version of the revised technology acceptance model (TAM) to assess the relevant beliefs and acceptance of HIT systems in a sample of health professionals (n = 133). Structured anonymous questionnaires were used and a cross-sectional design was employed. The main outcome measure was the intention to use HIT systems. ANOVA was employed to examine differences in TAM-related variables between nurses and medical doctors, and no significant differences were found. Multiple linear regression analysis was used to assess the predictors of HIT usage intentions. The findings showed that perceived ease of use, but not usefulness, relevance and subjective norms directly predicted HIT usage intentions. The present findings suggest that a modification of the original TAM approach is needed to better understand health professionals' support and endorsement of HIT. Perceived ease of use, relevance of HIT to the medical and nursing professions, as well as social influences, should be tapped by information campaigns aiming to enhance support for HIT in healthcare settings.
Seifritz, W.; Mennig, J.
Nonlinear dynamics are attaining greater interest in different fields of application. Since the early 1980s, these methods have been applied intensively to a variety of very different general problems, such as the description of political and economic processes as well as the symbiotic behavior in the flora and fauna. The authors have tried to apply these mathematical methods to the dynamic behavior inherent in the problem of the acceptance of nuclear energy. The model, which simplifies the real situation, is two-dimensional and describes the symbiosis of two individuals: the capacity of nuclear power plants P and their acceptance A by the public. It is clear that in reality the acceptance problem depends on a series of other variables as well. However, it is believed that our investigations reveal some universal properties inherent to our socioeconomic system: nonlinearity and dissipative processes.
Lutz, Thomas A.; Woods, Stephen C.
This is a review of animal models of obesity currently used in research. We have focused upon more commonly utilized models since there are far too many newly created models to consider, especially those caused by selective molecular genetic approaches modifying one or more genes in specific populations of cells. Further, we will not discuss the generation and use of inducible transgenic animals (induced knock-out or knock-in) even though they often bear significant advantages compared to traditional transgenic animals; influences of the genetic modification during the development of the animals can be minimized. The number of these animal models is simply too large to be covered in this chapter. PMID:22948848
Dai, Tianhong; Kharkwal, Gitika B; Tanaka, Masamitsu; Huang, Ying-Ying; Bil de Arce, Vida J
Background: Despite advances in traumatic wound care and management, infections remain a leading cause of mortality, morbidity and economic disruption in millions of wound patients around the world. Animal models have become standard tools for studying a wide array of external traumatic wound infections and testing new antimicrobial strategies. Results: Animal models of external traumatic wound infections reported by different investigators vary in animal species used, microorganism strains, the number of microorganisms applied, the size of the wounds and for burn infections, the length of time the heated object or liquid is in contact with the skin. Methods: This review covers experimental infections in animal models of surgical wounds, skin abrasions, burns, lacerations, excisional wounds and open fractures. Conclusions: As antibiotic resistance continues to increase, more new antimicrobial approaches are urgently needed. These should be tested using standard protocols for infections in external traumatic wounds in animal models. PMID:21701256
Whitelaw, C Bruce A; Sheets, Timothy P; Lillico, Simon G; Telugu, Bhanu P
The recent development of gene editing tools and methodology for use in livestock enables the production of new animal disease models. These tools facilitate site-specific mutation of the genome, allowing animals carrying known human disease mutations to be produced. In this review, we describe the various gene editing tools and how they can be used for a range of large animal models of diseases. This genomic technology is in its infancy but the expectation is that through the use of gene editing tools we will see a dramatic increase in animal model resources available for both the study of human disease and the translation of this knowledge into the clinic. Comparative pathology will be central to the productive use of these animal models and the successful translation of new therapeutic strategies.
Szczodry, Michal; Bruno, Stephen
Articular cartilage injury and degeneration are leading causes of disability. Animal studies are critically important to developing effective treatments for cartilage injuries. This review focuses on the use of animal models for the study of the repair and regeneration of focal cartilage defects. Animals commonly used in cartilage repair studies include murine, lapine, canine, caprine, porcine, and equine models. There are advantages and disadvantages to each model. Small animal rodent and lapine models are cost effective, easy to house, and useful for pilot and proof-of-concept studies. The availability of transgenic and knockout mice provide opportunities for mechanistic in vivo study. Athymic mice and rats are additionally useful for evaluating the cartilage repair potential of human cells and tissues. Their small joint size, thin cartilage, and greater potential for intrinsic healing than humans, however, limit the translational value of small animal models. Large animal models with thicker articular cartilage permit study of both partial thickness and full thickness chondral repair, as well as osteochondral repair. Joint size and cartilage thickness for canine, caprine, and mini-pig models remain significantly smaller than that of humans. The repair and regeneration of chondral and osteochondral defects of size and volume comparable to that of clinically significant human lesions can be reliably studied primarily in equine models. While larger animals may more closely approximate the human clinical situation, they carry greater logistical, financial, and ethical considerations. A multifactorial analysis of each animal model should be carried out when planning in vivo studies. Ultimately, the scientific goals of the study will be critical in determining the appropriate animal model. PMID:19831641
Morey-Holton, E.; Wronski, T. J.
NASA has developed a rat model to simulate on earth some aspects of the weightlessness alterations experienced in space, i.e., unloading and fluid shifts. Comparison of data collected from space flight and from the head-down rat suspension model suggests that this model system reproduces many of the physiological alterations induced by space flight. Data from various versions of the rat model are virtually identical for the same parameters; thus, modifications of the model for acute, chronic, or metabolic studies do not alter the results as long as the critical components of the model are maintained, i.e., a cephalad shift of fluids and/or unloading of the rear limbs.
van Leeuwen, Lisanne M.; van der Sar, Astrid M.; Bitter, Wilbert
Over the past decade the zebrafish (Danio rerio) has become an attractive new vertebrate model organism for studying mycobacterial pathogenesis. The combination of medium-throughput screening and real-time in vivo visualization has allowed new ways to dissect host pathogenic interaction in a vertebrate host. Furthermore, genetic screens on the host and bacterial sides have elucidated new mechanisms involved in the initiation of granuloma formation and the importance of a balanced immune response for control of mycobacterial pathogens. This article will highlight the unique features of the zebrafish–Mycobacterium marinum infection model and its added value for tuberculosis research. PMID:25414379
Khan, Asma; Hargreaves, Kenneth M
Pain is one of the most common reasons for which patients seek dental and medical care. Orofacial pain conditions consist of a wide range of disorders including odontalgia (toothache), temporomandibular disorders, trigeminal neuralgia and others. Most of these conditions are either inflammatory or neuropathic in nature. This chapter provides an overview of the commonly used models to study inflammatory and neuropathic orofacial pain.
Moskowitz, R W
Studies of osteoarthritis (OA) in humans are restricted by the slow rate at which the disease progresses, and the limited opportunity for study of the tissue changes over time. A range of animal models of OA have been developed which demonstrate histopathological and gross features typical of OA in humans. Animal models can be used to study OA, and to investigate the effects of a variety of agents, including so-called chondroprotective agents, on the progression of the disease.
Gretebeck, Lisa M; Subbarao, Kanta
The emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome coronavirus (MERS-CoV), two strains of animal coronaviruses that crossed the species barrier to infect and cause severe respiratory infections in humans within the last 12 years, have taught us that coronaviruses represent a global threat that does not recognize international borders. We can expect to see other novel coronaviruses emerge in the future. An ideal animal model should reflect the clinical signs, viral replication and pathology seen in humans. In this review, we present factors to consider in establishing an animal model for the study of novel coronaviruses and compare the different animal models that have been employed to study SARS-CoV and MERS-CoV. PMID:26184451
An, Y H; Friedman, R J
Prosthetic infection following total joint replacement can have catastrophic results both physically and psychologically for patients, leading to complete failure of the arthroplasty, possible amputation, prolonged hospitalization, and even death. Although with the use of prophylactic antibiotics and greatly improved operating room techniques the infection rate has decreased markedly during the years, challenges still remain for better preventive and therapeutic measures. In this review the in vivo experimental methods for studies of prosthetic infection are discussed, concentrating on (1) the animal models that have been established and the use of these animal models for studies of pathogenesis of bacteria, behavior of biofilm, effect of biomaterials on prosthetic infection rate, and the effect of infection on biomaterial surfaces, and (2) how to design and conduct an animal model of orthopedic prosthetic infection including animal selection, implant fabrication, bacterial inoculation, surgical technique, and the methods for evaluating the results.
Gretebeck, Lisa M; Subbarao, Kanta
The emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome coronavirus (MERS-CoV), two strains of animal coronaviruses that crossed the species barrier to infect and cause severe respiratory infections in humans within the last 12 years, have taught us that coronaviruses represent a global threat that does not recognize international borders. We can expect to see other novel coronaviruses emerge in the future. An ideal animal model should reflect the clinical signs, viral replication and pathology seen in humans. In this review, we present factors to consider in establishing an animal model for the study of novel coronaviruses and compare the different animal models that have been employed to study SARS-CoV and MERS-CoV.
Ramanan, Deva; Forsyth, David A; Barnard, Kobus
This paper argues that tracking, object detection, and model building are all similar activities. We describe a fully automatic system that builds 2D articulated models known as pictorial structures from videos of animals. The learned model can be used to detect the animal in the original video--in this sense, the system can be viewed as a generalized tracker (one that is capable of modeling objects while tracking them). The learned model can be matched to a visual library; here, the system can be viewed as a video recognition algorithm. The learned model can also be used to detect the animal in novel images--in this case, the system can be seen as a method for learning models for object recognition. We find that we can significantly improve the pictorial structures by augmenting them with a discriminative texture model learned from a texture library. We develop a novel texture descriptor that outperforms the state-of-the-art for animal textures. We demonstrate the entire system on real video sequences of three different animals. We show that we can automatically track and identify the given animal. We use the learned models to recognize animals from two data sets; images taken by professional photographers from the Corel collection, and assorted images from the Web returned by Google. We demonstrate quite good performance on both data sets. Comparing our results with simple baselines, we show that, for the Google set, we can detect, localize, and recover part articulations from a collection demonstrably hard for object recognition.
Chen, Shih-Pin; Tolner, Else A; Eikermann-Haerter, Katharina
Migraine is a highly prevalent and disabling neurological disorder with a strong genetic component. Rare monogenic forms of migraine, or syndromes in which migraine frequently occurs, help scientists to unravel pathogenetic mechanisms of migraine and its comorbidities. Transgenic mouse models for rare monogenic mutations causing familial hemiplegic migraine (FHM), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and familial advanced sleep-phase syndrome (FASPS), have been created. Here, we review the current state of research using these mutant mice. We also discuss how currently available experimental approaches, including epigenetic studies, biomolecular analysis and optogenetic technologies, can be used for characterization of migraine genes to further unravel the functional and molecular pathways involved in migraine.
Sidell, Douglas R.; Aghaloo, Tara; Tetradis, Sotirios; Lee, Min; Bezouglaia, Olga; DeConde, Adam; St. John, Maie A.
Objectives Segmental mandibular defects can result after the treatment of various pathologic processes, including osteoradionecrosis, tumor resection, or fracture nonunion with sequestration. The variety of etiologies and the frequency of occurrence make the reconstruction of segmental mandibular defects a topic of significant interest. Despite these incentives, a well-established small-animal model of the segmental mandibulectomy, including composite resection, does not exist. The objective of this study is the creation of a reliable animal model that can be used to study the reconstruction of en bloc mandibular defects. Surgical techniques and an array of reconstructive options are described. Study design Description of an animal model. Setting Animal laboratory at a quaternary care university medical center. Methods We present an Animal Research Oversight Committee–approved prospective analysis of survival operations in the rat model. A detailed, stepwise description of surgical technique and relevant intraoperative anatomy is presented. Postoperative management, early pitfalls, surgical complications, and future applications are discussed. Results A total of 72 operations were performed by a single individual between July and October 2010. Two intraoperative and 9 postoperative complications were recognized. There were 6 orocutaneous fistulas, 2 abscesses, and 1 seroma. There were 4 fatalities, which were attributed to anesthetic complications (2, intraoperative), hematoma formation (1, postoperative), and foreign-body aspiration (1, postoperative). Conclusion This novel animal model reliably replicates the en bloc segmental mandibular defects seen in our patient population and can be manipulated to achieve a wide variety of research objectives. PMID:22282867
Crabbe, John C
Nonhuman animals have been major contributors to the science of the genetics of addiction. Given the explosion of interest in genetics, it is fair to ask, are we making reasonable progress toward our goals with animal models? I will argue that our goals are changing and that overall progress has been steady and seems likely to continue apace. Genetics tools have developed almost incredibly rapidly, enabling both more reductionist and more synthetic or integrative approaches. I believe that these approaches to making progress have been unbalanced in biomedical science, favoring reductionism, particularly in animal genetics. I argue that substantial, novel progress is also likely to come in the other direction, toward synthesis and abstraction. Another area in which future progress with genetic animal models seems poised to contribute more is the reconciliation of human and animal phenotypes, or consilience. The inherent power of the genetic animal models could be more profitably exploited. In the end, animal research has continued to provide novel insights about how genes influence individual differences in addiction risk and consequences. The rules of the genetics game are changing so fast that it is hard to remember how comparatively little we knew even a generation ago. Rather than worry about whether we have been wasting time and resources asking the questions we have been, we should look to the future and see if we can come up with some new ones. The valuable findings from the past will endure, and the sidetracks will be forgotten.
Daunton, Nancy G.
Practical information on candidate animal models for motion sickness research and on methods used to elicit and detect motion sickness in these models is provided. Four good potential models for use in motion sickness experiments include the dog, cat, squirrel monkey, and rat. It is concluded that the appropriate use of the animal models, combined with exploitation of state-of-the-art biomedical techniques, should generate a great step forward in the understanding of motion sickness mechanisms and in the development of efficient and effective approaches to its prevention and treatment in humans.
Thele, M.; Schiffer, J.; Karden, E.; Surewaard, E.; Sauer, D. U.
This paper presents a model for flooded and VRLA batteries that is parameterized by impedance spectroscopy and includes the overcharging effects to allow charge-acceptance simulations (e.g. for regenerative-braking drive-cycle profiles). The full dynamic behavior and the short-term charge/discharge history is taken into account. This is achieved by a detailed modeling of the sulfate crystal growth and modeling of the internal gas recombination cycle. The model is applicable in the full realistic temperature and current range of automotive applications. For model validation, several load profiles (covering the dynamics and the current range appearing in electrically assisted or hybrid cars) are examined and the charge-acceptance limiting effects are elaborately discussed. The validation measurements have been performed for different types of lead-acid batteries (flooded and VRLA). The model is therefore an important tool for the development of automotive power nets, but it also allows to analyze different charging strategies and energy gains which can be achieved during regenerative-braking.
Mooij, Wolf M.; DeAngelis, Donald L.
Uncertainty in estimates of survival of dispersing animals is a vexing difficulty in conservation biology. The current notion is that this uncertainty decreases the usefulness of spatially explicit population models in particular. We examined this problem by comparing dispersal models of three levels of complexity: (1) an event-based binomial model that considers only the occurrence of mortality or arrival, (2) a temporally explicit exponential model that employs mortality and arrival rates, and (3) a spatially explicit grid-walk model that simulates the movement of animals through an artificial landscape. Each model was fitted to the same set of field data. A first objective of the paper is to illustrate how the maximum-likelihood method can be used in all three cases to estimate the means and confidence limits for the relevant model parameters, given a particular set of data on dispersal survival. Using this framework we show that the structure of the uncertainty for all three models is strikingly similar. In fact, the results of our unified approach imply that spatially explicit dispersal models, which take advantage of information on landscape details, suffer less from uncertainly than do simpler models. Moreover, we show that the proposed strategy of model development safeguards one from error propagation in these more complex models. Finally, our approach shows that all models related to animal dispersal, ranging from simple to complex, can be related in a hierarchical fashion, so that the various approaches to modeling such dispersal can be viewed from a unified perspective.
Grassman, J A; Masten, S A; Walker, N J; Lucier, G W
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent member of a class of chlorinated hydrocarbons that interact with the aryl hydrocarbon receptor (AhR). TCDD and dioxinlike compounds are environmentally and biologically stable and as a result, human exposure is chronic and widespread. Studies of highly exposed human populations show that dioxins produce developmental effects, chloracne, and an increase in all cancers and suggest that they may also alter immune and endocrine function. In contrast, the health effects of low-level environmental exposure have not been established. Experimental animal models can enhance the understanding of the effects of low-level dioxin exposure, particularly when there is evidence that humans respond similarly to the animal models. Although there are species differences in pharmacokinetics, experimental animal models demonstrate AhR-dependent health effects that are similar to those found in exposed human populations. Comparisons of biochemical changes show that humans and animal models have similar degrees of sensitivity to dioxin-induced effects. The information gained from animal models is important for developing mechanistic models of dioxin toxicity and critical for assessing the risks to human populations under different circumstances of exposure. PMID:9599728
Ng, Winnie; Lobach, Alexandra R M; Zhu, Xu; Chen, Xin; Liu, Feng; Metushi, Imir G; Sharma, Amy; Li, Jinze; Cai, Ping; Ip, Julia; Novalen, Maria; Popovic, Marija; Zhang, Xiaochu; Tanino, Tadatoshi; Nakagawa, Tetsuya; Li, Yan; Uetrecht, Jack
If we could predict and prevent idiosyncratic drug reactions (IDRs) it would have a profound effect on drug development and therapy. Given our present lack of mechanistic understanding, this goal remains elusive. Hypothesis testing requires valid animal models with characteristics similar to the idiosyncratic reactions that occur in patients. Although it has not been conclusively demonstrated, it appears that almost all IDRs are immune-mediated, and a dominant characteristic is a delay between starting the drug and the onset of the adverse reaction. In contrast, most animal models are acute and therefore involve a different mechanism than idiosyncratic reactions. There are, however, a few animal models such as the nevirapine-induced skin rash in rats that have characteristics very similar to the idiosyncratic reaction that occurs in humans and presumably have a very similar mechanism. These models have allowed testing hypotheses that would be impossible to test in any other way. In addition there are models in which there is a delayed onset of mild hepatic injury that resolves despite continued treatment similar to the "adaptation" reactions that are more common than severe idiosyncratic hepatotoxicity in humans. This probably represents the development of immune tolerance. However, most attempts to develop animal models by stimulating the immune system have been failures. A specific combination of MHC and T cell receptor may be required, but it is likely more complex. Animal studies that determine the requirements for an immune response would provide vital clues about risk factors for IDRs in patients.
Li, Xiao-Jiang; Li, Shihua
Huntington's disease is caused by the expansion of a polyglutamine repeat (>37 glutamines) in the disease protein huntingtin, which results in preferential neuronal loss in distinct brain regions. Mutant huntingtin causes late-onset neurological symptoms in patients in middle life, though the expression of mutant huntingtin is ubiquitous from early life. Thus, it is important to understand why mutant huntingtin selectively causes neuronal loss in an age-dependent manner. Transgenic animal models have been essential tools for uncovering the pathogenesis and therapeutic targets of neurodegenerative diseases. Genetic mouse models have been investigated extensively and have revealed the common pathological hallmark of age-dependent formation of aggregates or inclusions consisting of misfolded proteins. However, most genetic mouse models lack striking neurodegeneration that has been found in patient brains. Since there are considerable species differences between small and large animals, large animal models of Huntington's disease may allow one to identify the pathological features that are more similar to those in patients and also help uncover more effective therapeutic targets. This chapter will focus on the important findings from large animal models of Huntington's disease and discusses the use of large animal models to investigate the pathogenesis of Huntington's disease and develop new therapeutic strategies.
Fox, Robert A.
The advantages, and possible benefits of a valid, reliable animal model for nausea are discussed, and difficulties inherent to the development of a model are considered. A principle problem for developing models arises because nausea is a subjective sensation that can be identified only in humans. Several putative measures of nausea in animals are considered, with more detailed consideration directed to variation in cardiac rate, levels of vasopressin, and conditioned taste aversion. Demonstration that putative measures are associated with reported nausea in humans is proposed as a requirement for validating measures to be used in animal models. The necessity for a 'real-time' measure of nausea is proposed as an important factor for future research; and the need for improved understanding of the neuroanatomy underlying the emetic syndrome is discussed.
Nalberczak, Maria; Radwanska, Kasia
Our understanding of the neuronal and molecular basis of alcohol addiction is still not satisfactory. As a consequence we still miss successful therapy of alcoholism. One of the reasons for such state is the lack of appropriate animal models which would allow in-depth analysis of biological basis of addiction. Here we will present our efforts to create the animal model of alcohol addiction in the automated learning device, the IntelliCage setup. Applying this model to optogenetically modified mice with remotely controlled regulation of selected neuronal populations by light may lead to very precise identification of neuronal circuits involved in coding addiction-related behaviors.
Ogden, U; Kinnison, T; May, S A
Several reasons have been suggested for the elevated risk of suicide experienced by those in the veterinary profession. The current study aimed to investigate possible links between veterinarians' attitudes to 'convenience' or non-justified animal euthanasia and attitudes towards human euthanasia and suicide. Veterinary students and graduates had a negative attitude towards convenience animal euthanasia, but their attitudes changed over time (pre-clinical studies, clinical studies and recently graduated). A greater tolerance to euthanasia was displayed in the later years of study and post qualification - primarily by males. Attitudes towards both human euthanasia and suicide, however, remained stable over time and indicated on average a neutral stance. No correlations were found between attitudes to convenience euthanasia and either human euthanasia or suicide, suggesting a tolerance to convenience euthanasia of animals does not lead to desensitisation in valuing human life and a changed attitude to human euthanasia or suicide, or vice versa. Attitudes to human euthanasia and suicide were predictably correlated, perhaps suggesting an overarching attitude towards control over human death. The results of the current study throw into question the argument that it is the changes in attitudes to animal life that affect veterinarian's attitudes to human life and contribute to the high suicide rate.
Clippinger, Amy J; Hill, Erin; Curren, Rodger; Bishop, Patricia
Collaboration between industry and regulators resulted in the development of a decision tree approach using in vitro or ex vivo assays to replace animal tests when determining the eye irritation potential of antimicrobial cleaning products (AMCPs) under the United States Environmental Protection Agency (EPA) Office of Pesticide Programs' hazard classification and labeling system. A policy document issued by the EPA in 2013 and updated in 2015 describes the alternate testing framework that industry could apply to new registrations of AMCPs and, on a case-by-case basis, to conventional pesticide products. Despite the collaborative effort, the availability of relevant non-animal methods, and the EPA's change in policy, only a limited number of AMCPs have been registered using the framework. Companies continue to conduct animal tests when registering AMCPs due to various challenges surrounding adoption of the new testing framework; however, recent discussions between industry, regulators, and other interested parties have identified ways these challenges may be overcome. In this article we explore how use of the alternate framework could be expanded through efforts such as increasing international harmonization, more proactively publicizing the framework, and enhancing the training of regulatory reviewers. Not only can these strategies help to increase use of the EPA alternate eye irritation framework, they can also be applied to facilitate the uptake of other alternative approaches to animal testing in the future.
Barron, M.G.; Stehly, Guy R.; Hayton, W.L.
While clinical and toxicological applications of pharmacokinetics have continued to evolve both conceptually and experimentally, pharmacokinetics modeling in aquatic animals has not progressed accordingly. In this paper we present methods and concepts of pharmacokinetic modeling in aquatic animals using multicompartmental, clearance-based, non-compartmental and physiologically-based pharmacokinetic models. These models should be considered as alternatives to traditional approaches, which assume that the animal acts as a single homogeneous compartment based on apparent monoexponential elimination.
Lu, L; Chan, Ruby L Y; Luo, X M; Wu, William K K; Shin, Vivian Y; Cho, C H
Inflammation and cancer are the two major disorders in the gastrointestinal tract. They are causally related in their pathogenesis. It is important to study animal models' causal relationship and, in particular, to discover new therapeutic agents for such diseases. There are several criteria for these models in order to make them useful in better understanding the etiology and treatment of the said diseases in humans. In this regard, animal models should be similar as possible to human diseases and also be easy to produce and reproducible and also economic to allow a continuous replication in different laboratories. In this review, we summarize the various animal models for inflammatory and cancerous disorders in the upper and lower gastrointestinal tract. Experimental approaches are as simple as by giving a single oral dose of alcohol or other noxious agents or by injections of multiple dosages of ulcer inducing agents or by parenteral administration or in drinking water of carcinogens or by modifying the genetic makeups of animals to produce relatively long-term pathological changes in particular organs. With these methods they could induce consistent inflammatory responses or tumorigenesis in the gastrointestinal mucosa. These animal models are widely used in laboratories in understanding the pathogenesis as well as the mechanisms of action for therapeutic agents in the treatment of gastrointestinal inflammation and cancer.
Harding, John; Roberts, R Michael; Mirochnitchenko, Oleg
The field of regenerative medicine is approaching translation to clinical practice, and significant safety concerns and knowledge gaps have become clear as clinical practitioners are considering the potential risks and benefits of cell-based therapy. It is necessary to understand the full spectrum of stem cell actions and preclinical evidence for safety and therapeutic efficacy. The role of animal models for gaining this information has increased substantially. There is an urgent need for novel animal models to expand the range of current studies, most of which have been conducted in rodents. Extant models are providing important information but have limitations for a variety of disease categories and can have different size and physiology relative to humans. These differences can preclude the ability to reproduce the results of animal-based preclinical studies in human trials. Larger animal species, such as rabbits, dogs, pigs, sheep, goats, and non-human primates, are better predictors of responses in humans than are rodents, but in each case it will be necessary to choose the best model for a specific application. There is a wide spectrum of potential stem cell-based products that can be used for regenerative medicine, including embryonic and induced pluripotent stem cells, somatic stem cells, and differentiated cellular progeny. The state of knowledge and availability of these cells from large animals vary among species. In most cases, significant effort is required for establishing and characterizing cell lines, comparing behavior to human analogs, and testing potential applications. Stem cell-based therapies present significant safety challenges, which cannot be addressed by traditional procedures and require the development of new protocols and test systems, for which the rigorous use of larger animal species more closely resembling human behavior will be required. In this article, we discuss the current status and challenges of and several major directions
Helm, Ricki M
Specific food allergy is characterized by sensitization to innocuous food proteins with production of allergen-specific IgE that binds to receptors on basophils and mast cells. Upon recurrent exposure to the same allergen, an allergic response is induced by mediator release following cross-linking of cell-bound allergen-specific IgE. The determination of what makes an innocuous food protein an allergen in predisposed individuals is unknown; however, mechanistic and protein allergen predictive models are being actively investigated in a number of animal models. Currently, there is no animal model that will actively profile known food allergens, predict the allergic potential of novel food proteins, or demonstrate clinically the human food allergic sensitization/allergic response. Animal models under investigation include mice, rats, the guinea pig, atopic dog, and neonatal swine. These models are being assessed for production of IgE, clinical responses to re-exposure, and a ranking of food allergens (based on potency) including a nonfood allergen protein source. A selection of animal models actively being investigated that will contribute to our understanding of what makes a protein an allergen and future predictive models for assessing the allergenicity of novel proteins is presented in this review.
Jung, Soo Yeon; Kim, Ha Yeong; Park, Hae Sang; Yin, Xiang Yun; Chung, Sung Min; Kim, Han Su
Ideal hypoparathyroidism animal models are a prerequisite to developing new treatment modalities for this disorder. The purpose of this study was to evaluate the feasibility of a model whereby rats were parathyroidectomized (PTX) using a fluorescent-identification method and the ideal calcium content of the diet was determined. Thirty male rats were divided into surgical sham (SHAM, n = 5) and PTX plus 0, 0.5, and 2% calcium diet groups (PTX-FC (n = 5), PTX-NC (n = 10), and PTX-HC (n = 10), respectively). Serum parathyroid hormone levels decreased to non-detectable levels in all PTX groups. All animals in the PTX—FC group died within 4 days after the operation. All animals survived when supplied calcium in the diet. However, serum calcium levels were higher in the PTX-HC than the SHAM group. The PTX-NC group demonstrated the most representative modeling of primary hypothyroidism. Serum calcium levels decreased and phosphorus levels increased, and bone volume was increased. All animals survived without further treatment and did not show nephrotoxicity including calcium deposits. These findings demonstrate that PTX animal models produced by using the fluorescent-identification method, and fed a 0.5% calcium diet, are appropriate for hypoparathyroidism treatment studies. PMID:27695051
Xiong, Ye; Mahmood, Asim; Chopp, Michael
Traumatic brain injury (TBI) is a leading cause of mortality and morbidity in both civilian life and the battlefield worldwide. Survivors of TBI frequently experience long-term disabling changes in cognition, sensorimotor function and personality. Over the past three decades, animal models have been developed to replicate the various aspects of human TBI, to better understand the underlying pathophysiology and to explore potential treatments. Nevertheless, promising neuroprotective drugs, which were identified to be effective in animal TBI models, have all failed in phase II or phase III clinical trials. This failure in clinical translation of preclinical studies highlights a compelling need to revisit the current status of animal models of TBI and therapeutic strategies. PMID:23329160
Perdomini, Morgane; Hick, Aurore; Puccio, Hélène; Pook, Mark A
The development and use of animal and cellular models of Friedreich ataxia (FRDA) are essential requirements for the understanding of FRDA disease mechanisms and the investigation of potential FRDA therapeutic strategies. Although animal and cellular models of lower organisms have provided valuable information on certain aspects of FRDA disease and therapy, it is intuitive that the most useful models are those of mammals and mammalian cells, which are the closest in physiological terms to FRDA patients. To date, there have been considerable efforts put into the development of several different FRDA mouse models and relevant FRDA mouse and human cell line systems. We summarize the principal mammalian FRDA models, discuss the pros and cons of each system, and describe the ways in which such models have been used to address two of the fundamental, as yet unanswered, questions regarding FRDA. Namely, what is the exact pathophysiology of FRDA and what is the detailed genetic and epigenetic basis of FRDA?
Ćiçi, Ali; Ün, Cem Salih; Kirca, Zerrin
Supersymmetry (SUSY) is one of the forefront candidates for the models beyond the Standard Model (SM) in resolving the gauge hierarchy problem by proposing new supersymmetric partners for the SM fields. In SUSY, stop, the supersymmetric partner of top quark, is of a special importance, since it cancels the largest quadratic contributions to the Higgs boson mass from top quark loop. Despite heavy stop mass requirement from the Higgs boson searches and fine-tuning demands, it is still possible to find stops of mass about a few hundred GeV, even as light as top quark. In this study, we search for light stop solutions within the SUSY Grand Unified Theory (GUT) models in light of acceptable fine-tuning and current experimental constraints. Afterwards, we analyze the possible signals through which the implications can be tested at the Large Hadron Collider (LHC) experiments.
Royle, J. Andrew; Dorazio, R.M.
Much of animal ecology is devoted to studies of abundance and occurrence of species, based on surveys of spatially referenced sample units. These surveys frequently yield sparse counts that are contaminated by imperfect detection, making direct inference about abundance or occurrence based on observational data infeasible. This article describes a flexible hierarchical modeling framework for estimation and inference about animal abundance and occurrence from survey data that are subject to imperfect detection. Within this framework, we specify models of abundance and detectability of animals at the level of the local populations defined by the sample units. Information at the level of the local population is aggregated by specifying models that describe variation in abundance and detection among sites. We describe likelihood-based and Bayesian methods for estimation and inference under the resulting hierarchical model. We provide two examples of the application of hierarchical models to animal survey data, the first based on removal counts of stream fish and the second based on avian quadrat counts. For both examples, we provide a Bayesian analysis of the models using the software WinBUGS.
Wilson, Alastair J; Réale, Denis; Clements, Michelle N; Morrissey, Michael M; Postma, Erik; Walling, Craig A; Kruuk, Loeske E B; Nussey, Daniel H
1. Efforts to understand the links between evolutionary and ecological dynamics hinge on our ability to measure and understand how genes influence phenotypes, fitness and population dynamics. Quantitative genetics provides a range of theoretical and empirical tools with which to achieve this when the relatedness between individuals within a population is known. 2. A number of recent studies have used a type of mixed-effects model, known as the animal model, to estimate the genetic component of phenotypic variation using data collected in the field. Here, we provide a practical guide for ecologists interested in exploring the potential to apply this quantitative genetic method in their research. 3. We begin by outlining, in simple terms, key concepts in quantitative genetics and how an animal model estimates relevant quantitative genetic parameters, such as heritabilities or genetic correlations. 4. We then provide three detailed example tutorials, for implementation in a variety of software packages, for some basic applications of the animal model. We discuss several important statistical issues relating to best practice when fitting different kinds of mixed models. 5. We conclude by briefly summarizing more complex applications of the animal model, and by highlighting key pitfalls and dangers for the researcher wanting to begin using quantitative genetic tools to address ecological and evolutionary questions.
Tyagi, Pradeep; Smith, Phillip P; Kuchel, George A; de Groat, William C; Birder, Lori A; Chermansky, Christopher J; Adam, Rosalyn M; Tse, Vincent; Chancellor, Michael B; Yoshimura, Naoki
While the symptomology of underactive bladder (UAB) may imply a primary dysfunction of the detrusor muscle, insights into pathophysiology indicate that both myogenic and neurogenic mechanisms need to be considered. Due to lack of proper animal models, the current understanding of the UAB pathophysiology is limited, and much of what is known about the clinical etiology of the condition has been derived from epidemiological data. We hereby review current state of the art in the understanding of the pathophysiology of and animal models used to study the UAB.
Bowen, Joanne M; Gibson, Rachel J; Keefe, Dorothy M K
Alimentary mucositis is a major acute complication in the clinical setting, occurring in a large percentage of patients undergoing cytotoxic therapy. One of the major problems with alimentary mucositis is that the underlying mechanisms behind its development are not entirely understood, which makes it extremely difficult to develop effective interventions. Animal models provide a critical source of knowledge when sampling from patients is unavailable or interventions are yet to be fully tested. This review focuses on the animal models used to increase our understanding of the mechanisms of mucositis and translate new antimucotoxic agents into clinical trials.
Nair, Dhanya Venugopalan; Reddy, A. Gopala
The incidence of esophageal cancer is rapidly increasing especially in developing countries. The major risk factors include unhealthy lifestyle practices such as alcohol consumption, smoking, and chewing tobacco to name a few. Diagnosis at an advanced stage and poor prognosis make esophageal cancer one of the most lethal diseases. These factors have urged further research in understanding the pathophysiology of the disease. Animal models not only aid in understanding the molecular pathogenesis of esophageal cancer but also help in developing therapeutic interventions for the disease. This review throws light on the various recent laboratory animal models for esophageal cancer. PMID:27956773
Stroke is a leading cause of disability and death in many countries. Understanding the pathophysiology of ischemic injury and developing therapies is an important endeavor that requires much additional research. Animal stroke models provide an important mechanism for these activities. A large number of stroke models have been developed and are currently used in laboratories around the world. These models are overviewed as are approaches for measuring infarct size and functional outcome. PMID:20150985
Dodd, Rebecca D.; Mito, Jeffery K.; Kirsch, David G.
Soft-tissue sarcomas (STSs) are rare mesenchymal tumors that arise from muscle, fat and connective tissue. Currently, over 75 subtypes of STS are recognized. The rarity and heterogeneity of patient samples complicate clinical investigations into sarcoma biology. Model organisms might provide traction to our understanding and treatment of the disease. Over the past 10 years, many successful animal models of STS have been developed, primarily genetically engineered mice and zebrafish. These models are useful for studying the relevant oncogenes, signaling pathways and other cell changes involved in generating STSs. Recently, these model systems have become preclinical platforms in which to evaluate new drugs and treatment regimens. Thus, animal models are useful surrogates for understanding STS disease susceptibility and pathogenesis as well as for testing potential therapeutic strategies. PMID:20713645
Companies in Malaysia are beginning to use web-based training to reduce the cost of training and to provide employees with greater access to instruction. However, some people are uncomfortable with technology and prefer person-to-person methods of training. This study examines the acceptance of web-based training among a convenience sample of 261…
It is one of the central aims of the philosophy of science to elucidate the meanings of scientific terms and also to think critically about their application. The focus of this essay is the scientific term predict and whether there is credible evidence that animal models, especially in toxicology and pathophysiology, can be used to predict human outcomes. Whether animals can be used to predict human response to drugs and other chemicals is apparently a contentious issue. However, when one empirically analyzes animal models using scientific tools they fall far short of being able to predict human responses. This is not surprising considering what we have learned from fields such evolutionary and developmental biology, gene regulation and expression, epigenetics, complexity theory, and comparative genomics. PMID:19146696
Fisher, John T; Zhang, Yulong; Engelhardt, John F
Animal models of human diseases are critical for dissecting mechanisms of pathophysiology and developing therapies. In the context of cystic fibrosis (CF), mouse models have been the dominant species by which to study CF disease processes in vivo for the past two decades. Although much has been learned through these CF mouse models, limitations in the ability of this species to recapitulate spontaneous lung disease and several other organ abnormalities seen in CF humans have created a need for additional species on which to study CF. To this end, pig and ferret CF models have been generated by somatic cell nuclear transfer and are currently being characterized. These new larger animal models have phenotypes that appear to closely resemble human CF disease seen in newborns, and efforts to characterize their adult phenotypes are ongoing. This chapter will review current knowledge about comparative lung cell biology and cystic fibrosis transmembrane conductance regulator (CFTR) biology among mice, pigs, and ferrets that has implications for CF disease modeling in these species. We will focus on methods used to compare the biology and function of CFTR between these species and their relevance to phenotypes seen in the animal models. These cross-species comparisons and the development of both the pig and the ferret CF models may help elucidate pathophysiologic mechanisms of CF lung disease and lead to new therapeutic approaches.
Gookin, Jody L; Foster, Derek M; Harvey, Alice M; McWhorter, Dan
Understanding reticulorumen motility is important to the assessment of ruminant health and optimal production, and in the recognition, diagnosis, and treatment of disease. Accordingly, the teaching of reticulorumen motility is a staple of all veterinary curricula. This teaching has historically been based on written descriptions, line drawings, or pressure tracings obtained during contraction sequences. We developed an animated model of reticulorumen motility and hypothesized that veterinary students would prefer use of the model over traditional instructional methods. First-year veterinary students were randomly allocated to one of two online learning exercises: with the animated model (Group A) or with text and line drawings (Group B) depicting reticulorumen motility. Learning was assessed with a multiple-choice quiz and feedback on the learning alternatives was obtained by survey. Seventy-four students participated in the study, including 38/42 in Group A and 36/36 in Group B. Sixty-four out of 72 students (89%) responded that they would prefer use of the animated model if only one of the two learning methods was available. A majority of students agreed or strongly agreed that the animated model was easy to understand and improved their knowledge and appreciation of the importance of reticulorumen motility, and would recommend the model to other veterinary students. Interestingly, students in Group B achieved higher scores on examination than students in Group A. This could be speculatively attributed to the inclusion of an itemized list of contraction sequences in the text provided to Group B and failure of Group A students to read the text associated with the animations.
Yang, Shang-Hsun; Chan, Anthony W S
Huntington's disease (HD) is a devastating neurodegenerative disorder that currently has no cure. In order to develop effective treatment, an understanding of HD pathogenesis and the evaluation of therapeutic efficacy of novel medications with the aid of animal models are critical steps. Transgenic animals sharing similar genetic defects that lead to HD have provided important discoveries in HD mechanisms that cell models are not able to replicate, which include psychiatric impairment, cognitive behavioral impact, and motor functions. Although transgenic HD rodent models have been widely used in HD research, it is clear that an animal model with comparable physiology to man, similar genetic defects that lead to HD, and the ability to develop similar cognitive and behavioral impairments is critical for explaining HD pathogenesis and the development of cures. Compared to HD rodents, HD transgenic nonhuman primates have not only developed comparable neuropathology but also present HD clinical features such as rigidity, seizure, dystonia, bradykinesia, and chorea that no other animal model has been able to replicate. Distinctive degenerating neurons and the accumulation of neuropil aggregates observed in HD monkey brain strongly support the hypothesis that the unique neuropathogenic events seen in HD monkey brain recapitulate HD in man. The latest development of transgenic HD primates has opened a new era of animal modeling that better represents human genetic disorders such as HD, which will accelerate the development of diagnostic tools and identifying novel biomarkers through longitudinal studies including gene expression and metabolite profiling, and noninvasive imaging. Furthermore, novel treatments with predictable efficacy in human patients can be developed using HD monkeys because of comparable neuropathology and clinical features.
Silva, Zenildo Santos; Bussadori, Sandra Kalil; Fernandes, Kristianne Porta Santos; Huang, Ying-Ying; Hamblin, Michael R.
Photodynamic therapy (PDT) employs non-toxic dyes called photosensitizers (PSs), which absorb visible light to give the excited singlet state, followed by the long-lived triplet state that can undergo photochemistry. In the presence of ambient oxygen, reactive oxygen species (ROS), such as singlet oxygen and hydroxyl radicals are formed that are able to kill cancer cells, inactivate microbial pathogens and destroy unwanted tissue. Although there are already several clinically approved PSs for various disease indications, many studies around the world are using animal models to investigate the further utility of PDT. The present review will cover the main groups of animal models that have been described in the literature. Cancer comprises the single biggest group of models including syngeneic mouse/rat tumours that can either be subcutaneous or orthotopic and allow the study of anti-tumour immune response; human tumours that need to be implanted in immunosuppressed hosts; carcinogen-induced tumours; and mice that have been genetically engineered to develop cancer (often by pathways similar to those in patients). Infections are the second biggest class of animal models and the anatomical sites include wounds, burns, oral cavity, ears, eyes, nose etc. Responsible pathogens can include Gram-positive and Gram-negative bacteria, fungi, viruses and parasites. A smaller and diverse group of miscellaneous animal models have been reported that allow PDT to be tested in ophthalmology, atherosclerosis, atrial fibrillation, dermatology and wound healing. Successful studies using animal models of PDT are blazing the trail for tomorrow's clinical approvals. PMID:26415497
Dhondt, Kévin P; Horvat, Branka
The Henipavirus genus contains two highly lethal viruses, the Hendra and Nipah viruses and one, recently discovered, apparently nonpathogenic member; Cedar virus. These three, negative-sense single-stranded RNA viruses, are hosted by fruit bats and use EphrinB2 receptors for entry into cells. The Hendra and Nipah viruses are zoonotic pathogens that emerged in the middle of 90s and have caused severe, and often fatal, neurologic and/or respiratory diseases in both humans and different animals; including spillover into equine and porcine species. Development of relevant models is critical for a better understanding of viral pathogenesis, generating new diagnostic tools, and assessing anti-viral therapeutics and vaccines. This review summarizes available data on several animal models where natural and/or experimental infection has been demonstrated; including pteroid bats, horses, pigs, cats, hamsters, guinea pigs, ferrets, and nonhuman primates. It recapitulates the principal features of viral pathogenesis in these animals and current knowledge on anti-viral immune responses. Lastly it describes the recently characterized murine animal model, which provides the possibility to use numerous and powerful tools available for mice to further decipher henipaviruses immunopathogenesis, prophylaxis, and treatment. The utility of different models to analyze important aspects of henipaviruses-induced disease in humans, potential routes of transmission, and therapeutic approaches are equally discussed.
Dhondt, Kévin P.; Horvat, Branka
The Henipavirus genus contains two highly lethal viruses, the Hendra and Nipah viruses and one, recently discovered, apparently nonpathogenic member; Cedar virus. These three, negative-sense single-stranded RNA viruses, are hosted by fruit bats and use EphrinB2 receptors for entry into cells. The Hendra and Nipah viruses are zoonotic pathogens that emerged in the middle of 90s and have caused severe, and often fatal, neurologic and/or respiratory diseases in both humans and different animals; including spillover into equine and porcine species. Development of relevant models is critical for a better understanding of viral pathogenesis, generating new diagnostic tools, and assessing anti-viral therapeutics and vaccines. This review summarizes available data on several animal models where natural and/or experimental infection has been demonstrated; including pteroid bats, horses, pigs, cats, hamsters, guinea pigs, ferrets, and nonhuman primates. It recapitulates the principal features of viral pathogenesis in these animals and current knowledge on anti-viral immune responses. Lastly it describes the recently characterized murine animal model, which provides the possibility to use numerous and powerful tools available for mice to further decipher henipaviruses immunopathogenesis, prophylaxis, and treatment. The utility of different models to analyze important aspects of henipaviruses-induced disease in humans, potential routes of transmission, and therapeutic approaches are equally discussed. PMID:25437037
Vainzof, Mariz; Ayub-Guerrieri, Danielle; Onofre, Paula C G; Martins, Poliana C M; Lopes, Vanessa F; Zilberztajn, Dinorah; Maia, Lucas S; Sell, Karen; Yamamoto, Lydia U
The neuromuscular disorders are a heterogeneous group of genetic diseases, caused by mutations in genes coding sarcolemmal, sarcomeric, and citosolic muscle proteins. Deficiencies or loss of function of these proteins leads to variable degree of progressive loss of motor ability. Several animal models, manifesting phenotypes observed in neuromuscular diseases, have been identified in nature or generated in laboratory. These models generally present physiological alterations observed in human patients and can be used as important tools for genetic, clinic, and histopathological studies. The mdx mouse is the most widely used animal model for Duchenne muscular dystrophy (DMD). Although it is a good genetic and biochemical model, presenting total deficiency of the protein dystrophin in the muscle, this mouse is not useful for clinical trials because of its very mild phenotype. The canine golden retriever MD model represents a more clinically similar model of DMD due to its larger size and significant muscle weakness. Autosomal recessive limb-girdle MD forms models include the SJL/J mice, which develop a spontaneous myopathy resulting from a mutation in the Dysferlin gene, being a model for LGMD2B. For the human sarcoglycanopahties (SG), the BIO14.6 hamster is the spontaneous animal model for delta-SG deficiency, whereas some canine models with deficiency of SG proteins have also been identified. More recently, using the homologous recombination technique in embryonic stem cell, several mouse models have been developed with null mutations in each one of the four SG genes. All sarcoglycan-null animals display a progressive muscular dystrophy of variable severity and share the property of a significant secondary reduction in the expression of the other members of the sarcoglycan subcomplex and other components of the Dystrophin-glycoprotein complex. Mouse models for congenital MD include the dy/dy (dystrophia-muscularis) mouse and the allelic mutant dy(2J)/dy(2J) mouse
Pérez-Rial, Sandra; Girón-Martínez, Álvaro; Peces-Barba, Germán
Animal models of disease have always been welcomed by the scientific community because they provide an approach to the investigation of certain aspects of the disease in question. Animal models of COPD cannot reproduce the heterogeneity of the disease and usually only manage to represent the disease in its milder stages. Moreover, airflow obstruction, the variable that determines patient diagnosis, not always taken into account in the models. For this reason, models have focused on the development of emphysema, easily detectable by lung morphometry, and have disregarded other components of the disease, such as airway injury or associated vascular changes. Continuous, long-term exposure to cigarette smoke is considered the main risk factor for this disease, justifying the fact that the cigarette smoke exposure model is the most widely used. Some variations on this basic model, related to exposure time, the association of other inducers or inhibitors, exacerbations or the use of transgenic animals to facilitate the identification of pathogenic pathways have been developed. Some variations or heterogeneity of this disease, then, can be reproduced and models can be designed for resolving researchers' questions on disease identification or treatment responses.
Frith, Daniel; Cohen, Mitchell J; Brohi, Karim
Resurgent study of trauma-induced coagulopathy (TIC) has delivered considerable improvements in survival after injury. Robust, valid and clinically relevant experimental models of TIC are essential to support the evolution of our knowledge and management of this condition. The aims of this study were to identify and analyze contemporary animal models of TIC with regard to their ability to accurately characterize known mechanisms of coagulopathy and/or to test the efficacy of therapeutic agents. A literature review was performed. Structured search of the indexed online database MEDLINE/PubMed in July 2010 identified 43 relevant articles containing 23 distinct animal models of TIC. The main aim of 26 studies was to test a therapeutic and the other 17 were conducted to investigate pathophysiology. A preponderance of porcine models was identified. Three new models demonstrating an endogenous acute traumatic coagulopathy (ATC) have offered new insights into the pathophysiology of TIC. Independent or combined effects of induced hypothermia and metabolic acidosis have been extensively evaluated. Recently, a pig model of TIC has been developed that features all major etiologies of TIC, although not in correct chronological order. This review identifies a general lack of experimental research to keep pace with clinical developments. Tissue injury and hemorrhagic shock are fundamental initiating events that prime the hemostatic system for subsequent iatrogenic insults. New animal models utilizing a variety of species that accurately simulate the natural clinical trajectory of trauma are urgently needed.
Camacho, Paula; Fan, Huimin; Liu, Zhongmin; He, Jia-Qiang
There is an urgent clinical need to develop new therapeutic approaches for treating cardiovascular disease, but the biology of cardiovascular regeneration is complex. Model systems are required to advance our understanding of the pathogenesis, progression, and mechanisms underlying cardiovascular disease as well as to test therapeutic approaches to regenerate tissue and restore cardiac function following injury. An ideal model system should be inexpensive, easily manipulated, reproducible, physiologically representative of human disease, and ethically sound. The choice of animal model needs to be considered carefully since it affects experimental outcomes and whether findings of the study can be reasonably translated to humans. This review presents a guideline for the commonly used small animal models (mice, rats, rabbits, and cats) used in cardiac research as an effort to standardize the most relevant procedures and obtain translatable and reproducible results. PMID:27679742
Sumpter, David J T; Mann, Richard P; Perna, Andrea
Collective animal behaviour is the study of how interactions between individuals produce group level patterns, and why these interactions have evolved. This study has proved itself uniquely interdisciplinary, involving physicists, mathematicians, engineers as well as biologists. Almost all experimental work in this area is related directly or indirectly to mathematical models, with regular movement back and forth between models, experimental data and statistical fitting. In this paper, we describe how the modelling cycle works in the study of collective animal behaviour. We classify studies as addressing questions at different levels or linking different levels, i.e. as local, local to global, global to local or global. We also describe three distinct approaches-theory-driven, data-driven and model selection-to these questions. We show, with reference to our own research on species across different taxa, how we move between these different levels of description and how these various approaches can be applied to link levels together.
Wong, Kung-Teck; Teo, Timothy; Russo, Sharon
The purpose of this study is to validate the technology acceptance model (TAM) in an educational context and explore the role of gender and computer teaching efficacy as external variables. From the literature, it appeared that only limited studies had developed models to explain statistically the chain of influence of computer teaching efficacy…
Oye, N. D.; Iahad, N. A.; Rahim, N. Ab.
This paper started with the review of the history of technology acceptance model from TRA to UTAUT. The expected contribution is to bring to lime light the current development stage of the technology acceptance model. Based on this, the paper examined the impact of UTAUT model on ICT acceptance and usage in HEIs. The UTAUT model theory was…
Rodríguez-Garay, Emilio Alberto
Cholestasis may result from a failure in bile secretion in hepatocytes or ductular cells, or from a blockade to the free bile flow. Human cholestasis may be induced by many drugs, being antibiotics the more common. Other types of cholestasis seen in humans are a group of familial cholestatic disorders, obstructive cholestasis, primary biliary cirrhosis, extrahepatic biliary atresia, primary sclerosing cholangitis, cholestasis of pregnancy, oral contraceptive-induced cholestasis, and sepsis-induced cholestasis. Experimental animal models allow the understanding of pathophysiological mechanisms involved and their clinical correlates. The most common experimental models of intrahepatic cholestasis are estrogen-induced, endotoxin-induced and drug-induced cholestasis. A well known model of extrahepatic biliary obstruction is common bile duct ligation. Drug-induced cholestasis were described using different drugs. On this regard, alpha naphthylisothiocyanate treatment has been extensively used, permitting to describe not only cholestatic alterations but also compensatory mechanisms. Congenital defficiency of transport proteins also were studied in natural rat models of cholestasis. The experimental animal models allow to define down-regulated alterations of hepatocyte transport proteins, and up-regulated ones acting as compensatory mechanisms. In conclusion, animal model and transport protein studies are necessary for the progressive understanding of congenital and acquired human cholestasis, and regulatory mechanisms that operate on liver cells.
Warawa, Jonathan Mark
Burkholderia pseudomallei is the Gram-negative bacterial pathogen responsible for the disease melioidosis. B. pseudomallei establishes disease in susceptible individuals through multiple routes of infection, all of which may proceed to a septicemic disease associated with a high mortality rate. B. pseudomallei opportunistically infects humans and a wide range of animals directly from the environment, and modeling of experimental melioidosis has been conducted in numerous biologically relevant models including mammalian and invertebrate hosts. This review seeks to summarize published findings related to established animal models of melioidosis, with an aim to compare and contrast the virulence of B. pseudomallei in these models. The effect of the route of delivery on disease is also discussed for intravenous, intraperitoneal, subcutaneous, intranasal, aerosol, oral, and intratracheal infection methodologies, with a particular focus on how they relate to modeling clinical melioidosis. The importance of the translational validity of the animal models used in B. pseudomallei research is highlighted as these studies have become increasingly therapeutic in nature. PMID:21772830
Mizutani, Hitoshi; Yamanaka, Keiichi; Konishi, Hiroshi; Murakami, Takaaki
Investigation of psoriasis and pustular psoriasis is presently hampered by the lack of appropriate animal models. So far, more than ten models have been developed in mice by spontaneous gene mutations and by gene manipulation. However, none of them has satisfactorily reproduced the clinicopathological and immunopathological phenotypes of these diseases. Xenotransplantation techniques have been used for designing models of psoriasis vulgaris, in which CD4(+) T cells have been shown to play an important role. An ideal model for pustular psoriasis should have an immunological background and fulfill the diagnostic criteria of psoriasis.
Helm, Ricki M; Ermel, Richard W; Frick, Oscar L
Food allergy can present as immediate hypersensitivity [manifestations mediated by immunoglobulin (Ig)E], delayed-type hypersensitivity (reactions associated with specific T lymphocytes), and inflammatory reactions caused by immune complexes. For reasons of ethics and efficacy, investigations in humans to determine sensitization and allergic responses of IgE production to innocuous food proteins are not feasible. Therefore, animal models are used a) to bypass the innate tendency to develop tolerance to food proteins and induce specific IgE antibody of sufficient avidity/affinity to cause sensitization and upon reexposure to induce an allergic response, b) to predict allergenicity of novel proteins using characteristics of known food allergens, and c) to treat food allergy by using immunotherapeutic strategies to alleviate life-threatening reactions. The predominant hypothesis for IgE-mediated food allergy is that there is an adverse reaction to exogenous food proteins or food protein fragments, which escape lumen hydrolysis, and in a polarized helper T cell subset 2 (Th2) environment, immunoglobulin class switching to allergen-specific IgE is generated in the immune system of the gastrointestinal-associated lymphoid tissues. Traditionally, the immunologic characterization and toxicologic studies of small laboratory animals have provided the basis for development of animal models of food allergy; however, the natural allergic response in large animals, which closely mimic allergic diseases in humans, can also be useful as models for investigations involving food allergy.
Workman, Joanna L; Nelson, Randy J
Seasonal affective disorder (SAD) is characterized by depressive episodes during winter that are alleviated during summer and by morning bright light treatment. Currently, there is no animal model of SAD. However, it may be possible to use rodents that respond to day length (photoperiod) to understand how photoperiod can shape the brain and behavior in humans. As nights lengthen in the autumn, the duration of the nightly elevation of melatonin increase; seasonally breeding animals use this information to orchestrate seasonal changes in physiology and behavior. SAD may originate from the extended duration of nightly melatonin secretion during fall and winter. These similarities between humans and rodents in melatonin secretion allows for comparisons with rodents that express more depressive-like responses when exposed to short day lengths. For instance, Siberian hamsters, fat sand rats, Nile grass rats, and Wistar rats display a depressive-like phenotype when exposed to short days. Current research in depression and animal models of depression suggests that hippocampal plasticity may underlie the symptoms of depression and depressive-like behaviors, respectively. It is also possible that day length induces structural changes in human brains. Many seasonally breeding rodents undergo changes in whole brain and hippocampal volume in short days. Based on strict validity criteria, there is no animal model of SAD, but rodents that respond to reduced day lengths may be useful to approximate the neurobiological phenomena that occur in people with SAD, leading to greater understanding of the etiology of the disorder as well as novel therapeutic interventions.
Morton, A Jennifer; Howland, David S
The dominant nature of the Huntington's disease gene mutation has allowed genetic models to be developed in multiple species, with the mutation causing an abnormal neurological phenotype in all animals in which it is expressed. Many different rodent models have been generated. The most widely used of these, the transgenic R6/2 mouse, carries the mutation in a fragment of the human huntingtin gene and has a rapidly progressive and fatal neurological phenotype with many relevant pathological changes. Nevertheless, their rapid decline has been frequently questioned in the context of a disease that takes years to manifest in humans, and strenuous efforts have been made to make rodent models that are genetically more 'relevant' to the human condition, including full length huntingtin gene transgenic and knock-in mice. While there is no doubt that we have learned, and continue to learn much from rodent models, their usefulness is limited by two species constraints. First, the brains of rodents differ significantly from humans in both their small size and their neuroanatomical organization. Second, rodents have much shorter lifespans than humans. Here, we review new approaches taken to these challenges in the development of models of Huntington's disease in large brained, long-lived animals. We discuss the need for such models, and how they might be used to fill specific niches in preclinical Huntington's disease research, particularly in testing gene-based therapeutics. We discuss the advantages and disadvantages of animals in which the prodromal period of disease extends over a long time span. We suggest that there is considerable 'value added' for large animal models in preclinical Huntington's disease research.
Guidetti, Roberto; Baraldi, Laura; Calzolai, Caterina; Pini, Lorenza; Veronesi, Paola; Pederzoli, Aurora
Background Science curricula and teachers should emphasize evolution in a manner commensurate with its importance as a unifying concept in science. The concept of adaptation represents a first step to understand the results of natural selection. We settled an experimental project of alternative didactic to improve knowledge of organism adaptation. Students were involved and stimulated in learning processes by creative activities. To set adaptation in a historic frame, fossil records as evidence of past life and evolution were considered. Results The experimental project is schematized in nine phases: review of previous knowledge; lesson on fossils; lesson on fantastic animals; planning an imaginary world; creation of an imaginary animal; revision of the imaginary animals; adaptations of real animals; adaptations of fossil animals; and public exposition. A rubric to evaluate the student's performances is reported. The project involved professors and students of the University of Modena and Reggio Emilia and of the "G. Marconi" Secondary School of First Degree (Modena, Italy). Conclusion The educational objectives of the project are in line with the National Indications of the Italian Ministry of Public Instruction: knowledge of the characteristics of living beings, the meanings of the term "adaptation", the meaning of fossils, the definition of ecosystem, and the particularity of the different biomes. At the end of the project, students will be able to grasp particular adaptations of real organisms and to deduce information about the environment in which the organism evolved. This project allows students to review previous knowledge and to form their personalities. PMID:17767729
Philipson, Casandra W.; Bassaganya-Riera, Josep; Hontecillas, Raquel
Enteroaggregative Escherichia coli (EAEC) has been acknowledged as an emerging cause of gastroenteritis worldwide for over two decades. Epidemiologists are revealing the role of EAEC in diarrheal outbreaks as a more common occurrence than ever suggested before. EAEC induced diarrhea is most commonly associated with travelers, children and immunocompromised individuals however its afflictions are not limited to any particular demographic. Many attributes have been discovered and characterized surrounding the capability of EAEC to provoke a potent pro-inflammatory immune response, however cellular and molecular mechanisms underlying initiation, progression and outcomes are largely unknown. This limited understanding can be attributed to heterogeneity in strains and the lack of adequate animal models. This review aims to summarize current knowledge about EAEC etiology, pathogenesis and clinical manifestation. Additionally, current animal models and their limitations will be discussed along with the value of applying systems-wide approaches such as computational modeling to study host-EAEC interactions. PMID:23680797
Hui Yin, Yow; Ahmad, Nurulumi; Makmor-Bakry, Mohd
Epilepsy is one of the most common chronic disorders affecting individuals of all ages. A greater understanding of pathogenesis in epilepsy will likely provide the basis fundamental for development of new antiepileptic therapies that aim to prevent the epileptogenesis process or modify the progression of epilepsy in addition to treatment of epilepsy symptomatically. Therefore, several investigations have embarked on advancing knowledge of the mechanism underlying epileptogenesis, understanding in mechanism of pharmacoresistance and discovering antiepileptogenic or disease-modifying therapy. Animal models play a crucial and significant role in providing additional insight into mechanism of epileptogenesis. With the help of these models, epileptogenesis process has been demonstrated to be involved in various molecular and biological pathways or processes. Hence, this article will discuss the known and postulated mechanisms of epileptogenesis and challenges in using the animal models. PMID:24494063
Liao, Jiawei; Huang, Wei; Liu, George
Cardiovascular disease, predominantly coronary heart disease and stroke, leads to high morbidity and mortality not only in developed worlds but also in underdeveloped regions. The dominant pathologic foundation for cardiovascular disease is atherosclerosis and as to coronary heart disease, coronary atherosclerosis and resulting lumen stenosis, even total occlusions. In translational research, several animals, such as mice, rabbits and pigs, have been used as disease models of human atherosclerosis and related cardiovascular disorders. However, coronary lesions are either naturally rare or hard to be fast induced in these models, hence, coronary heart disease induction mostly relies on surgical or pharmaceutical interventions with no or limited primary coronary lesions, thus unrepresentative of human coronary heart disease progression and pathology. In this review, we will describe the progress of animal models of coronary heart disease following either spontaneous or diet-accelerated coronary lesions.
Sah, Sangeeta Pilkhwal; Singh, Barinder; Choudhary, Supriti; Kumar, Anil
Insulin resistance can be seen as a molecular and genetic mystery, with a role in the pathophysiology of type 2 diabetes mellitus. It is a basis for a number of chronic diseases like hypertension, dyslipidemia, glucose intolerance, coronary heart disease, cerebral vascular disease along with T2DM, thus the key is to cure and prevent insulin resistance. Critical perspicacity into the etiology of insulin resistance have been gained by the use of animal models where insulin action has been modulated by various transgenic and non-transgenic models which is not possible in human studies. The following review comprises the pathophysiology involved in insulin resistance, various factors causing insulin resistance, their screening and various genetic and non-genetic animal models highlighting the pathological and metabolic characteristics of each.
Singh, Amrit Pal; Junemann, Anselm; Muthuraman, Arunachalam; Jaggi, Amteshwar Singh; Singh, Nirmal; Grover, Kuldeep; Dhawan, Ravi
The animal models are pivotal for understanding the characteristics of acute renal failure (ARF) and development of effective therapy for its optimal management. Since the etiology for induction of renal failure is multifold, therefore, a large number of animal models have been developed to mimic the clinical conditions of renal failure. Glycerol-induced renal failure closely mimics the rhabdomyolysis; ischemia-reperfusion-induced ARF simulate the hemodynamic changes-induced changes in renal functioning; drug-induced such as gentamicin, cisplatin, NSAID, ifosfamide-induced ARF mimics the renal failure due to clinical administration of respective drugs; uranium, potassium dichromate-induced ARF mimics the occupational hazard; S-(1,2-dichlorovinyl)-L-cysteine-induced ARF simulate contaminated water-induced renal dysfunction; sepsis-induced ARF mimics the infection-induced renal failure and radiocontrast-induced ARF mimics renal failure in patients during use of radiocontrast media at the time of cardiac catheterization. Since each animal model has been created with specific methodology, therefore, it is essential to describe the model in detail and consequently interpret the results in the context of a specific model.
Afari-Kumah, Eben; Achampong, Akwasi Kyere
This study aims to examine the computer usage intentions of Ghanaian Tertiary Students. The Technology Acceptance Model was adopted as the theoretical framework to ascertain whether it could help explain behavioral intentions of individuals to accept and use technology. Factor analysis was used to assess the construct validity of the initial…
Krishnan, Vaishnav; Nestler, Eric J.
Much of the current understanding about the pathogenesis of altered mood, impaired concentration and neurovegetative symptoms in major depression has come from animal models. However, because of the unique and complex features of human depression, the generation of valid and insightful depression models has been less straightforward than modeling other disabling diseases like cancer or autoimmune conditions. Today’s popular depression models creatively merge ethologically valid behavioral assays with the latest technological advances in molecular biology and automated video-tracking. This chapter reviews depression assays involving acute stress (e.g., forced swim test), models consisting of prolonged physical or social stress (e.g., social defeat), models of secondary depression, genetic models, and experiments designed to elucidate the mechanisms of antidepressant action. These paradigms are critically evaluated in relation to their ease, validity and replicability, the molecular insights that they have provided, and their capacity to offer the next generation of therapeutics for depression. PMID:21225412
Smith, Darci R; Holbrook, Michael R; Gowen, Brian B
The term "viral hemorrhagic fever" (VHF) designates a syndrome of acute febrile illness, increased vascular permeability and coagulation defects which often progresses to bleeding and shock and may be fatal in a significant percentage of cases. The causative agents are some 20 different RNA viruses in the families Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae, which are maintained in a variety of animal species and are transferred to humans through direct or indirect contact or by an arthropod vector. Except for dengue, which is transmitted among humans by mosquitoes, the geographic distribution of each type of VHF is determined by the range of its animal reservoir. Treatments are available for Argentine HF and Lassa fever, but no approved countermeasures have been developed against other types of VHF. The development of effective interventions is hindered by the sporadic nature of most infections and their occurrence in geographic regions with limited medical resources. Laboratory animal models that faithfully reproduce human disease are therefore essential for the evaluation of potential vaccines and therapeutics. The goal of this review is to highlight the current status of animal models that can be used to study the pathogenesis of VHF and test new countermeasures.
de Jong, Johannes W; Vanderschuren, Louk J M J; Adan, Roger A H
The dramatically increasing prevalence of obesity, associated with potentially life-threatening health problems, including cardiovascular diseases and type II diabetes, poses an enormous public health problem. It has been proposed that the obesity epidemic can be explained by the concept of 'food addiction'. In this review we focus on possible similarities between binge eating disorder (BED), which is highly prevalent in the obese population, and drug addiction. Indeed, both behavioral and neural similarities between addiction and BED have been demonstrated. Behavioral similarities are reflected in the overlap in DSM-IV criteria for drug addiction with the (suggested) criteria for BED and by food addiction-like behavior in animals after prolonged intermittent access to palatable food. Neural similarities include the overlap in brain regions involved in food and drug craving. Decreased dopamine D2 receptor availability in the striatum has been found in animal models of binge eating, after cocaine self-administration in animals as well as in drug addiction and obesity in humans. To further explore the neurobiological basis of food addiction, it is essential to have an animal model to test the addictive potential of palatable food. A recently developed animal model for drug addiction involves three behavioral characteristics that are based on the DSM-IV criteria: i) extremely high motivation to obtain the drug, ii) difficulty in limiting drug seeking even in periods of explicit non-availability, iii) continuation of drug-seeking despite negative consequences. Indeed, it has been shown that a subgroup of rats, after prolonged cocaine self-administration, scores positive on these three criteria. If food possesses addictive properties, then food-addicted rats should also meet these criteria while searching for and consuming food. In this review we discuss evidence from literature regarding food addiction-like behavior. We also suggest future experiments that could
Gyamfi, Stephen Adu
This study extends the technology acceptance model to identify factors that influence technology acceptance among pre-service teachers in Ghana. Data from 380 usable questionnaires were tested against the research model. Utilising the extended technology acceptance model (TAM) as a research framework, the study found that: pre-service teachers'…
Challa, Siva Reddy
One of the biggest challenges for discovering more efficacious drugs for the control of neuropathic pain has been the diversity of chronic pain states in humans. It is now acceptable that different mechanisms contribute to normal physiologic pain, pain arising from tissue damage and pain arising from injury to the nervous system. To study pain transmission, spot novel pain targets and characterize the potential analgesic profile of new chemical entities, numerous experimental animal pain models have been developed that attempt to simulate the many human pain conditions. Among the neuropathic pain models, surgical models have paramount importance in the induction of pain states. Many surgical animal models exist, like the chronic constriction injury (CCI) to the sciatic nerve, partial sciatic nerve ligation (pSNL), spinal nerve ligation (SNL), spared nerve injury (SNI), brachial plexus avulsion (BPA), sciatic nerve transaction (SNT) and sciatic nerve trisection. Most of these models induce responses similar to those found in causalgia, a syndrome of sustained burning pain often seen in the distal extremity after partial peripheral nerve injury in humans. Researchers most commonly use these surgical models in both rats and mice during drug discovery to screen new chemical entities for efficacy in the area of neuropathic pain. However, there is scant literature that provides a comparative discussion of all these surgical models. Each surgical model has its own benefits and limitations. It is very difficult for a researcher to choose a suitable surgical animal model to suit their experimental set-up. Therefore, particular attention has been given in this review to comparatively provide the pros and cons of each model of surgically induced neuropathic pain.
Jalal, Azlin Abd; Ayub, Ahmad Fauzi Mohd; Tarmizi, Rohani Ahmad
The integration and effectiveness of eBook utilization in Mathematics teaching and learning greatly relied upon the teachers, hence the need to understand their perceptions and beliefs. The eBook, an individual laptop completed with digitized textbook sofwares, were provided for each students in line with the concept of 1 student:1 laptop. This study focuses on predicting a model on the acceptance of the eBook among Mathematics teachers. Data was collected from 304 mathematics teachers in selected schools using a survey questionnaire. The selection were based on the proportionate stratified sampling. Structural Equation Modeling (SEM) were employed where the model was tested and evaluated and was found to have a good fit. The variance explained for the teachers' attitude towards eBook is approximately 69.1% where perceived usefulness appeared to be a stronger determinant compared to perceived ease of use. This study concluded that the attitude of mathematics teachers towards eBook depends largely on the perception of how useful the eBook is on improving their teaching performance, implying that teachers should be kept updated with the latest mathematical application and sofwares to use with the eBook to ensure positive attitude towards using it in class.
Macpherson, A J; McCoy, K D
An appreciation of the importance of interactions between microbes and multicellular organisms is currently driving research in biology and biomedicine. Many human diseases involve interactions between the host and the microbiota, so investigating the mechanisms involved is important for human health. Although microbial ecology measurements capture considerable diversity of the communities between individuals, this diversity is highly problematic for reproducible experimental animal models that seek to establish the mechanistic basis for interactions within the overall host-microbial superorganism. Conflicting experimental results may be explained away through unknown differences in the microbiota composition between vivaria or between the microenvironment of different isolated cages. In this position paper, we propose standardised criteria for stabilised and defined experimental animal microbiotas to generate reproducible models of human disease that are suitable for systematic experimentation and are reproducible across different institutions. PMID:25492472
Gahete, Manuel D; Luque, Raul M; Castaño, Justo P
Growth hormone (GH) is a peptide hormone released from pituitary somatotrope cells that promotes growth, cell division and regeneration by acting directly through the GH receptor (GHR), or indirectly via hepatic insulin-like growth factor 1 (IGF1) production. GH deficiency (GHD) can cause severe consequences, such as growth failure, changes in body composition and altered insulin sensitivity, depending of the origin, time of onset (childhood or adulthood) or duration of GHD. The highly variable clinical phenotypes of GHD can now be better understood through research on transgenic and naturally-occurring animal models, which are widely employed to investigate the origin, phenotype, and consequences of GHD, and particularly the underlying mechanisms of metabolic disorders associated to GHD. Here, we reviewed the most salient aspects of GH biology, from somatotrope development to GH actions, linked to certain GHD types, as well as the animal models employed to reproduce these GHD-associated alterations.
Pennesi, Mark E; Neuringer, Martha; Courtney, Robert J
Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations.
Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.
Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444
Salama, Alan D.; Little, Mark A
This review seeks to provide an update on the experimental models that have been developed recapitulating clinical ANCA associated vasculitis. The recent insights regarding the application of the models in the study of pathogenesis, and the therapeutic implications of this, are covered in the article by van Timmeren and Heeringa in this issue. Recent findings Rodent models of both MPO- and PR3 ANCA associated vasculitis have been developed, which have provided important insights into the pathogenesis of ANCA associated pulmonary and renal disease. The vast majority of in vivo work in this field has concerned MPO-ANCA associated disease, although the last year has seen some advances in modelling of anti-PR3 disease. As with all experimental animal models they are flawed in one way or another, by virtue of the means by which they are induced, but they have already provided novel directions for future intervention in these complex diseases. To date there are no good models that replicate the granulomatous lesions found in granulomatosis with polyangiitis (GPA, formerly Wegener’s), or the development of vasculitis lesions in organs other than the lungs or kidneys. However, use of a combination of the available models should allow greater understanding of the critical requirements for disease and how these may be potentially monitored and modified in patients. Summary ANCA associated vasculitis can be induced in various forms in susceptible rodents. Further refinements are required for the full spectrum of disease phenotype to be replicated in animals, but critical new targets have been proposed based on use of molecular blocking agents and transgenic animals to elucidate disease pathways. PMID:22089094
Suzui, Masumi; Morioka, Takamitsu; Yoshimi, Naoki
The animal model is a powerful and fundamental tool in the field of biochemical research including toxicology, carcinogenesis, cancer therapeutics and prevention. In the carcinogenesis animal model system, numerous examples of preneoplastic lesions have been isolated and investigated from various perspectives. This may indicate that several options of endpoints to evaluate carcinogenesis effect or therapeutic outcome are presently available; however, classification of preneoplastic lesions has become complicated. For instance, these lesions include aberrant crypt foci (ACF), dysplastic ACF, flat ACF, β-catenin accumulated crypts, and mucin-depleted foci. These lesions have been induced by commonly used chemical carcinogens such as azoxymethane (AOM), 1,2-dimethylhydrazine (DMH), methylnitrosourea (MUN), or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Investigators can choose any procedures or methods to examine colonic preneoplastic lesions according to their interests and the objectives of their experiments. Based on topographical, histopathological, and biological features of colon cancer preneoplastic lesions in the animal model, we summarize and discuss the character and implications of these lesions. PMID:24526805
Di Segni, Matteo; Patrono, Enrico; Patella, Loris; Puglisi-Allegra, Stefano; Ventura, Rossella
Eating disorders are multifactorial conditions that can involve a combination of genetic, metabolic, environmental, and behavioral factors. Studies in humans and laboratory animals show that eating can also be regulated by factors unrelated to metabolic control. Several studies suggest a link between stress, access to highly palatable food, and eating disorders. Eating "comfort foods" in response to a negative emotional state, for example, suggests that some individuals overeat to self-medicate. Clinical data suggest that some individuals may develop addiction-like behaviors from consuming palatable foods. Based on this observation, "food addiction" has emerged as an area of intense scientific research. A growing body of evidence suggests that some aspects of food addiction, such as compulsive eating behavior, can be modeled in animals. Moreover, several areas of the brain, including various neurotransmitter systems, are involved in the reinforcement effects of both food and drugs, suggesting that natural and pharmacological stimuli activate similar neural systems. In addition, several recent studies have identified a putative connection between neural circuits activated in the seeking and intake of both palatable food and drugs. The development of well-characterized animal models will increase our understanding of the etiological factors of food addiction and will help identify the neural substrates involved in eating disorders such as compulsive overeating. Such models will facilitate the development and validation of targeted pharmacological therapies.
Panfil, Amanda R; Al-Saleem, Jacob J; Green, Patrick L
Since the isolation and discovery of human T-cell leukemia virus type 1 (HTLV-1) over 30 years ago, researchers have utilized animal models to study HTLV-1 transmission, viral persistence, virus-elicited immune responses, and HTLV-1-associated disease development (ATL, HAM/TSP). Non-human primates, rabbits, rats, and mice have all been used to help understand HTLV-1 biology and disease progression. Non-human primates offer a model system that is phylogenetically similar to humans for examining viral persistence. Viral transmission, persistence, and immune responses have been widely studied using New Zealand White rabbits. The advent of molecular clones of HTLV-1 has offered the opportunity to assess the importance of various viral genes in rabbits, non-human primates, and mice. Additionally, over-expression of viral genes using transgenic mice has helped uncover the importance of Tax and Hbz in the induction of lymphoma and other lymphocyte-mediated diseases. HTLV-1 inoculation of certain strains of rats results in histopathological features and clinical symptoms similar to that of humans with HAM/TSP. Transplantation of certain types of ATL cell lines in immunocompromised mice results in lymphoma. Recently, "humanized" mice have been used to model ATL development for the first time. Not all HTLV-1 animal models develop disease and those that do vary in consistency depending on the type of monkey, strain of rat, or even type of ATL cell line used. However, the progress made using animal models cannot be understated as it has led to insights into the mechanisms regulating viral replication, viral persistence, disease development, and, most importantly, model systems to test disease treatments.
Salcido, Richard; Popescu, Adrian; Ahn, Chulhyun
Background/Objective: Research targeting the pathophysiology, prevention, and treatment of pressure ulcers (PrUs) continue to be a significant priority for clinical and basic science research. Spinal cord injury patients particularly benefit from PrU research, because the prevalence of chronic wounds in this category is increasing despite standardized medical care. Because of practical, ethical, and safety considerations, PrUs in the human environment are limited to studies involving patients with pre-existing ulcers. Therefore, we are limited in our basic knowledge pertaining to the development, progression, and healing environment in this devastating disease. Methods: This review provides a synopsis of literature and a discussion of techniques used to induce PrUs in animal models. The question of what animal model best mimics the human PrU environment has been a subject of debate by investigators, peer review panels, and editors. The similarities in wound development and healing in mammalian tissue make murine models a relevant model for understanding the causal factors as well as the wound healing elements. Although we are beginning to understand some of the mechanisms of PrU development, a key dilemma of what makes an apparently healthy tissue develop a PrU waits to be solved. Results and Conclusions: No single method of induction and exploring PrUs in animals can address all the aspects of the pathology of chronic wounds. Each model has its particular strengths and weaknesses. Certain types of models can selectively identify specific aspects of wound development, quantify the extent of lesions, and assess outcomes from interventions. The appropriate interpretation of these methods is significant for proper study design, an understanding of the results, and extrapolation to clinical relevance. PMID:17591222
Rohner, Ronald P.
Guided by specific theoretical and methodological points of view--the phylogenetic perspective and the universalistic approach respectively--this paper reports on a worldwide study of the antecedents and effects of parental acceptance and rejection. Parental acceptance-rejection theory postulates that rejected children throughout our species share…
Zhang, Wei; Xu, Peng
Few studies in technology acceptance have explicitly addressed the acceptance of replacement technologies, technologies that replace legacy ones that have been in use. This article explores this issue through the theoretical lens of mental models. We contend that accepting replacement technologies entails both mental model maintenance and mental…
The major concern of this study is changes in self-acceptance as related to different college classroom models. The specific research hypothesis is that self-acceptance increases as a function of the encounter classroom model. This was confirmed. Increased self-acceptance also appeared stable over time. (NG)
Lu, Peng; Sodhi, Chhinder P; Jia, Hongpeng; Shaffiey, Shahab; Good, Misty; Branca, Maria F; Hackam, David J
Necrotizing enterocolitis is the leading cause of morbidity and mortality from gastrointestinal disease in premature infants and is characterized by initial feeding intolerance and abdominal distention followed by the rapid progression to coagulation necrosis of the intestine and death in many cases. Although the risk factors for NEC development remain well accepted, namely premature birth and formula feeding, the underlying mechanisms remain incompletely understood. Current thinking indicates that NEC develops in response to an abnormal interaction between the mucosal immune system of the premature host and an abnormal indigenous microflora, leading to an exaggerated mucosal inflammatory response and impaired mesenteric perfusion. In seeking to understand the molecular and cellular events leading to NEC, various animal models have been developed. However, the large number and variability between the available animal models and the unique characteristics of each has raised important questions regarding the validity of particular models for NEC research. In an attempt to provide some guidance to the growing community of NEC researchers, we now seek to review the key features of the major NEC models that have been developed in mammalian and nonmammalian species and to assess the advantages, disadvantage, challenges and major scientific discoveries yielded by each. A strategy for model validation is proposed, the principal models are compared, and future directions and challenges within the field of NEC research are explored.
Lu, Peng; Sodhi, Chhinder P.; Jia, Hongpeng; Shaffiey, Shahab; Good, Misty; Branca, Maria F.
Necrotizing enterocolitis is the leading cause of morbidity and mortality from gastrointestinal disease in premature infants and is characterized by initial feeding intolerance and abdominal distention followed by the rapid progression to coagulation necrosis of the intestine and death in many cases. Although the risk factors for NEC development remain well accepted, namely premature birth and formula feeding, the underlying mechanisms remain incompletely understood. Current thinking indicates that NEC develops in response to an abnormal interaction between the mucosal immune system of the premature host and an abnormal indigenous microflora, leading to an exaggerated mucosal inflammatory response and impaired mesenteric perfusion. In seeking to understand the molecular and cellular events leading to NEC, various animal models have been developed. However, the large number and variability between the available animal models and the unique characteristics of each has raised important questions regarding the validity of particular models for NEC research. In an attempt to provide some guidance to the growing community of NEC researchers, we now seek to review the key features of the major NEC models that have been developed in mammalian and nonmammalian species and to assess the advantages, disadvantage, challenges and major scientific discoveries yielded by each. A strategy for model validation is proposed, the principal models are compared, and future directions and challenges within the field of NEC research are explored. PMID:24763555
Simmons, Kaitlyn E.; Hoffman, Christy L.
Long-distance dog transfer programs are a topic of burgeoning interest in the animal welfare community, but little research has focused on such programs. This exploratory study, which surveyed 193 individuals associated with animal shelter and rescue organizations in the United States, evaluated factors that impacted organizations’ decisions to transfer in dogs over long distances (>100 miles) and assessed what criteria were commonly valued by destination organizations. Specifically, we examined the following aspects of long-distance transfer programs: (1) logistics of long-distance dog transfers; (2) factors impacting dog selection; (3) medical requirements; (4) partnerships formed between source and destination organizations; and (5) perceptions of long-distance dog transfer programs by individuals affiliated with the destination organizations. This study revealed that many logistical considerations factor into transfer decisions and the formation of healthy partnerships between source and destination organizations. Participants indicated their organization’s willingness to receive dogs of various sizes, coat colors and ages, but organizations often had restrictions regarding the breeds they would accept. Study findings indicate some organizations have strict quarantine policies and pre-transfer medical requirements, while others have no such requirements. PMID:26848694
Kostic, Corinne; Arsenijevic, Yvan
Disease-causing variants of a large number of genes trigger inherited retinal degeneration leading to photoreceptor loss. Because cones are essential for daylight and central vision such as reading, mobility, and face recognition, this review focuses on a variety of animal models for cone diseases. The pertinence of using these models to reveal genotype/phenotype correlations and to evaluate new therapeutic strategies is discussed. Interestingly, several large animal models recapitulate human diseases and can serve as a strong base from which to study the biology of disease and to assess the scale-up of new therapies. Examples of innovative approaches will be presented such as lentiviral-based transgenesis in pigs and adeno-associated virus (AAV)-gene transfer into the monkey eye to investigate the neural circuitry plasticity of the visual system. The models reported herein permit the exploration of common mechanisms that exist between different species and the identification and highlighting of pathways that may be specific to primates, including humans.
Hatziioannou, Theodora; Evans, David T.
The AIDS pandemic continues to present us with unique scientific and public health challenges. Although the development of effective antiretroviral therapy has been a major triumph, the emergence of drug resistance requires active management of treatment regimens and the continued development of new antiretroviral drugs. Moreover, despite nearly 30 years of intensive investigation, we still lack the basic scientific knowledge necessary to produce a safe and effective vaccine against HIV-1. Animal models offer obvious advantages in the study of HIV/AIDS, allowing for a more invasive investigation of the disease and for preclinical testing of drugs and vaccines. Advances in humanized mouse models, non-human primate immunogenetics and recombinant challenge viruses have greatly increased the number and sophistication of available mouse and simian models. Understanding the advantages and limitations of each of these models is essential for the design of animal studies to guide the development of vaccines and antiretroviral therapies for the prevention and treatment of HIV-1 infection. PMID:23154262
Samaranayake, Yuthika H.; Samaranayake, Lakshman P.
Oral candidiasis is as much the final outcome of the vulnerability of the host as of the virulence of the invading organism. We review here the extensive literature on animal experiments mainly appertaining to the host predisposing factors that initiate and perpetuate these infections. The monkey, rat, and mouse are the choice models for investigating oral candidiasis, but comparisons between the same or different models appear difficult, because of variables such as the study design, the number of animals used, their diet, the differences in Candida strains, and the duration of the studies. These variables notwithstanding, the following could be concluded. (i) The primate model is ideal for investigating Candida-associated denture stomatitis since both erythematous and pseudomembranous lesions have been produced in monkeys with prosthetic plates; they are, however, expensive and difficult to obtain and maintain. (ii) The rat model (both Sprague-Dawley and Wistar) is well proven for observing chronic oral candidal colonization and infection, due to the ease of breeding and handling and their ready availability. (iii) Mice are similar, but in addition there are well characterized variants simulating immunologic and genetic abnormalities (e.g., athymic, euthymic, murine-acquired immune deficiency syndrome, and severe combined immunodeficient models) and hence are used for short-term studies relating the host immune response and oral candidiasis. Nonetheless, an ideal, relatively inexpensive model representative of the human oral environment in ecological and microbiological terms is yet to be described. Until such a model is developed, researchers should pay attention to standardization of the experimental protocols described here to obtain broadly comparable and meaningful data. PMID:11292645
Human respiratory syncytial virus (hRSV) is a major cause of respiratory disease and hospitalisation of infants, worldwide, and is also responsible for significant morbidity in adults and excess deaths in the elderly. There is no licensed hRSV vaccine or effective therapeutic agent. However, there are a growing number of hRSV vaccine candidates that have been developed targeting different populations at risk of hRSV infection. Animal models of hRSV play an important role in the preclinical testing of hRSV vaccine candidates and although many have shown efficacy in preclinical studies, few have progressed to clinical trials or they have had only limited success. This is, at least in part, due to the lack of animal models that fully recapitulate the pathogenesis of hRSV infection in humans. This review summarises the strengths and limitations of animal models of hRSV, which include those in which hRSV is used to infect non-human mammalian hosts, and those in which non-human pneumoviruses, such as bovine (b)RSV and pneumonia virus of mice (PVM) are studied in their natural host. Apart from chimpanzees, other non-human primates (NHP) are only semi-permissive for hRSV replication and experimental infection with large doses of virus result in little or no clinical signs of disease, and generally only mild pulmonary pathology. Other animal models such as cotton rats, mice, ferrets, guinea pigs, hamsters, chinchillas, and neonatal lambs are also only semi-permissive for hRSV. Nevertheless, mice and cotton rats have been of value in the development of monoclonal antibody prophylaxis for infants at high risk of severe hRSV infection and have provided insights into mechanisms of immunity to and pathogenesis of hRSV. However, the extent to which they predict hRSV vaccine efficacy and safety is unclear and several hRSV vaccine candidates that are completely protective in rodent models are poorly effective in chimpanzees and other NHP, such as African Green monkeys. Furthermore
Domestic animals are unique models for biomedical research due to their long history (thousands of years) of strong phenotypic selection. This process has enriched for novel mutations that have contributed to phenotype evolution in domestic animals. The characterization of such mutations provides insights in gene function and biological mechanisms. This review summarizes genetic dissection of about 50 genetic variants affecting pigmentation, behaviour, metabolic regulation, and the pattern of locomotion. The variants are controlled by mutations in about 30 different genes, and for 10 of these our group was the first to report an association between the gene and a phenotype. Almost half of the reported mutations occur in non-coding sequences, suggesting that this is the most common type of polymorphism underlying phenotypic variation since this is a biased list where the proportion of coding mutations are inflated as they are easier to find. The review documents that structural changes (duplications, deletions, and inversions) have contributed significantly to the evolution of phenotypic diversity in domestic animals. Finally, we describe five examples of evolution of alleles, which means that alleles have evolved by the accumulation of several consecutive mutations affecting the function of the same gene. PMID:26479863
Domestic animals are unique models for biomedical research due to their long history (thousands of years) of strong phenotypic selection. This process has enriched for novel mutations that have contributed to phenotype evolution in domestic animals. The characterization of such mutations provides insights in gene function and biological mechanisms. This review summarizes genetic dissection of about 50 genetic variants affecting pigmentation, behaviour, metabolic regulation, and the pattern of locomotion. The variants are controlled by mutations in about 30 different genes, and for 10 of these our group was the first to report an association between the gene and a phenotype. Almost half of the reported mutations occur in non-coding sequences, suggesting that this is the most common type of polymorphism underlying phenotypic variation since this is a biased list where the proportion of coding mutations are inflated as they are easier to find. The review documents that structural changes (duplications, deletions, and inversions) have contributed significantly to the evolution of phenotypic diversity in domestic animals. Finally, we describe five examples of evolution of alleles, which means that alleles have evolved by the accumulation of several consecutive mutations affecting the function of the same gene.
Overby, Darryl R; Clark, Abbot F
Glucocorticoid (GC) therapy is widely used to treat a variety of inflammatory diseases and conditions. While unmatched in their anti-inflammatory and immunosuppressive activities, GC therapy is often associated with the significant ocular side effect of GC-induced ocular hypertension (OHT) and iatrogenic open-angle glaucoma. Investigators have generated GC-induced OHT and glaucoma in at least 8 different species besides man. These models mimic many features of this condition in man and provide morphologic and molecular insights into the pathogenesis of GC-OHT. In addition, there are many clinical, morphological, and molecular similarities between GC-induced glaucoma and primary open-angle glaucoma (POAG), making animals models of GC-induced OHT and glaucoma attractive models in which to study specific aspects of POAG.
Iyer, Balaji V. S.; Arya, Gaurav
Polymer models tied together by constraints of looping and confinement have been used to explain many of the observed organizational characteristics of interphase chromosomes. Here we introduce a simple lattice animal representation of interphase chromosomes that combines the features of looping and confinement constraints into a single framework. We show through Monte Carlo simulations that this model qualitatively captures both the leveling off in the spatial distance between genomic markers observed in fluorescent in situ hybridization experiments and the inverse decay in the looping probability as a function of genomic separation observed in chromosome conformation capture experiments. The model also suggests that the collapsed state of chromosomes and their segregation into territories with distinct looping activities might be a natural consequence of confinement.
Overby, Darryl R.; Clark, Abbot F.
Glucocorticoid (GC) therapy is widely used to treat a variety of inflammatory diseases and conditions. While unmatched in their anti-inflammatory and immunosuppressive activities, GC therapy is often associated with the significant ocular side effect of GC-induced ocular hypertension (OHT) and iatrogenic open-angle glaucoma. Investigators have generated GC-induced OHT and glaucoma in at least 8 different species besides man. These models mimic many features of this condition in man and provide morphologic and molecular insights into the pathogenesis of GC-OHT. In addition, there are many clinical, morphological, and molecular similarities between GC-induced glaucoma and primary open-angle glaucoma (POAG), making animals models of GC-induced OHT and glaucoma attractive models in which to study specific aspects of POAG. PMID:26051991
Haley, Sheila A; Atwood, Walter J
JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML), a demyelinating disease in humans. The disease, once considered fatal, is now managed with immune reconstitution therapy; however, surviving patients remain severely debilitated. Until now, there has been no animal model to study JCV in the brain, and research into treatment has relied on cell culture systems. In this issue of the JCI, Kondo and colleagues developed a mouse model in which human glial cells are engrafted into neonatal mice that are both immunodeficient and deficient for myelin basic protein. When challenged intracerebrally with JCV, these mice exhibit some of the characteristics of PML. The establishment of this chimeric mouse model is a significant advance toward understanding the mechanism of JCV pathogenesis and the identification of drugs to treat or prevent the disease.
Waldinger, Marcel D; Olivier, Berend
Most of our current understanding of the neurobiology of sexual behavior and ejaculatory function has been derived from animal studies using rats with normal sexual behaviour. However, none of these proposed models adequately represents human ejaculatory disorders. Based on the "ejaculation distribution theory", which postulates that the intravaginal ejaculation latency time in men is represented by a biological continuum, we have developed an animal model for the research of premature and delayed ejaculation. In this model, a large number of male Wistar rats are investigated during 4-6 weekly sexual behavioural tests. Based on the number of ejaculations during 30 min tests, rapid and sluggish ejaculating rats are distinguished, each representing approximately 10% at both ends of a Gaussian distribution. Together with other parameters, such as ejaculation latency time, these rats at either side of the spectrum resemble men with premature and delayed ejaculation, respectively. Comparable to the human situation, in a normal population of rats, endophenotypes exist with regard to basal sexual (ejaculatory) performance.
Mérida, Salvador; Palacios, Elena; Bosch-Morell, Francisco
Resident and infiltrated macrophages play relevant roles in uveitis as effectors of innate immunity and inductors of acquired immunity. They are major effectors of tissue damage in uveitis and are also considered to be potent antigen-presenting cells. In the last few years, experimental animal models of uveitis have enabled us to enhance our understanding of the leading role of macrophages in eye inflammation processes, including macrophage polarization in experimental autoimmune uveoretinitis and the major role of Toll-like receptor 4 in endotoxin-induced uveitis. This improved knowledge should guide advantageous iterative research to establish mechanisms and possible therapeutic targets for human uveitis resolution. PMID:26078494
Carson, R. P.; Appalsamy, M.; Diedrich, A.; Davis, T. L.; Robertson, D.
Clinically relevant autonomic dysfunction can result from either complete or partial loss of sympathetic outflow to effector organs. Reported animal models of autonomic neuropathy have aimed to achieve complete lesions of sympathetic nerves, but incomplete lesions might be more relevant to certain clinical entities. We hypothesized that loss of sympathetic innervation would result in a predicted decrease in arterial pressure and a compensatory increase in heart rate. Increased heart rate due to loss of sympathetic innervation is seemingly paradoxical, but it provides a mechanistic explanation for clinical autonomic syndromes such as neuropathic postural tachycardia syndrome. Partially dysautonomic animals were generated by selectively lesioning postganglionic sympathetic neurons with 150 mg/kg 6-hydroxydopamine hydrobromide in male Sprague-Dawley rats. Blood pressure and heart rate were monitored using radiotelemetry. Systolic blood pressure decreased within hours postlesion (Delta>20 mm Hg). Within 4 days postlesion, heart rate rose and remained elevated above control levels. The severity of the lesion was determined functionally and pharmacologically by spectral analysis and responsiveness to tyramine. Low-frequency spectral power of systolic blood pressure was reduced postlesion and correlated with the diminished tyramine responsiveness (r=0.9572, P=0.0053). The tachycardia was abolished by treatment with the beta-antagonist propranolol, demonstrating that it was mediated by catecholamines acting on cardiac beta-receptors. Partial lesions of the autonomic nervous system have been hypothesized to underlie many disorders, including neuropathic postural tachycardia syndrome. This animal model may help us better understand the pathophysiology of autonomic dysfunction and lead to development of therapeutic interventions.
Pikman, R; Kivity, S; Levy, Y; Arango, M-T; Chapman, J; Yonath, H; Shoenfeld, Y; Gofrit, S G
Animal models are a key element in disease research and treatment. In the field of neuropsychiatric lupus research, inbred, transgenic and disease-induced mice provide an opportunity to study the pathogenic routes of this multifactorial illness. In addition to achieving a better understanding of the immune mechanisms underlying the disease onset, supplementary metabolic and endocrine influences have been discovered and investigated. The ever-expanding knowledge about the pathologic events that occur at disease inception enables us to explore new drugs and therapeutic approaches further and to test them using the same animal models. Discovery of the molecular targets that constitute the pathogenic basis of the disease along with scientific advancements allow us to target these molecules with monoclonal antibodies and other specific approaches directly. This novel therapy, termed "targeted biological medication" is a promising endeavor towards producing drugs that are more effective and less toxic. Further work to discover additional molecular targets in lupus' pathogenic mechanism and to produce drugs that neutralize their activity is needed to provide patients with safe and efficient methods of controlling and treating the disease.
Wang, Jinjun; Yang, Guo-Xiang; Tsuneyama, Koichi; Gershwin, M Eric; Ridgway, William M; Leung, Patrick S C
Within the last decade, several mouse models that manifest characteristic features of primary biliary cirrhosis (PBC) with antimitochondrial antibodies (AMAs) and immune-mediated biliary duct pathology have been reported. Here, the authors discuss the current findings on two spontaneous (nonobese diabetic autoimmune biliary disease [NOD.ABD] and dominant negative transforming growth factor-β receptor II [dnTGFβRII]) and two induced (chemical xenobiotics and microbial immunization) models of PBC. These models exhibit the serological, immunological, and histopathological features of human PBC. From these animal models, it is evident that the etiology of PBC is multifactorial and requires both specific genetic predispositions and environmental insults (either xenobiotic chemicals or microbial), which lead to the breaking of tolerance and eventually liver pathology. Human PBC is likely orchestrated by multiple factors and hence no single model can fully mimic the immunopathophysiology of human PBC. Nevertheless, knowledge gained from these models has greatly advanced our understanding of the major immunological pathways as well as the etiology of PBC.
Lee, Yunjong; Dawson, Valina L.; Dawson, Ted M.
Parkinson's disease (PD) is a complex genetic disorder that is associated with environmental risk factors and aging. Vertebrate genetic models, especially mice, have aided the study of autosomal-dominant and autosomal-recessive PD. Mice are capable of showing a broad range of phenotypes and, coupled with their conserved genetic and anatomical structures, provide unparalleled molecular and pathological tools to model human disease. These models used in combination with aging and PD-associated toxins have expanded our understanding of PD pathogenesis. Attempts to refine PD animal models using conditional approaches have yielded in vivo nigrostriatal degeneration that is instructive in ordering pathogenic signaling and in developing therapeutic strategies to cure or halt the disease. Here, we provide an overview of the generation and characterization of transgenic and knockout mice used to study PD followed by a review of the molecular insights that have been gleaned from current PD mouse models. Finally, potential approaches to refine and improve current models are discussed. PMID:22960626
Elwood, Susan; Changchit, Chuleeporn; Cutshall, Robert
Purpose: This study aims to examine students' perceptions and their acceptance towards implementing a laptop program. Design/methodology/approach: Extensive research has been carried out on the technology acceptance model (TAM) to better understand the behavioral intention of individuals to accept and use technology. Therefore, the TAM was adopted…
Lawson, William E.; Oury, Tim D.; Sisson, Thomas H.; Raghavendran, Krishnan; Hogaboam, Cory M.
Interstitial lung fibrosis can develop as a consequence of occupational or medical exposure, as a result of genetic defects, and after trauma or acute lung injury leading to fibroproliferative acute respiratory distress syndrome, or it can develop in an idiopathic manner. The pathogenesis of each form of lung fibrosis remains poorly understood. They each result in a progressive loss of lung function with increasing dyspnea, and most forms ultimately result in mortality. To better understand the pathogenesis of lung fibrotic disorders, multiple animal models have been developed. This review summarizes the common and emerging models of lung fibrosis to highlight their usefulness in understanding the cell–cell and soluble mediator interactions that drive fibrotic responses. Recent advances have allowed for the development of models to study targeted injuries of Type II alveolar epithelial cells, fibroblastic autonomous effects, and targeted genetic defects. Repetitive dosing in some models has more closely mimicked the pathology of human fibrotic lung disease. We also have a much better understanding of the fact that the aged lung has increased susceptibility to fibrosis. Each of the models reviewed in this report offers a powerful tool for studying some aspect of fibrotic lung disease. PMID:23526222
Silver, Ellen Johnson; Dean, Randa; Perez, Amanda; Rivera, Angelic
We present the feasibility and acceptability of a parent sexuality education program led by peer educators in community settings. We also report the results of an outcome evaluation with 71 parents who were randomized to the intervention or a control group, and surveyed one month prior to and six months after the 4-week intervention. The program was highly feasible and acceptable to participants, and the curriculum was implemented with a high level of fidelity and facilitator quality. Pilot data show promising outcomes for increasing parental knowledge, communication, and monitoring of their adolescent children. PMID:24883051
Nalca, Aysegul; Fellows, Patricia F; Whitehouse, Chris A
Arthropod-borne viruses ("arboviruses") cause significant human illness ranging from mild, asymptomatic infection to fatal encephalitis or hemorrhagic fever. The most significant arboviruses causing human illness belong to genera in three viral families, Togaviridae, Flaviviridae, and Bunyaviridae. These viruses represent a significant public health threat to many parts of the world, and, as evidenced by the recent introduction of the West Nile virus (WNV) to the Western Hemisphere, they can no longer be considered specific to any one country or region of the world. Like most viral diseases, there are no specific therapies for the arboviral encephalitides; therefore, effective vaccines remain the front line of defense for these diseases. With this in mind, the development of new, more effective vaccines and the appropriate animal models in which to test them become paramount. In fact, for many important arboviruses (e.g. California serogroup and St. Louis encephalitis viruses), there are currently no approved vaccines available for human use. For others, such as the alphaviruses, human vaccines are available only as Investigational New Drugs, and thus are not in widespread use. On the other hand, safe and effective vaccines against tick-borne encephalitis virus (TBEV) and Japanese encephalitis virus (JEV) have been in use for decades. New challenges in vaccine development have been met with new technologies in vaccine research. Many of the newer vaccines are now being developed by recombinant DNA technology. For example, chimeric virus vaccines have been developed using infectious clone technology for many of the arboviruses including, WNV, JEV, and TBEV. Other successful approaches have involved the use of naked DNA encoding and subsequently expressing the desired protective epitopes. Naked DNA vaccines have been used for TBEV and JEV and are currently under development for use against WNV. The development of less expensive, more authentic animal models to
Ahmed, Hassan M. Selim
E-learning tools and technologies have been used to supplement conventional courses in higher education institutions creating a "hybrid" e-learning module that aims to enhance the learning experiences of students. Few studies have addressed the acceptance of hybrid e-learning by learners and the factors affecting the learners'…
Murillo, Óscar; El-Haj, Cristina
Multiresistant Gram-positive infections continue to pose a major clinical challenge and the development of new antibiotics is always desirable. Dalbavancin is a lipoglycopeptide with a prolonged half-life that allows long dosing intervals. In experimental models, its activity has been evaluated in distinct models and microorganisms, which limits the conclusions that can be drawn; however, the largest number of studies have been conducted in Staphylococcus aureus infection. Overall, dalbavancin has shown concentration-dependent efficacy and the parameters best explaining its activity are maximal pharmacodynamic concentration/minimal inhibitory concentration and the area under the curve/minimal inhibitory concentration. In these experimental models, dalbavancin has shown good distribution, a prolonged half-life in all animal species and efficacy that is mostly similar to that of previous glycopeptides but with lower doses and with longer dosing intervals. Of note, the efficacy of dalbavancin is not altered by methicillin resistance or the glycopeptide sensitivity of S. aureus. In the case of difficult-to-treat staphylococcal infections (eg, endocarditis, foreign body infections), an adequate dosing interval and high dosage seem to play an important role in the efficacy of the drug. All in all, experimental models can still provide greater knowledge of this new antibiotic to guide clinical research and determine its role in the treatment of distinct infections produced by Gram-positive microorganisms.
Moessinger, A C
Rat fetuses were paralyzed by daily transuterine injections of curare from day 18 of gestation until term (day 21). The following anomalies were noted at the time of delivery: multiple joint contractures, pulmonary hypoplasia, micrognathia, fetal growth retardation, short umbilical cords, and polyhydramnios. Neither sham-operated nor untouched littermate control fetuses had any of these anomalies. The group of anomalies (or deformation sequence) obtained with this animal model is presumed to result from the paralytic effect of curare. This phenotype bears a striking resemblance to the syndrome of ankyloses, facial anomalies, and pulmonary hypoplasia (also known as Pena and Shokeir I), presumably inherited in an autosomal recessive manner. It is suggested that this phenotype is not specific but, rather, represents a deformation sequence which results from fetal immobilization or akinesia. Diagnostic evaluation of patients with this group of anomalies should include the identification of the underlying pathologic process (etiology of the akinesia) to allow for proper classification and genetic counseling.
Pasupuleti, Mohan Kumar; Molahally, Subramanya Shetty; Salwaji, Supraja
Laboratory animal models serve as a facilitator to investigate the etiopathogenesis of periodontal disease, are used to know the efficacy of reconstructive and regenerative procedures, and are also helpful in evaluation of newer therapeutic techniques including laser and implant therapies prior to application in the human beings. The aim of this review is to know the different animal models used in various specialties of dental research and to know the ethical guidelines prior to the usage of experimental models with main emphasis on how to refine, replace, and reduce the number of animal models usage in the laboratory. An online search for experimental animal models used in dental research was performed using MEDLINE/PubMed database. Publications from 2009 to May 2013 in the specialty of periodontics were included in writing this review. A total of 652 references were published in PubMed/MEDLINE databases based on the search terms used. Out of 245 studies, 241 were related to the periodontal research published in English from 2009 to 2013. Relevant papers were chosen according to the inclusion and exclusion criteria. After extensive electronic and hand search on animal models, it has been observed that various animal models were used in dental research. Search on animal models used for dental research purpose revealed that various animals such as rats, mice, guinea pigs, rabbit, beagle dogs, goats, and nonhuman primates were extensively used. However, with the new advancement of ex vivo animal models, it has become easy to investigate disease pathogenesis and to test the efficacy of newer therapeutic modalities with the reduced usage of animal models. This review summarized the large amount of literature on animal models used in periodontal research with main emphasis on ethical guidelines and on reducing the animal model usage in future perspective. PMID:28298815
Lee, Sara; Riley-Behringer, Maureen; Rose, Jeanmarie C; Meropol, Sharon B; Lazebnik, Rina
This study explores how parents' intentions regarding vaccination prior to their children's visit were associated with actual vaccine acceptance. A convenience sample of parents accompanying 6-week-old to 17-year-old children completed a written survey at 2 pediatric practices. Using hierarchical logistic regression, for hospital-based participants (n = 216), vaccine refusal history (P < .01) and vaccine decision made before the visit (P < .05) explained 87% of vaccine refusals. In community-based participants (n = 100), vaccine refusal history (P < .01) explained 81% of refusals. Over 1 in 5 parents changed their minds about vaccination during the visit. Thirty parents who were previous vaccine refusers accepted current vaccines, and 37 who had intended not to vaccinate choose vaccination. Twenty-nine parents without a refusal history declined vaccines, and 32 who did not intend to refuse before the visit declined vaccination. Future research should identify key factors to nudge parent decision making in favor of vaccination.
Bewley, Kevin R
Q fever, caused by the pathogen Coxiella burnetii, is an acute disease that can progress to become a serious chronic illness. The organism leads an obligate, intracellular lifecycle, during which it multiplies in the phagolytic compartments of the phagocytic cells of the immune system of its hosts. This characteristic makes study of the organism particularly difficult and is perhaps one of the reasons why, more than 70 y after its discovery, much remains unknown about the organism and its pathogenesis. A variety of animal species have been used to study both the acute and chronic forms of the disease. Although none of the models perfectly mimics the disease process in humans, each opens a window onto an important aspect of the pathology of the disease. We have learned that immunosuppression, overexpression of IL10, or physical damage to the heart muscle in mice and guinea pigs can induce disease that is similar to the chronic disease seen in humans, suggesting that this aspect of disease may eventually be fully understood. Models using species from mice to nonhuman primates have been used to evaluate and characterize vaccines to protect against the disease and may ultimately yield safer, less expensive vaccines. PMID:24326221
Leung, K S; Siu, W S; Cheung, N M; Lui, P Y; Chow, D H; James, A; Qin, L
A large osteopenic animal model that resembles human osteoporotic changes is essential for osteoporosis research. This study aimed at establishing a large osteopenic animal model in goats. Twenty-five Chinese mountain goats were used in which they were either ovariectomized (OVX) and fed with a low-calcium diet (n = 16) or sham-operated (SHAM; n = 9). Monthly photodensitometric analysis on proximal tibial metaphysis and calcaneus was performed. Two iliac crest biopsy specimens obtained before and 6 months after OVX were used for bone mineral density (BMD) measurement with peripheral quantitative computed tomography (pQCT). Lumbar vertebrae (L2 and L7), humeral heads, and calcanei were collected for BMD measurement after euthanasia. The humeral heads and calcanei were used in biomechanical indentation test. BMD measurement showed a significant 25.0% (p = 0.006) decrease in BMD of the iliac crest biopsy specimens 6 months after OVX. It also was statistically significant when compared with the SHAM (p = 0.028). BMD at L2, L7, calcaneus, and humeral head reduced by 24-33% (p ranged from 0.001 to 0.011) when compared with the SHAM. Photodensitometry showed a continuous decrease in bone density after OVX. There were significant decreases of 18.9% in proximal tibial metaphysis (p = 0.003) and 21.8% in calcaneus (p = 0.023) in the OVX group 6 months postoperatively. Indentation test on the humeral head and calcaneus showed a significant decrease 52% (p = 0.006) and 54% (p = 0.001), respectively, in energy required for displacement of 3 mm in the OVX group compared with the SHAM group. The decreases correlated significantly to the decrease in BMD of the corresponding specimens (r2 = 0.439 and 0.581; p < 0.001 for both). In conclusion, this study showed that OVX plus a low-calcium diet could induce significant osteopenia and deterioration of mechanical properties of the cancellous bone in goats.
Sato, Hitoshi; Hall, Candice M; Griffith, Grant W; Johnson, Kent F; McGillicuddy, John W; Bartlett, Robert H; Cook, Keith E
A large animal model is needed to study artificial lung attachment in a setting simulating chronic lung disease with significant pulmonary hypertension (PH). This study sought to create a sheep model that develops significant PH within 60 days with a low rate of mortality. Sephadex beads were injected in the pulmonary circulation of sheep every other day for 60 days at doses of 0.5, 0.75, and 1 g (n = 10, 10, 7). Mean pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output were obtained every 2 weeks. In the 0.5, 0.75, and 1-g groups, 90, 70, and 14.3% of sheep completed the study, respectively, with the remainder experiencing heart failure. By the 60th day, pulmonary vascular resistance had increased (p < 0.01) from 0.89 +/- 0.3 to 3.2 +/- 0.9 mm Hg/(L/min) and from 0.9 +/- 0.3 to 4.3 +/- 3.2 mm Hg/(L/min) in the 0.5 and 0.75-g groups, respectively. Significant right ventricular hypertrophy was observed in the 0.75-g group but not in the 0.5-g group. Data from the 1-g group were insufficient for analysis due to high mortality. Thus, the 0.5 and 0.75-g groups generate significant PH, but the 0.75-g group is a better model of chronic PH in lung disease due to the development of right ventricular hypertrophy.
Shin, Dong-Hee; Kim, Won-Yong; Kim, Won-Young
This study explores attitudinal and behavioral patterns when using Cyworld by adopting an expanded Technology Acceptance Model (TAM). A model for Cyworld acceptance is used to examine how various factors modified from the TAM influence acceptance and its antecedents. This model is examined through an empirical study involving Cyworld users using structural equation modeling techniques. The model shows reasonably good measurement properties and the constructs are validated. The results not only confirm the model but also reveal general factors applicable to Web2.0. A set of constructs in the model can be the Web2.0-specific factors, playing as enhancing factor to attitudes and intention.
Hayes, Steven C.; Pistorello, Jacqueline; Levin, Michael E.
The present article summarizes the assumptions, model, techniques, evidence, and diversity/social justice commitments of Acceptance and Commitment Therapy (ACT). ACT focused on six processes (acceptance, defusion, self, now, values, and action) that bear on a single overall target (psychological flexibility). The ACT model of behavior change has…
... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Model code provisions for use in partially accepted code jurisdictions. 200.926c Section 200.926c Housing and Urban Development Regulations... Minimum Property Standards § 200.926c Model code provisions for use in partially accepted...
Background Mycoplasma fermentans has been associated with respiratory, genitourinary tract infections and rheumatoid diseases but its role as pathogen is controversial. The purpose of this study was to probe that Mycoplasma fermentans is able to produce respiratory tract infection and migrate to several organs on an experimental infection model in hamsters. One hundred and twenty six hamsters were divided in six groups (A-F) of 21 hamsters each. Animals of groups A, B, C were intratracheally injected with one of the mycoplasma strains: Mycoplasma fermentans P 140 (wild strain), Mycoplasma fermentans PG 18 (type strain) or Mycoplasma pneumoniae Eaton strain. Groups D, E, F were the negative, media, and sham controls. Fragments of trachea, lungs, kidney, heart, brain and spleen were cultured and used for the histopathological study. U frequency test was used to compare recovery of mycoplasmas from organs. Results Mycoplasmas were detected by culture and PCR. The three mycoplasma strains induced an interstitial pneumonia; they also migrated to several organs and persisted there for at least 50 days. Mycoplasma fermentans P 140 induced a more severe damage in lungs than Mycoplasma fermentans PG 18. Mycoplasma pneumoniae produced severe damage in lungs and renal damage. Conclusions Mycoplasma fermentans induced a respiratory tract infection and persisted in different organs for several weeks in hamsters. This finding may help to explain the ability of Mycoplasma fermentans to induce pneumonia and chronic infectious diseases in humans. PMID:23298636
Marco, Eva M; Llorente, Ricardo; López-Gallardo, Meritxell; Mela, Virginia; Llorente-Berzal, Álvaro; Prada, Carmen; Viveros, María-Paz
Early life stress, in the form of MD (24h at pnd 9), interferes with brain developmental trajectories modifying both behavioral and neurobiochemical parameters. MD has been reported to enhance neuroendocrine responses to stress, to affect emotional behavior and to impair cognitive function. More recently, changes in body weight gain, metabolic parameters and immunological responding have also been described. Present data give support to the fact that neuronal degeneration and/or astrocyte proliferation are present in specific brain regions, mainly hippocampus, prefrontal cortex and hypothalamus, which are particularly vulnerable to the effects of neonatal stress. The MD animal model arises as a valuable tool for the investigation of the brain processes occurring at the narrow time window comprised between pnd 9 and 10 that are critical for the establishment of brain circuitries critical for the regulation of behavior, metabolism and energy homeostasis. In the present review we will discuss three possible mechanisms that might be crucial for the effects of MD, namely, the rapid increase in glucocorticoids, the lack of the neonatal leptin surge, and the enhanced endocannabinoid signaling during the specific critical period of MD. A better understanding of the mechanisms underlying the detrimental consequences of MD is a concern for public health and may provide new insights into mental health prevention strategies and into novel therapeutic approaches in neuropsychiatry.
McNamee, Kay; Williams, Richard; Seed, Michael
Animal models of arthritis are widely used to de-convolute disease pathways and to identify novel drug targets and therapeutic approaches. However, the high attrition rates of drugs in Phase II/III rates means that a relatively small number of drugs reach the market, despite showing efficacy in pre-clinical models. There is also increasing awareness of the ethical issues surrounding the use of animal models of disease and it is timely, therefore, to review the relevance and translatability of animal models of arthritis. In this paper we review the most commonly used animal models in terms of their pathological similarities to human rheumatoid arthritis as well as their response to drug therapy. In general, the ability of animal models to predict efficacy of biologics in man has been good. However, the predictive power of animal models for small molecules has been variable, probably because of differences in the levels of target knockdown achievable in vivo.
Louz, Derrick; Bergmans, Hans E; Loos, Birgit P; Hoeben, Rob C
Viral diseases are important threats to public health worldwide. With the number of emerging viral diseases increasing the last decades, there is a growing need for appropriate animal models for virus studies. The relevance of animal models can be limited in terms of mimicking human pathophysiology. In this review, we discuss the utility of animal models for studies of influenza A viruses, HIV and SARS-CoV in light of viral emergence, assessment of infection and transmission risks, and regulatory decision making. We address their relevance and limitations. The susceptibility, immune responses, pathogenesis, and pharmacokinetics may differ between the various animal models. These complexities may thwart translating results from animal experiments to the humans. Within these constraints, animal models are very informative for studying virus immunopathology and transmission modes and for translation of virus research into clinical benefit. Insight in the limitations of the various models may facilitate further improvements of the models.
Lebreton, Jean-Dominique; Nichols, James D.; Barker, Richard J.; Pradel, Roger; Spendelow, Jeffrey A.
Many fields of science begin with a phase of exploration and description, followed by investigations of the processes that account for observed patterns. The science of ecology is no exception, and recent decades have seen a focus on understanding key processes underlying the dynamics of ecological systems. In population ecology, emphasis has shifted from the state variable of population size to the demographic processes responsible for changes in this state variable: birth, death, immigration, and emigration. In evolutionary ecology, some of these same demographic processes, rates of birth and death, are also the determinants of fitness. In animal population ecology, the estimation of state variables and their associated vital rates is especially problematic because of the difficulties in sampling such populations and detecting individual animals. Indeed, early capture–recapture models were developed for the purpose of estimating population size, given the reality that all animals are not caught or detected at any sampling occasion. More recently, capture–recapture models for open populations were developed to draw inferences about survival in the face of these same sampling problems. The focus of this paper is on multi‐state mark–recapture models (MSMR), which first appeared in the 1970s but have undergone substantial development in the last 15 years. These models were developed to deal explicitly with biological variation, in that animals in different “states” (classes defined by location, physiology, behavior, reproductive status, etc.) may have different probabilities of survival and detection. Animal transitions between states are also stochastic and themselves of interest. These general models have proven to be extremely useful and provide a way of thinking about a remarkably wide range of important ecological processes. These methods are now at a stage of refinement and sophistication where they can readily be used by biologists to tackle a wide
Marietta, Eric V; Murray, Joseph A
The initial development and maintenance of tolerance to dietary antigens is a complex process that, when prevented or interrupted, can lead to human disease. Understanding the mechanisms by which tolerance to specific dietary antigens is attained and maintained is crucial to our understanding of the pathogenesis of diseases related to intolerance of specific dietary antigens. Two diseases that are the result of intolerance to a dietary antigen are celiac disease (CD) and dermatitis herpetiformis (DH). Both of these diseases are dependent upon the ingestion of gluten (the protein fraction of wheat, rye, and barley) and manifest in the gastrointestinal tract and skin, respectively. These gluten-sensitive diseases are two examples of how devastating abnormal immune responses to a ubiquitous food can be. The well-recognized risk genotype for both is conferred by either of the HLA class II molecules DQ2 or DQ8. However, only a minority of individuals who carry these molecules will develop either disease. Also of interest is that the age at diagnosis can range from infancy to 70-80 years of age. This would indicate that intolerance to gluten may potentially be the result of two different phenomena. The first would be that, for various reasons, tolerance to gluten never developed in certain individuals, but that for other individuals, prior tolerance to gluten was lost at some point after childhood. Of recent interest is the concept of non-celiac gluten sensitivity, which manifests as chronic digestive or neurologic symptoms due to gluten, but through mechanisms that remain to be elucidated. This review will address how animal models of gluten-sensitive disorders have substantially contributed to a better understanding of how gluten intolerance can arise and cause disease.
Hart, Danielle; McNeil, Mary Ann; Hegarty, Cullen; Rush, Robert; Chipman, Jeffery; Clinton, Joseph; Reihsen, Troy; Sweet, Robert
There are many models currently used for teaching and assessing performance of trauma-related airway, breathing, and hemorrhage procedures. Although many programs use live animal (live tissue [LT]) models, there is a congressional effort to transition to the use of nonanimal- based methods (i.e., simulators, cadavers) for military trainees. We examined the existing literature and compared the efficacy, acceptability, and validity of available models with a focus on comparing LT models with synthetic systems. Literature and Internet searches were conducted to examine current models for seven core trauma procedures. We identified 185 simulator systems. Evidence on acceptability and validity of models was sparse. We found only one underpowered study comparing the performance of learners after training on LT versus simulator models for tube thoracostomy and cricothyrotomy. There is insufficient data-driven evidence to distinguish superior validity of LT or any other model for training or assessment of critical trauma procedures.
Schiffelers, Marie-Jeanne W A; Blaauboer, Bas J; Bakker, Wieger E; Beken, Sonja; Hendriksen, Coenraad F M; Koëter, Herman B W M; Krul, Cyrille
Pharmaceuticals and chemicals are subjected to regulatory safety testing accounting for approximately 25% of laboratory animal use in Europe. This testing meets various objections and has led to the development of a range of 3R models to Replace, Reduce or Refine the animal models. However, these models must overcome many barriers before being accepted for regulatory risk management purposes. This paper describes the barriers and drivers and options to optimize this acceptance process as identified by two expert panels, one on pharmaceuticals and one on chemicals. To untangle the complex acceptance process, the multilevel perspective on technology transitions is applied. This perspective defines influences at the micro-, meso- and macro level which need alignment to induce regulatory acceptance of a 3R model. This paper displays that there are many similar mechanisms within both sectors that prevent 3R models from becoming accepted for regulatory risk assessment and management. Shared barriers include the uncertainty about the value of the new 3R models (micro level), the lack of harmonization of regulatory requirements and acceptance criteria (meso level) and the high levels of risk aversion (macro level). In optimizing the process commitment, communication, cooperation and coordination are identified as critical drivers.
Priyadharsini, Raman P
Atherosclerosis is a multifactorial condition characterized by endothelial injury, fatty streak deposition, and stiffening of the blood vessels. The pathogenesis is complex and mediated by adhesion molecules, inflammatory cells, and smooth muscle cells. Statins have been the major drugs in treating hypercholesterolemia for the past two decades despite little efficacy. There is an urgent need for new drugs that can replace statins or combined with statins. The preclinical studies evaluating atherosclerosis require an ideal animal model which resembles the disease condition, but there is no single animal model which mimics the disease. The animal models used are rabbits, rats, mice, hamsters, mini pigs, etc. Each animal model has its own advantages and disadvantages. The method of induction of atherosclerosis includes diet, chemical induction, mechanically induced injuries, and genetically manipulated animal models. This review mainly focuses on the various animal models, method of induction, the advantages, disadvantages, and the current perspectives with regard to preclinical studies on atherosclerosis.
Lee, Yi-Hsuan; Hsieh, Yi-Chuan; Chen, Yen-Hsun
The purpose of this study is to apply the technology acceptance model to examine the employees' attitudes and acceptance of electronic learning (e-learning) systems in organisations. This study examines four factors (organisational support, computer self-efficacy, prior experience and task equivocality) that are believed to influence employees'…
Schaeffer, L R
The assumption of a single permanent environmental (PE) effect contributing to every record made by an animal is questioned. An alternative model where new PE effects accumulate with each record made by an animal is proposed. An example is used to illustrate the differences between the traditional model and the proposed model.
Gremonprez, Félix; Willaert, Wouter; Ceelen, Wim
The development of suitable animal models is essential to experimental research on intraperitoneal chemotherapy (IPC). This review of the English literature (MEDLINE) presents a detailed analysis of current animal models and gives recommendations for future experimental research. Special consideration should be given to cytotoxic drug dose and concentration, tumor models, and outcome parameters.
Cook, Guerry J; Pardee, Timothy S
Animal models have been invaluable in the efforts to better understand and ultimately treat patients suffering from leukemia. While important insights have been gleaned from these models, limitations must be acknowledged. In this review, we will highlight the various animal models of leukemia and describe their contributions to the improved understanding and treatment of these cancers.
Cook, Guerry J; Pardee, Timothy S.
Animal models have been invaluable in the efforts to better understand and ultimately treat patients suffering from leukemia. While important insights have been gleaned from these models, limitations must be acknowledged. In this review, we will highlight the various animal models of leukemia and describe their contributions to the improved understanding and treatment of these cancers. PMID:23081702
A simple model incorporating linear radiation characteristics, along with the optical trains and geometrical concentration ratios of solar concentrators is presented with performance examples for optical trains of HCPV, LCPV and benchmark flat-plate PV.
There is a wealth of literature on neurotoxicological outcomes of acute and short-term exposure to pesticides in laboratory animals, but there are relatively few reports of long-term exposure. Reports in the literature describing "chronic" exposures to pesticides are, in fact, a...
There is a wealth of literature on neurotoxicological outcomes of acute and short-term exposure to pesticides in laboratory animals, but there are relatively few studies of- long-term exposure. Many reports in the literature describing ;chronic' exposures to pesticides are, in fa...
Brabb, Thea; Carbone, Larry; Snyder, Jessica; Phillips, Nona
Peripheral neuropathy and neuropathic pain are debilitating, life-altering conditions that affect a significant proportion of the human population. Animal models, used to study basic disease mechanisms and treatment modalities, are diverse and provide many challenges for institutional animal care and use committee (IACUC) review and postapproval monitoring. Items to consider include regulatory and ethical imperatives in animal models that may be designed to study pain, the basic mechanism of neurodegeneration, and different disease processes for which neuropathic pain is a side effect. Neuropathic pain can be difficult to detect or quantify in many models, and pain management is often unsuccessful in both humans and animals, inspiring the need for more research. Design of humane endpoints requires clear communication of potential adverse outcomes and solutions. Communication with the IACUC, researchers, and veterinary staff is also key for successful postapproval monitoring of these challenging models. PMID:24615447
Hooten, Mevin B.; Buderman, Frances E.; Brost, Brian M.; Hanks, Ephraim M.; Ivans, Jacob S.
New methods for modeling animal movement based on telemetry data are developed regularly. With advances in telemetry capabilities, animal movement models are becoming increasingly sophisticated. Despite a need for population-level inference, animal movement models are still predominantly developed for individual-level inference. Most efforts to upscale the inference to the population level are either post hoc or complicated enough that only the developer can implement the model. Hierarchical Bayesian models provide an ideal platform for the development of population-level animal movement models but can be challenging to fit due to computational limitations or extensive tuning required. We propose a two-stage procedure for fitting hierarchical animal movement models to telemetry data. The two-stage approach is statistically rigorous and allows one to fit individual-level movement models separately, then resample them using a secondary MCMC algorithm. The primary advantages of the two-stage approach are that the first stage is easily parallelizable and the second stage is completely unsupervised, allowing for an automated fitting procedure in many cases. We demonstrate the two-stage procedure with two applications of animal movement models. The first application involves a spatial point process approach to modeling telemetry data, and the second involves a more complicated continuous-time discrete-space animal movement model. We fit these models to simulated data and real telemetry data arising from a population of monitored Canada lynx in Colorado, USA.
Martin, Larry L.; Nivens, Maryruth K.
A model extrapolates from E. Kubler-Ross' conception of the stages of grief to apply to parent and family reactions when an exceptionality is identified. A chart lists possible parent feelings and reactions, possible school reactions to the parent in grief, and the child's reactions during each of five stages: denial, rage and anger, bargaining,…
... Minimum Property Standards § 200.926c Model code provisions for use in partially accepted code... Chapter 3. (e) Materials standards Chapter 26. (f) Construction components Part III. (g) Glass Chapter 2... dwellings (NFPA 70A-1990)....
Models have been a tool of science at least since the 18th century and serve a variety of purposes from focusing abstract thoughts to representing scaled down version of things for study. Generally, animal models are needed when it is impractical or unethical to study the target animal. Biologists...
Gottlieb, Gilbert; Lickliter, Robert
In this article, the authors take a very conservative view of the contribution of animal models to an understanding of human development. We do not think that homologies can be readily documented with even our most closely related relatives' behavior and psychological functioning. The major contribution of animal models is their provision of food…
Hohl, Tobias M.
Fungi represent emerging infectious threats to human populations worldwide. Mice and other laboratory animals have proved invaluable in modeling clinical syndromes associated with superficial and life-threatening invasive mycoses. This review outlines salient features of common vertebrate animal model systems to study fungal pathogenesis, host antifungal immune responses, and antifungal compounds. PMID:24709390
Lanham, Stuart A; Bertram, Caroline; Cooper, Cyrus; Oreffo, Richard O C
It is widely accepted that the likelihood of offspring developing heart disease, stroke, or diabetes in later life, is influenced by the their in utero environment and maternal nutrition. There is increasing epidemiological evidence that osteoporosis in the offspring may also be influenced by the mother's nutrition during pregnancy. This review provides evidence from a range of animal models that supports the epidemiological data; suggesting that lifelong bone development and growth in offspring is determined during gestation.
Huber, Ludwig; Gajdon, Gyula K
The ability to act on information flexibly is one of the cornerstones of intelligent behavior. As particularly informative example, tool-oriented behavior has been investigated to determine to which extent nonhuman animals understand means-end relations, object affordances, and have specific motor skills. Even planning with foresight, goal-directed problem solving and immediate causal inference have been a focus of research. However, these cognitive abilities may not be restricted to tool-using animals but may be found also in animals that show high levels of curiosity, object exploration and manipulation, and extractive foraging behavior. The kea, a New Zealand parrot, is a particularly good example. We here review findings from laboratory experiments and field observations of keas revealing surprising cognitive capacities in the physical domain. In an experiment with captive keas, the success rate of individuals that were allowed to observe a trained conspecific was significantly higher than that of naive control subjects due to their acquisition of some functional understanding of the task through observation. In a further experiment using the string-pulling task, a well-probed test for means-end comprehension, we found the keas finding an immediate solution that could not be improved upon in nine further trials. We interpreted their performance as insightful in the sense of being sensitive of the relevant functional properties of the task and thereby producing a new adaptive response without trial-and-error learning. Together, these findings contribute to the ongoing debate on the distribution of higher cognitive skills in the animal kingdom by showing high levels of sensorimotor intelligence in animals that do not use tools. In conclusion, we suggest that the 'Technical intelligence hypothesis' (Byrne, Machiavellian intelligence II: extensions and evaluations, pp 289-211, 1997), which has been proposed to explain the origin of the ape/monkey grade-shift in
Smith, J David; Zakrzewski, Alexandria C; Church, Barbara A
Ongoing research explores whether animals have precursors to metacognition-that is, the capacity to monitor mental states or cognitive processes. Comparative psychologists have tested apes, monkeys, rats, pigeons, and a dolphin using perceptual, memory, foraging, and information-seeking paradigms. The consensus is that some species have a functional analog to human metacognition. Recently, though, associative modelers have used formal-mathematical models hoping to describe animals' "metacognitive" performances in associative-behaviorist ways. We evaluate these attempts to reify formal models as proof of particular explanations of animal cognition. These attempts misunderstand the content and proper application of models. They embody mistakes of scientific reasoning. They blur fundamental distinctions in understanding animal cognition. They impede theoretical development. In contrast, an energetic empirical enterprise is achieving strong success in describing the psychology underlying animals' metacognitive performances. We argue that this careful empirical work is the clear path to useful theoretical development. The issues raised here about formal modeling-in the domain of animal metacognition-potentially extend to biobehavioral research more broadly.
Bem, Reinout A; Domachowske, Joseph B; Rosenberg, Helene F
Infection with the human pneumovirus pathogen, respiratory syncytial virus (hRSV), causes a wide spectrum of respiratory disease, notably among infants and the elderly. Laboratory animal studies permit detailed experimental modeling of hRSV disease and are therefore indispensable in the search for novel therapies and preventative strategies. Present animal models include several target species for hRSV, including chimpanzees, cattle, sheep, cotton rats, and mice, as well as alternative animal pneumovirus models, such as bovine RSV and pneumonia virus of mice. These diverse animal models reproduce different features of hRSV disease, and their utilization should therefore be based on the scientific hypothesis under investigation. The purpose of this review is to summarize the strengths and limitations of each of these animal models. Our intent is to provide a resource for investigators and an impetus for future research.
Peters, Suzanne M; Pothuizen, Helen H J; Spruijt, Berry M
The translational value of animal models is an issue of ongoing discussion. We argue that 'Refinement' of animal experiments is needed and this can be achieved by exploiting an ethological approach when setting up and conducting experiments. Ethology aims to assess the functional meaning of behavioral changes, due to experimental manipulation or treatment, in animal models. Although the use of ethological concepts is particularly important for studies involving the measurement of animal behavior (as is the case for most studies on neuro-psychiatric conditions), it will also substantially benefit other disciplines, such as those investigating the immune system or inflammatory response. Using an ethological approach also involves using more optimal testing conditions are employed that have a biological relevance to the animal. Moreover, using a more biological relevant analysis of the data will help to clarify the functional meaning of the modeled readout (e.g. whether it is psychopathological or adaptive in nature). We advocate for instance that more behavioral studies should use animals in group-housed conditions, including the recording of their ultrasonic vocalizations, because (1) social behavior is an essential feature of animal models for human 'social' psychopathologies, such as autism and schizophrenia, and (2) social conditions are indispensable conditions for appropriate behavioral studies in social species, such as the rat. Only when taking these elements into account, the validity of animal experiments and, thus, the translation value of animal models can be enhanced.
The purpose of this web-based study was to explain and predict consumers' acceptance and usage behavior of Internet health information and services. Toward this goal, the Information and Communication Technology Acceptance Model (ICTAM) was developed and tested. Individuals who received a flyer through the LISTSERV of HealthGuide were eligible to participate. The study population was eighteen years old and older who had used Internet health information and services for a minimum of 6 months. For the analyses, SPSS (version 13.0) and AMOS (version 5.0) were employed. More than half of the respondents were women (n = 110, 55%). The average age of the respondents was 35.16 years (S.D. = 10.07). A majority reported at least some college education (n = 126, 63%). All of the observed factors accounted for 75.53% of the total variance explained. The fit indices of the structural model were within an acceptable range: chi2/df = 2.38 (chi2 = 1786.31, df = 752); GFI = .71; RMSEA = .08; CFI = .86; NFI = .78. The results of this study provide empirical support for the continued development of ICTAM in the area of health consumers' information and communication technology acceptance.
Chianese, Rosanna; Chioccarelli, Teresa; Cacciola, Giovanna; Ciaramella, Vincenza; Fasano, Silvia; Pierantoni, Riccardo; Meccariello, Rosaria; Cobellis, Gilda
Many advances have been carried out on the estrogens, GnRH and endocannabinoid system that have impact in the reproductive field. Indeed, estrogens, the generally accepted female hormones, have performed an unsuspected role in male sexual functions thanks to studies on non-mammalian vertebrates. Similarly, these animal models have provided important contributions to the identification of several GnRH ligand and receptor variants and their possible involvement in sexual behavior and gonadal function regulation. Moreover, the use of non-mammalian animal models has contributed to a better comprehension about the endocannabinoid system action in several mammalian reproductive events. We wish to highlight here how non-mammalian vertebrate animal model research contributes to advancements with implications on human health as well as providing a phylogenetic perspective on the evolution of reproductive systems in vertebrates.
The benefits of healthcare technologies can only be attained if nurses accept and intend to fully use them. One of the most common models utilized to understand user acceptance of technology is the Technology Acceptance Model. This model and modified versions of it have only recently been applied in the healthcare literature among nurse participants. An integrative literature review was conducted on this topic. Ovid/MEDLINE, PubMed, Google Scholar, and CINAHL were searched yielding a total of 982 references. Upon eliminating duplicates and applying the inclusion and exclusion criteria, the review included a total of four dissertations, three symposium proceedings, and 13 peer-reviewed journal articles. These documents were appraised and reviewed. The results show that a modified Technology Acceptance Model with added variables could provide a better explanation of nurses' acceptance of healthcare technology. These added variables to modified versions of the Technology Acceptance Model are discussed, and the studies' methodologies are critiqued. Limitations of the studies included in the integrative review are also examined.
Yael, Dorin; Israelashvili, Michal; Bar-Gad, Izhar
Tourette syndrome (TS) is a childhood onset disorder characterized by motor and vocal tics and associated with multiple comorbid symptoms. Over the last decade, the accumulation of findings from TS patients and the emergence of new technologies have led to the development of novel animal models with high construct validity. In addition, animal models which were previously associated with other disorders were recently attributed to TS. The proliferation of TS animal models has accelerated TS research and provided a better understanding of the mechanism underlying the disorder. This newfound success generates novel challenges, since the conclusions that can be drawn from TS animal model studies are constrained by the considerable variation across models. Typically, each animal model examines a specific subset of deficits and centers on one field of research (physiology/genetics/pharmacology/etc.). Moreover, different studies do not use a standard lexicon to characterize different properties of the model. These factors hinder the evaluation of individual model validity as well as the comparison across models, leading to a formation of a fuzzy, segregated landscape of TS pathophysiology. Here, we call for a standardization process in the study of TS animal models as the next logical step. We believe that a generation of standard examination criteria will improve the utility of these models and enable their consolidation into a general framework. This should lead to a better understanding of these models and their relationship to TS, thereby improving the research of the mechanism underlying this disorder and aiding the development of new treatments. PMID:27065791
Higginson, Ellen E; Simon, Raphael; Tennant, Sharon M
Salmonellosis remains an important cause of human disease worldwide. While there are several licensed vaccines for Salmonella enterica serovar Typhi, these vaccines are generally ineffective against other Salmonella serovars. Vaccines that target paratyphoid and nontyphoidal Salmonella serovars are very much in need. Preclinical evaluation of candidate vaccines is highly dependent on the availability of appropriate scientific tools, particularly animal models. Many different animal models exist for various Salmonella serovars, from whole-animal models to smaller models, such as those recently established in insects. Here, we discuss various mouse, rat, rabbit, calf, primate, and insect models for Salmonella infection, all of which have their place in research. However, choosing the right model is imperative in selecting the best vaccine candidates for further clinical testing. In this minireview, we summarize the various animal models that are used to assess salmonellosis, highlight some of the advantages and disadvantages of each, and discuss their value in vaccine development.
Higginson, Ellen E.; Simon, Raphael
Salmonellosis remains an important cause of human disease worldwide. While there are several licensed vaccines for Salmonella enterica serovar Typhi, these vaccines are generally ineffective against other Salmonella serovars. Vaccines that target paratyphoid and nontyphoidal Salmonella serovars are very much in need. Preclinical evaluation of candidate vaccines is highly dependent on the availability of appropriate scientific tools, particularly animal models. Many different animal models exist for various Salmonella serovars, from whole-animal models to smaller models, such as those recently established in insects. Here, we discuss various mouse, rat, rabbit, calf, primate, and insect models for Salmonella infection, all of which have their place in research. However, choosing the right model is imperative in selecting the best vaccine candidates for further clinical testing. In this minireview, we summarize the various animal models that are used to assess salmonellosis, highlight some of the advantages and disadvantages of each, and discuss their value in vaccine development. PMID:27413068
Greek, Ray; Menache, Andre
Systematic reviews are currently favored methods of evaluating research in order to reach conclusions regarding medical practice. The need for such reviews is necessitated by the fact that no research is perfect and experts are prone to bias. By combining many studies that fulfill specific criteria, one hopes that the strengths can be multiplied and thus reliable conclusions attained. Potential flaws in this process include the assumptions that underlie the research under examination. If the assumptions, or axioms, upon which the research studies are based, are untenable either scientifically or logically, then the results must be highly suspect regardless of the otherwise high quality of the studies or the systematic reviews. We outline recent criticisms of animal-based research, namely that animal models are failing to predict human responses. It is this failure that is purportedly being corrected via systematic reviews. We then examine the assumption that animal models can predict human outcomes to perturbations such as disease or drugs, even under the best of circumstances. We examine the use of animal models in light of empirical evidence comparing human outcomes to those from animal models, complexity theory, and evolutionary biology. We conclude that even if legitimate criticisms of animal models were addressed, through standardization of protocols and systematic reviews, the animal model would still fail as a predictive modality for human response to drugs and disease. Therefore, systematic reviews and meta-analyses of animal-based research are poor tools for attempting to reach conclusions regarding human interventions. PMID:23372426
Greek, Ray; Menache, Andre
Systematic reviews are currently favored methods of evaluating research in order to reach conclusions regarding medical practice. The need for such reviews is necessitated by the fact that no research is perfect and experts are prone to bias. By combining many studies that fulfill specific criteria, one hopes that the strengths can be multiplied and thus reliable conclusions attained. Potential flaws in this process include the assumptions that underlie the research under examination. If the assumptions, or axioms, upon which the research studies are based, are untenable either scientifically or logically, then the results must be highly suspect regardless of the otherwise high quality of the studies or the systematic reviews. We outline recent criticisms of animal-based research, namely that animal models are failing to predict human responses. It is this failure that is purportedly being corrected via systematic reviews. We then examine the assumption that animal models can predict human outcomes to perturbations such as disease or drugs, even under the best of circumstances. We examine the use of animal models in light of empirical evidence comparing human outcomes to those from animal models, complexity theory, and evolutionary biology. We conclude that even if legitimate criticisms of animal models were addressed, through standardization of protocols and systematic reviews, the animal model would still fail as a predictive modality for human response to drugs and disease. Therefore, systematic reviews and meta-analyses of animal-based research are poor tools for attempting to reach conclusions regarding human interventions.
Ma, Xiaohan; Deng, Zhigang
In recent years, data-driven speech animation approaches have achieved significant successes in terms of animation quality. However, how to automatically evaluate the realism of novel synthesized speech animations has been an important yet unsolved research problem. In this paper, we propose a novel statistical model (called SAQP) to automatically predict the quality of on-the-fly synthesized speech animations by various data-driven techniques. Its essential idea is to construct a phoneme-based, Speech Animation Trajectory Fitting (SATF) metric to describe speech animation synthesis errors and then build a statistical regression model to learn the association between the obtained SATF metric and the objective speech animation synthesis quality. Through delicately designed user studies, we evaluate the effectiveness and robustness of the proposed SAQP model. To the best of our knowledge, this work is the first-of-its-kind, quantitative quality model for data-driven speech animation. We believe it is the important first step to remove a critical technical barrier for applying data-driven speech animation techniques to numerous online or interactive talking avatar applications.
King, Aileen JF
Diabetes is a disease characterized by a relative or absolute lack of insulin, leading to hyperglycaemia. There are two main types of diabetes: type 1 diabetes and type 2 diabetes. Type 1 diabetes is due to an autoimmune destruction of the insulin-producing pancreatic beta cells, and type 2 diabetes is caused by insulin resistance coupled by a failure of the beta cell to compensate. Animal models for type 1 diabetes range from animals with spontaneously developing autoimmune diabetes to chemical ablation of the pancreatic beta cells. Type 2 diabetes is modelled in both obese and non-obese animal models with varying degrees of insulin resistance and beta cell failure. This review outlines some of the models currently used in diabetes research. In addition, the use of transgenic and knock-out mouse models is discussed. Ideally, more than one animal model should be used to represent the diversity seen in human diabetic patients. LINKED ARTICLES Animal Models This paper is the latest in a series of publications on the use of animal models in pharmacology research. Readers might be interested in the previous papers. Robinson V (2009). Less is more: reducing the reliance on animal models for nausea and vomiting research. Holmes AM, Rudd JA, Tattersall FD, Aziz Q, Andrews PLR (2009). Opportunities for the replacement of animals in the study of nausea and vomiting. Giacomotto J and Ségalat L (2010). High-throughput screening and small animal models, where are we? McGrath JC, Drummond GB, McLachlan EM, Kilkenny C, Wainwright CL (2010). Guidelines for reporting experiments involving animals: the ARRIVE guidelines. Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG (2010). The ARRIVE guidelines. Emerson M (2010). Refinement, reduction and replacement approaches to in vivo cardiovascular research. Berge O-G (2011). Predictive validity of behavioural animal models for chronic pain. Vickers SP, Jackson HC and Cheetham SC (2011). The utility of animal models to evaluate
Vestergaard, Bill; Agersø, Henrik; Lykkesfeldt, Jens
Early understanding of the pharmacokinetics and metabolic patterns of new drug candidates is essential for selection of optimal candidates to move further in to the drug development process. In vitro methodologies can be used to investigate metabolic patterns, but in general, they lack several aspects of the whole-body physiology. In contrast, the complexity of intact animals does not necessarily allow individual processes to be identified. Animal models lacking a major excretion organ can be used to investigate these individual metabolic processes. Animal models of nephrectomy and hepatectomy have considerable potential as tools in preclinical pharmacokinetics to assess organs of importance for drug clearance and thereby knowledge of potential metabolic processes to manipulate to improve pharmacokinetic properties of the molecules. Detailed knowledge of anatomy and surgical techniques is crucial to successfully establish the models, and a well-balanced anaesthesia and adequate monitoring of the animals are also of major importance. An obvious drawback of animal models lacking an organ is the disruption of normal homoeostasis and the induction of dramatic and ultimately mortal systemic changes in the animals. Refining of the surgical techniques and the post-operative supportive care of the animals can increase the value of these models by minimizing the systemic changes induced, and thorough validation of nephrectomy and hepatectomy models is needed before use of such models as a tool in preclinical pharmacokinetics. The present MiniReview discusses pros and cons of the available techniques associated with establishing nephrectomy and hepatectomy models.
Singer, Alexander; Salman, Mo; Thulke, Hans-Hermann
Animal health is of societal importance as it affects human welfare, and anthropogenic interests shape decision making to assure animal health. Scientific advice to support decision making is manifold. Modelling, as one piece of the scientific toolbox, is appreciated for its ability to describe and structure data, to give insight in complex processes and to predict future outcome. In this paper we study the application of scientific modelling to support practical animal health decisions. We reviewed the 35 animal health related scientific opinions adopted by the Animal Health and Animal Welfare Panel of the European Food Safety Authority (EFSA). Thirteen of these documents were based on the application of models. The review took two viewpoints, the decision maker's need and the modeller's approach. In the reviewed material three types of modelling questions were addressed by four specific model types. The correspondence between tasks and models underpinned the importance of the modelling question in triggering the modelling approach. End point quantifications were the dominating request from decision makers, implying that prediction of risk is a major need. However, due to knowledge gaps corresponding modelling studies often shed away from providing exact numbers. Instead, comparative scenario analyses were performed, furthering the understanding of the decision problem and effects of alternative management options. In conclusion, the most adequate scientific support for decision making - including available modelling capacity - might be expected if the required advice is clearly stated.
Imanina, N. H. Noor; Kwe Lu, Tan; Fadhilah, A. R.
Issues such as environmental problem and energy insecurity keep worsening as a result of energy use from household to huge industries including automotive industry. Recently, a new type of zero emission vehicle, hydrogen fuel cell vehicle (HFCV) has received attention. Although there are argues on the feasibility of hydrogen as the future fuel, there is another important issue, which is the acceptance of HFCV. The study of technology acceptance in the early stage is a vital key for a successful introduction and penetration of a technology. This paper proposes a model of factors influencing green vehicle acceptance, specifically HFCV. This model is built base on two technology acceptance theories and other empirical studies of vehicle acceptance. It aims to provide a base for finding the key factors influencing new sustainable energy fuelled vehicle, HFCV acceptance which is achieved by explaining intention to accept HFCV. Intention is influenced by attitude, subjective norm and perceived behavioural control from Theory of Planned Behaviour and personal norm from Norm Activation Theory. In the framework, attitude is influenced by perceptions of benefits and risks, and social trust. Perceived behavioural control is influenced by government interventions. Personal norm is influenced by outcome efficacy and problem awareness.
Tech Directions, 2008
Art and animation work is the most significant part of electronic game development, but is also found in television commercials, computer programs, the Internet, comic books, and in just about every visual media imaginable. It is the part of the project that makes an abstract design idea concrete and visible. Animators create the motion of life in…
Schaper, Louise K; Pervan, Graham P
There is evidence to suggest that health professionals are reluctant to accept and utilise information and communication technologies (ICT) and concern is growing within health informatics research that this is contributing to the lag in adoption and utilisation of ICT across the health sector. Technology acceptance research within the field of information systems has been limited in its application to health and there is a concurrent need to develop and gain empirical support for models of technology acceptance within health and to examine acceptance and utilisation issues amongst health professionals to improve the success of information system implementation in this arena. This paper outlines a project that examines ICT acceptance and utilisation by Australian occupational therapists. It describes the theoretical basis behind the development of a research model and the methodology being employed to empirically validate the model using substantial quantitative, qualitative and longitudinal data. Preliminary results from Phase II of the study are presented. The theoretical significance of this work is that it uses a thoroughly constructed research model, with potentially the largest sample size ever tested, to extend technology acceptance research into the health sector.
Weingartl, Hana M; Berhane, Yohannes; Czub, Markus
Hendra virus (HeV) and Nipah virus (NiV) form a separate genus Henipavirus within the family Paramyxoviridae, and are classified as biosafety level four pathogens due to their high case fatality rate following human infection and because of the lack of effective vaccines or therapy. Both viruses emerged from their natural reservoir during the last decade of the 20th century, causing severe disease in humans, horses and swine, and infecting a number of other mammalian species. The current review summarises current published data relating to experimental infection of small and large animals, including the natural reservoir species, the Pteropus bat, with HeV or NiV. Susceptibility to infection and virus distribution in the individual species is discussed, along with the pathogenesis, pathological changes, and potential routes of transmission.
Gerdts, Volker; Wilson, Heather L; Meurens, Francois; van Drunen Littel-van den Hurk, Sylvia; Wilson, Don; Walker, Stewart; Wheler, Colette; Townsend, Hugh; Potter, Andrew A
The development of human vaccines continues to rely on the use of animals for research. Regulatory authorities require novel vaccine candidates to undergo preclinical assessment in animal models before being permitted to enter the clinical phase in human subjects. Substantial progress has been made in recent years in reducing and replacing the number of animals used for preclinical vaccine research through the use of bioinformatics and computational biology to design new vaccine candidates. However, the ultimate goal of a new vaccine is to instruct the immune system to elicit an effective immune response against the pathogen of interest, and no alternatives to live animal use currently exist for evaluation of this response. Studies identifying the mechanisms of immune protection; determining the optimal route and formulation of vaccines; establishing the duration and onset of immunity, as well as the safety and efficacy of new vaccines, must be performed in a living system. Importantly, no single animal model provides all the information required for advancing a new vaccine through the preclinical stage, and research over the last two decades has highlighted that large animals more accurately predict vaccine outcome in humans than do other models. Here we review the advantages and disadvantages of large animal models for human vaccine development and demonstrate that much of the success in bringing a new vaccine to market depends on choosing the most appropriate animal model for preclinical testing.
Albelda, N; Joel, D
During the last 30 years there have been many attempts to develop animal models of obsessive compulsive disorder (OCD), in the hope that they may provide a route for furthering our understanding and treatment of this disorder. The present review provides the reader with an overview of the currently active animal models of OCD, their strengths and limitations, so that the reader can use the review as a guide for establishing new animal models of OCD, evaluating existing animal models and choosing among them according to one's needs. We review current genetic, pharmacological, neurodevelopmental and behavioral animal models of OCD, and evaluate their face validity (derived from phenomenological similarity between the behavior in the animal model and the specific symptoms of the human condition), predictive validity (derived from similarity in response to treatment) and construct validity (derived from similarity in the underlying mechanisms [physiological or psychological]). On the basis of this evaluation we discuss the usefulness of the different models for screening drugs for anti-compulsive activity, detecting new targets for high frequency stimulation, studying the neural mechanisms of OCD and unraveling the role of gonadal hormones. We then describe potential new treatment strategies that emerge from the convergence of data obtained in different models on the one hand, and how different models can be used to model different subtypes or dimensions of OCD, on the other hand.
Lwin, Seint T; Edwards, Claire M; Silbermann, Rebecca
Multiple myeloma is an incurable plasma-cell malignancy characterized by osteolytic bone disease and immunosuppression. Murine models of multiple myeloma and myeloma bone disease are critical tools for an improved understanding of the pathogenesis of the disease and the development of novel therapeutic strategies. This review will cover commonly used immunocompetent and xenograft models of myeloma, describing the advantages and disadvantages of each model system. In addition, this review provides detailed protocols for establishing systemic and local models of myeloma using both murine and human myeloma cell lines. PMID:26909147
Chismar, William G.; Wiley-Patton, Sonja
There is growing recognition of the importance of the Internet and, more generally, information technology to pediatric care. However, acceptance of these technologies has been low. Attitudes of physicians can play a pivotal role in the adoption session. This study tests the extension to a widely used model in the information systems literature: the Technology Acceptance Model (TAM). Data were collected in a survey of pediatricians to see how well the extended model, TAM2, fits in the medical arena. Our results partially confirm the model; significant parts of the model were not confirmed. The primary factors in pediatricians' acceptance of technology applications relate to their usefulness and job relevance. Little weight is given to ease of use and social factors. We discuss possible explanations for the discrepancies and suggest future research. PMID:12463806
Chismar, William G; Wiley-Patton, Sonja
There is growing recognition of the importance of the Internet and, more generally, information technology to pediatric care. However, acceptance of these technologies has been low. Attitudes of physicians can play a pivotal role in the adoption session. This study tests the extension to a widely used model in the information systems literature: the Technology Acceptance Model (TAM). Data were collected in a survey of pediatricians to see how well the extended model, TAM2, fits in the medical arena. Our results partially confirm the model; significant parts of the model were not confirmed. The primary factors in pediatricians' acceptance of technology applications relate to their usefulness and job relevance. Little weight is given to ease of use and social factors. We discuss possible explanations for the discrepancies and suggest future research.
Hollis, Fiona; Kabbaj, Mohamed
Depression is one of the most disabling medical conditions in the world today, yet its etiologies remain unclear and current treatments are not wholly effective. Animal models are a powerful tool to investigate possible causes and treatments for human diseases. We describe an animal model of social defeat as a possible model for human depression. We discuss the paradigm, behavioral correlates to depression, and potential underlying neurobiological mechanisms with an eye toward possible future therapies.
Laman, Jon D; Kooistra, Susanne M; Clausen, Björn E
In light of an enhanced awareness of ethical questions and ever increasing costs when working with animals in biomedical research, there is a dedicated and sometimes fierce debate concerning the (lack of) reproducibility of animal models and their relevance for human inflammatory diseases. Despite evident advancements in searching for alternatives, that is, replacing, reducing, and refining animal experiments-the three R's of Russel and Burch (1959)-understanding the complex interactions of the cells of the immune system, the nervous system and the affected tissue/organ during inflammation critically relies on in vivo models. Consequently, scientific advancement and ultimately novel therapeutic interventions depend on improving the reproducibility of animal inflammation models. As a prelude to the remaining hands-on protocols described in this volume, here, we summarize potential pitfalls of preclinical animal research and provide resources and background reading on how to avoid them.
Olivier, Alicia K; Gibson-Corley, Katherine N; Meyerholz, David K
Multiple organ systems, including the gastrointestinal tract, pancreas, and hepatobiliary systems, are affected by cystic fibrosis (CF). Many of these changes begin early in life and are difficult to study in young CF patients. Recent development of novel CF animal models has expanded opportunities in the field to better understand CF pathogenesis and evaluate traditional and innovative therapeutics. In this review, we discuss manifestations of CF disease in gastrointestinal, pancreatic, and hepatobiliary systems of humans and animal models. We also compare the similarities and limitations of animal models and discuss future directions for modeling CF.
Olivier, Alicia K.; Gibson-Corley, Katherine N.
Multiple organ systems, including the gastrointestinal tract, pancreas, and hepatobiliary systems, are affected by cystic fibrosis (CF). Many of these changes begin early in life and are difficult to study in young CF patients. Recent development of novel CF animal models has expanded opportunities in the field to better understand CF pathogenesis and evaluate traditional and innovative therapeutics. In this review, we discuss manifestations of CF disease in gastrointestinal, pancreatic, and hepatobiliary systems of humans and animal models. We also compare the similarities and limitations of animal models and discuss future directions for modeling CF. PMID:25591863
Dehay, Benjamin; Vila, Miquel; Bezard, Erwan; Brundin, Patrik; Kordower, Jeffrey H
Aggregation of alpha-synuclein is implicated in several neurodegenerative diseases collectively termed synucleinopathies. Emerging evidence strongly implicates cell-to-cell transmission of misfolded alpha-synuclein as a common pathogenetic mechanism in synucleinopathies. The impact of alpha-synuclein pathology on neuronal dysfunction and behavioral impairments is being explored in animal models. This review provides an update on how research in animal models supports the concept that misfolded alpha-synuclein spreads from cell to cell and describes how findings in animal models might relate to the disease process in humans. Finally, we discuss the current underlying molecular and cellular mechanisms and future therapeutic strategies targeting alpha-synuclein propagation.
Reizner, W.; Hunter, J.G.; O’Malley, N.T.; Southgate, R.D.; Schwarz, E.M.; Kates, S.L.
Staphylococcus aureus (S. aureus) osteomyelitis is a significant complication for orthopaedic patients undergoing surgery, particularly with fracture fixation and arthroplasty. Given the difficulty in studying S. aureus infections in human subjects, animal models serve an integral role in exploring the pathogenesis of osteomyelitis, and aid in determining the efficacy of prophylactic and therapeutic treatments. Animal models should mimic the clinical scenarios seen in patients as closely as possible to permit the experimental results to be translated to the corresponding clinical care. To help understand existing animal models of S. aureus, we conducted a systematic search of PubMed & Ovid MEDLINE to identify in vivo animal experiments that have investigated the management of S. aureus osteomyelitis in the context of fractures and metallic implants. In this review, experimental studies are categorized by animal species and are further classified by the setting of the infection. Study methods are summarized and the relevant advantages and disadvantages of each species and model are discussed. While no ideal animal model exists, the understanding of a model’s strengths and limitations should assist clinicians and researchers to appropriately select an animal model to translate the conclusions to the clinical setting. PMID:24668594
Forrest, Alexandra D.; Coto, Carlos A.; Siegel, Steven J.
Psychosis is an abnormal mental state characterized by disorganization, delusions and hallucinations. Animal models have become an increasingly important research tool in the effort to understand both the underlying pathophysiology and treatment of psychosis. There are multiple animal models for psychosis, with each formed by the coupling of a manipulation and a measurement. In this manuscript we do not address the diseases of which psychosis is a prominent comorbidity. Instead, we summarize the current state of affairs and future directions for animal models of psychosis. To accomplish this, our manuscript will first discuss relevant behavioral and electrophysiological measurements. We then provide an overview of the different manipulations that are combined with these measurements to produce animal models. The strengths and limitations of each model will be addressed in order to evaluate its cross-species comparability. PMID:25215267
Soboleva, A G; Mezentsev, A V; Bruskin, S A
Psoriasis is a chronic autoimmune skin disorder. Experimental models of psoriasis can be used to study the disease in controlled conditions. Moreover, the experimental models allow to study a certain aspect of the pathological process. Although none of the multiple mouse models reproduces the human disease precisely, lab animals as model systems can be very helpful because of two reasons. First, introduction of new mutations into animal genome allows to reveal the new genes that may play a certain role in pathogenesis of the disease. Second, the experiments that are carried on the lab animals can be used for testing the new drugs and selection of the most efficient chemical agents from a variety of the proposed experimental preparations. The aim of this paper was to summarize the data on the lab animals that serve as experimental models of psoriasis.
The rapid expansion and evolution of epigenetics as a core scientific discipline have raised new questions about how endogenous and environmental factors can inform the mechanisms through which biological form and function are regulated. Existing and proposed animal models used for epigenetic research have targeted a myriad of health and disease endpoints that may be acute, chronic, and transgenerational in nature. Initiating events and outcomes may extend across the entire lifespan to elicit unanticipated phenotypes that are of particular concern to institutional animal care and use committees (IACUCs). The dynamics and plasticity of epigenetic mechanisms produce effects and consequences that are manifest differentially within discreet spatial and temporal contexts, including prenatal development, stem cells, assisted reproductive technologies, production of sexual dimorphisms, senescence, and others. Many dietary and nutritional interventions have also been shown to have a significant impact on biological functions and disease susceptibilities through altered epigenetic programming. The environmental, chemical, toxic, therapeutic, and psychosocial stressors used in animal studies to elicit epigenetic changes can become extreme and should raise IACUC concerns for the well-being and proper care of all research animals involved. Epigenetics research is rapidly becoming an integral part of the search for mechanisms in every major area of biomedical and behavioral research and will foster the continued development of new animal models. From the IACUC perspective, care must be taken to acknowledge the particular needs and concerns created by superimposition of epigenetic mechanisms over diverse fields of investigation to ensure the proper care and use of animals without impeding scientific progress.
Lek, Angela; Rahimov, Fedik; Jones, Peter L.; Kunkel, Louis M.
Facioscapulohumeral dystrophy (FSHD) is a unique and complex genetic disease that is not entirely solved. Recent advances in the field have led to a consensus genetic premise for the disorder, enabling researchers to now pursue the design of preclinical models. In this review, we explore all available FSHD models (DUX4-dependent and -independent) for their utility in therapeutic discovery and potential to yield novel disease insights. Due to the complex nature of FSHD, there is currently no single model that accurately recapitulates the genetic and pathophysiological spectrum of the disorder. Existing models are limited to emphasize only specific aspects of the disease, thus highlighting the need for more collaborative research and novel paradigms to advance the translational research space of FSHD. PMID:25801126
Fernández-Borges, Natalia; Elezgarai, Saioa R; Eraña, Hasier; Castilla, Joaquín
Prion diseases belong to a group of fatal infectious diseases with no effective therapies available. Throughout the last 35 years, less than 50 different drugs have been tested in different experimental animal models without hopeful results. An important limitation when searching for new drugs is the existence of appropriate models of the disease. The three different possible origins of prion diseases require the existence of different animal models for testing anti-prion compounds. Wild type, over-expressing transgenic mice and other more sophisticated animal models have been used to evaluate a diversity of compounds which some of them were previously tested in different in vitro experimental models. The complexity of prion diseases will require more pre-screening studies, reliable sporadic (or spontaneous) animal models and accurate chemical modifications of the selected compounds before having an effective therapy against human prion diseases. This review is intended to put on display the more relevant animal models that have been used in the search of new antiprion therapies and describe some possible procedures when handling chemical compounds presumed to have anti-prion activity prior to testing them in animal models.
HOLDEN, RICHARD J.; KARSH, BEN-TZION
Increasing interest in end users’ reactions to health information technology (IT) has elevated the importance of theories that predict and explain health IT acceptance and use. This paper reviews the application of one such theory, the Technology Acceptance Model (TAM), to health care. We reviewed 16 data sets analyzed in over 20 studies of clinicians using health IT for patient care. Studies differed greatly in samples and settings, health ITs studied, research models, relationships tested, and construct operationalization. Certain TAM relationships were consistently found to be significant, whereas others were inconsistent. Several key relationships were infrequently assessed. Findings show that TAM predicts a substantial portion of the use or acceptance of health IT, but that the theory may benefit from several additions and modifications. Aside from improved study quality, standardization, and theoretically motivated additions to the model, an important future direction for TAM is to adapt the model specifically to the health care context, using beliefs elicitation methods. PMID:19615467
Holden, Richard J; Karsh, Ben-Tzion
Increasing interest in end users' reactions to health information technology (IT) has elevated the importance of theories that predict and explain health IT acceptance and use. This paper reviews the application of one such theory, the Technology Acceptance Model (TAM), to health care. We reviewed 16 data sets analyzed in over 20 studies of clinicians using health IT for patient care. Studies differed greatly in samples and settings, health ITs studied, research models, relationships tested, and construct operationalization. Certain TAM relationships were consistently found to be significant, whereas others were inconsistent. Several key relationships were infrequently assessed. Findings show that TAM predicts a substantial portion of the use or acceptance of health IT, but that the theory may benefit from several additions and modifications. Aside from improved study quality, standardization, and theoretically motivated additions to the model, an important future direction for TAM is to adapt the model specifically to the health care context, using beliefs elicitation methods.
Mabunga, Darine Froy N.; Gonzales, Edson Luck T.; Kim, Ji-woon; Kim, Ki Chan
The valproic acid (VPA) animal model of autism spectrum disorder (ASD) is one of the most widely used animal model in the field. Like any other disease models, it can't model the totality of the features seen in autism. Then, is it valid to model autism? This model demonstrates many of the structural and behavioral features that can be observed in individuals with autism. These similarities enable the model to define relevant pathways of developmental dysregulation resulting from environmental manipulation. The uncovering of these complex pathways resulted to the growing pool of potential therapeutic candidates addressing the core symptoms of ASD. Here, we summarize the validity points of VPA that may or may not qualify it as a valid animal model of ASD. PMID:26713077
Critics of animal modeling have advanced a variety of arguments against the validity of the practice. The point of one such form of argument is to establish that animal modeling is pointless and therefore immoral. In this article, critical arguments of this form are divided into three types, the pseudoscience argument, the disanalogy argument, and the predictive validity argument. I contend that none of these criticisms currently succeed, nor are they likely to. However, the connection between validity and morality is important, suggesting that critical efforts would be instructive if they addressed it in a more nuanced way.
Lynch, Wendy J; Nicholson, Katherine L; Dance, Mario E; Morgan, Richard W; Foley, Patricia L
Substance abuse and addiction are well recognized public health concerns, with 2 NIH institutes (the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism) specifically targeting this societal problem. As such, this is an important area of research for which animal experiments play a critical role. This overview presents the importance of substance abuse and addiction in society; reviews the development and refinement of animal models that address crucial areas of biology, pathophysiology, clinical treatments, and drug screening for abuse liability; and discusses some of the unique veterinary, husbandry, and IACUC challenges associated with these models.
Fineman, R M; Schoenwolf, G C
The chicken embryo is a useful animal model for investigating problems in developmental biology and teratology. Here we report data that further define the causes of 2 different patterns of malformation (one associated with amnion abnormalities, the other with isolated neural tube defects) and death induced by making a window in the shell and subshell membranes during the first day of incubation. The interpretation of these data suggests to us the following hypotheses. An early amnion deficit spectrum or syndrome (EADS) in chicken embryos is caused by a brief (less than 10 sec) perturbation that occurs during the windowing procedure. This perturbation results in an acute increase in mechanical tension to the developing embryo and support structures, dehydration localized to the area of the blastoderm, and/or increased friction between the blastoderm and overlying vitelline and shell membranes. Isolated neural tube defects (NTDs) are caused by a longer perturbation (greater than 3 hr) consisting of increased mechanical stress across the blastoderm. The mechanical stress is associated with the introduction of a new air space over the animal pole of the yolk during windowing. The new air space causes the shape of the yolk to change (ie, to be deformed), resulting in an increase in mechanical tension across the vitelline membrane and blastoderm. NTDs involving the head are associated with significant early embryonic mortality, whereas those involving the trunk are not. Death may also be caused by cardiovascular anomalies observed in EADS. It is concluded that disturbances in morphogenesis and death in this model are, therefore, the result of extrinsic forces (eg, mechanical stress, localized dehydration, or friction) acting on different tissue types at various critical times in development. Intensity and duration of these forces on the developing blastoderm are important variables.
SP, Grover; CE, Evans; AS, Patel; B, Modarai; P, Saha; A, Smith
Deep vein thrombosis and common complications, including pulmonary embolism and post thrombotic syndrome, represent a major source of morbidity and mortality worldwide. Experimental models of venous thrombosis have provided considerable insight into the cellular and molecular mechanisms that regulate thrombus formation and subsequent resolution. Here we critically appraise the ex vivo and in vivo techniques used to assess venous thrombosis in these models. Particular attention is paid to imaging modalities, including magnetic resonance imaging, micro computed tomography and high frequency ultrasound that facilitate longitudinal assessment of thrombus size and composition. PMID:26681755
Contemporary biological psychiatry uses experimental animal models to increase our understanding of affective disorder pathogenesis. Modern anxiolytic drug discovery mainly targets specific pathways and molecular determinants within a single phenotypic domain. However, greater understanding of the mechanisms of action is possible through animal models. Primarily developed with rats, animal models in anxiety have been adapted with mixed success for mice, easy-to-use mammals with better genetic possibilities than rats. In this review, we focus on the three most common animal models of anxiety in mice used in the screening of anxiolytics. Both conditioned and unconditioned models are described, in order to represent all types of animal models of anxiety. Behavioral studies require careful attention to variable parameters linked to environment, handling, or paradigms; this is also discussed. Finally, we focus on the consequences of re-exposure to the apparatus. Test-retest procedures can provide new answers, but should be intensively studied in order to revalidate the entire paradigm as an animal model of anxiety. PMID:26487810
Contemporary biological psychiatry uses experimental animal models to increase our understanding of affective disorder pathogenesis. Modern anxiolytic drug discovery mainly targets specific pathways and molecular determinants within a single phenotypic domain. However, greater understanding of the mechanisms of action is possible through animal models. Primarily developed with rats, animal models in anxiety have been adapted with mixed success for mice, easy-to-use mammals with better genetic possibilities than rats. In this review, we focus on the three most common animal models of anxiety in mice used in the screening of anxiolytics. Both conditioned and unconditioned models are described, in order to represent all types of animal models of anxiety. Behavioral studies require careful attention to variable parameters linked to environment, handling, or paradigms; this is also discussed. Finally, we focus on the consequences of re-exposure to the apparatus. Test-retest procedures can provide new answers, but should be intensively studied in order to revalidate the entire paradigm as an animal model of anxiety.
Ng, Chun-Yi; Jaarin, Kamsiah
Hypertension and atherosclerosis are among the most common causes of mortality in both developed and developing countries. Experimental animal models of hypertension and atherosclerosis have become a valuable tool for providing information on etiology, pathophysiology, and complications of the disease and on the efficacy and mechanism of action of various drugs and compounds used in treatment. An animal model has been developed to study hypertension and atherosclerosis for several reasons. Compared to human models, an animal model is easily manageable, as compounding effects of dietary and environmental factors can be controlled. Blood vessels and cardiac tissue samples can be taken for detailed experimental and biomolecular examination. Choice of animal model is often determined by the research aim, as well as financial and technical factors. A thorough understanding of the animal models used and complete analysis must be validated so that the data can be extrapolated to humans. In conclusion, animal models for hypertension and atherosclerosis are invaluable in improving our understanding of cardiovascular disease and developing new pharmacological therapies. PMID:26064920
Kollias, George; Papadaki, Piyi; Apparailly, Florence; Vervoordeldonk, Margriet J; Holmdahl, Rikard; Baumans, Vera; Desaintes, Christian; Di Santo, James; Distler, Jörg; Garside, Paul; Hegen, Martin; Huizinga, Tom W J; Jüngel, Astrid; Klareskog, Lars; McInnes, Iain; Ragoussis, Ioannis; Schett, Georg; Hart, Bert 't; Tak, Paul P; Toes, Rene; van den Berg, Wim; Wurst, Wolfgang; Gay, Steffen
The development of novel treatments for rheumatoid arthritis (RA) requires the interplay between clinical observations and studies in animal models. Given the complex molecular pathogenesis and highly heterogeneous clinical picture of RA, there is an urgent need to dissect its multifactorial nature and to propose new strategies for preventive, early and curative treatments. Research on animal models has generated new knowledge on RA pathophysiology and aetiology and has provided highly successful paradigms for innovative drug development. Recent focus has shifted towards the discovery of novel biomarkers, with emphasis on presymptomatic and emerging stages of human RA, and towards addressing the pathophysiological mechanisms and subsequent efficacy of interventions that underlie different disease variants. Shifts in the current paradigms underlying RA pathogenesis have also led to increased demand for new (including humanised) animal models. There is therefore an urgent need to integrate the knowledge on human and animal models with the ultimate goal of creating a comprehensive 'pathogenesis map' that will guide alignment of existing and new animal models to the subset of disease they mimic. This requires full and standardised characterisation of all models at the genotypic, phenotypic and biomarker level, exploiting recent technological developments in 'omics' profiling and computational biology as well as state of the art bioimaging. Efficient integration and dissemination of information and resources as well as outreach to the public will be necessary to manage the plethora of data accumulated and to increase community awareness and support for innovative animal model research in rheumatology.
Avila, Guillermina; Teran, Nancy; Aguilar-Vega, Laura; Maravilla, Pablo; Mata-Miranda, Pilar; Flisser, Ana
Human beings are the only hosts of adult Taenia solium; thus, many aspects of the host-parasite relationship are unknown. The development of successful experimental models of taeniasis allows in-depth investigations of the host-parasite relationship. We established experimental models in hamsters, gerbils and chinchillas. Here we review our findings regarding the characteristics of the tapeworms, their anchoring site and development, as well as the humoral and cellular immune response they elicit. We also used statistics to analyze the data obtained in different infections performed along several years. Furthermore, we compared the size of T. solium rostellum and strobila recovered from hamsters and gerbils to those obtained from humans. Our data indicate that these rodents are adequate experimental models for studying T. solium in its adult stage; that parasites induce immune responses and that hamsters seem to be more permissive hosts than gerbils, since parasites survive for longer times, grow longer and develop more, and the inflammatory response in the intestinal mucosa against T. solium is moderate. Finally, chinchillas are the most successful experimental definitive model for adult T. solium, since tapeworms with gravid proglottids are obtained, and the life cycle can be continued to the intermediate host.
Rittscher, Jens; Blake, Andrew; Hoogs, Anthony; Stein, Gees
Our aim is to enable a machine to observe and interpret the behaviour of others. Mathematical models are employed to describe certain biological motions. The main challenge is to design models that are both tractable and meaningful. In the first part we will describe how computer vision techniques, in particular visual tracking, can be applied to recognize a small vocabulary of human actions in a constrained scenario. Mainly the problems of viewpoint and scale invariance need to be overcome to formalize a general framework. Hence the second part of the article is devoted to the question whether a particular human action should be captured in a single complex model or whether it is more promising to make extensive use of semantic knowledge and a collection of low-level models that encode certain motion primitives. Scene context plays a crucial role if we intend to give a higher-level interpretation rather than a low-level physical description of the observed motion. A semantic knowledge base is used to establish the scene context. This approach consists of three main components: visual analysis, the mapping from vision to language and the search of the semantic database. A small number of robust visual detectors is used to generate a higher-level description of the scene. The approach together with a number of results is presented in the third part of this article. PMID:12689374
Kane, Alice E; Hilmer, Sarah N; Mach, John; Mitchell, Sarah J; de Cabo, Rafael; Howlett, Susan E
The ethical, logistical, and biological complications of working with an older population of people inherently limits clinical studies of frailty. The recent development of animal models of frailty, and tools for assessing frailty in animal models provides an invaluable opportunity for frailty research. This review summarizes currently published animal models of frailty including the interleukin-10 knock-out mouse, the mouse frailty phenotype assessment tool, and the mouse clinical frailty index. It discusses both current and potential roles of these models in research into mechanisms of frailty, interventions to prevent/delay frailty, and the effect of frailty on outcomes. Finally, this review discusses some of the challenges and opportunities of translating research findings from animals to humans.
Geisbert, Thomas W; Feldmann, Heinz; Broder, Christopher C
The henipaviruses, Hendra virus (HeV), and Nipah virus (NiV), are enigmatic emerging pathogens that causes severe and often fatal neurologic and/or respiratory disease in both animals and humans. Amongst people, case fatality rates range between 40 and 75% and there are no vaccines or treatments approved for human use. A number of species of animals including guinea pigs, hamsters, cats, ferrets, pigs, and African green monkeys have been employed as animal models of human henipavirus infection. Here, we review the development of animal models for henipavirus infection, discuss the pathology and pathogenesis of these models, and assess the utility of each model to recapitulate important aspects of henipavirus-mediated disease seen in humans.
Kane, Alice E; Hilmer, Sarah N; Mach, John; Mitchell, Sarah J; de Cabo, Rafael; Howlett, Susan E
The ethical, logistical, and biological complications of working with an older population of people inherently limits clinical studies of frailty. The recent development of animal models of frailty, and tools for assessing frailty in animal models provides an invaluable opportunity for frailty research. This review summarizes currently published animal models of frailty including the interleukin-10 knock-out mouse, the mouse frailty phenotype assessment tool, and the mouse clinical frailty index. It discusses both current and potential roles of these models in research into mechanisms of frailty, interventions to prevent/delay frailty, and the effect of frailty on outcomes. Finally, this review discusses some of the challenges and opportunities of translating research findings from animals to humans. PMID:27822024
... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Model code provisions for use in... Minimum Property Standards § 200.926c Model code provisions for use in partially accepted code jurisdictions. If a lender or other interested party is notified that a State or local building code has...
Ahmad, Tunku Badariah Tunku; Madarsha, Kamal Basha; Zainuddin, Ahmad Marzuki; Ismail, Nik Ahmad Hisham; Nordin, Mohamad Sahari
The first aim of the present study is to validate an extended technology acceptance model (TAME) on the data derived from the faculty members of a university in an ongoing, computer mediated work setting. The study extended the original TAM model by including an intrinsic motivation component--computer self efficacy. In so doing, the study…
Chow, Meyrick; Herold, David Kurt; Choo, Tat-Ming; Chan, Kitty
Learners need to have good reasons to engage and accept e-learning. They need to understand that unless they do, the outcomes will be less favourable. The technology acceptance model (TAM) is the most widely recognized model addressing why users accept or reject technology. This study describes the development and evaluation of a virtual…
Maeda, Akiko; Palczewski, Krzysztof
Continuous generation of visual chromophore through the visual (retinoid) cycle is essential to maintain eyesight and retinal heath. Impairments in this cycle and related pathways adversely affect vision. In this review, we summarize the chemical reactions of vitamin A metabolites involved in the retinoid cycle and describe animal models of associated human diseases. Development of potential therapies for retinal disorders in these animal models is also introduced. PMID:25210527
Gagliardi, Christine; Bunnell, Bruce A
he development of therapeutic interventions for genetic disorders and diseases that affect the central nervous system (CNS) has proven challenging. There has been significant progress in the development of gene therapy strategies in murine models of human disease, but gene therapy outcomes in these models do not always translate to the human setting. Therefore, large animal models are crucial to the development of diagnostics, treatments, and eventual cures for debilitating neurological disorders. This review focuses on the description of large animal models of neurological diseases such as lysosomal storage diseases, Parkinsons disease, Huntingtons disease, and neuroAIDS. The review also describes the contributions of these models to progress in gene therapy research.
Melas, Christos D; Zampetakis, Leonidas A; Dimopoulou, Anastasia; Moustakis, Vassilis
Recent empirical research has utilized the Technology Acceptance Model (TAM) to advance the understanding of doctors' and nurses' technology acceptance in the workplace. However, the majority of the reported studies are either qualitative in nature or use small convenience samples of medical staff. Additionally, in very few studies moderators are either used or assessed despite their importance in TAM based research. The present study focuses on the application of TAM in order to explain the intention to use clinical information systems, in a random sample of 604 medical staff (534 physicians) working in 14 hospitals in Greece. We introduce physicians' specialty as a moderator in TAM and test medical staff's information and communication technology (ICT) knowledge and ICT feature demands, as external variables. The results show that TAM predicts a substantial proportion of the intention to use clinical information systems. Findings make a contribution to the literature by replicating, explaining and advancing the TAM, whereas theory is benefited by the addition of external variables and medical specialty as a moderator. Recommendations for further research are discussed.
navigation strategies in complex environments. In Proceedings of the 2003 Intl. Confer- ence on Humanoid Robots , October 2003. 4.7.3  Wallace Ching and...generate spatial and temporal variants from a small amount of data. We think of our work as one step towards the problem of motion variation; we...Treuille and his colleagues  generate crowd motions by thinking of crowds of agents as particles in a fluid. They model a potential field in
Pekarsky, Yuri; Zanesi, Nicola; Aqeilan, Rami I; Croce, Carlo M
B-cell chronic lymphocytic leukemia (B-CLL), the most common leukemia in the Western world, results from an expansion of a rare population of CD5+ mature B-lymphocytes. Although clinical features and genomic abnormalities in B-CLL have been studied in considerable detail, the molecular mechanisms underlying disease development has remained unclear until recently. In the last 4 years, several transgenic mouse models for B-CLL were generated. Investigations of these mouse models revealed that deregulation of three pathways, Tcl1-Akt pathway, TNF-NF-kB pathway, and Bcl2-mediated anti-apoptotic pathway, result in the development of B-CLL. While deregulation of TCL1 alone caused a B-CLL phenotype in mice, overexpression of Bcl2 required aberrantly activated TNF-NF-kB pathway signaling to yield the disease phenotype. In this article, we present what has been learned from mice with B-CLL phenotype and how these mouse models of B-CLL were used to test therapeutic treatments for this common leukemia.
Crystal, Jonathon D
Representations of unique events from one's past constitute the content of episodic memories. A number of studies with non-human animals have revealed that animals remember specific episodes from their past (referred to as episodic-like memory). The development of animal models of memory holds enormous potential for gaining insight into the biological bases of human memory. Specifically, given the extensive knowledge of the rodent brain, the development of rodent models of episodic memory would open new opportunities to explore the neuroanatomical, neurochemical, neurophysiological, and molecular mechanisms of memory. Development of such animal models holds enormous potential for studying functional changes in episodic memory in animal models of Alzheimer's disease, amnesia, and other human memory pathologies. This article reviews several approaches that have been used to assess episodic-like memory in animals. The approaches reviewed include the discrimination of what, where, and when in a radial arm maze, dissociation of recollection and familiarity, object recognition, binding, unexpected questions, and anticipation of a reproductive state. The diversity of approaches may promote the development of converging lines of evidence on the difficult problem of assessing episodic-like memory in animals.
Ceciliani, Fabrizio; Restelli, Laura; Lecchi, Cristina
The need to provide in vivo complex environments to understand human diseases strongly relies on the use of animal models, which traditionally include small rodents and rabbits. It is becoming increasingly evident that the few species utilised to date cannot be regarded as universal. There is a great need for new animal species that are naturally endowed with specific features relevant to human diseases. Farm animals, including pigs, cows, sheep and horses, represent a valid alternative to commonly utilised rodent models. There is an ample scope for the application of proteomic techniques in farm animals, and the establishment of several proteomic maps of plasma and tissue has clearly demonstrated that farm animals provide a disease environment that closely resembles that of human diseases. The present review offers a snapshot of how proteomic techniques have been applied to farm animals to improve their use as biomedical models. Focus will be on specific topics of biomedical research in which farm animal models have been characterised through the application of proteomic techniques.
Chapleau, Kristine M; Oswald, Debra L
Power and sex are thought to be important factors associated with sexual aggression. The goal of this study was to offer a dual-process model to determine how both an implicit power-sex association and explicit power-sex beliefs contribute to rape myth acceptance and rape proclivity. In Study 1, an explicit measure of power-sex beliefs was developed using a participant sample of 131 college students (54% female; age: M = 20.2 years, SD = 3.5 years). In Study 2, 108 male college students (age: M = 19.1 years, SD = 1.3 years) completed a power-sex implicit association test and three explicit measures assessing power-sex beliefs, rape myth acceptance, and rape proclivity. Two models of rape proclivity were compared. The best-fitting model showed that rape myth acceptance mediated the relationships between rape proclivity and an implicit power-sex association, as well as explicit power-sex beliefs.
Swerdlow, Neal R; Sutherland, Ashley N
The science of Tourette Syndrome (TS) is advancing at multiple levels of analysis and will be enhanced through the use of animal models. Particular challenges in the development of TS animal models reflect complex features of this disorder, including its waxing and waning course and its "invisible" sensory and psychic symptoms. Animal models can achieve face, predictive, or construct validity based on their particular features. Predictive validity, of most direct relevance to drug development for TS, is achieved to some degree by a several animal models, although the reliance of most of these models on measures of motor suppression may ultimately limit their utility. Other models achieve construct validity with proposed pathophysiological mechanisms related to the immune and neural circuit etiologies of TS. One model-deficient sensorimotor gating of the startle reflex-is discussed in terms of its present and future applications towards advancing our understanding of the pathophysiology and treatment of TS. In addition to models that will advance the pharmacotherapy of TS, other animal models may enhance the utility of nonpharmacologic TS treatments, ranging from behavior therapy to deep brain stimulation (DBS).
Kuyinu, Emmanuel L; Narayanan, Ganesh; Nair, Lakshmi S; Laurencin, Cato T
Osteoarthritis (OA) is one of the most commonly occurring forms of arthritis in the world today. It is a debilitating chronic illness causing pain and immense discomfort to the affected individual. Significant research is currently ongoing to understand its pathophysiology and develop successful treatment regimens based on this knowledge. Animal models have played a key role in achieving this goal. Animal models currently used to study osteoarthritis can be classified based on the etiology under investigation, primary osteoarthritis, and post-traumatic osteoarthritis, to better clarify the relationship between these models and the pathogenesis of the disease. Non-invasive animal models have shown significant promise in understanding early osteoarthritic changes. Imaging modalities play a pivotal role in understanding the pathogenesis of OA and the correlation with pain. These imaging studies would also allow in vivo surveillance of the disease as a function of time in the animal model. This review summarizes the current understanding of the disease pathogenesis, invasive and non-invasive animal models, imaging modalities, and pain assessment techniques in the animals.
Barboriak, J J; Knoblock, H W; Hensley, G T; Gombas, O F; Fink, J N
Groups of rats exposed to daily inhalation challenge with aerosolized pigeon serum developed precipitating antibody within 2 weeks and definitive granulomatous inflammatory changes in the lung after 7 weeks of exposure. The dissociation of the two responses to an inhalation challenge indicate that the rat model may serve for screening of the various inhalant antigens for their sensitizing potential, and for investigation of the contributory role of some of the factors involved in the pathogenesis of hypersensitivity pneumonitis. Images FIG. 1 FIG. 2 PMID:939055
Casals, Juliana B; Pieri, Naira CG; Feitosa, Matheus LT; Ercolin, Anna CM; Roballo, Kelly CS; Barreto, Rodrigo SN; Bressan, Fabiana F; Martins, Daniele S; Miglino, Maria A; Ambrósio, Carlos E
Stroke has been identified as the second leading cause of death worldwide. Stroke is a focal neurologic deficit caused by a change in cerebral circulation. The use of animal models in recent years has improved our understanding of the physiopathology of this disease. Rats and mice are the most commonly used stroke models, but the demand for larger models, such as rabbits and even nonhuman primates, is increasing so as to better understand the disease and its treatment. Although the basic mechanisms of stroke are nearly identical among mammals, we here discuss the differences between the human encephalon and various animals. In addition, we compare common surgical techniques used to induce animal models of stroke. A more complete anatomic knowledge of the cerebral vessels of various model species is needed to develop more reliable models for objective results that improve knowledge of the pathology of stroke in both human and veterinary medicine. PMID:22330245
Vaugeois, J-M; El Yacoubi, M; Costentin, J
Depression is a multifactorial illness and genetic factors play a role in its etiology. The understanding of its pathophysiology relies on the availability of experimental models potentially mimicking the disease. Here is presented a model built up by selective breeding of mice with strikingly different responses in the tail suspension test, a stress paradigm aimed at screening potential antidepressants. Indeed, "helpless" mice are essentially immobile in the tail suspension test, as well as the Porsolt forced-swim test, and they show reduced consumption of a palatable 2% sucrose solution. In addition, helpless mice exhibit sleep-wakefulness alterations resembling those classically observed in depressed patients, notably a lighter and more fragmented sleep, with an increase pressure of rapid eye movement sleep. Compared with "nonhelpless" mice, they display higher basal serum corticosterone levels and lower serotonin metabolism index in the hippocampus. Remarkably, serotonin1A autoreceptor stimulation induced greatest hypothermia and inhibition of serotoninergic neuronal firing in the nucleus raphe dorsalis in helpless than in nonhelpless mice. Thus, helpless mice exhibit a decrease in serotoninergic tone, which evokes that associated with endogenous depression in humans. Finally, both the behavioral impairments and the serotoninergic dysfunction can be improved by chronic treatment with the antidepressant fluoxetine. The helpless line of mice may provide an opportunity to approach genes influencing susceptibility to depression and to investigate neurophysiological and neurochemical substrates underlying antidepressant effects.
Mattar, Citra N; Biswas, Arijit; Choolani, Mahesh; Chan, Jerry K Y
Intrauterine gene therapy (IUGT) potentially enables the treatment and possible cure of monogenic -diseases that cause severe fetal damage. The main benefits of this approach will be the ability to correct the disorder before the onset of irreversible pathology and inducing central immune tolerance to the vector and transgene if treatment is instituted in early gestation. Cure has been demonstrated in small animal models, but because of the significant differences in immune ontogeny and the much shorter gestation compared to humans, it is unlikely that questions of long-term efficacy and safety will be adequately addressed in rodents. The nonhuman primate (NHP) allows investigation of key issues, in particular, the different outcomes in early and late-gestation IUGT associated with different stages of immune maturity, longevity of transgene expression, and delayed-onset adverse events in treated offspring and mothers including insertional mutagenesis. Here, we describe a model based on the Macaca fascicularis using ultrasound and fetoscopic approaches to systemic vector delivery and the processes involved in vector administration and longitudinal analyses.
McElvaney, Noel G.
Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The resultant characteristic ion transport defect results in decreased mucociliary clearance, bacterial colonisation, and chronic neutrophil-dominated inflammation. Much knowledge surrounding the pathophysiology of the disease has been gained through the generation of animal models, despite inherent limitations in each. The failure of certain mouse models to recapitulate the phenotypic manifestations of human disease has initiated the generation of larger animals in which to study CF, including the pig and the ferret. This review will summarise the basic phenotypes of three animal models and describe the contributions of such animal studies to our current understanding of CF. PMID:27340661
Mitchell, Bryan F; Taggart, Michael J
Preterm birth remains the most serious complication of pregnancy and is associated with increased rates of infant death or permanent neurodevelopmental disability. Our understanding of the regulation of parturition remains inadequate. The scientific literature, largely derived from rodent animal models, suggests two major mechanisms regulating the timing of parturition: the withdrawal of the steroid hormone progesterone and a proinflammatory response by the immune system. However, available evidence strongly suggests that parturition in the human has significantly different regulators and mediators from those in most of the animal models. Our objectives are to critically review the data and concepts that have arisen from use of animal models for parturition and to rationalize the use of a new model. Many animal models have contributed to advances in our understanding of the regulation of parturition. However, we suggest that those animals dependent on progesterone withdrawal to initiate parturition clearly have a limitation to their translation to the human. In such models, a linear sequence of events (e.g., luteolysis, progesterone withdrawal, uterine activation, parturition) gives rise to the concept of a "trigger" mechanism. Conversely, we propose that human parturition may arise from the concomitant maturation of several systems in parallel. We have termed this novel concept "modular accumulation of physiological systems" (MAPS). We also emphasize the urgency to determine the precise role of the immune system in the process of parturition in situations other than intrauterine infection. Finally, we accentuate the need to develop a nonprimate animal model whose physiology is more relevant to human parturition. We suggest that the guinea pig displays several key physiological characteristics of gestation that more closely resemble human pregnancy than do currently favored animal models. We conclude that the application of novel concepts and new models are
McDaid, James; Scott, Christopher J; Kissenpfennig, Adrien; Chen, Huifang; Martins, Paulo N
The immune system comprises an integrated network of cellular interactions. Some responses are predictable, while others are more stochastic. While in vitro the outcome of stimulating a single type of cell may be stereotyped and reproducible, in vivo this is often not the case. This phenomenon often merits the use of animal models in predicting the impact of immunosuppressant drugs. A heavy burden of responsibility lies on the shoulders of the investigator when using animal models to study immunosuppressive agents. The principles of the three R׳s: refine (less suffering,), reduce (lower animal numbers) and replace (alternative in vitro assays) must be applied, as described elsewhere in this issue. Well designed animal model experiments have allowed us to develop all the immunosuppressive agents currently available for treating autoimmune disease and transplant recipients. In this review, we examine the common animal models used in developing immunosuppressive agents, focusing on drugs used in transplant surgery. Autoimmune diseases, such as multiple sclerosis, are covered elsewhere in this issue. We look at the utility and limitations of small and large animal models in measuring potency and toxicity of immunosuppressive therapies.
Thyroid hormone plays a crucial role in the development and functional maintenance of the central nervous system including the cerebellum. To study the molecular mechanisms of thyroid hormone action, various animal models have been used. These are classified: (1) congenital hypothyroid animals due to thyroid gland dysgenesis or thyroid dyshormonogenesis, (2) thyroid hormone receptor (TR) gene-mutated animals, and (3) thyroid hormone transport or metabolism-modified animals. TR is a ligand-activated transcription factor. In the presence of ligand, it activates transcription of target gene, whereas it represses the transcription without ligand. Thus, phenotype of TR-knockout mouse is different from that of hypothyroid animal (low thyroid hormone level), in which unliganded TR actively represses the transcription. On the other hand, human patient harboring mutant TR expresses different phenotypes depending on the function of mutated TR. To mimic this phenotype, other animal models are generated. In addition, recent human studies have shown that thyroid hormone transporters such as monocarboxylate transporter (MCT) 8 may play an important role in thyroid hormone-mediated brain development. However, MCT8 knockout mouse show different phenotypes from a human patient. This article introduces representative animal models currently used to study various aspects of thyroid hormone, particularly to study the involvement of the thyroid hormone system on the development and functional maintenance of the cerebellum.
Kokras, N; Dalla, C
Psychiatric disorders are characterized by sex differences in their prevalence, symptomatology and treatment response. Animal models have been widely employed for the investigation of the neurobiology of such disorders and the discovery of new treatments. However, mostly male animals have been used in preclinical pharmacological studies. In this review, we highlight the need for the inclusion of both male and female animals in experimental studies aiming at gender-oriented prevention, diagnosis and treatment of psychiatric disorders. We present behavioural findings on sex differences from animal models of depression, anxiety, post-traumatic stress disorder, substance-related disorders, obsessive–compulsive disorder, schizophrenia, bipolar disorder and autism. Moreover, when available, we include studies conducted across different stages of the oestrous cycle. By inspection of the relevant literature, it is obvious that robust sex differences exist in models of all psychiatric disorders. However, many times results are conflicting, and no clear conclusion regarding the direction of sex differences and the effect of the oestrous cycle is drawn. Moreover, there is a lack of considerable amount of studies using psychiatric drugs in both male and female animals, in order to evaluate the differential response between the two sexes. Notably, while in most cases animal models successfully mimic drug response in both sexes, test parameters and treatment-sensitive behavioural indices are not always the same for male and female rodents. Thus, there is an increasing need to validate animal models for both sexes and use standard procedures across different laboratories. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20 PMID:24697577
Cynomolgus Macaque as an Animal Model for Severe Acute Respiratory Syndrome James V. Lawler 1¤a , Timothy P. Endy 2¤b , Lisa E. Hensley 2 , Aura...model for severe acute respiratory syndrome . PLoS Med 3(5): e149. Received: July 5, 2005 Accepted: January 10, 2006 Published: April 18, 2006 DOI...United States of America A B S T R A C T Background The emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and
Balietti, Marta; Tamagnini, Francesco; Fattoretti, Patrizia; Burattini, Costanza; Casoli, Tiziana; Platano, Daniela; Lattanzio, Fabrizia
Abstract Aging is associated with a gradual decline in cognitive functions, and more dramatic cognitive impairments occur in patients affected by Alzheimer's disease (AD). Electrophysiological and molecular studies performed in aged animals and in animal models of AD have shown that cognitive decline is associated with significant modifications in synaptic plasticity (i.e., activity-dependent changes in synaptic strength) and have elucidated some of the cellular mechanisms underlying this process. Morphological studies have revealed a correlation between the quality of memory performance and the extent of structural changes of synaptic contacts occurring during memory consolidation. We briefly review recent experimental evidence here. PMID:22533439
Alonso, Pino; López-Solà, Clara; Real, Eva; Segalàs, Cinto; Menchón, José Manuel
Obsessive–compulsive disorder (OCD) is a disabling and common neuropsychiatric condition of poorly known etiology. Many attempts have been made in the last few years to develop animal models of OCD with the aim of clarifying the genetic, neurochemical, and neuroanatomical basis of the disorder, as well as of developing novel pharmacological and neurosurgical treatments that may help to improve the prognosis of the illness. The latter goal is particularly important given that around 40% of patients with OCD do not respond to currently available therapies. This article summarizes strengths and limitations of the leading animal models of OCD including genetic, pharmacologically induced, behavioral manipulation-based, and neurodevelopmental models according to their face, construct, and predictive validity. On the basis of this evaluation, we discuss that currently labeled “animal models of OCD” should be regarded not as models of OCD but, rather, as animal models of different psychopathological processes, such as compulsivity, stereotypy, or perseverance, that are present not only in OCD but also in other psychiatric or neurological disorders. Animal models might constitute a challenging approach to study the neural and genetic mechanism of these phenomena from a trans-diagnostic perspective. Animal models are also of particular interest as tools for developing new therapeutic options for OCD, with the greatest convergence focusing on the glutamatergic system, the role of ovarian and related hormones, and the exploration of new potential targets for deep brain stimulation. Finally, future research on neurocognitive deficits associated with OCD through the use of analogous animal tasks could also provide a genuine opportunity to disentangle the complex etiology of the disorder. PMID:26346234
Le, Weidong; Sayana, Pavani; Jankovic, Joseph
Parkinson's disease (PD) is a progressive, neurodegenerative disorder of unknown etiology, although a complex interaction between environmental and genetic factors has been implicated as a pathogenic mechanism of selected neuronal loss. A better understanding of the etiology, pathogenesis, and molecular mechanisms underlying the disease process may be gained from research on animal models. While cell and tissue models are helpful in unraveling involved molecular pathways, animal models are much better suited to study the pathogenesis and potential treatment strategies. The animal models most relevant to PD include those generated by neurotoxic chemicals that selectively disrupt the catecholaminergic system such as 6-hydroxydopamine; 1-methyl-1,2,3,6-tetrahydropiridine; agricultural pesticide toxins, such as rotenone and paraquat; the ubiquitin proteasome system inhibitors; inflammatory modulators; and several genetically manipulated models, such as α-synuclein, DJ-1, PINK1, Parkin, and leucine-rich repeat kinase 2 transgenic or knock-out animals. Genetic and nongenetic animal models have their own unique advantages and limitations, which must be considered when they are employed in the study of pathogenesis or treatment approaches. This review provides a summary and a critical review of our current knowledge about various in vivo models of PD used to test novel therapeutic strategies.
Malkesman, Oz; Pine, Daniel S; Tragon, Tyson; Austin, Daniel R; Henter, Ioline D; Chen, Guang; Manji, Husseini K
Although antidepressants are moderately effective in treating major depressive disorder (MDD), concerns have arisen that selective serotonin-reuptake inhibitors (SSRIs) are associated with suicidal thinking and behavior, especially in children, adolescents and young adults. Almost no experimental research in model systems has considered the mechanisms by which SSRIs might be associated with this potential side effect in some susceptible individuals. Suicide is a complex behavior and impossible to fully reproduce in an animal model. However, by investigating traits that show strong cross-species parallels in addition to associations with suicide in humans, animal models might elucidate the mechanisms by which SSRIs are associated with suicidal thinking and behavior. Traits linked with suicide in humans that can be successfully modeled in rodents include aggression, impulsivity, irritability and hopelessness/helplessness. Modeling these relevant traits in animals can help to clarify the impact of SSRIs on these traits, suggesting avenues for reducing suicide risk in this vulnerable population.
Takahashi, Yoshihisa; Soejima, Yurie; Fukusato, Toshio
Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH give crucial information, not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents. An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH. Animal models of NAFLD/NASH are divided into genetic, dietary, and combination models. In this paper, we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages. PMID:22654421
Takahashi, Yoshihisa; Soejima, Yurie; Fukusato, Toshio
Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH give crucial information, not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents. An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH. Animal models of NAFLD/NASH are divided into genetic, dietary, and combination models. In this paper, we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.
Trobridge, G D; Kiem, H-P
Large animal models have been instrumental in advancing hematopoietic stem cell (HSC) gene therapy. Here we review the advantages of large animal models, their contributions to the field of HSC gene therapy and recent progress in this field. Several properties of human HSCs including their purification, their cell-cycle characteristics, their response to cytokines and the proliferative demands placed on them after transplantation are more similar in large animal models than in mice. Progress in the development and use of retroviral vectors and ex vivo transduction protocols over the last decade has led to efficient gene transfer in both dogs and nonhuman primates. Importantly, the approaches developed in these models have translated well to the clinic. Large animals continue to be useful to evaluate the efficacy and safety of gene therapy, and dogs with hematopoietic diseases have now been cured by HSC gene therapy. Nonhuman primates allow evaluation of aspects of transplantation as well as disease-specific approaches such as AIDS (acquired immunodeficiency syndrome) gene therapy that can not be modeled well in the dog. Finally, large animal models have been used to evaluate the genotoxicity of viral vectors by comparing integration sites in hematopoietic repopulating cells and monitoring clonality after transplantation.
Jones, Bernadette; Donovan, Chantal; Liu, Gang; Gomez, Henry M; Chimankar, Vrushali; Harrison, Celeste L; Wiegman, Cornelis H; Adcock, Ian M; Knight, Darryl A; Hirota, Jeremy A; Hansbro, Philip M
COPD is a major cause of global mortality and morbidity but current treatments are poorly effective. This is because the underlying mechanisms that drive the development and progression of COPD are incompletely understood. Animal models of disease provide a valuable, ethically and economically viable experimental platform to examine these mechanisms and identify biomarkers that may be therapeutic targets that would facilitate the development of improved standard of care. Here, we review the different established animal models of COPD and the various aspects of disease pathophysiology that have been successfully recapitulated in these models including chronic lung inflammation, airway remodelling, emphysema and impaired lung function. Furthermore, some of the mechanistic features, and thus biomarkers and therapeutic targets of COPD identified in animal models are outlined. Some of the existing therapies that suppress some disease symptoms that were identified in animal models and are progressing towards therapeutic development have been outlined. Further studies of representative animal models of human COPD have the strong potential to identify new and effective therapeutic approaches for COPD.
Bazin, J-E; Constantin, J-M; Gindre, G
different animal species and human and animals about the effects of anaesthetic agents are very hazardous. Great differences exist between the effects observed in vitro and in whole animals. The effects of the anaesthetics could be totally different if they are used alone or in association. The same anaesthetic could have opposite effects from an organ to another. For results validation, the anaesthesia side effects (hypoventilation, hypotension, cooling em leader ) have to be minimized. All new experimental models should require discussing the possible interferences between anaesthesia and results and to compare results obtained with different anaesthetic protocols.
Fuller, C. A.; Philips, R. W.; Ballard, R. W.
Use of animals in NASA space programs is reviewed. Animals are needed because life science experimentation frequently requires long-term controlled exposure to environments, statistical validation, invasive instrumentation or biological tissue sampling, tissue destruction, exposure to dangerous or unknown agents, or sacrifice of the subject. The availability and use of human subjects inflight is complicated by the multiple needs and demands upon crew time. Because only living organisms can sense, integrate and respond to the environment around them, the sole use of tissue culture and computer models is insufficient for understanding the influence of the space environment on intact organisms. Equipment for spaceborne experiments with animals is described.
... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false Model code provisions for use in partially accepted code jurisdictions. 200.926c Section 200.926c Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR...
Wong, Kung-Teck; Osman, Rosma bt; Goh, Pauline Swee Choo; Rahmat, Mohd Khairezan
This study sets out to validate and test the Technology Acceptance Model (TAM) in the context of Malaysian student teachers' integration of their technology in teaching and learning. To establish factorial validity, data collected from 302 respondents were tested against the TAM using confirmatory factor analysis (CFA), and structural equation…
Hsu, Hsiao-hui; Chang, Yu-ying
The increasing online access to courses, programs, and information has shifted the control and responsibility of learning process from instructors to learners. Learners' perceptions of and attitudes toward e-learning constitute a critical factor to the success of such system. The purpose of this study is to take TAM (technology acceptance model)…
Chang, Chi-Cheng; Yan, Chi-Fang; Tseng, Ju-Shih
Since convenience is one of the features for mobile learning, does it affect attitude and intention of using mobile technology? The technology acceptance model (TAM), proposed by David (1989), was extended with perceived convenience in the present study. With regard to English language mobile learning, the variables in the extended TAM and its…
Fusilier, Marcelline; Durlabhji, Subhash; Cucchi, Alain
National background of users may influence the process of technology acceptance. The present study explored this issue with the new, integrated technology use model proposed by Sun and Zhang (2006). Data were collected from samples of college students in India, Mauritius, Reunion Island, and United States. Questionnaire methodology and…
Ong, Jason C; Ulmer, Christi S; Manber, Rachel
While there is an accumulating evidence to suggest that therapies using mindfulness and acceptance-based approaches have benefits for improving the symptoms of insomnia, it is unclear how these treatments work. The goal of this paper is to present a conceptual framework for the cognitive mechanisms of insomnia based upon mindfulness and acceptance approaches. The existing cognitive and behavioral models of insomnia are first reviewed and a two-level model of cognitive (primary) and metacognitive (secondary) arousal is presented in the context of insomnia. We then focus on the role of metacognition in mindfulness and acceptance-based therapies, followed by a review of these therapies in the treatment of insomnia. A conceptual framework is presented detailing the mechanisms of metacognition in the context of insomnia treatments. This model proposes that increasing awareness of the mental and physical states that are present when experiencing insomnia symptoms and then learning how to shift mental processes can promote an adaptive stance to one's response to these symptoms. These metacognitive processes are characterized by balanced appraisals, cognitive flexibility, equanimity, and commitment to values and are posited to reduce sleep-related arousal, leading to remission from insomnia. We hope that this model will further the understanding and impact of mindfulness and acceptance-based approaches to insomnia.
Nworji, Alexander O.
Most organizations spend millions of dollars due to the impact of improperly implemented database application systems as evidenced by poor data quality problems. The purpose of this quantitative study was to use, and extend, the technology acceptance model (TAM) to assess the impact of information quality and technical quality factors on database…
The purposes of this study were to determine factors and predictors that influence nurses' intention to use the eICU technology, to examine the applicability of the Technology Acceptance Model in explaining nurses' intention to use the eICU technology in healthcare settings, and to provide psychometric evidence of the measurement scales used in the study. The study involved 117 participants from two healthcare systems. The Telemedicine Technology Acceptance Model was developed based on the original Technology Acceptance Model that was initially developed by Fred Davis in 1986. The eICU Acceptance Survey was used as an instrument for the study. Content validity was examined, and the reliability of the instrument was tested. The results show that perceived usefulness is the most influential factor that influences nurses' intention to use the eICU technology. The principal factors that influence perceived usefulness are perceived ease of use, support from physicians, and years working in the hospital. The model fit was reasonably adequate and able to explain 58% of the variance (R = 0.58) in intention to use the eICU technology with the nursing sample.
Ahmad, Tunku Badariah Tunku; Madarsha, Kamal Basha; Zainuddin, Ahmad Marzuki; Ismail, Nik Ahmad Hisham; Khairani, Ahmad Zamri; Nordin, Mohamad Sahari
In this study, we examined the likelihood of a TAME (extended technology acceptance model), in which the interrelationships among computer self-efficacy, perceived usefulness, intention to use and self-reported use of computer-mediated technology were tested. In addition, the gender- and age-invariant of its causal structure were evaluated. The…
Gardner, Eliot L
Although addiction is a uniquely human phenomenon, some of its pathognomonic features can be modeled at the animal level. Such features include the euphoric "high" produced by acute administration of addictive drugs; the dysphoric "crash" produced by acute withdrawal; drug-seeking and drug-taking behaviors; and relapse to drug-seeking behavior after achieving successful abstinence. Animal models exist for each of these features. In this review, I focus on various animal models of addiction and how they can be used to search for clinically effective antiaddiction medications. I conclude by noting some of the new and novel medications that have been developed preclinically using such models and the hope for further developments along such lines.
Gardner, Eliot L.
Although addiction is a uniquely human phenomenon, some of its pathognomonic features can be modeled at the animal level. Such features include the euphoric “high” produced by acute administration of addictive drugs; the dysphoric “crash” produced by acute withdrawal, drug-seeking, and drug-taking behaviors; and relapse to drug-seeking behavior after achieving successful abstinence. Animal models exist for each of these features. In this review, I focus on various animal models of addiction and how they can be used to search for clinically effective antiaddiction medications. I conclude by noting some of the new and novel medications that have been developed preclinically using such models and the hope for further developments along such lines. PMID:18803910
Pinho, Salomé S; Carvalho, Sandra; Cabral, Joana; Reis, Celso A; Gärtner, Fátima
The enormous biologic complexity of human cancer has stimulated the development of more appropriate experimental models that could resemble in a natural and spontaneous manner the physiopathologic aspects of cancer biology. Companion animals have many desired characteristics that fill the gap between in vitro and in vivo studies, and these characteristics have proven to be important in understanding many complex molecular aspects of human cancer. Spontaneous tumors in dogs share a wide variety of epidemiologic, biologic, and clinical features with human cancer, which makes this animal model both attractive and underused in oncology research. In this review, we summarize the importance of naturally occurring canine tumors as valuable tools for studying numerous aspects of human cancer as well as the potential use of this animal model for the development of new cancer treatments. We address specifically the use of canine mammary tumors as an increasingly powerful model to study human breast cancer.
Couri, Bruna M; Lenis, Andrew T; Borazjani, Ali; Paraiso, Marie Fidela R; Damaser, Margot S
Pelvic organ prolapse is a vaginal protrusion of female pelvic organs. It has high prevalence worldwide and represents a great burden to the economy. The pathophysiology of pelvic organ prolapse is multifactorial and includes genetic predisposition, aberrant connective tissue, obesity, advancing age, vaginal delivery and other risk factors. Owing to the long course prior to patients becoming symptomatic and ethical questions surrounding human studies, animal models are necessary and useful. These models can mimic different human characteristics – histological, anatomical or hormonal, but none present all of the characteristics at the same time. Major animal models include knockout mice, rats, sheep, rabbits and nonhuman primates. In this article we discuss different animal models and their utility for investigating the natural progression of pelvic organ prolapse pathophysiology and novel treatment approaches. PMID:22707980
Hendra (HeV) and Nipah (NiV) viruses (genus Henipavirus (HNV; family Paramyxoviridae) are emerging zoonotic agents that can cause severe respiratory distress and acute encephalitis in humans. Given the lack of effective therapeutics and vaccines for human use, these viruses are considered as public health concerns. Several experimental animal models of HNV infection have been developed in recent years. Here, we review the current status of four of the most promising experimental animal models (mice, hamsters, ferrets, and African green monkeys) and their suitability for modeling the clinical disease, transmission, pathogenesis, prevention, and treatment for HNV infection in humans.
Devine, Darragh P
Self-injurious behaviour is highly prevalent in neurodevelopmental disorders. Interestingly, it is not restricted to any individual diagnostic group. Rather, it is exhibited in various forms across patient groups with distinct genetic defects and classifications of disorders. This suggests that there may be shared neuropathology that confers vulnerability. Convergent evidence from clinical pharmacotherapy, brain imaging studies, postmortem neurochemical analyses, and animal models indicates that dopaminergic insufficiency is a key culprit. This chapter provides an overview of studies in which animal models have been used to investigate the biochemical basis of self-injury, and highlights the convergence in findings between these models and expression of self-injury in humans.
Goswami, Sonal; Rodríguez-Sierra, Olga; Cascardi, Michele; Paré, Denis
Post-traumatic stress disorder (PTSD) is a debilitating condition that develops in a proportion of individuals following a traumatic event. Despite recent advances, ethical limitations associated with human research impede progress in understanding PTSD. Fortunately, much effort has focused on developing animal models to help study the pathophysiology of PTSD. Here, we provide an overview of animal PTSD models where a variety of stressors (physical, psychosocial, or psychogenic) are used to examine the long-term effects of severe trauma. We emphasize models involving predator threat because they reproduce human individual differences in susceptibility to, and in the long-term consequences of, psychological trauma. PMID:23754973
Experimental animals may serve as models for human beings, if analogies between animal and human functions exist. Therefore, the selection of species and strain plays an important role in the development of such models. Knowledge of the nutritional and physiological characteristics of a species is a prerequisite for the composition of complete diets. Often, preliminary work has to begin at the breeding farm in order to make use of such curative models possible. Only when the high requirements of standardization of experimental animals are met can clinical and subclinical symptoms be determined distinctly. By means of sensitive biochemical reactions, imbalances and interactions of nutritive and active ingredients, as well as successful substitutions, can be recorded. The study of absorption and metabolism of preparations is made possible by observing these reactions. However, negative influence on the results of analysis must be eliminated by correct selection of narcotics, and the proper excision and storage of organs. Because of its importance for the planning and evaluation of experiments, biometry is an integral part of every research project. The scientific information which must be gained from the whole experimental animal cannot be substituted by either isolated organs and cell cultures, or by means of computer simulation. A demanding effort, which includes biotechnological methods, is necessary to further reduce the number of experimental animals and, simultaneously, to enhance experimental evidence. In any case, all scientific aims must be in accordance with the ethical principles of the Society for the Prevention of Cruelty to Animals.
Lawson, Cheryl A; Martin, Douglas R
GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay–Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay–Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. PMID:27499644
Zhou, Xianyu; Luo, Xusong; Liu, Fei; Gu, Chuan; Wang, Xi; Yang, Qun; Qian, Yunliang; Yang, Jun
Several animal models of skin flap construction were reported using biomaterials in a way similar to prefabrication. However, there are few animal model using biomaterials similar to prelamination, another main way of clinical skin flap construction that has been proved to be reliable. Can biomaterials be added in skin flap prelamination to reduce the use of autogenous tissues? Beside individual clinical attempts, animal model is needed for randomized controlled trial to objectively evaluate the feasibility and further investigation. Combining human Acellular Dermal Matrix (hADM) and autologous skin graft, we prelaminated flaps based on inguinal fascia. One, two, three and four weeks later, hADM exhibited a sound revascularization and host cell infiltration. Prelaminated skin flaps were then raised and microsurgically transplanted back to groin region. Except for flaps after one week of prelamination, flaps from other subgroups successfully reconstructed defects. After six to sixteen weeks of transplantation, hADM was proved to being able to maintain its original structure, having a wealth of host tissue cells and achieving full revascularization.To our knowledge, this is the first animal model of prelaminating skin flap with biomaterials. Success of this animal model indicates that novel flap prelamination with biomaterials is feasible.
Scharfman, Helen E
Alzheimer’s disease (AD) and epilepsy are separated in the medical community, but seizures occur in some patients with AD, and AD is a risk factor for epilepsy. Furthermore, memory impairment is common in patients with epilepsy. The relationship between AD and epilepsy remains an important question because ideas for therapeutic approaches could be shared between AD and epilepsy research laboratories if AD and epilepsy were related. Here we focus on one of the many types of epilepsy, temporal lobe epilepsy (TLE), because patients with TLE often exhibit memory impairment, depression and other comorbidities that occur in AD. Moreover, the seizures that occur in patients with AD may be nonconvulsive, which occur in patients with TLE. Here we first compare neuropathology in TLE and AD with an emphasis on the hippocampus, which is central to both AD and TLE research. Then we compare animal models of AD pathology with animal models of TLE. Although many aspects of the comparisons are still controversial, there is one conclusion that we suggest is clear: some animal models of TLE could be used to help address questions in AD research, and some animal models of AD pathology are bona fide animal models of epilepsy. PMID:22723738
Zhou, Xianyu; Luo, Xusong; Liu, Fei; Gu, Chuan; Wang, Xi; Yang, Qun; Qian, Yunliang; Yang, Jun
Several animal models of skin flap construction were reported using biomaterials in a way similar to prefabrication. However, there are few animal model using biomaterials similar to prelamination, another main way of clinical skin flap construction that has been proved to be reliable. Can biomaterials be added in skin flap prelamination to reduce the use of autogenous tissues? Beside individual clinical attempts, animal model is needed for randomized controlled trial to objectively evaluate the feasibility and further investigation. Combining human Acellular Dermal Matrix (hADM) and autologous skin graft, we prelaminated flaps based on inguinal fascia. One, two, three and four weeks later, hADM exhibited a sound revascularization and host cell infiltration. Prelaminated skin flaps were then raised and microsurgically transplanted back to groin region. Except for flaps after one week of prelamination, flaps from other subgroups successfully reconstructed defects. After six to sixteen weeks of transplantation, hADM was proved to being able to maintain its original structure, having a wealth of host tissue cells and achieving full revascularization.To our knowledge, this is the first animal model of prelaminating skin flap with biomaterials. Success of this animal model indicates that novel flap prelamination with biomaterials is feasible. PMID:27659066
Lawson, Cheryl A; Martin, Douglas R
GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay-Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay-Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described.
Uzal, Francisco A.; McClane, Bruce A.; Cheung, Jackie K.; Theoret, James; Garcia, Jorge P.; Moore, Robert J.; Rood, Julian I.
The most common animal models used to study Clostridium perfringens infections in humans and animals are reviewed here. The classical C. perfringens-mediated histotoxic disease of humans is clostridial myonecrosis or gas gangrene and the use of a mouse myonecrosis model coupled with genetic studies has contributed greatly to our understanding of disease pathogenesis. Similarly, the use of a chicken model has enhanced our understanding of type A-mediated necrotic enteritis in poultry and has led to the identification of NetB as the primary toxin involved in disease. C. perfringens type A food poisoning is a highly prevalent bacterial illness in the USA and elsewhere. Rabbits and mice are the species most commonly used to study the action of enterotoxin, the causative toxin. Other animal models used to study the effect of this toxin are rats, non-human primates, sheep and cattle. In rabbits and mice, CPE produces severe necrosis of the small intestinal epithelium along with fluid accumulation. C. perfringens type D infection has been studied by inoculating epsilon toxin (ETX) intravenously into mice, rats, sheep, goats and cattle, and by intraduodenal inoculation of whole cultures of this microorganism in mice, sheep, goats and cattle. Molecular Koch's postulates have been fulfilled for enterotoxigenic C. perfringens type A in rabbits and mice, for C. perfringens type A necrotic enteritis and gas gangrene in chickens and mice, respectively, for C. perfringens type C in mice, rabbits and goats, and for C. perfringens type D in mice, sheep and goats. PMID:25770894
Uzal, Francisco A; McClane, Bruce A; Cheung, Jackie K; Theoret, James; Garcia, Jorge P; Moore, Robert J; Rood, Julian I
The most common animal models used to study Clostridium perfringens infections in humans and animals are reviewed here. The classical C. perfringens-mediated histotoxic disease of humans is clostridial myonecrosis or gas gangrene and the use of a mouse myonecrosis model coupled with genetic studies has contributed greatly to our understanding of disease pathogenesis. Similarly, the use of a chicken model has enhanced our understanding of type A-mediated necrotic enteritis in poultry and has led to the identification of NetB as the primary toxin involved in disease. C. perfringens type A food poisoning is a highly prevalent bacterial illness in the USA and elsewhere. Rabbits and mice are the species most commonly used to study the action of enterotoxin, the causative toxin. Other animal models used to study the effect of this toxin are rats, non-human primates, sheep and cattle. In rabbits and mice, CPE produces severe necrosis of the small intestinal epithelium along with fluid accumulation. C. perfringens type D infection has been studied by inoculating epsilon toxin (ETX) intravenously into mice, rats, sheep, goats and cattle, and by intraduodenal inoculation of whole cultures of this microorganism in mice, sheep, goats and cattle. Molecular Koch's postulates have been fulfilled for enterotoxigenic C. perfringens type A in rabbits and mice, for C. perfringens type A necrotic enteritis and gas gangrene in chickens and mice, respectively, for C. perfringens type C in mice, rabbits and goats, and for C. perfringens type D in mice, sheep and goats.
Nathanielsz, Peter W
Human epidemiological and animal laboratory studies show that suboptimal environments in the womb and during early neonatal life alter development and predispose the individual to lifelong health problems. The concept of the developmental origins of adult diseases has become well accepted because of the compelling animal studies that have precisely defined the outcomes of specific exposures such as nutrient restriction, overfeeding during pregnancy, maternal stress, and exogenously administered glucocorticoids. This review focuses on the use of animal models to evaluate exposures, mechanisms, and outcomes involved in developmental programming of hypertension, diabetes, obesity, and altered pituitary-adrenal function in offspring in later life. Ten principles of developmental programming are described as fundamental, regardless of the exposure during development and the physiological system involved in the altered outcome. The 10 principles are discussed in the context of the physiological systems involved and the animal model studies that have been conducted to evaluate exposures, mechanisms, and outcomes. For example, the fetus responds to challenges such as hypoxia and nutrient restriction in ways that help to ensure its survival, but this "developmental plasticity" may have long-term consequences that may not be beneficial in adult life. To understand developmental programming, which represents the interaction of nature and nurture, it is necessary to integrate whole animal systems physiology, in vitro cellular biology, and genomic and proteomic approaches, and to use animal models that are carefully characterized and appropriate for the questions under study. Animal models play an important role in this evaluation because they permit combined in vivo and in vitro study at different critical time windows during the exposure and the ensuing developmental responses.
Bovenkerk, Bernice; Kaldewaij, Frederike
Animal models are used in experiments in the behavioural neurosciences that aim to contribute to the prevention and treatment of cognitive and affective disorders in human beings, such as anxiety and depression. Ironically, those animals that are likely to be the best models for psychopathology are also likely to be considered the ones that are most morally problematic to use, if it seems probable that (and if indeed they are initially selected as models because) they have experiences that are similar to human experiences that we have strong reasons to avoid causing, and indeed aim to alleviate (such as pain, anxiety or sadness). In this paper, against the background of contemporary discussions in animal ethics and the philosophy of animal minds, we discuss the views that it is morally permissible to use animals in these kinds of experiments, and that it is better to use less cognitively complex animals (such as zebrafish) than more complex animals (such as dogs). First, we criticise some justifications for the claim that human beings and more complex animals have higher moral status. We argue that contemporary approaches that attribute equal moral status to all beings that are capable of conscious strivings strivings (e.g. avoiding pain and anxiety; aiming to eat and play) are based on more plausible assumptions. Second, we argue that it is problematic to assume that less cognitively complex animals have a lesser sensory and emotional experience than more complex beings across the board. In specific cases, there might be good reasons to assume that more complex beings would be harmed more by a specific physical or environmental intervention, but it might also be that they sometimes are harmed less because of a better ability to cope. Determining whether a specific experiment is justified is therefore a complex issue. Our aim in this chapter is to stimulate further reflection on these common assumptions behind the use of animal models for psychopathologies. In
Cheng, Zhichao; Xiong, Yang; Xu, Yiwen
An opinion dynamic model with decision-making groups was proposed to study the process of adopting new opinions or ideas by individuals. The opinion's acceptability is introduced to distinguish the general character of different opinions. The simulation results on a free-scale network demonstrate that when two opinions have similar acceptability, the opinion supported by more decision-making groups in the beginning will eventually win the support of more agents, whereas an opinion supported by fewer decision-making groups in the beginning may be supported by the majority at the end only if it has better acceptability, and if the tolerance threshold of the society is higher than a specific value.
Barrett, James E
Berend Olivier has had a long-standing interest in the utility of animal models for a wide variety of therapeutic indications. His work has spanned multiple types of models, blending ethological, or species typical and naturalistic behaviors, along with methodologies based on learned behavior. He has consistently done so, from an analytical as well as predictive perspective, and has made multiple contributions while working in both the pharmaceutical industry and within an academic institution. Although focused primarily on psychiatric disorders, Berend has conducted research in the area of pain in humans and in animals, demonstrating an expansive appreciation for the breadth, scope and significance of the science and applications of the discipline of pharmacology to these diverse areas. This review focuses on the use of animal models in pain research from the perspective of the long-standing deficiencies in the development of therapeutics in this area and from a preclinical perspective where the translational weaknesses have been quite problematic. The challenges confronting animal models of pain, however, are not unique to this area of research, as they cut across several therapeutic areas. Despite the deficiencies, failures and concerns, existing animal models of pain continue to be of widespread use and are essential to progress in pain research as well as in other areas. Although not focusing on specific animal models of pain, this paper seeks to examine general issues facing the use of these models. It does so by exploring alternative approaches which capture recent developments, which build upon principles and concepts we have learned from Berend's contributions, and which provide the prospect of helping to address the absence of novel therapeutics in this area.
Badyal, Dinesh K; Modgill, Vikas; Kaur, Jasleen
It has become increasingly difficult to perform animal experiments, because of issues related to the procurement of animals, and strict regulations and ethical issues related to their use. As a result, it is felt that the teaching of pharmacology should be more clinically oriented and that unnecessary animal experimentation should be avoided. Although a number of computer simulation models (CSMs) are available, they are not being widely used. Interactive demonstrations were conducted to encourage the departmental faculty to use CSMs. Four different animal experiments were selected, that dealt with actions of autonomic drugs. The students observed demonstrations of animal experiments involving conventional methods and the use of CSMs. This was followed by hands-on experience of the same experiment, but using CSMs in small groups, instead of hands-on experience with the animal procedures. Test scores and feedback showed that there was better understanding of the mechanisms of action of the drugs, gained in a shorter time. The majority of the students found the teaching programme used to be good to excellent. CSMs can be used repeatedly and independently by students, and this avoids unnecessary experimentation and also causing pain and trauma to animals. The CSM programme can be implemented in existing teaching schedules for pharmacology undergraduate teaching with basic infrastructure support, and is readily adaptable for use by other institutes.
Nichols, Timothy C.
Advances in treatment of hemophilia and von Willebrand disease (VWD) depend heavily on the availability of well-characterized animal models. These animals faithfully recapitulate the severe bleeding phenotype that occurs in humans with these inherited bleeding disorders. Research in these animal models represents important early and intermediate steps of translational research aimed at addressing current limitations in treatment such as the development of inhibitory antibodies to coagulation factors VIII and IX (FVIII, FIX) or von Willebrand factor (VWF), the life-long need for frequent venous access, the expense of therapy, and the ongoing need for improved ex vivo coagulation assays and in vivo methods for assessing hemostasis. The primary strengths of research that utilizes these highly relevant animal models include the development of better and safer treatments for hemophilia and VWD. Careful consideration of the strengths and limitations of the specific models is essential for optimizing chances for successful translation of advances to clinical medicine that benefits humans and animals. PMID:26052366
Gigliuto, Carmelo; De Gregori, Manuela; Malafoglia, Valentina; Raffaeli, William; Compagnone, Christian; Visai, Livia; Petrini, Paola; Avanzini, Maria Antonietta; Muscoli, Carolina; Viganò, Jacopo; Calabrese, Francesco; Dominioni, Tommaso; Allegri, Massimo; Cobianchi, Lorenzo
In the last two decades, animal models have become important tools in understanding and treating pain, and in predicting analgesic efficacy. Although rodent models retain a dominant role in the study of pain mechanisms, large animal models may predict human biology and pharmacology in certain pain conditions more accurately. Taking into consideration the anatomical and physiological characteristics common to man and pigs (median body size, digestive apparatus, number, size, distribution and communication of vessels in dermal skin, epidermal-dermal junctions, the immunoreactivity of peptide nerve fibers, distribution of nociceptive and non-nociceptive fiber classes, and changes in axonal excitability), swines seem to provide the most suitable animal model for pain assessment. Locomotor function, clinical signs, and measurements (respiratory rate, heart rate, blood pressure, temperature, electromyography), behavior (bright/quiet, alert, responsive, depressed, unresponsive), plasma concentration of substance P and cortisol, vocalization, lameness, and axon reflex vasodilatation by laser Doppler imaging have been used to assess pain, but none of these evaluations have proved entirely satisfactory. It is necessary to identify new methods for evaluating pain in large animals (particularly pigs), because of their similarities to humans. This could lead to improved assessment of pain and improved analgesic treatment for both humans and laboratory animals.
Burggren, Warren W; Warburton, Stephen
The concept of animal models is well honored, and amphibians have played a prominent part in the success of using key species to discover new information about all animals. As animal models, amphibians offer several advantages that include a well-understood basic physiology, a taxonomic diversity well suited to comparative studies, tolerance to temperature and oxygen variation, and a greater similarity to humans than many other currently popular animal models. Amphibians now account for approximately 1/4 to 1/3 of lower vertebrate and invertebrate research, and this proportion is especially true in physiological research, as evident from the high profile of amphibians as animal models in Nobel Prize research. Currently, amphibians play prominent roles in research in the physiology of musculoskeletal, cardiovascular, renal, respiratory, reproductive, and sensory systems. Amphibians are also used extensively in physiological studies aimed at generating new insights in evolutionary biology, especially in the investigation of the evolution of air breathing and terrestriality. Environmental physiology also utilizes amphibians, ranging from studies of cryoprotectants for tissue preservation to physiological reactions to hypergravity and space exploration. Amphibians are also playing a key role in studies of environmental endocrine disruptors that are having disproportionately large effects on amphibian populations and where specific species can serve as sentinel species for environmental pollution. Finally, amphibian genera such as Xenopus, a genus relatively well understood metabolically and physiologically, will continue to contribute increasingly in this new era of systems biology and "X-omics."
Gigliuto, Carmelo; De Gregori, Manuela; Malafoglia, Valentina; Raffaeli, William; Compagnone, Christian; Visai, Livia; Petrini, Paola; Avanzini, Maria Antonietta; Muscoli, Carolina; Viganò, Jacopo; Calabrese, Francesco; Dominioni, Tommaso; Allegri, Massimo; Cobianchi, Lorenzo
In the last two decades, animal models have become important tools in understanding and treating pain, and in predicting analgesic efficacy. Although rodent models retain a dominant role in the study of pain mechanisms, large animal models may predict human biology and pharmacology in certain pain conditions more accurately. Taking into consideration the anatomical and physiological characteristics common to man and pigs (median body size, digestive apparatus, number, size, distribution and communication of vessels in dermal skin, epidermal–dermal junctions, the immunoreactivity of peptide nerve fibers, distribution of nociceptive and non-nociceptive fiber classes, and changes in axonal excitability), swines seem to provide the most suitable animal model for pain assessment. Locomotor function, clinical signs, and measurements (respiratory rate, heart rate, blood pressure, temperature, electromyography), behavior (bright/quiet, alert, responsive, depressed, unresponsive), plasma concentration of substance P and cortisol, vocalization, lameness, and axon reflex vasodilatation by laser Doppler imaging have been used to assess pain, but none of these evaluations have proved entirely satisfactory. It is necessary to identify new methods for evaluating pain in large animals (particularly pigs), because of their similarities to humans. This could lead to improved assessment of pain and improved analgesic treatment for both humans and laboratory animals. PMID:24855386
Stables, Catherine L; Glasser, Rebecca L; Feldman, Eva L
Cardiac autonomic neuropathy (CAN) is a relatively common and often devastating complication of diabetes. The major clinical signs are tachycardia, exercise intolerance, and orthostatic hypotension, but the most severe aspects of this complication are high rates of cardiac events and mortality. One of the earliest manifestations of CAN is reduced heart rate variability, and detection of this, along with abnormal results in postural blood pressure testing and/or the Valsalva maneuver, are central to diagnosis of the disease. The treatment options for CAN, beyond glycemic control, are extremely limited and lack evidence of efficacy. The underlying molecular mechanisms are also poorly understood. Thus, CAN is associated with a poor prognosis and there is a compelling need for research to understand, prevent, and reverse CAN. In this review of the literature we examine the use and usefulness of animal models of CAN in diabetes. Compared to other diabetic complications, the number of animal studies of CAN is very low. The published studies range across a variety of species, methods of inducing diabetes, and timescales examined, leading to high variability in study outcomes. The lack of well-characterized animal models makes it difficult to judge the relevance of these models to the human disease. One major advantage of animal studies is the ability to probe underlying molecular mechanisms, and the limited numbers of mechanistic studies conducted to date are outlined. Thus, while animal models of CAN in diabetes are crucial to better understanding and development of therapies, they are currently under-used.
Botella, Jimmy; Trusov, Yuri
G-proteins are universal signal transducers mediating many cellular responses. Plant G-protein signaling has been modeled on the well-established animal paradigm but accumulated experimental evidence indicates that G-protein-dependent signaling in plants has taken a very different evolutionary path. Here we review the differences between plant and animal G-proteins reported over past two decades. Most importantly, while in animal systems the G-protein signaling cycle is activated by seven transmembrane-spanning G-protein coupled receptors, the existence of these type of receptors in plants is highly controversial. Instead plant G-proteins have been proven to be functionally associated with atypical receptors such as the Arabidopsis RGS1 and a number of receptor-like kinases. We propose that, instead of the GTP/GDP cycle used in animals, plant G-proteins are activated/de-activated by phosphorylation/de-phosphorylation. We discuss the need of a fresh new look at these signaling molecules and provide a hypothetical model that departs fromthe accepted animal paradigm.
Trusov, Yuri; Botella, José R.
G-proteins are universal signal transducers mediating many cellular responses. Plant G-protein signaling has been modeled on the well-established animal paradigm but accumulated experimental evidence indicates that G-protein-dependent signaling in plants has taken a very different evolutionary path. Here we review the differences between plant and animal G-proteins reported over past two decades. Most importantly, while in animal systems the G-protein signaling cycle is activated by seven transmembrane-spanning G-protein coupled receptors, the existence of these type of receptors in plants is highly controversial. Instead plant G-proteins have been proven to be functionally associated with atypical receptors such as the Arabidopsis RGS1 and a number of receptor-like kinases. We propose that, instead of the GTP/GDP cycle used in animals, plant G-proteins are activated/de-activated by phosphorylation/de-phosphorylation. We discuss the need of a fresh new look at these signaling molecules and provide a hypothetical model that departs from the accepted animal paradigm. PMID:27252940
Wagner, M. J.; Mehos, M. S.; Kearney, D. W.; McMahan, A. C.
As deployment of parabolic trough concentrating solar power (CSP) systems ramps up, the need for reliable and robust performance acceptance test guidelines for the solar field is also amplified. Project owners and/or EPC contractors often require extensive solar field performance testing as part of the plant commissioning process in order to ensure that actual solar field performance satisfies both technical specifications and performance guaranties between the involved parties. Performance test code work is currently underway at the National Renewable Energy Laboratory (NREL) in collaboration with the SolarPACES Task-I activity, and within the ASME PTC-52 committee. One important aspect of acceptance testing is the selection of a robust technology performance model. NREL1 has developed a detailed parabolic trough performance model within the SAM software tool. This model is capable of predicting solar field, sub-system, and component performance. It has further been modified for this work to support calculation at subhourly time steps. This paper presents the methodology and results of a case study comparing actual performance data for a parabolic trough solar field to the predicted results using the modified SAM trough model. Due to data limitations, the methodology is applied to a single collector loop, though it applies to larger subfields and entire solar fields. Special consideration is provided for the model formulation, improvements to the model formulation based on comparison with the collected data, and uncertainty associated with the measured data. Additionally, this paper identifies modeling considerations that are of particular importance in the solar field acceptance testing process and uses the model to provide preliminary recommendations regarding acceptable steady-state testing conditions at the single-loop level.
Seki, Yoshinori; Williams, Lyda; Vuguin, Patricia M; Charron, Maureen J
A growing body of evidence suggests that the intrauterine (IU) environment has a significant and lasting effect on the long-term health of the growing fetus and the development of metabolic disease in later life as put forth in the fetal origins of disease hypothesis. Metabolic diseases have been associated with alterations in the epigenome that occur without changes in the DNA sequence, such as cytosine methylation of DNA, histone posttranslational modifications, and micro-RNA. Animal models of epigenetic modifications secondary to an altered IU milieu are an invaluable tool to study the mechanisms that determine the development of metabolic diseases, such as diabetes and obesity. Rodent and nonlitter bearing animals are good models for the study of disease, because they have similar embryology, anatomy, and physiology to humans. Thus, it is feasible to monitor and modify the IU environment of animal models in order to gain insight into the molecular basis of human metabolic disease pathogenesis. In this review, the database of PubMed was searched for articles published between 1999 and 2011. Key words included epigenetic modifications, IU growth retardation, small for gestational age, animal models, metabolic disease, and obesity. The inclusion criteria used to select studies included animal models of epigenetic modifications during fetal and neonatal development associated with adult metabolic syndrome. Experimental manipulations included: changes in the nutritional status of the pregnant female (calorie-restricted, high-fat, or low-protein diets during pregnancy), as well as the father; interference with placenta function, or uterine blood flow, environmental toxin exposure during pregnancy, as well as dietary modifications during the neonatal (lactation) as well as pubertal period. This review article is focused solely on studies in animal models that demonstrate epigenetic changes that are correlated with manifestation of metabolic disease, including diabetes
Quik, Maryka; O'Neill, Michael; Perez, Xiomara A
Parkinson's disease is a neurodegenerative movement disorder that is characterized by a loss of nigrostriatal dopamine-containing neurons. Unexpectedly, there is a reduced incidence of Parkinson's disease in tobacco users. This finding is important because the identification of the component(s) responsible for this effect could lead to therapeutic strategies to slow down or halt the progression of Parkinson's disease. Results from cell culture models consistently show that nicotine protects against neurotoxicity. However, data from animal models of nigrostriatal damage are conflicting, thus raising questions about a neuroprotective role of nicotine. Accumulating evidence indicates that discrepancies are observed primarily in mouse models of the disease. By contrast, reproducible protection occurs in rat models and in a nonhuman primate parkinsonian model that closely resembles the human disease. These findings highlight the need to use the appropriate animal model and treatment conditions when testing putative neuroprotective agents.
Hanks, Ephraim M.; Hooten, Mevin B.; Alldredge, Mat W.
The processes influencing animal movement and resource selection are complex and varied. Past efforts to model behavioral changes over time used Bayesian statistical models with variable parameter space, such as reversible-jump Markov chain Monte Carlo approaches, which are computationally demanding and inaccessible to many practitioners. We present a continuous-time discrete-space (CTDS) model of animal movement that can be fit using standard generalized linear modeling (GLM) methods. This CTDS approach allows for the joint modeling of location-based as well as directional drivers of movement. Changing behavior over time is modeled using a varying-coefficient framework which maintains the computational simplicity of a GLM approach, and variable selection is accomplished using a group lasso penalty. We apply our approach to a study of two mountain lions (Puma concolor) in Colorado, USA.
Jiménez-Díaz, María Belén; Viera, Sara; Fernández-Alvaro, Elena; Angulo-Barturen, Iñigo
The emergence of resistance to artemisinins and the renewed efforts to eradicate malaria demand the urgent development of new drugs. In this endeavour, the evaluation of efficacy in animal models is often a go/no go decision assay in drug discovery. This important role relies on the capability of animal models to assess the disposition, toxicology and efficacy of drugs in a single test. Although the relative merits of each efficacy model of malaria as human surrogate have been extensively discussed, there are no critical analyses on the use of such models in current drug discovery. In this article, we intend to analyse how efficacy models are used to discover new antimalarial drugs. Our analysis indicates that testing drug efficacy is often the last assay in each discovery stage and the experimental designs utilized are not optimized to expedite decision-making and inform clinical development. In light of this analysis, we propose new ways to accelerate drug discovery using efficacy models.
Avci, Pinar; Sadasivam, Magesh; Gupta, Asheesh; De Melo, Wanessa CMA; Huang, Ying-Ying; Yin, Rui; Rakkiyappan, Chandran; Kumar, Raj; Otufowora, Ayodeji; Nyame, Theodore; Hamblin, Michael R
Introduction Discovery of novel drugs, treatments, and testing of consumer products in the field of dermatology is a multi-billion dollar business. Due to the distressing nature of many dermatological diseases, and the enormous consumer demand for products to reverse the effects of skin photodamage, aging, and hair loss, this is a very active field. Areas covered In this paper, we will cover the use of animal models that have been reported to recapitulate to a greater or lesser extent the features of human dermatological disease. There has been a remarkable increase in the number and variety of transgenic mouse models in recent years, and the basic strategy for constructing them is outlined. Expert opinion Inflammatory and autoimmune skin diseases are all represented by a range of mouse models both transgenic and normal. Skin cancer is mainly studied in mice and fish. Wound healing is studied in a wider range of animal species, and skin infections such as acne and leprosy also have been studied in animal models. Moving to the more consumer-oriented area of dermatology, there are models for studying the harmful effect of sunlight on the skin, and testing of sunscreens, and several different animal models of hair loss or alopecia. PMID:23293893
Lo, Amy C. Y.
Diabetic retinopathy (DR) is a microvascular complication associated with chronic exposure to hyperglycemia and is a major cause of blindness worldwide. Although clinical assessment and retinal autopsy of diabetic patients provide information on the features and progression of DR, its underlying pathophysiological mechanism cannot be deduced. In order to have a better understanding of the development of DR at the molecular and cellular levels, a variety of animal models have been developed. They include pharmacological induction of hyperglycemia and spontaneous diabetic rodents as well as models of angiogenesis without diabetes (to compensate for the absence of proliferative DR symptoms). In this review, we summarize the existing protocols to induce diabetes using STZ. We also describe and compare the pathological presentations, in both morphological and functional aspects, of the currently available DR animal models. The advantages and disadvantages of using different animals, ranging from zebrafish, rodents to other higher-order mammals, are also discussed. Until now, there is no single model that displays all the clinical features of DR as seen in human. Yet, with the understanding of the pathological findings in these animal models, researchers can select the most suitable models for mechanistic studies or drug screening. PMID:24286086
Hast, M. W.; Zuskov, A.; Soslowsky, L. J.
Tendinopathy is a debilitating musculoskeletal condition which can cause significant pain and lead to complete rupture of the tendon, which often requires surgical repair. Due in part to the large spectrum of tendon pathologies, these disorders continue to be a clinical challenge. Animal models are often used in this field of research as they offer an attractive framework to examine the cascade of processes that occur throughout both tendon pathology and repair. This review discusses the structural, mechanical, and biological changes that occur throughout tendon pathology in animal models, as well as strategies for the improvement of tendon healing. Cite this article: Bone Joint Res 2014;3:193–202. PMID:24958818
Ortiz, Alberto; Sanchez-Niño, Maria D; Izquierdo, Maria C; Martin-Cleary, Catalina; Garcia-Bermejo, Laura; Moreno, Juan A; Ruiz-Ortega, Marta; Draibe, Juliana; Cruzado, Josep M; Garcia-Gonzalez, Miguel A; Lopez-Novoa, Jose M; Soler, Maria J; Sanz, Ana B
Acute kidney injury (AKI) and chronic kidney disease (CKD) are associated with decreased renal function and increased mortality risk, while the therapeutic armamentarium is unsatisfactory. The availability of adequate animal models may speed up the discovery of biomarkers for disease staging and therapy individualization as well as design and testing of novel therapeutic strategies. Some longstanding animal models have failed to result in therapeutic advances in the clinical setting, such as kidney ischemia-reperfusion injury and diabetic nephropathy models. In this regard, most models for diabetic nephropathy are unsatisfactory in that they do not evolve to renal failure. Satisfactory models for additional nephropathies are needed. These include anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, IgA nephropathy, anti-phospholipase-A2-receptor (PLA2R) membranous nephropathy and Fabry nephropathy. However, recent novel models hold promise for clinical translation. Thus, the AKI to CKD translation has been modeled, in some cases with toxins of interest for human CKD such as aristolochic acid. Genetically modified mice provide models for Alport syndrome evolving to renal failure that have resulted in clinical recommendations, polycystic kidney disease models that have provided clues for the development of tolvaptan, that was recently approved for the human disease in Japan; and animal models also contributed to target C5 with eculizumab in hemolytic uremic syndrome. Some ongoing trials explore novel concepts derived from models, such TWEAK targeting as tissue protection for lupus nephritis. We now review animal models reproducing diverse, genetic and acquired, causes of AKI and CKD evolving to kidney failure and discuss the contribution to clinical translation and prospects for the future.
Ross, Victoria L; Fielding, Kelly S; Louis, Winnifred R
Faced with a severe drought, the residents of the regional city of Toowoomba, in South East Queensland, Australia were asked to consider a potable wastewater reuse scheme to supplement drinking water supplies. As public risk perceptions and trust have been shown to be key factors in acceptance of potable reuse projects, this research developed and tested a social-psychological model of trust, risk perceptions and acceptance. Participants (N = 380) were surveyed a few weeks before a referendum was held in which residents voted against the controversial scheme. Analysis using structural equation modelling showed that the more community members perceived that the water authority used fair procedures (e.g., consulting with the community and providing accurate information), the greater their sense of shared identity with the water authority. Shared social identity in turn influenced trust via increased source credibility, that is, perceptions that the water authority is competent and has the community's interest at heart. The findings also support past research showing that higher levels of trust in the water authority were associated with lower perceptions of risk, which in turn were associated with higher levels of acceptance, and vice versa. The findings have a practical application for improving public acceptance of potable recycled water schemes.
This study extended the Technology Acceptance Model (TAM) by examining the roles of two aspects of e-resource characteristics, namely, information quality and system quality, in predicting public health students' intention to use e-resources for completing research paper assignments. Both focus groups and a questionnaire were used to collect data. Descriptive analysis, data screening, and Structural Equation Modeling (SEM) techniques were used for data analysis. The study found that perceived usefulness played a major role in determining students' intention to use e-resources. Perceived usefulness and perceived ease of use fully mediated the impact that information quality and system quality had on behavior intention. The research model enriches the existing technology acceptance literature by extending TAM. Representing two aspects of e-resource characteristics provides greater explanatory information for diagnosing problems of system design, development, and implementation.
Santos, Arnoldo; Fernández-Friera, Leticia; Villalba, María; López-Melgar, Beatriz; España, Samuel; Mateo, Jesús; Mota, Ruben A; Jiménez-Borreguero, Jesús; Ruiz-Cabello, Jesús
Cardiovascular imaging has become an indispensable tool for patient diagnosis and follow up. Probably the wide clinical applications of imaging are due to the possibility of a detailed and high quality description and quantification of cardiovascular system structure and function. Also phenomena that involve complex physiological mechanisms and biochemical pathways, such as inflammation and ischemia, can be visualized in a non-destructive way. The widespread use and evolution of imaging would not have been possible without animal studies. Animal models have allowed for instance, (i) the technical development of different imaging tools, (ii) to test hypothesis generated from human studies and finally, (iii) to evaluate the translational relevance assessment of in vitro and ex-vivo results. In this review, we will critically describe the contribution of animal models to the use of biomedical imaging in cardiovascular medicine. We will discuss the characteristics of the most frequent models used in/for imaging studies. We will cover the major findings of animal studies focused in the cardiovascular use of the repeatedly used imaging techniques in clinical practice and experimental studies. We will also describe the physiological findings and/or learning processes for imaging applications coming from models of the most common cardiovascular diseases. In these diseases, imaging research using animals has allowed the study of aspects such as: ventricular size, shape, global function, and wall thickening, local myocardial function, myocardial perfusion, metabolism and energetic assessment, infarct quantification, vascular lesion characterization, myocardial fiber structure, and myocardial calcium uptake. Finally we will discuss the limitations and future of imaging research with animal models.
Ronovsky, Marianne; Berger, Stefanie; Molz, Barbara; Berger, Angelika; Pollak, Daniela D.
Abstract: Background Depression and schizophrenia are debilitating mental illnesses with significant socio-economic impact. The high degree of comorbidity between the two disorders, and shared symptoms and risk factors, suggest partly common pathogenic mechanisms. Supported by human and animal studies, maternal immune activation (MIA) has been intimately associated with the development of schizophrenia. However, the link between MIA and depression has remained less clear, in part due to the lack of appropriate animal models. Objective Here we aim to summarize findings obtained from studies using MIA animal models and discuss their relevance for preclinical depression research. Methods Results on molecular, cellular and behavioral phenotypes in MIA animal models were collected by literature search (PubMed) and evaluated for their significance for depression. Results Several reports on offspring depression-related behavioral alterations indicate an involvement of MIA in the development of depression later in life. Depression-related behavioral phenotypes were frequently paralleled by neurogenic and neurotrophic deficits and modulated by several genetic and environmental factors. Conclusion Literature evidence analyzed in this review supports a relevance of MIA as animal model for a specific early life adversity, which may prime an individual for the development of distinct psychopathologies later life. MIA animal models may present a unique tool for the identification of additional exogenous and endogenous factors, which are required for the manifestation of a specific neuropsychiatric disorder, such as depression, later in life. Hereby, novel insights into the molecular mechanisms involved in the pathophysiology of depression may be obtained, supporting the identification of alternative therapeutic strategies. PMID:26666733
Gopinath, Chitra; Nathar, Trupti Job; Ghosh, Arkasubhra; Hickstein, Dennis Durand; Remington Nelson, Everette Jacob
Over the past three decades, gene therapy has been making considerable progress as an alternative strategy in the treatment of many diseases. Since 2009, several studies have been reported in humans on the successful treatment of various diseases. Animal models mimicking human disease conditions are very essential at the preclinical stage before embarking on a clinical trial. In gene therapy, for instance, they are useful in the assessment of variables related to the use of viral vectors such as safety, efficacy, dosage and localization of transgene expression. However, choosing a suitable disease-specific model is of paramount importance for successful clinical translation. This review focuses on the animal models that are most commonly used in gene therapy studies, such as murine, canine, non-human primates, rabbits, porcine, and a more recently developed humanized mice. Though small and large animals both have their own pros and cons as disease-specific models, the choice is made largely based on the type and length of study performed. While small animals with a shorter life span could be well-suited for degenerative/aging studies, large animals with longer life span could suit longitudinal studies and also help with dosage adjustments to maximize therapeutic benefit. Recently, humanized mice or mouse-human chimaeras have gained interest in the study of human tissues or cells, thereby providing a more reliable understanding of therapeutic interventions. Thus, animal models are of great importance with regard to testing new vector technologies in vivo for assessing safety and efficacy prior to a gene therapy clinical trial.
Santos, Arnoldo; Fernández-Friera, Leticia; Villalba, María; López-Melgar, Beatriz; España, Samuel; Mateo, Jesús; Mota, Ruben A.; Jiménez-Borreguero, Jesús; Ruiz-Cabello, Jesús
Cardiovascular imaging has become an indispensable tool for patient diagnosis and follow up. Probably the wide clinical applications of imaging are due to the possibility of a detailed and high quality description and quantification of cardiovascular system structure and function. Also phenomena that involve complex physiological mechanisms and biochemical pathways, such as inflammation and ischemia, can be visualized in a non-destructive way. The widespread use and evolution of imaging would not have been possible without animal studies. Animal models have allowed for instance, (i) the technical development of different imaging tools, (ii) to test hypothesis generated from human studies and finally, (iii) to evaluate the translational relevance assessment of in vitro and ex-vivo results. In this review, we will critically describe the contribution of animal models to the use of biomedical imaging in cardiovascular medicine. We will discuss the characteristics of the most frequent models used in/for imaging studies. We will cover the major findings of animal studies focused in the cardiovascular use of the repeatedly used imaging techniques in clinical practice and experimental studies. We will also describe the physiological findings and/or learning processes for imaging applications coming from models of the most common cardiovascular diseases. In these diseases, imaging research using animals has allowed the study of aspects such as: ventricular size, shape, global function, and wall thickening, local myocardial function, myocardial perfusion, metabolism and energetic assessment, infarct quantification, vascular lesion characterization, myocardial fiber structure, and myocardial calcium uptake. Finally we will discuss the limitations and future of imaging research with animal models. PMID:26539113
In silico models have prompted considerable interest and debate because of their potential value in predicting the properties of chemical substances for regulatory purposes. The European REACH legislation promotes innovation and encourages the use of alternative methods, but in practice the use of in silico models is still very limited. There are many stakeholders influencing the regulatory trajectory of quantitative structure-activity relationships (QSAR) models, including regulators, industry, model developers and consultants. Here we outline some of the issues and challenges involved in the acceptance of these methods for regulatory purposes. PMID:21982269
Van Dam, Debby; De Deyn, Peter Paul
With increasing feasibility of predicting conversion of mild cognitive impairment to dementia based on biomarker profiling, the urgent need for efficacious disease-modifying compounds has become even more critical. Despite intensive research, underlying pathophysiological mechanisms remain insufficiently documented for purposeful target discovery. Translational research based on valid animal models may aid in alleviating some of the unmet needs in the current Alzheimer's disease pharmaceutical market, which includes disease-modification, increased efficacy and safety, reduction of the number of treatment unresponsive patients and patient compliance. The development and phenotyping of animal models is indeed essential in Alzheimer's disease-related research as valid models enable the appraisal of early pathological processes – which are often not accessible in patients, and subsequent target discovery and evaluation. This review paper summarizes and critically evaluates currently available animal models, and discusses their value to the Alzheimer drug discovery pipeline. Models dealt with include spontaneous models in various species, including senescence-accelerated mice, chemical and lesion-induced rodent models, and genetically modified models developed in Drosophila melanogaster, Caenorhabditis elegans, Danio rerio and rodents. Although highly valid animal models exist, none of the currently available models recapitulates all aspects of human Alzheimer's disease, and one should always be aware of the potential dangers of uncritical extrapolating from model organisms to a human condition that takes decades to develop and mainly involves higher cognitive functions. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21371009
Lee, Yi-Hsuan; Hsieh, Yi-Chuan; Hsu, Chia-Ning
This study intends to investigate factors affecting business employees' behavioral intentions to use the e-learning system. Combining the innovation diffusion theory (IDT) with the technology acceptance model (TAM), the present study proposes an extended technology acceptance model. The proposed model was tested with data collected from 552…
Miszczyk, Eliza; Walencka, Maria; Mikołajczyk-Chmiela, Magdalena
The Gram-negative bacillus Helicobacter pylori is widely recognized as a major etiologic agent responsible for chronic active gastritis, peptic ulcers, the development of gastric cancer and mucosa-associated lymphoid tissue (MALT lymphoma). Still, little is known about the natural history of H. pylori infection, since patients usually after many years of not suffering from symptoms of the infection are simply asymptomatic. Since the research investigators carried out on human models has many limitations, there is an urgent need for the development of an animal model optimal and suitable for the monitoring of H. pylori infections. This review summarizes the recent findings on the suitability of animal models used in H. pylori research. Several animal models are useful for the assessment of pathological, microbiological and immunological consequences of infection, which makes it possible to monitor the natural history of H. pylori infection. Preclinical investigations on animal models are an essential stage of research which enrich the knowledge on treatment and prevention strategies.
Abi-Nader, Khalil N; Boyd, Michael; Flake, Alan W; Mehta, Vedanta; Peebles, Donald; David, Anna L
Large animal experiments are vital in the field of prenatal gene therapy, to allow translation from small animals into man. Sheep provide many advantages for such experiments. They have been widely used in research into fetal physiology and pregnancy and the sheep fetus is a similar size to that in the human. Sheep are tolerant to in utero manipulations such as fetoscopy or even hysterotomy, and they are cheaper and easier to maintain than non-human primates. In this chapter, we describe the animal husbandry involved in generating time-mated sheep pregnancies, the large number of injection routes in the fetus that can be achieved using ultrasound or fetoscopic-guided injection, and laparotomy when these more minimally invasive routes of injection are not feasible.
Gagliardi, Christine; Bunnell, Bruce A.
The development of therapeutic interventions for genetic disorders and diseases that affect the central nervous system (CNS) has proven challenging. There has been significant progress in the development of gene therapy strategies in murine models of human disease, but gene therapy outcomes in these models do not always translate to the human setting. Therefore, large animal models are crucial to the development of diagnostics, treatments, and eventual cures for debilitating neurological disorders. This review focuses on the description of large animal models of neurological diseases such as lysosomal storage diseases, Parkinson’s disease, Huntington’s disease, and neuroAIDS. The review also describes the contributions of these models to progress in gene therapy research. PMID:19293458
Struebing, Felix L; Geisert, Eldon E
Well defined animal models facilitate the study of ocular diseases. Each model brings a unique perspective to the understanding of the disease process, and in some cases, the models are critical to the development of therapeutic approaches for treatments. This is especially the case for glaucoma. Glaucoma is a family of diseases that can be caused by very different biological processes. The one thing in common is the end result, the loss of retinal ganglion cells and blindness. In this review, we will attempt to relate the findings from a number of animal models to specific types of glaucoma, emphasizing the contributions that each of the models makes to our overall understanding of the complex collection of diseases we call glaucoma.
Cuestas, Eduardo; Caceres, Alfredo; Palacio, Santiago
Animal models of injury and repair in developing brain. Brain injury is a major contributor to neonatal morbidity and mortality, a considerable group of these children will develop long term neurological sequels. Despite the great clinical and social significance and the advances in neonatal medicine, no therapy yet does exist that prevent or decrease detrimental effects in cases of neonatal brain injury. Our objective was to review recent research in relation to the hypothesis for repair mechanism in the developing brain, based in animal models that show developmental compensatory mechanisms that promote neural and functional plasticity. A better understanding of these adaptive mechanisms will help clinicians to apply knowledge derived from animals to human clinical situations.
Meagher, Mary W; Johnson, Robin R; Vichaya, Elisabeth Good; Young, Erin E; Lunt, Shannon; Welsh, C Jane
A growing body of evidence suggests that social conflict is associated with inflammatory disease onset and exacerbations in multiple sclerosis (MS) patients and in animal models of MS. This review illustrates how animal research can be used to elucidate the biobehavioral mechanisms underlying the adverse health effects of social conflict. The authors review studies indicating that social conflict exacerbates a virally initiated animal model of MS. This research suggests that the deleterious effects of social conflict may be partially mediated by stress-induced increases in pro-inflammatory cytokine levels in the central nervous system. In addition, they provide evidence that the adverse health effects of social conflict can be prevented by blocking the stress-induced increases in cytokine activity. This suggests that interventions designed to prevent or reverse the stress-induced increases in cytokine activity may be able to prevent or reverse some of the negative health effects of social conflict in humans.
Czéh, Boldizsár; Fuchs, Eberhard; Wiborg, Ove; Simon, Mária
Major depressive disorder is a common, complex, and potentially life-threatening mental disorder that imposes a severe social and economic burden worldwide. Over the years, numerous animal models have been established to elucidate pathophysiology that underlies depression and to test novel antidepressant treatment strategies. Despite these substantial efforts, the animal models available currently are of limited utility for these purposes, probably because none of the models mimics this complex disorder fully. It is presumable that psychiatric illnesses, such as affective disorders, are related to the complexity of the human brain. Here, we summarize the animal models that are used most commonly for depression, and discuss their advantages and limitations. We discuss genetic models, including the recently developed optogenetic tools and the stress models, such as the social stress, chronic mild stress, learned helplessness, and early-life stress paradigms. Moreover, we summarize briefly the olfactory bulbectomy model, as well as models that are based on pharmacological manipulations and disruption of the circadian rhythm. Finally, we highlight common misinterpretations and often-neglected important issues in this field.
Crews, Fulton T
Human studies have found alcoholics to have a smaller brain size than moderate drinkers; however, these studies are complicated by many uncontrollable factors, including timing and amount of alcohol use. Animal experiments, which can control many factors, have established that alcohol can cause damage to brain cells (i.e., neurons), which results in their loss of structure or function (i.e., neurodegeneration) in multiple brain regions, similar to the damage found in human alcoholics. In addition, animal studies indicate that inhibition of the creation of neurons (i.e., neurogenesis) and other brain-cell genesis contributes to alcoholic neurodegeneration. Animal studies also suggest that neurodegeneration changes cognition, contributing to alcohol use disorders. Risk factors such as adolescent age and genetic predisposition toward alcohol consumption worsen neurodegeneration. Mild impairment of executive functions similar to that found in humans occurs in animals following binge alcohol treatment. Thus, animal studies suggest that heavy alcohol use contributes to neurodegeneration and the progressive loss of control over drinking. Despite the negative consequences of heavy drinking, there is hope of recovery with abstinence, which in animal models can result in neural stem-cell proliferation and the formation of new neurons and other brain cells, indicative of brain growth.
Yi, Haijin; Guo, Weiwei; Chen, Wei; Chen, Lei; Ye, Jingying; Yang, Shiming
The objective of this paper was to investigate the suitability of the miniature pig as a large animal model of cochlear implantation (CI). Micro-CT scanning and three-dimensional reconstructions of the inner ear were completed in six animals. Photographs of the procedures and measurements of the inner ear were made. The CI procedure was simulated in 10 animals. Electrically evoked auditory brain stem responses (EABRs) and radiographic images were evaluated during or after the CI procedure. Morphological examination and measurements of inner ears of the miniature pigs were completed by micro-CT scanning. The height of the scala tympani was 873.12 µm in the 1st turn, 641.46 µm in the 2nd turn, 445.13 µm in the third turn and 339.19 µm in the fourth turn. The length of the cochlea was 38.6 mm, larger than other animal models (7.2 mm in rats and 22 mm in macaque, for example) and similar to that in the human (36 mm). Commercial electrodes used in humans (870 µm at the end and 630 µm at the tip in diameter) were implanted in the pig’s cochlea, through which normal eABRs were obtained. Radiographic images after the CI procedure revealed electrodes located in the scala tympani of the first and second turns. Compared with traditional animal models, greater similarities of the inner ear between miniature pigs and humans make this animal a potentially useful model for CI studies. PMID:28078020
Mazur, J E
Three mathematical models of choice--the contextual-choice model (R. Grace, 1994), delay-reduction theory (N. Squires & E. Fantino, 1971), and a new model called the hyperbolic value-added model--were compared in their ability to predict the results from a wide variety of experiments with animal subjects. When supplied with 2 or 3 free parameters, all 3 models made fairly accurate predictions for a large set of experiments that used concurrent-chain procedures. One advantage of the hyperbolic value-added model is that it is derived from a simpler model that makes accurate predictions for many experiments using discrete-trial adjusting-delay procedures. Some results favor the hyperbolic value-added model and delay-reduction theory over the contextual-choice model, but more data are needed from choice situations for which the models make distinctly different predictions.
Hoffman, Andrew M; Dow, Steven W
Studies to evaluate the therapeutic potential of stem cells in humans would benefit from more realistic animal models. In veterinary medicine, companion animals naturally develop many diseases that resemble human conditions, therefore, representing a novel source of preclinical models. To understand how companion animal disease models are being studied for this purpose, we reviewed the literature between 2008 and 2015 for reports on stem cell therapies in dogs and cats, excluding laboratory animals, induced disease models, cancer, and case reports. Disease models included osteoarthritis, intervertebral disc degeneration, dilated cardiomyopathy, inflammatory bowel diseases, Crohn's fistulas, meningoencephalomyelitis (multiple sclerosis-like), keratoconjunctivitis sicca (Sjogren's syndrome-like), atopic dermatitis, and chronic (end-stage) kidney disease. Stem cells evaluated in these studies included mesenchymal stem-stromal cells (MSC, 17/19 trials), olfactory ensheathing cells (OEC, 1 trial), or neural lineage cells derived from bone marrow MSC (1 trial), and 16/19 studies were performed in dogs. The MSC studies (13/17) used adipose tissue-derived MSC from either allogeneic (8/13) or autologous (5/13) sources. The majority of studies were open label, uncontrolled studies. Endpoints and protocols were feasible, and the stem cell therapies were reportedly safe and elicited beneficial patient responses in all but two of the trials. In conclusion, companion animals with naturally occurring diseases analogous to human conditions can be recruited into clinical trials and provide realistic insight into feasibility, safety, and biologic activity of novel stem cell therapies. However, improvements in the rigor of manufacturing, study design, and regulatory compliance will be needed to better utilize these models. Stem Cells 2016;34:1709-1729.
Animal models are needed to assess novel proteins produced through biotechnology for potential dietary allergenicity. The exact characteristics that give certain foods allergenic potential are unclear, but must include both the potential to sensitize (induce IgE) as well as the c...
Hourihane, J. O.; Crawshaw, P. A.; Hall, M. A.
Trainees rarely see a neonatal pneumothorax because of the combination of decreased doctors' hours, the use of surfactant, and modern ventilator techniques. An animal model, using a dead rabbit, is described that could be used to train doctors and others in the management of this serious complication of neonatal care. PMID:7712271
Öz, Gülin; Tkáč, Ivan; Uğurbil, Kamil
A plethora of magnetic resonance (MR) techniques developed in the last two decades provide unique and noninvasive measurement capabilities for studies of basic brain function and brain diseases in humans. Animal model experiments have been an indispensible part of this development. MR imaging and spectroscopy measurements have been employed in animal models, either by themselves or in combination with complementary and often invasive techniques, to enlighten us about the information content of such MR methods and/or verify observations made in the human brain. They have also been employed, with or independently of human efforts, to examine mechanisms underlying pathological developments in the brain, exploiting the wealth of animal models available for such studies. In this endeavor, the desire to push for ever-higher spatial and/or spectral resolution, better signal-to-noise ratio, and unique image contrast has inevitably led to the introduction of increasingly higher magnetic fields. As a result, today, animal model studies are starting to be conducted at magnetic fields ranging from ~ 11 to 17 Tesla, significantly enhancing the armamentarium of tools available for the probing brain function and brain pathologies.
Gonzalez-Rivas, Diego; Fernández-Prado, Ricardo; Delgado, María; Fieira, Eva M.; Centeno, Alberto
We introduce the training on uniportal video-assisted thoracoscopic (VATS) lobectomy in sheep. This animal model is helpful to learn the different view, the importance of lung exposure and the key points of the instrumentation. In this article we present three videos with the left upper lobectomy, the left lower lobectomy and the right upper lobectomy in the sheep. PMID:25379206
A wide range of internationally harmonized toxicity test guidelines employing aquatic animal models have been established for regulatory use. For fish alone, there are over a dozen internationally harmonized toxicity test guidelines that have been, or are being, validated. To dat...
To characterize the optimal aerosol dosage of Brucella abortus strain 2308 (S2308) and B. melitensis (S16M) in a laboratory animal model of brucellosis, dosages of 10**3 to 10**10 CFU were nebulized to mice. Although tissue weights were minimally influenced, total colony-forming units (CFU) per tis...
Hörmannsperger, G; Schaubeck, M; Haller, D
The intestinal microbiota has long been known to play an important role in the maintenance of health. In addition, alterations of the intestinal microbiota have recently been associated with a range of immune-mediated and metabolic disorders. Characterizing the composition and functionality of the intestinal microbiota, unravelling relevant microbe-host interactions, and identifying disease-relevant microbes are therefore currently of major interest in scientific and medical communities. Experimental animal models for the respective diseases of interest are pivotal in order to address functional questions on microbe-host interaction and to clarify the clinical relevance of microbiome alterations associated with disease initiation and development. This review presents an overview of the outcomes of highly sophisticated experimental studies on microbe-host interaction in animal models of inflammatory diseases, with a focus on inflammatory bowel disease (IBD). We will address the advantages and drawbacks of analyzing microbe-host interaction in complex colonized animal models compared with gnotobiotic animal models using monoassociation, simplified microbial consortia (SMC), or microbial humanization.
Jena, Ananta Kumar
Adenosine triphosphate (ATP) is the molecular unit of intracellular energy and it is the product of oxidative phosphorylation of cellular respiration uses in cellular processes. The study explores the growth of the misconception levels amongst the learners and evaluates the effectiveness of animation model over traditional methods. The data…
Background Today, people use the Internet to satisfy health-related information and communication needs. In Malaysia, Internet use for health management has become increasingly significant due to the increase in the incidence of chronic diseases, in particular among urban women and their desire to stay healthy. Past studies adopted the Technology Acceptance Model (TAM) and Health Belief Model (HBM) independently to explain Internet use for health-related purposes. Although both the TAM and HBM have their own merits, independently they lack the ability to explain the cognition and the related mechanism in which individuals use the Internet for health purposes. Objective This study aimed to examine the influence of perceived health risk and health consciousness on health-related Internet use based on the HBM. Drawing on the TAM, it also tested the mediating effects of perceived usefulness of the Internet for health information and attitude toward Internet use for health purposes for the relationship between health-related factors, namely perceived health risk and health consciousness on health-related Internet use. Methods Data obtained for the current study were collected using purposive sampling; the sample consisted of women in Malaysia who had Internet access. The partial least squares structural equation modeling method was used to test the research hypotheses developed. Results Perceived health risk (β=.135, t 1999=2.676) and health consciousness (β=.447, t 1999=9.168) had a positive influence on health-related Internet use. Moreover, perceived usefulness of the Internet and attitude toward Internet use for health-related purposes partially mediated the influence of health consciousness on health-related Internet use (β=.025, t 1999=3.234), whereas the effect of perceived health risk on health-related Internet use was fully mediated by perceived usefulness of the Internet and attitude (β=.029, t 1999=3.609). These results suggest the central role of
FELASA recommendations for the education and training of laboratory animal technicians: category A: report of the Federation of European Laboratory Animal Science Associations Working Group on Education of Animal Technicians (Category A) accepted by the FELASA Board of Management.
Weiss Convenor, J; Bukelskiene, V; Chambrier, Ph; Ferrari, L; van der Meulen, M; Moreno, M; Mulkens, F; Sigg, H; Yates, N
The future laboratory animal technician in Europe will be provided with three different levels of education. All candidates have to start with an introductory course to reach level A0. At this level (A0) they will be able to assist in the laboratory animal facility by undertaking limited specific duties under supervision. Most A0 assistants will continue their education and training for at least one year while in full-time employment. This process will include continual assessment with the option of a final examination to become qualified at level A1. A1 represents a comprehensively educated laboratory animal technician with theoretical background knowledge and practical skills. Some of the A1 laboratory animal technicians may continue specific education for at least another year of full-time employment. They will develop knowledge and expertise as well as supervisory and basic managerial skills in order to obtain level A2.
Briz-Ponce, Laura; García-Peñalvo, Francisco José
The evolution and the growth of mobile applications ("apps") in our society is a reality. This general trend is still upward and the app use has also penetrated the medical education community. However, there is a lot of unawareness of the students' and professionals' point of view about introducing "apps" within Medical School curriculum. The aim of this research is to design, implement and verify that the Technology Acceptance Model (TAM) can be employed to measure and explain the acceptance of mobile technology and "apps" within Medical Education. The methodology was based on a survey distributed to students and medical professionals from University of Salamanca. This model explains 46.7% of behavioral intention to use mobile devise or "apps" for learning and will help us to justify and understand the current situation of introducing "apps" into the Medical School curriculum.
Ablain, Julien; Nasr, Rihab; Zhu, Jun; Bazarbachi, Ali; Lallemand-Breittenbach, Valérie; de Thé, Hugues
The relative genetic simplicity of leukaemias, the development of which likely relies on a limited number of initiating events has made them ideal for disease modelling, particularly in the mouse. Animal models provide incomparable insights into the mechanisms of leukaemia development and allow exploration of the molecular pillars of disease maintenance, an aspect often biased in cell lines or ex vivo systems. Several of these models, which faithfully recapitulate the characteristics of the human disease, have been used for pre-clinical purposes and have been instrumental in predicting therapy response in patients. We plea for a wider use of genetically defined animal models in the design of clinical trials, with a particular focus on reassessment of existing cancer or non-cancer drugs, alone or in combination.
Supsavhad, Wachiraphan; Dirksen, Wessel P; Martin, Chelsea K; Rosol, Thomas J
Head and neck squamous cell carcinoma (HNSCC) is the most common oral cancer worldwide. Local bone invasion into the maxilla or mandible and metastasis to regional lymph nodes often result in a poor prognosis, decreased quality of life and shortened survival time for HNSCC patients. Poor response to treatment and clinical outcomes are the major concerns in this aggressive cancer. Multiple animal models have been developed to replicate spontaneous HNSCC and investigate genetic alterations and novel therapeutic targets. This review provides an overview of HNSCC as well as the traditional animal models used in HNSCC preclinical research. The value and challenges of each in vivo model are discussed. Similarity between HNSCC in humans and cats and the possibility of using spontaneous feline oral squamous cell carcinoma (FOSCC) as a model for HNSCC in translational research are highlighted.
Richie, Christopher T.; Hoffer, Barry J.; Airavaara, Mikko
The identification of genes linked to neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and Parkinson's disease (PD) has led to the development of animal models for studying mechanism and evaluating potential therapies. None of the transgenic models developed based on disease-associated genes have been able to fully recapitulate the behavioral and pathological features of the corresponding disease. However, there has been enormous progress made in identifying potential therapeutic targets and understanding some of the common mechanisms of neurodegeneration. In this review, we will discuss transgenic animal models for AD, ALS, HD and PD that are based on human genetic studies. All of the diseases discussed have active or complete clinical trials for experimental treatments that benefited from transgenic models of the disease. PMID:20931247
Shaikh, A.S.; Somani, R.S.
Diabetic neuropathy (DN) is a multifactor complication of diabetes. It is a late finding in type 1 diabetes, but can be an early finding in type 2 diabetes. The cause of DN is still unclear and, like other complications of diabetes, it may be the result of various pathological conditions. Animal models and biomarkers of DN have been extensively used in neuropathic research. The most useful model of DN should exhibit the key feature present in human pathology. Diabetic rodents show behavioral, functional, structural and molecular biomarkers and they are widely used as models to investigate the etiology of DN as well as to screen the efficacy of the potential therapeutic interventions. We have reviewed the different animal models and biomarkers of neuropathy in diabetic rodents of either type 1 or type 2 diabetes. PMID:20871761
Yi, Sun Shin
Human life span has dramatically increased over several decades, and the quality of life has been considered to be equally important. However, diabetes mellitus (DM) characterized by problems related to insulin secretion and recognition has become a serious health problem in recent years that threatens human health by causing decline in brain functions and finally leading to neurodegenerative diseases. Exercise is recognized as an effective therapy for DM without medication administration. Exercise studies using experimental animals are a suitable option to overcome this drawback, and animal studies have improved continuously according to the needs of the experimenters. Since brain health is the most significant factor in human life, it is very important to assess brain functions according to the different exercise conditions using experimental animal models. Generally, there are two types of DM; insulin-dependent type 1 DM and an insulin-independent type 2 DM (T2DM); however, the author will mostly discuss brain functions in T2DM animal models in this review. Additionally, many physiopathologic alterations are caused in the brain by DM such as increased adiposity, inflammation, hormonal dysregulation, uncontrolled hyperphagia, insulin and leptin resistance, and dysregulation of neurotransmitters and declined neurogenesis in the hippocampus and we describe how exercise corrects these alterations in animal models. The results of changes in the brain environment differ according to voluntary, involuntary running exercises and resistance exercise, and gender in the animal studies. These factors have been mentioned in this review, and this review will be a good reference for studying how exercise can be used with therapy for treating DM.
Hagstrom, Danielle; Cochet-Escartin, Olivier; Zhang, Siqi; Khuu, Cindy; Collins, Eva-Maria S
Traditional toxicology testing has relied on low-throughput, expensive mammalian studies; however, timely testing of the large number of environmental toxicants requires new in vitro and in vivo platforms for inexpensive medium- to high-throughput screening. Herein, we describe the suitability of the asexual freshwater planarian Dugesia japonica as a new animal model for the study of developmental neurotoxicology. As these asexual animals reproduce by binary fission, followed by regeneration of missing body structures within approximately 1 week, development and regeneration occur through similar processes allowing us to induce neurodevelopment "at will" through amputation. This short time scale and the comparable sizes of full and regenerating animals enable parallel experiments in adults and developing worms to determine development-specific aspects of toxicity. Because the planarian brain, despite its simplicity, is structurally and molecularly similar to the mammalian brain, we are able to ascertain neurodevelopmental toxicity that is relevant to humans. As a proof of concept, we developed a 5-step semiautomatic screening platform to characterize the toxicity of 9 known neurotoxicants (consisting of common solvents, pesticides, and detergents) and a neutral agent, glucose, and quantified effects on viability, stimulated and unstimulated behavior, regeneration, and brain structure. Comparisons of our findings with other alternative toxicology animal models, such as zebrafish larvae and nematodes, demonstrated that planarians are comparably sensitive to the tested chemicals. In addition, we found that certain compounds induced adverse effects specifically in developing animals. We thus conclude that planarians offer new complementary opportunities for developmental neurotoxicology animal models.
Hagstrom, Danielle; Cochet-Escartin, Olivier; Zhang, Siqi; Khuu, Cindy; Collins, Eva-Maria S.
Traditional toxicology testing has relied on low-throughput, expensive mammalian studies; however, timely testing of the large number of environmental toxicants requires new in vitro and in vivo platforms for inexpensive medium- to high-throughput screening. Herein, we describe the suitability of the asexual freshwater planarian Dugesia japonica as a new animal model for the study of developmental neurotoxicology. As these asexual animals reproduce by binary fission, followed by regeneration of missing body structures within approximately 1 week, development and regeneration occur through similar processes allowing us to induce neurodevelopment “at will” through amputation. This short time scale and the comparable sizes of full and regenerating animals enable parallel experiments in adults and developing worms to determine development-specific aspects of toxicity. Because the planarian brain, despite its simplicity, is structurally and molecularly similar to the mammalian brain, we are able to ascertain neurodevelopmental toxicity that is relevant to humans. As a proof of concept, we developed a 5-step semiautomatic screening platform to characterize the toxicity of 9 known neurotoxicants (consisting of common solvents, pesticides, and detergents) and a neutral agent, glucose, and quantified effects on viability, stimulated and unstimulated behavior, regeneration, and brain structure. Comparisons of our findings with other alternative toxicology animal models, such as zebrafish larvae and nematodes, demonstrated that planarians are comparably sensitive to the tested chemicals. In addition, we found that certain compounds induced adverse effects specifically in developing animals. We thus conclude that planarians offer new complementary opportunities for developmental neurotoxicology animal models. PMID:26116028
Meyer, Urs; Feldon, Joram
Human epidemiological studies have provided compelling evidence that the risk of developing schizophrenia is significantly enhanced following prenatal and/or perinatal exposure to various environmental insults, including maternal exposure to stress, infection and/or immune activation, nutritional deficiencies and obstetric complications. Based on these associations, a great deal of interest has been centered upon the establishment of neurodevelopmental animal models which are based on prenatal and/or perinatal exposure to such environmental stimuli. In the present review, we describe this relatively novel class of epidemiology-based animal models in relation to the etiology, neurobiology and psychopharmacology of schizophrenia. Thereby, we discuss the general design and practical implementation of these models, and we provide an integrative summary of experimental findings derived from diverse epidemiology-based models, including models of maternal exposure to psychological stress, glucocorticoid treatment, viral infection, immune activating agents, protein deprivation, vitamin D deficiency, as well as models of obstetric complications in the form of birth by Caesarian section and perinatal/postnatal hypoxia. We highlight that the long-term consequences of prenatal exposure to these environmental challenges in animals successfully capture a broad spectrum of structural and functional brain abnormalities implicated in schizophrenia, some of which can be normalized by acute and/or chronic antipsychotic drug treatment. We thus conclude that epidemiology-driven neurodevelopmental models of schizophrenia are characterized by a high level of face, construct and predictive validity, including intrinsic etiological significance to the disorder. They also fulfill the expectation of the neurodevelopmental theory, such that the effects of prenatal environmental insults often only emerge after puberty. Epidemiologically based animal models not only provide indispensable
Vowles, Kevin E; Sowden, Gail; Ashworth, Julie
The therapeutic model underlying Acceptance and Commitment Therapy (ACT) is reasonably well-established as it applies to chronic pain. Several studies have examined measures of single ACT processes, or subsets of processes, and have almost uniformly indicated reliable relations with patient functioning. To date, however, no study has performed a comprehensive examination of the entire ACT model, including all of its component processes, as it relates to functioning. The present study performed this examination in 274 individuals with chronic pain presenting for an assessment appointment. Participants completed a battery of self-report questionnaires, assessing multiple aspects of the ACT model, as well as pain intensity, disability, and emotional distress. Initial exploratory factor analyses examined measures of the ACT model and measures of patient functioning separately with each analysis identifying three factors. Next, the fit of a model including ACT processes on the one hand and patient functioning on the other was examined using Structural Equation Modeling. Overall model fit was acceptable and indicated moderate correlations among the ACT processes themselves, as well as significant relations with pain intensity, emotional distress, and disability. These analyses build on the existing literature by providing, to our knowledge, the most comprehensive evaluation of the ACT theoretical model in chronic pain to date.
Mayer, E A; Bradesi, S; Chang, L; Spiegel, B M R; Bueller, J A; Naliboff, B D
Despite considerable efforts by academic researchers and by the pharmaceutical industry, the development of novel pharmacological treatments for irritable bowel syndrome (IBS) and other functional gastrointestinal (GI) disorders has been slow and disappointing. The traditional approach to identifying and evaluating novel drugs for these symptom-based syndromes has relied on a fairly standard algorithm using animal models, experimental medicine models and clinical trials. In the current article, the empirical basis for this process is reviewed, focusing on the utility of the assessment of visceral hypersensitivity and GI transit, in both animals and humans, as well as the predictive validity of preclinical and clinical models of IBS for identifying successful treatments for IBS symptoms and IBS-related quality of life impairment. A review of published evidence suggests that abdominal pain, defecation-related symptoms (urgency, straining) and psychological factors all contribute to overall symptom severity and to health-related quality of life. Correlations between readouts obtained in preclinical and clinical models and respective symptoms are small, and the ability to predict drug effectiveness for specific as well as for global IBS symptoms is limited. One possible drug development algorithm is proposed which focuses on pharmacological imaging approaches in both preclinical and clinical models, with decreased emphasis on evaluating compounds in symptom-related animal models, and more rapid screening of promising candidate compounds in man. PMID:17965064
Investigations of preclinical biomarkers for major depressive disorder (MDD) encompass the quantification of proteins, peptides, mRNAs, or small molecules in blood or urine of animal models. Most studies aim at characterising the animal model by including the assessment of analytes or hormones affected in depressive patients. The ultimate objective is to validate the model to better understand the neurobiological basis of MDD. Stress hormones or inflammation-related analytes associated with MDD are frequently measured. In contrast, other investigators evaluate peripheral analytes in preclinical models to translate the results in clinical settings afterwards. Large-scale, hypothesis-free studies are performed in MDD models to identify candidate biomarkers. Other studies wish to propose new targets for drug discovery. Animal models endowed with predictive validity are investigated, and the assessment of peripheral analytes, such as stress hormones or immune molecules, is comprised to increase the confidence in the target. Finally, since the mechanism of action of antidepressants is incompletely understood, studies investigating molecular alterations associated with antidepressant treatment may include peripheral analyte levels. In conclusion, preclinical biomarker studies aid the identification of new candidate analytes to be tested in clinical trials. They also increase our understanding of MDD pathophysiology and help to identify new pharmacological targets.
Oheim, R; Amling, M; Ignatius, A; Pogoda, P
Osteoporosis is a chronic systemic disease characterised by bone loss and microarchitectural deterioration. Since the underlying regulatory mechanisms are still not fully understood and treatment options are not satisfactorily resolved, massive efforts are underway to further investigate this critical illness. Large animal models are stipulated, e.g. by the Food and Drug Administration, for preclinical prevention and intervention studies related to osteoporosis research; in this context, the ewe has already proven its value for orthopaedic research. Although oestrogen deficiency doubtless influences bone metabolism in sheep, the ovariectomised ewe seems unsuitable as a model for postmenopausal osteoporosis and bone loss induction due to its unreliable impact on bone mass and structure. In contrast, glucocorticoid treatment has a major impact on bone turnover and leads to bone conditions comparable to those found in steroid-treated humans. However, adverse side effects can be dramatic resulting in unacceptable discomfort and illness of the experimental animals. Further improvements are therefore essential to judge this model as ethically appropriate. Additionally, models for osteoporosis induced by surgical interventions of central regulatory mechanisms seem to be attractive, as remarkable bone loss is induced by only one surgical procedure without any further treatment. Taken together, different ewe models for osteoporosis have been successfully established and are invaluable for orthopaedic research. However, the search for a 'perfect' large remodelling animal model - in terms of mimicking the human disease and compatibility of bone loss, and without ethical concerns - is still on-going.
Simmons, Sarah B.; Pierson, Emily R.; Lee, Sarah Y.; Goverman, Joan M.
Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system manifested with varying clinical course, pathology, and inflammatory patterns. There are multiple animal models that reflect different aspects of this heterogeneity. Collectively, these models reveal a balance between pathogenic and regulatory CD4+ T cells, CD8+ T cells and B cells that influences the incidence, timing, and severity of central nervous system autoimmunity. In this review we discuss experimental autoimmune encephalomyelitis (EAE) models that have been used to study the pathogenic and regulatory roles of these immune cells, models that recapitulate different aspects of the disease seen in patients with MS, and questions remaining for future studies. PMID:23707039
Reinwald, Susan; Burr, David
Large animal models are required for preclinical prevention and intervention studies related to osteoporosis research. The challenging aspect of this requirement is that no single animal model exactly mimics the progression of this human-specific chronic condition. There are pros and cons associated with the skeletal, hormonal, and metabolic conditions of each species that influence their relevance and applicability to human physiology. Of all larger mammalian species, nonhuman primates (NHPs) are preeminent in terms of replicating important aspects of human physiology. However, NHPs are very expensive, putting them out of reach of the vast majority of researchers. Practical, cost-effective alternatives to NHPs are sought after among ungulate (porcine, caprine, and ovine) and canine species that are the focus of this review. The overriding caveat to using large lower-order species is to take the time in advance to understand and appreciate the limitations and strengths of each animal model. Under these circumstances, experiments can be strategically designed to optimize the potential of an animal to develop the cardinal features of postmenopausal bone loss and/or yield information of relevance to treatment. PMID:18505374
Kollias, Christina M; Huneke, Richard B; Wigdahl, Brian; Jennings, Stephen R
Herpes simplex viruses are ubiquitous human pathogens represented by two distinct serotypes: herpes simplex virus (HSV) type 1 (HSV-1); and HSV type 2 (HSV-2). In the general population, adult seropositivity rates approach 90% for HSV-1 and 20-25% for HSV-2. These viruses cause significant morbidity, primarily as mucosal membrane lesions in the form of facial cold sores and genital ulcers, with much less common but more severe manifestations causing death from encephalitis. HSV infections in humans are difficult to study in many cases because many primary infections are asymptomatic. Moreover, the neurotropic properties of HSV make it much more difficult to study the immune mechanisms controlling reactivation of latent infection within the corresponding sensory ganglia and crossover into the central nervous system of infected humans. This is because samples from the nervous system can only be routinely obtained at the time of autopsy. Thus, animal models have been developed whose use has led to a better understanding of multiple aspects of HSV biology, molecular biology, pathogenesis, disease, and immunity. The course of HSV infection in a spectrum of animal models depends on important experimental parameters including animal species, age, and genotype; route of infection; and viral serotype, strain, and dose. This review summarizes the animal models most commonly used to study HSV pathogenesis and its establishment, maintenance, and reactivation from latency. It focuses particularly on the immune response to HSV during acute primary infection and the initial invasion of the ganglion with comparisons to the events governing maintenance of viral latency.
Lelovas, Pavlos P; Xanthos, Theodoros T; Thoma, Sofia E; Lyritis, George P; Dontas, Ismene A
Osteoporosis is an important systemic disorder, affecting mainly Caucasian women, with a diverse and multifactorial etiology. A large variety of animal species, including rodents, rabbits, dogs, and primates, have been used as animal models in osteoporosis research. Among these, the laboratory rat is the preferred animal for most researchers. Its skeleton has been studied extensively, and although there are several limitations to its similarity to the human condition, these can be overcome through detailed knowledge of its specific traits or with certain techniques. The rat has been used in many experimental protocols leading to bone loss, including hormonal interventions (ovariectomy, orchidectomy, hypophysectomy, parathyroidectomy), immobilization, and dietary manipulations. The aim of the current review is not only to present the ovariectomized rat and its advantages as an appropriate model for the research of osteoporosis, but also to provide information about the most relevant age and bone site selection according to the goals of each experimental protocol. In addition, several methods of bone mass evaluation are assessed, such as biochemical markers, densitometry, histomorphometry, and bone mechanical testing, that are used for monitoring and evaluation of this animal model in preventive or therapeutic strategies for osteoporosis. PMID:19004367
Williams, Jacqueline P.; Brown, Stephen L.; Georges, George E.; Hauer-Jensen, Martin; Hill, Richard P.; Huser, Amy K.; Kirsch, David G.; MacVittie, Thomas J.; Mason, Kathy A.; Medhora, Meetha M.; Moulder, John E.; Okunieff, Paul; Otterson, Mary F.; Robbins, Michael E.; Smathers, James B.; McBride, William H.
Since September 11, 2001, there has been the recognition of a plausible threat from acts of terrorism, including radiological or nuclear attacks. A network of Centers for Medical Countermeasures against Radiation (CMCRs) has been established across the U.S.; one of the missions of this network is to identify and develop mitigating agents that can be used to treat the civilian population after a radiological event. The development of such agents requires comparison of data from many sources and accumulation of information consistent with the “Animal Rule” from the Food and Drug Administration (FDA). Given the necessity for a consensus on appropriate animal model use across the network to allow for comparative studies to be performed across institutions, and to identify pivotal studies and facilitate FDA approval, in early 2008, investigators from each of the CMCRs organized and met for an Animal Models Workshop. Working groups deliberated and discussed the wide range of animal models available for assessing agent efficacy in a number of relevant tissues and organs, including the immune and hematopoietic systems, gastrointestinal tract, lung, kidney and skin. Discussions covered the most appropriate species and strains available as well as other factors that may affect differential findings between groups and institutions. This report provides the workshop findings. PMID:20334528
Zheng, Hua-Chuan; Takano, Yasuo
The incidence of lung adenocarcinoma has been remarkably increasing in recent years due to the introduction of filter cigarettes and secondary-hand smoking because the people are more exposed to higher amounts of nitrogen oxides, especially 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK), which is widely applied in animal model of lung tumors. In NNK-induced lung tumors, genetic mutation, chromosome instability, gene methylation, and activation of oncogenes have been found so as to disrupt the expression profiles of some proteins or enzymes in various cellular signal pathways. Transgenic animal with specific alteration of lung cancer-related molecules have also been introduced to clarify the molecular mechanisms of NNK in the pathogenesis and development of lung tumors. Based on these animal models, many antioxidant ingredients and antitumor chemotherapeutic agents have been proved to suppress the NNK-induced lung carcinogenesis. In the future, it is necessary to delineate the most potent biomarkers of NNK-induced lung tumorigenesis, and to develop efficient methods to fight against NNK-associated lung cancer using animal models. PMID:21559252
Nakayama, Eri; Saijo, Masayuki
Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics. PMID:24046765
Goes, Tiago Costa; Antunes, Fabrício Dias; Teixeira-Silva, Flavia
It is believed that subjects with high trait anxiety levels tend to present state anxiety reactions with greater intensity than individuals with low trait anxiety levels. In order to verify if this premise is valid for animal models of anxiety, the present work investigated the possible correlation between two behavioral tests: the elevated plus-maze, a classic model of state-anxiety, and the free-exploratory paradigm, which has been proposed as a model of trait anxiety. The behavior of 46 drug-naive, adult, Wistar, male rats was measured in these two models on two occasions, 1 week apart. Subsequently, the intraclass correlation coefficient (ICC) was calculated for the parameters "percentage of time in the novel side" (%TNS; free-exploratory paradigm), "percentage of time in the open arms" (%TOA; elevated plus-maze) and "percentage of entries into the open arms" (%EOA; elevated plus-maze). These parameters were also used to classify the animals into groups presenting high, medium or low levels of anxiety in both tests, so that the concordance between the models could be evaluated through the kappa test. The analysis resulted in low ICC (%TNSx%TOA: -0.127; %TNSx%EOA: 0.040) and low kappa index (%TNSx%TOA: -0.017; %TNSx%EOA: -0.044), suggesting a poor correspondence between the free-exploratory paradigm and the elevated plus-maze. In conclusion, the data presented here indicate that the premise of correlation between trait and state anxiety is not necessarily true for animal models of anxiety and, therefore, care must be exercised when using state anxiety models in order to determine animals' anxiety profile.
Cellini, L; Marzio, L; Ferrero, G; Del Vino, A; Di Campli, E; Grossi, L; Toracchio, S; Artese, L
An experimental murine model was studied to evaluate the orogastrointestinal colonization of Helicobacter pylori and the animal-to-animal transmission. Balb/C mice were infected with H. pylori and housed with uninoculated mice in cages with and without a grate on the floor. Mice were killed after 7, 14, 30, and 45 days, and samples from the esophagus, stomach, small intestine, colon, and rectum were analyzed for H. pylori by PCR and immunohistochemistry and for histological changes. Bacterial colonization was assessed also by culture from stomach samples. H. pylori was cultured by stomach samples of infected mice at 7, 14, and 30 days. Using PCR and immunohistochemistry, H. pylori was detected in inoculated and uninoculated mice in all areas examined, with an high percentage of positive samples in the esophagus and stomach. Moreover transmission was detected, without differences, regardless of whether mice were housed with or without a grate on the floor, supporting an orooral animal transmission.
The use of animals as experimental organisms has been critical to the development of addiction research from the nineteenth century. They have been used as a means of generating reliable data regarding the processes of addiction that was not available from the study of human subjects. Their use, however, has been far from straightforward. Through focusing on the study of alcoholism, where the nonhuman animal proved a most reluctant collaborator, this paper will analyze the ways in which scientists attempted to deal with its determined sobriety and account for their consistent failure to replicate the volitional consumption of ethanol to the point of physical dependency. In doing so, we will see how the animal model not only served as a means of interrogating a complex pathology, but also came to embody competing definitions of alcoholism as a disease process, and alternative visions for the very structure and purpose of a research field.
Ramírez-Sandoval, Roxana; Luévano-Rodríguez, Nayeli; Rodríguez-Rodríguez, Mayra; Pérez-Pérez, María Elena; Saldívar-Elias, Sergio; Gurrola-Carlos, Reinaldo; Avalos-Díaz, Esperanza; Bollain-y-Goytia, Juan José; Herrera-Esparza, Rafael
Autoimmune nephritis triggered by metallic ions was assessed in a Long-Evans rat model. The parameters evaluated included antinuclear autoantibody production, kidney damage mediated by immune complexes detected by immunofluorescence, and renal function tested by retention of nitrogen waste products and proteinuria. To accomplish our goal, the animals were treated with the following ionic metals: HgCl2, CuSO4, AgNO3, and Pb(NO3)2. A group without ionic metals was used as the control. The results of the present investigation demonstrated that metallic ions triggered antinuclear antibody production in 60% of animals, some of them with anti-DNA specificity. Furthermore, all animals treated with heavy metals developed toxic glomerulonephritis with immune complex deposition along the mesangium and membranes. These phenomena were accompanied by proteinuria and increased concentrations of urea. Based on these results, we conclude that metallic ions may induce experimental autoimmune nephritis.
Tsukiyama-Kohara, Kyoko; Kohara, Michinori
Tupaias, or tree shrews, are small mammals that are similar in appearance to squirrels. The morphological and behavioral characteristics of the group have been extensively characterized, and despite previously being classified as primates, recent studies have placed the group in its own family, the Tupaiidae. Genomic analysis has revealed that the genus Tupaia is closer to humans than it is to rodents. In addition, tupaias are susceptible to hepatitis B virus and hepatitis C virus. The only other experimental animal that has been demonstrated to be sensitive to both of these viruses is the chimpanzee, but restrictions on animal testing have meant that experiments using chimpanzees have become almost impossible. Consequently, the development of the tupaia for use as an animal infection model could become a powerful tool for hepatitis virus research and in preclinical studies on drug development. PMID:25048261
The use of animals as experimental organisms has been critical to the development of addiction research from the nineteenth century. They have been used as a means of generating reliable data regarding the processes of addiction that was not available from the study of human subjects. Their use, however, has been far from straightforward. Through focusing on the study of alcoholism, where the nonhuman animal proved a most reluctant collaborator, this paper will analyze the ways in which scientists attempted to deal with its determined sobriety and account for their consistent failure to replicate the volitional consumption of ethanol to the point of physical dependency. In doing so, we will see how the animal model not only served as a means of interrogating a complex pathology, but also came to embody competing definitions of alcoholism as a disease process, and alternative visions for the very structure and purpose of a research field. PMID:25740698
Tsubokawa, Daigo; Sugiyama, Hiromu; Mikami, Fusako; Shibata, Katsumasa; Shibahara, Toshiyuki; Fukuda, Koichi; Takamiya, Shinzaburo; Yamasaki, Hiroshi; Nakamura, Takeshi; Tsuji, Naotoshi
Although observing the eggs of human parasitic helminth is essential for medical education in parasitology, opportunities for collection of the eggs are limited. Collection of the eggs using experimental animal models is needed for a sustainable supply. The metacercariae of three trematode species, Paragonimus westermani, Clonorchis sinensis and Metagonimus yokogawai, were collected from the second intermediate hosts: freshwater crabs and fishes, which were obtained using online shopping in Japan, and inoculated to experimental animal rat and dog. Consequently, eggs of the three trematode species were obtained abundantly from the feces of the animals. The eggs are being used for student training in several Japanese universities. In this article, we introduce the collection procedures for trematode eggs.
Wu, Xiaoyu; Gao, Yuan
This paper applies the extended technology acceptance model (exTAM) in information systems research to the use of clickers in student learning. The technology acceptance model (TAM) posits that perceived ease of use and perceived usefulness of technology influence users' attitudes toward using and intention to use technology. Research subsequent…
Jackson, Mark P; Rahman, Asif; Lafon, Belen; Kronberg, Gregory; Ling, Doris; Parra, Lucas C; Bikson, Marom
The objective of this review is to summarize the contribution of animal research using direct current stimulation (DCS) to our understanding of the physiological effects of transcranial direct current stimulation (tDCS). We comprehensively address experimental methodology in animal studies, broadly classified as: (1) transcranial stimulation; (2) direct cortical stimulation in vivo and (3) in vitro models. In each case advantages and disadvantages for translational research are discussed including dose translation and the overarching "quasi-uniform" assumption, which underpins translational relevance in all animal models of tDCS. Terminology such as anode, cathode, inward current, outward current, current density, electric field, and uniform are defined. Though we put key animal experiments spanning decades in perspective, our goal is not simply an exhaustive cataloging of relevant animal studies, but rather to put them in context of ongoing efforts to improve tDCS. Cellular targets, including excitatory neuronal somas, dendrites, axons, interneurons, glial cells, and endothelial cells are considered. We emphasize neurons are always depolarized and hyperpolarized such that effects of DCS on neuronal excitability can only be evaluated within subcellular regions of the neuron. Findings from animal studies on the effects of DCS on plasticity (LTP/LTD) and network oscillations are reviewed extensively. Any endogenous phenomena dependent on membrane potential changes are, in theory, susceptible to modulation by DCS. The relevance of morphological changes (galvanotropy) to tDCS is also considered, as we suggest microscopic migration of axon terminals or dendritic spines may be relevant during tDCS. A majority of clinical studies using tDCS employ a simplistic dose strategy where excitability is singularly increased or decreased under the anode and cathode, respectively. We discuss how this strategy, itself based on classic animal studies, cannot account for the
Flores, Gonzalo; Morales-Medina, Julio César; Diaz, Alfonso
Schizophrenia, a severe and debilitating disorder with a high social burden, affects 1% of the adult world population. Available therapies are unable to treat all the symptoms, and result in strong side effects. For this reason, numerous animal models have been generated to elucidate the pathophysiology of this disorder. All these models present neuronal remodeling and abnormalities in spine stability. It is well known that the complexity in dendritic arborization determines the number of receptive synaptic contacts. Also the loss of dendritic spines and arbor stability are strongly associated with schizophrenia. This review evaluates changes in spine density and dendritic arborization in animal models of schizophrenia. By understanding these changes, pharmacological treatments can be designed to target specific neural systems to attenuate neuronal remodeling and associated behavioral deficits.
Ibrahim, Samar H.; Hirsova, Petra; Malhi, Harmeet; Gores, Gregory J.
With the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become a public health problem with increasing prevalence. The mechanism of disease progression remains obscure and effective therapy is lacking. Therefore, there is a need to understand the pathogenic mechanisms responsible for disease development and progression in order to develop innovative therapies. To accomplish this goal, experimental animal models that recapitulate the human disease are necessary, especially, since causative mechanistic studies of NAFLD are more difficult or unethical to perform in humans. A large number of studies regarding the pathophysiology and treatment of NASH have been undertaken in mice to model human NAFLD and nonalcoholic steatohepatitis (NASH). This review discusses the known dietary, genetic and inflammation based animal models of NASH described in recent years, with a focus on the major advances made in this field. PMID:26626909
Klopfleisch, R; Olias, P
Haemochromatosis is one of the most common human hereditary diseases. It is defined as a pathological condition with normal iron-driven erythropoiesis, but toxic accumulation of iron in vital organs, which is caused by mutations in any gene that encodes a protein involved in limiting the entry of iron into the blood. Iron storage diseases have also been described in several mammalian and avian species and these have been proposed as comparative animal models for human haemochromatosis. Genetically engineered mouse strains with mutations in iron metabolism genes model several aspects of human haemochromatosis and study of these animals has facilitated understanding of the disease. Spontaneously arising iron storage diseases in non-murine species also overlap in some clinicopathological aspects with human haemochromatosis. However, the lack of conclusive information on the molecular biology of theses species-specific diseases and the common impact of dietary iron concentration on disease progression in most species limit their usefulness as comparative models.
Tian, David H.; Perera, Chamini J.; Moalem-Taylor, Gila
Neuropathic pain is a frequent chronic presentation in autoimmune diseases of the nervous system, such as multiple sclerosis (MS) and Guillain-Barre syndrome (GBS), causing significant individual disablement and suffering. Animal models of experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune neuritis (EAN) mimic many aspects of MS and GBS, respectively, and are well suited to study the pathophysiology of these autoimmune diseases. However, while much attention has been devoted to curative options, research into neuropathic pain mechanisms and relief has been somewhat lacking. Recent studies have demonstrated a variety of sensory abnormalities in different EAE and EAN models, which enable investigations of behavioural changes, underlying mechanisms, and potential pharmacotherapies for neuropathic pain associated with these diseases. This review examines the symptoms, mechanisms, and clinical therapeutic options in these conditions and highlights the value of EAE and EAN animal models for the study of neuropathic pain in MS and GBS. PMID:23737643
Fickert, Peter; Pollheimer, Marion J; Beuers, Ulrich; Lackner, Carolin; Hirschfield, Gideon; Housset, Chantal; Keitel, Verena; Schramm, Christoph; Marschall, Hanns-Ulrich; Karlsen, Tom H; Melum, Espen; Kaser, Arthur; Eksteen, Bertus; Strazzabosco, Mario; Manns, Michael; Trauner, Michael
Primary sclerosing cholangitis (PSC) is a chronic cholangiopathy characterized by biliary fibrosis, development of cholestasis and end stage liver disease, high risk of malignancy, and frequent need for liver transplantation. The poor understanding of its pathogenesis is also reflected in the lack of effective medical treatment. Well-characterized animal models are utterly needed to develop novel pathogenetic concepts and study new treatment strategies. Currently there is no consensus on how to evaluate and characterize potential PSC models, which makes direct comparison of experimental results and effective exchange of study material between research groups difficult. The International Primary Sclerosing Cholangitis Study Group (IPSCSG) has therefore summarized these key issues in a position paper proposing standard requirements for the study of animal models of PSC.
Chiu, Chong-Chi; Liao, Yi-En; Yang, Ling-Yu; Wang, Jing-Ya; Tweedie, David; Karnati, Hanuma K.; Greig, Nigel H.; Wang, Jia-Yi
Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. Neuroinflammation is prominent in the short and long-term consequences of neuronal injuries that occur after TBI. Neuroinflammation involves the activation of glia, including microglia and astrocytes, to release inflammatory mediators within the brain, and the subsequent recruitment of peripheral immune cells. Various animal models of TBI have been developed that have proved valuable to elucidate the pathophysiology of the disorder and to assess the safety and efficacy of novel therapies prior to clinical trials. These models provide an excellent platform to delineate key injury mechanisms that associate with types of injury (concussion, contusion, and penetration injuries) that occur clinically for the investigation of mild, moderate, and severe forms of TBI. Additionally, TBI modeling in genetically engineered mice, in particular, has aided the identification of key molecules and pathways for putative injury mechanisms, as targets for development of novel therapies for human TBI. This Review details the evidence showing that neuroinflammation, characterized by the activation of microglia and astrocytes and elevated production of inflammatory mediators, is a critical process occurring in various TBI animal models, provides a broad overview of commonly used animal models of TBI, and overviews representative techniques to quantify markers of the brain inflammatory process. A better understanding of neuroinflammation could open therapeutic avenues for abrogation of secondary cell death and behavioral symptoms that may mediate the progression of TBI. PMID:27382003
Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by the three cardinal pathological features, comprising aberrant immune activation, vasculopathy and tissue fibrosis, with unknown etiology. Although many inducible and genetic animal models mimicking the selected aspects of SSc have been well documented, the lack of models encompassing the full clinical manifestations hindered the development and preclinical testing of therapies against this disease. Under this situation, three new genetic animal models have recently been established, such as Fra2 transgenic mice, urokinase-type plasminogen activator receptor deficient mice and Klf5(+/-) ;Fli1(+/-) mice, all of which recapitulate the pathological cascade of SSc. The former two murine models demonstrate endothelial cell apoptosis and capillary loss followed by tissue fibrosis, whereas the immune systems show no remarkable abnormality. Klf5(+/-) ;Fli1(+/-) mice develop immune activation, vasculopathy and tissue fibrosis in this sequence, eventually resulting in the development of dermal fibrosis, interstitial lung disease and pulmonary vascular involvement resembling those of SSc. Because Krueppel-like factor (KLF)5 and Friend leukemia integration 1 transcription factor (Fli1) are the transcription factors epigenetically suppressed in SSc dermal fibroblasts, the reproduction of SSc manifestations in Klf5(+/-) ;Fli1(+/-) mice supports the canonical idea that environmental influences play a central role in the development of SSc in genetically predisposed individuals. These new animal models offer important clues for the better understanding of the underlying molecular mechanisms of SSc pathology and the identification of potential molecular targets for the treatment of this incurable disease.
Bellavite, Paolo; Ortolani, Riccardo; Conforti, Anita
A search of the literature and the experiments carried out by the authors of this review show that there are a number of animal models where the effect of homeopathic dilutions or the principles of homeopathic medicine have been tested. The results relate to the immunostimulation by ultralow doses of antigens, the immunological models of the ‘simile’, the regulation of acute or chronic inflammatory processes and the use of homeopathic medicines in farming. The models utilized by different research groups are extremely etherogeneous and differ as the test medicines, the dilutions and the outcomes are concerned. Some experimental lines, particularly those utilizing mice models of immunomodulation and anti-inflammatory effects of homeopathic complex formulations, give support to a real effect of homeopathic high dilutions in animals, but often these data are of preliminary nature and have not been independently replicated. The evidence emerging from animal models is supporting the traditional ‘simile’ rule, according to which ultralow doses of compounds, that in high doses are pathogenic, may have paradoxically a protective or curative effect. Despite a few encouraging observational studies, the effectiveness of the homeopathic prevention or therapy of infections in veterinary medicine is not sufficiently supported by randomized and controlled trials. PMID:16786046
Poi, Sharon (Inventor); Bell, Brad N. (Inventor)
The invention is directed toward a method and apparatus for generating an animated sequence through the movement of three-dimensional graphical models. A plurality of pre-defined graphical models are stored and manipulated in response to interactive commands or by means of a pre-defined command file. The models may be combined as part of a hierarchical structure to represent physical systems without need to create a separate model which represents the combined system. System motion is simulated through the introduction of translation, rotation and scaling parameters upon a model within the system. The motion is then transmitted down through the system hierarchy of models in accordance with hierarchical definitions and joint movement limitations. The present invention also calls for a method of editing hierarchical structure in response to interactive commands or a command file such that a model may be included, deleted, copied or moved within multiple system model hierarchies. The present invention also calls for the definition of multiple viewpoints or cameras which may exist as part of a system hierarchy or as an independent camera. The simulated movement of the models and systems is graphically displayed on a monitor and a frame is recorded by means of a video controller. Multiple movement and hierarchy manipulations are then recorded as a sequence of frames which may be played back as an animation sequence on a video cassette recorder.
Mavanji, Vijayakumar; Billington, Charles J; Kotz, Catherine M; Teske, Jennifer A
The rapid rise in obesity prevalence in the modern world parallels a significant reduction in restorative sleep (Agras et al., 2004; Dixon et al., 2007, 2001; Gangwisch and Heymsfield, 2004; Gupta et al., 2002; Sekine et al., 2002; Vioque et al., 2000; Wolk et al., 2003). Reduced sleep time and quality increases the risk for obesity, but the underlying mechanisms remain unclear (Gangwisch et al., 2005; Hicks et al., 1986; Imaki et al., 2002; Jennings et al., 2007; Moreno et al., 2006). A majority of the theories linking human sleep disturbances and obesity rely on self-reported sleep. However, studies with objective measurements of sleep/wake parameters suggest a U-shaped relationship between sleep and obesity. Studies in animal models are needed to improve our understanding of the association between sleep disturbances and obesity. Genetic and experimenter-induced models mimicking characteristics of human obesity are now available and these animal models will be useful in understanding whether sleep disturbances determine propensity for obesity, or result from obesity. These models exhibit weight gain profiles consistently different from control animals. Thus a careful evaluation of animal models will provide insight into the relationship between sleep disturbances and obesity in humans. In this review we first briefly consider the fundamentals of sleep and key sleep disturbances, such as sleep fragmentation and excessive daytime sleepiness (EDS), observed in obese individuals. Then we consider sleep deprivation studies and the role of circadian alterations in obesity. We describe sleep/wake changes in various rodent models of obesity and obesity resistance. Finally, we discuss possible mechanisms linking sleep disturbances with obesity.
An, Ji-Young; Hayman, Laura L; Panniers, Teresa; Carty, Barbara
About 110 million American adults are looking for health information and services on the Internet. Identification of the factors influencing healthcare consumers' technology acceptance is requisite to understanding their acceptance and usage behavior of online health information and related services. The purpose of this article is to describe the development of the Information and Communication Technology Acceptance Model (ICTAM). From the literature reviewed, ICTAM was developed with emphasis on integrating multidisciplinary perspectives from divergent frameworks and empirical findings into a unified model with regard to healthcare consumers' acceptance and usage behavior of information and services on the Internet.
Silva, Afonso C.; Liu, Junjie V.; Hirano, Yoshiyuki; Leoni, Renata F.; Merkle, Hellmut; Mackel, Julie B.; Zhang, Xian Feng; Nascimento, George C.; Stefanovic, Bojana
Functional magnetic resonance imaging (fMRI) has had an essential role in furthering our understanding of brain physiology and function. fMRI techniques are nowadays widely applied in neuroscience research, as well as in translational and clinical studies. The use of animal models in fMRI studies has been fundamental in helping elucidate the mechanisms of cerebral blood flow regulation, and in the exploration of basic neuroscience questions, such as the mechanisms of perception, behavior, and cognition. Because animals are inherently noncompliant, most fMRI performed to date have required the use of anesthesia, which interferes with brain function and compromises interpretability and applicability of results to our understanding of human brain function. An alternative approach that eliminates the need for anesthesia involves training the animal to tolerate physical restraint during the data acquisition. In the present work we review these two different approaches to obtaining fMRI data from animal models, with a specific focus on the acquisition of longitudinal data from the same subjects. PMID:21279608
Becker, Jill B.
The purpose of this review is to discuss ways to think about and study sex differences in preclinical animal models. We use the framework of addiction, in which animal models have excellent face and construct validity, to illustrate the importance of considering sex differences. There are four types of sex differences: qualitative, quantitative, population, and mechanistic. A better understanding of the ways males and females can differ will help scientists design experiments to characterize better the presence or absence of sex differences in new phenomena that they are investigating. We have outlined major quantitative, population, and mechanistic sex differences in the addiction domain using a heuristic framework of the three established stages of the addiction cycle: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. Female rats, in general, acquire the self-administration of drugs and alcohol more rapidly, escalate their drug taking with extended access more rapidly, show more motivational withdrawal, and (where tested in animal models of “craving”) show greater reinstatement. The one exception is that female rats show less motivational withdrawal to alcohol. The bases for these quantitative sex differences appear to be both organizational, in that estradiol-treated neonatal animals show the male phenotype, and activational, in that the female phenotype depends on the effects of gonadal hormones. In animals, differences within the estrous cycle can be observed but are relatively minor. Such hormonal effects seem to be most prevalent during the acquisition of drug taking and less influential once compulsive drug taking is established and are linked largely to progesterone and estradiol. This review emphasizes not only significant differences in the phenotypes of females and males in the domain of addiction but emphasizes the paucity of data to date in our understanding of those differences. PMID:26772794
Rush, Catherine M.; Govan, Brenda L.; Sikder, Suchandan; Williams, Natasha L.; Ketheesan, Natkunam
Rheumatic fever (RF) and rheumatic heart disease (RHD) are sequelae of group A streptococcal (GAS) infection. Although an autoimmune process has long been considered to be responsible for the initiation of RF/RHD, it is only in the last few decades that the mechanisms involved in the pathogenesis of the inflammatory condition have been unraveled partly due to experimentation on animal models. RF/RHD is a uniquely human condition and modeling this disease in animals is challenging. Antibody and T cell responses to recombinant GAS M protein (rM) and the subsequent interactions with cardiac tissue have been predominantly investigated using a rat autoimmune valvulitis model. In Lewis rats immunized with rM, the development of hallmark histological features akin to RF/RHD, both in the myocardial and in valvular tissue have been reported, with the generation of heart tissue cross-reactive antibodies and T cells. Recently, a Lewis rat model of Sydenham’s chorea and related neuropsychiatric disorders has also been described. Rodent models are very useful for assessing disease mechanisms due to the availability of reagents to precisely determine sequential events following infection with GAS or post-challenge with specific proteins and or carbohydrate preparations from GAS. However, studies of cardiac function are more problematic in such models. In this review, a historical overview of animal models previously used and those that are currently available will be discussed in terms of their usefulness in modeling different aspects of the disease process. Ultimately, cardiologists, microbiologists, immunologists, and physiologists may have to resort to diverse models to investigate different aspects of RF/RHD. PMID:25414841
Tarhini, Ali; Hone, Kate; Liu, Xiaohui
The success of an e-learning intervention depends to a considerable extent on student acceptance and use of the technology. Therefore, it has become imperative for practitioners and policymakers to understand the factors affecting the user acceptance of e-learning systems in order to enhance the students' learning experience. Based on an extended…
Sanches, Sheila Cristina L.; Ramalho, Leandra Naira Z.; Augusto, Marlei Josiele; da Silva, Deisy Mara; Ramalho, Fernando Silva
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, which occurs in the absence of alcohol abuse. NAFLD can evolve into progressive liver injury and fibrosis in the form of nonalcoholic steatohepatitis (NASH). Several animal models have been developed to attempt to represent the morphological, biochemical, and clinical features of human NASH. The actual review presents a critical analysis of the most commonly used experimental models of NAFLD/NASH development. These models can be classified into genetic, nutritional, and a combination of genetic and nutritional factors. The main genetic models are ob/ob and db/db mutant mice and Zucker rats. The principal nutritional models employ methionine- and choline-deficient, high-fat, high-cholesterol and high-cholate, cafeteria, and high-fructose diets. Currently, associations between high-fructose and various compositions of high-fat diets have been widely studied. Previous studies have encountered significant difficulties in developing animal models capable of reproducing human NASH. Some models produce consistent morphological findings, but the induction method differs significantly compared with the pathophysiology of human NASH. Other models precisely represent the clinical and etiological contexts of this disease but fail to provide accurate histopathological representations mainly in the progression from steatosis to liver fibrosis. PMID:26064924
Strickland, Justin C; Smith, Mark A
Social learning theories of drug abuse propose that individuals imitate drug use behaviors modeled by social peers, and that these behaviors are selectively reinforced and/or punished depending on group norms. Historically, animal models of social influence have focused on distal factors (i.e., those factors outside the drug-taking context) in drug self-administration studies. Recently, several investigators have developed novel models, or significantly modified existing models, to examine the role of proximal factors (i.e., those factors that are immediately present at the time of drug taking) on measures of drug self-administration. Studies using these newer models have revealed several important conclusions regarding the effects of social learning on drug abuse: 1) the presence of a social partner influences drug self-administration, 2) the behavior of a social partner determines whether social contact will increase or decrease drug intake, and 3) social partners can model and imitate specific patterns of drug self-administration. These findings are congruent with those obtained in the human laboratory, providing support for the cross-species generality and validity of these preclinical models. This mini-review describes in detail some of the preclinical animal models used to study social contact and drug self-administration to guide future research on social learning and drug abuse.
Peterson, Mark E
Since first discovered just 35 years ago, the incidence of spontaneous feline hyperthyroidism has increased dramatically to the extent that it is now one of the most common disorders seen in middle-aged to senior domestic cats. Hyperthyroid cat goiters contain single or multiple autonomously (i.e. TSH-independent) functioning and growing thyroid nodules. Thus, hyperthyroidism in cats is clinically and histologically similar to toxic nodular goiter in humans. The disease in cats is mechanistically different from Graves' disease, because neither the hyperfunction nor growth of these nodules depends on extrathyroidal circulating stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells, but iodine deficiency, other nutritional goitrogens, or environmental disruptors may play a role in the disease pathogenesis. Clinical features of feline toxic nodular goiter include one or more palpable thyroid nodules, together with signs of hyperthyroidism (e.g. weight loss despite an increased appetite). Diagnosis of feline hyperthyroidism is confirmed by finding the increased serum concentrations of thyroxine and triiodothyronine, undetectable serum TSH concentrations, or increased thyroid uptake of radioiodine. Thyroid scintigraphy demonstrates a heterogeneous pattern of increased radionuclide uptake, most commonly into both thyroid lobes. Treatment options for toxic nodular goiter in cats are similar to that used in humans and include surgical thyroidectomy, radioiodine, and antithyroid drugs. Most authorities agree that ablative therapy with radioiodine is the treatment of choice for most cats with toxic nodular goiter, because the animals are older, and the disease will never go into remission.
Chayama, Kazuaki; Hayes, C Nelson; Hiraga, Nobuhiko; Abe, Hiromi; Tsuge, Masataka; Imamura, Michio
Human hepatitis B virus (HBV) and hepatitis C virus (HCV) infect only chimpanzees and humans. Analysis of both viruses has long been hampered by the absence of a small animal model. The recent development of human hepatocyte chimeric mice has enabled us to carry out studies on viral replication and cellular changes induced by replication of human hepatitis viruses. Various therapeutic agents have also been tested using this model. In the present review, we summarize published studies using chimeric mice and discuss the merits and shortcomings of this model.
Horowitz, J. M.
The present review evaluates several assumptions common to a variety of current models for thermoregulation in cold-stressed animals. Three areas covered by the models are discussed: signals to and from the central nervous system (CNS), portions of the CNS involved, and the arrangement of neurons within networks. Assumptions in each of these categories are considered. The evaluation of the models is based on the experimental foundations of the assumptions. Regions of the nervous system concerned here include the hypothalamus, the skin, the spinal cord, the hippocampus, and the septal area of the brain.
Nowlan, Niamh C.; Sharpe, James; Roddy, Karen A.; Prendergast, Patrick J.; Murphy, Paula
A range of clinical conditions in which foetal movement is reduced or prevented can have a severe effect on skeletal development. Animal models have been instrumental to our understanding of the interplay between mechanical forces and skeletal development, in particular the mouse and the chick model systems. In the chick, the most commonly used means of altering the mechanical environment is by pharmaceutical agents which induce paralysis, while genetically modified mice with non-functional or absent skeletal muscle offer a valuable tool for examining the interplay between muscle forces and skeletogenesis in mammals. This article reviews the body of research on animal models of bone or joint formation in vivo in the presence of an altered or abnormal mechanical environment. In both immobilised chicks and ‘muscleless limb’ mice, a range of effects are seen, such as shorter rudiments with less bone formation, changes in rudiment and joint shape and abnormal joint cavitation. However, while all bones and synovial joints are affected in immobilised chicks, some rudiments and joints are unaffected in muscleless mice. We propose that extrinsic mechanical forces from movements of the mother or littermates impact on skeletogenesis in mammals, while the chick embryo is reliant on intrinsic movement for mechanical stimulation. The insights gained from animal models into the mechanobiology of embryonic skeletal development could provide valuable cues to prospective tissue engineers of cartilage and bone, and contribute to new or improved treatments to minimise the impact on skeletal development of human disorders of reduced movement in utero. PMID:20860060
Despite decades of research, the neural circuit abnormalities underlying schizophrenia remain elusive. Although studies on schizophrenia patients have yielded important insights they have not been able to fully reveal the details of how neural circuits are disrupted in the disease, which is essential for understanding its pathophysiology and developing new treatment strategies. Animal models of schizophrenia are likely to play an important role in this effort. Such models allow neural circuit dysfunction to be investigated in detail and the role of risk factors and pathophysiological mechanisms to be experimentally assessed. The goal of this review is to summarize what we have learned from electrophysiological studies that have examined neural circuit function in animal models of schizophrenia. Although these studies have revealed diverse manifestations of neural circuit dysfunction spanning multiple levels of analysis, common themes have nevertheless emerged across different studies and animal models, revealing a core set of neural circuit abnormalities. These include an imbalance between excitation and inhibition, deficits in synaptic plasticity, disruptions in local and long-range synchrony and abnormalities in dopaminergic signaling. The relevance of these findings to the pathophysiology of the disease is discussed, as well as outstanding questions for future research.
Bleasel, Jonathan M; Halliday, Glenda M; Kim, Woojin Scott
Multiple system atrophy (MSA) is a rare, yet rapidly-progressive neurodegenerative disease that presents clinically with autonomic failure in combination with parkinsonism or cerebellar ataxia. The definitive neuropathology differentiating MSA from Lewy body diseases is the presence of α-synuclein aggregates in oligodendrocytes (called glial cytoplasmic inclusion or GCI) rather than the fibrillar aggregates in neurons (called Lewy bodies). This makes the pathological pathway(s) in MSA unique in that oligodendrocytes are involved rather than predominantly neurons, as is most other neurodegenerative disorders. MSA is therefore regarded as an oligodendrogliopathy. The etiology of MSA is unknown. No definitive risk factors have been identified, although α-synuclein and other genes have been variably linked to MSA risk. Utilization of postmortem brain tissues has greatly advanced our understanding of GCI pathology and the subsequent neurodegeneration. However, extrapolating the early pathogenesis of MSA from such resource has been difficult and limiting. In recent years, cell and animal models developed for MSA have been instrumental in delineating unique MSA pathological pathways, as well as aiding in clinical phenotyping. The purpose of this review is to bring together and discuss various animal models that have been developed for MSA and how they have advanced our understanding of MSA pathogenesis, particularly the dynamics of α-synuclein aggregation. This review will also discuss how animal models have been used to explore potential therapeutic avenues for MSA, and future directions of MSA modeling.
Ormandy, Elisabeth H; Schuppli, Catherine A; Weary, Daniel M
The Three Rs--Reduction, Replacement and Refinement--which were first proposed in 1959 by Russell and Burch, have become widely accepted principles in the governance of humane animal research. However, there is substantial variation in the ways in which different countries document the numbers and types of research animals used, making it difficult to determine how effectively the Three Rs are being implemented. Here, we provide the first data illustrating worldwide trends in animal use for research purposes. To document global trends in animal use, we sampled 2691 articles from 24 countries, published between 1983 and 2007, in four scientific journals. We show that the percentage of articles reporting animal use has risen in the past 15 years. The rising popularity of genetic modification methods has contributed to this trend: reported genetically-modified animal use has more than doubled since 1997. We also show that mice are the most commonly-used species for genetic modification, and that, even in 2007, relatively inefficient random integration methods were still widely used to achieve genetic modification. These results illustrate shortcomings in the effort to implement the Three Rs in animal research.
The aim of this study is to examine the factors that influenced the use of Facebook among university students. Using an extended technology acceptance model (TAM) with emotional attachment (EA) as an external variable, a sample of 498 students from a public-funded Thailand university were surveyed on their responses to five variables hypothesized…
Lukashevich, Igor S
Lassa virus (LASV) is the most prevalent arenavirus in West Africa and is responsible for several hundred thousand infections and thousands of deaths annually. The sizeable disease burden, numerous imported cases of Lassa fever (LF) and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Currently there is no licensed LF vaccine and research and devlopment is hampered by the high cost of nonhuman primate animal models and by biocontainment requirements (BSL-4). In addition, a successful LF vaccine has to induce a strong cell-mediated cross-protective immunity against different LASV lineages. All of these challenges will be addressed in this review in the context of available and novel animal models recently described for evaluation of LF vaccine candidates.
Esakov, Jeffrey; Badler, Norman I.; Jung, Moon
Graphical manipulation of human figures is essential for certain types of human factors analyses such as reach, clearance, fit, and view. In many situations, however, the animation of simulated people performing various tasks may be based on more complicated functions involving multiple simultaneous reaches, critical timing, resource availability, and human performance capabilities. One rather effective means for creating such a simulation is through a natural language description of the tasks to be carried out. Given an anthropometrically-sized figure and a geometric workplace environment, various simple actions such as reach, turn, and view can be effectively controlled from language commands or standard NASA checklist procedures. The commands may also be generated by external simulation tools. Task timing is determined from actual performance models, if available, such as strength models or Fitts' Law. The resulting action specification are animated on a Silicon Graphics Iris workstation in real-time.
Thangavel, Rajagowthamee R.; Bouvier, Nicole M.
In humans, infection with an influenza A or B virus manifests typically as an acute and self-limited upper respiratory tract illness characterized by fever, cough, sore throat, and malaise. However, influenza can present along a broad spectrum of disease, ranging from sub-clinical or even asymptomatic infection to a severe primary viral pneumonia requiring advanced medical supportive care. Disease severity depends upon the virulence of the influenza virus strain and the immune competence and previous influenza exposures of the patient. Animal models are used in influenza research not only to elucidate the viral and host factors that affect influenza disease outcomes in and spread among susceptible hosts, but also to evaluate interventions designed to prevent or reduce influenza morbidity and mortality in man. This review will focus on the three animal models currently used most frequently in influenza virus research -- mice, ferrets, and guinea pigs -- and discuss the advantages and disadvantages of each. PMID:24709389
The etiology of the polycystic ovary syndrome (PCOS) remains unclear, despite its high prevalence among infertility disorders in women of reproductive age. Although there is evidence for a genetic component of the disorder, other causes, such as prenatal insults are considered among the potential factors that may contribute to the development of the syndrome. Over the past few decades, several animal models have been developed in an attempt to understand the potential contribution of exposure to excess steroids on the development of this syndrome. The current review summarizes the phenotypes of current animal models exposed to excess steroid during the prenatal and early postnatal period and how they compare with the phenotype seen in women with PCOS. PMID:23701728
Baehr, Wolfgang; Frederick, Jeanne M.
Naturally occurring and laboratory generated animal models serve as powerful tools with which to investigate the etiology of human retinal degenerations, especially retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), cone dystrophies (CD) and macular degeneration (MD). Much progress has been made in elucidating gene defects underlying disease, in understanding mechanisms leading to disease, and in designing molecules for translational research and gene-based therapy to interfere with the progression of disease. Key to this progress has been study of naturally occurring murine and canine retinal degeneration mutants. This article will review the history, phenotypes and gene defects of select animal models with outer retina (photoreceptor and retinal pigment epithelium) degeneration phenotypes. PMID:19375447
Kostic, Aleksandar D.; Howitt, Michael R.; Garrett, Wendy S.
The animal and bacterial kingdoms have coevolved and coadapted in response to environmental selective pressures over hundreds of millions of years. The meta'omics revolution in both sequencing and its analytic pipelines is fostering an explosion of interest in how the gut microbiome impacts physiology and propensity to disease. Gut microbiome studies are inherently interdisciplinary, drawing on approaches and technical skill sets from the biomedical sciences, ecology, and computational biology. Central to unraveling the complex biology of environment, genetics, and microbiome interaction in human health and disease is a deeper understanding of the symbiosis between animals and bacteria. Experimental model systems, including mice, fish, insects, and the Hawaiian bobtail squid, continue to provide critical insight into how host–microbiota homeostasis is constructed and maintained. Here we consider how model systems are influencing current understanding of host–microbiota interactions and explore recent human microbiome studies. PMID:23592793
Hagerling, Catharina; Werb, Zena
Neutrophils have a crucial role in tumor development and metastatic progression. The contribution of neutrophils in tumor development is multifaceted and contradictory. On the one hand, neutrophils prompt tumor inception, promote tumor development by mediating the initial angiogenic switch and facilitate colonization of circulating tumor cells, and on the other hand, have cytotoxic and anti-metastatic capabilities. Our understanding of the role of neutrophils in tumor development has greatly depended on different experimental animal models of cancer. In this review we cover important findings that have been made about neutrophils in experimental animal models of cancer, point to their advantages and limitations, and discuss novel techniques that can be used to expand our knowledge of how neutrophils influence tumor progression. PMID:26976824
Obstructive sleep apnea (OSA) is caused by repetitive collapse of a narrow upper airway during sleep with the main risk factor being obesity. Apneas are followed by hypoxia, sympathetic activation, intrathoracic pressure swings and arousals. In most animal studies, only the cyclical pattern of hypoxia characteristic of OSA is simulated, however, more complex models have also been developed which additionally reflect the other pathophysiological changes associated with sleep-disordered breathing. These models have contributed to a deeper understanding of the cardiovascular and metabolic consequences of OSA. From other experiments the concept of the pharynx behaving like a collapsible tube, i. e. a Starling resistor, has emerged. Finally, the neurotransmitter modulation of upper airway muscle tone has been elucidated by using IN VIVO microdialysis of the caudal medulla of rats. It is hoped that findings from animal studies will in the future impact on the management of patients with OSA, in particular if they are non-compliant with CPAP therapy.
Lukashevich, Igor S
Lassa virus (LASV) is the most prevalent arenavirus in West Africa and is responsible for several hundred thousand infections and thousands of deaths annually. The sizeable disease burden, numerous imported cases of Lassa fever (LF) and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Currently there is no licensed LF vaccine and research and devlopment is hampered by the high cost of nonhuman primate animal models and by biocontainment requirements (BSL-4). In addition, a successful LF vaccine has to induce a strong cell-mediated cross-protective immunity against different LASV lineages. All of these challenges will be addressed in this review in the context of available and novel animal models recently described for evaluation of LF vaccine candidates. PMID:23256740
Réus, Gislaine Z; Dos Santos, Maria Augusta B; Abelaira, Helena M; Quevedo, João
Anxiety disorders pose one of the largest threats to global mental health, and they predominantly emerge early in life. Social anxiety disorder, also known as social phobia, is the most common of all anxiety disorders. Moreover, it has severe consequences and is a disabling disorder that can cause an individual to be unable to perform the tasks of daily life. Social anxiety disorder is associated with the subsequent development of major depression and other mental diseases, as well as increased substance abuse. Although some neurobiological alterations have been found to be associated with social anxiety disorder, little is known about this disorder. Animal models are useful tools for the investigation of this disorder, as well as for finding new pharmacological targets for treatment. Thus, this review will highlight the main animal models of anxiety associated with social phobia.
D'Orazio, Sarah E. F.
Listeria monocytogenes has been recognized as a food borne pathogen in humans since the 1980s, but we still understand very little about oral transmission of L. monocytogenes or the host factors that determine susceptibility to gastrointestinal infection, due to the lack of an appropriate small animal model of oral listeriosis. Early feeding trials suggested that many animals were highly resistant to oral infection, and the more reproducible intravenous or intraperitoneal routes of inoculation soon came to be favored. There are a fair number of previously published studies using an oral infection route, but the work varies widely in terms of bacterial strain choice, the methods used for oral transmission, and various manipulations used to enhance infectivity. This mini review summarizes the published literature using oral routes of L. monocytogenes infection and highlights recent technological advances that make oral infection a more attractive model system. PMID:24575393
Tardive dyskinesia remains an elusive and significant clinical entity that can possibly be understood via experimentation with animal models. We conducted a literature review on tardive dyskinesia modeling. Subchronic antipsychotic drug exposure is a standard approach to model tardive dyskinesia in rodents. Vacuous chewing movements constitute the most common pattern of expression of purposeless oral movements and represent an impermanent response, with individual and strain susceptibility differences. Transgenic mice are also used to address the contribution of adaptive and maladaptive signals induced during antipsychotic drug exposure. An emphasis on non-human primate modeling is proposed, and past experimental observations reviewed in various monkey species. Rodent and primate models are complementary, but the non-human primate model appears more convincingly similar to the human condition and better suited to address therapeutic issues against tardive dyskinesia. PMID:22404856
Lewis, Mark H; Tanimura, Yoko; Lee, Linda W; Bodfish, James W
Restricted, repetitive behavior, along with deficits in social reciprocity and communication, is diagnostic of autism. Animal models relevant to this domain generally fall into three classes: repetitive behavior associated with targeted insults to the CNS; repetitive behavior induced by pharmacological agents; and repetitive behavior associated with restricted environments and experience. The extant literature provides potential models of the repetitive behavioral phenotype in autism rather than attempts to model the etiology or pathophysiology of restricted, repetitive behavior, as these are poorly understood. This review focuses on our work with deer mice which exhibit repetitive behaviors associated with environmental restriction. Repetitive behaviors are the most common category of abnormal behavior observed in confined animals and larger, more complex environments substantially reduce the development and expression of such behavior. Studies with this model, including environmental enrichment effects, suggest alterations in cortical-basal ganglia circuitry in the development and expression of repetitive behavior. Considerably more work needs to be done in this area, particularly in modeling the development of aberrant repetitive behavior. As mutant mouse models continue to proliferate, there should be a number of promising genetic models to pursue.
Kipp, Markus; Nyamoya, Stella; Hochstrasser, Tanja; Amor, Sandra
There is a broad consensus that multiple sclerosis (MS) represents more than an inflammatory disease: it harbors several characteristic aspects of a classical neurodegenerative disorder, that is, damage to axons, synapses and nerve cell bodies. While we are equipped with appropriate therapeutic options to prevent immune-cell driven relapses, effective therapeutic options to prevent the progressing neurodegeneration are still missing. In this review article, we will discuss to what extent pathology of the progressive disease stage can be modeled in MS animal models. While acute and relapsing-remitting forms of experimental autoimmune encephalomyelitis (EAE), which are T cell dependent, are aptly suited to model relapsing-remitting phases of MS, other EAE models, especially the secondary progressive EAE stage in Biozzi ABH mice is better representing the secondary progressive phase of MS, which is refractory to many immune therapies. Besides EAE, the cuprizone model is rapidly gaining popularity to study the formation and progression of demyelinating CNS lesions without T cell involvement. Here, we discuss these two non-popular MS models. It is our aim to point out the pathological hallmarks of MS, and discuss which pathological aspects of the disease can be best studied in the various animal models available.
Pinto, Carla M. A.; Santos, Alexandra P.
The study of locomotor patterns has been a major research goal in the last decades. Understanding how intralimb and interlimb coordination works out so well in animals' locomotion is a hard and challenging task. Many models have been proposed to model animal's rhythms. These models have also been applied to the control of rhythmic movements of adaptive legged robots, namely biped, quadruped and other designs. In this paper we study gait transition in a central pattern generator (CPG) model for bipeds, the 4-cells model. This model is proposed by Golubitsky, Stewart, Buono and Collins and is studied further by Pinto and Golubitsky. We briefly resume the work done by Pinto and Golubitsky. We compute numerically gait transition in the 4-cells CPG model for bipeds. We use Morris-Lecar equations and Wilson-Cowan equations as the internal dynamics for each cell. We also consider two types of coupling between the cells: diffusive and synaptic. We obtain secondary gaits by bifurcation of primary gaits, by varying the coupling strengths. Nevertheless, some bifurcating branches could not be obtained, emphasizing the fact that despite analytically those bifurcations exist, finding them is a hard task and requires variation of other parameters of the equations. We note that the type of coupling did not influence the results.
van Doremalen, Neeltje; Munster, Vincent J.
The emergence of the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second time that a new, highly pathogenic coronavirus has emerged in the human population in the 21st century. In this review, we discuss the current state of knowledge of animal models of MERS-CoV infection. Commonly used laboratory animal species such as Syrian hamsters, mice and ferrets are not susceptible to MERS-CoV, due to differences in the MERS-CoV receptor dipeptyl peptidase 4 (DPP4). The initially developed animal models comprise two nonhuman primate species, the rhesus macaque and the common marmoset. Rhesus macaques develop a mild to moderate respiratory disease upon inoculation, reminiscent of milder MERS cases, whereas marmosets develop a moderate to severe respiratory disease, recapitulating the severe disease observed in some patients. Dromedary camels, considered to be the reservoir for MERS-CoV, develop a mild upper respiratory tract infection with abundant viral shedding. Although normal mice are not susceptible to MERS-CoV, expression of the human DPP4 (hDPP4) overcomes the lack of susceptibility. Transgenic hDPP4 mice develop severe and lethal respiratory disease upon inoculation with MERS-CoV. These hDPP4 transgenic mice are potentially the ideal first line animal model for efficacy testing of therapeutic and prophylactic countermeasures. Further characterization of identified countermeasures would ideally be performed in the common marmoset model, due to the more severe disease outcome. This article forms part of a symposium in Antiviral Research on “From SARS to MERS: research on highly pathogenic human coronaviruses.” PMID:26192750
Tsai, Peter T
Autism is a prevalent neurodevelopmental disorder whose origins are not well understood. Cerebellar involvement has been implicated in the pathogenesis of autism spectrum disorders with increasing evidence from both clinical studies and animal models supporting an important role for cerebellar dysfunction in autism spectrum disorders. This article discusses the various cerebellar contributions to autism spectrum disorders. Both clinical and preclinical studies are discussed and future research directions highlighted.
Godar, Sean C.; Mosher, Laura J.; Di Giovanni, Giuseppe; Bortolato, Marco
Tics are repetitive, sudden movements and/or vocalizations, typically enacted as maladaptive responses to intrusive premonitory urges. The most severe tic disorder, Tourette syndrome (TS), is a childhood-onset condition featuring multiple motor and at least one phonic tic for a duration longer than 1 year. The pharmacological treatment of TS is mainly based on antipsychotic agents; while these drugs are often effective in reducing tic severity and frequency, their therapeutic compliance is limited by serious motor and cognitive side effects. The identification of novel therapeutic targets and development of better treatments for tic disorders is conditional on the development of animal models with high translational validity. In addition, these experimental tools can prove extremely useful to test hypotheses on the etiology and neurobiological bases of TS and related conditions. In recent years, the translational value of these animal models has been enhanced, thanks to a significant re-organization of our conceptual framework of neuropsychiatric disorders, with a greater focus on endophenotypes and quantitative indices, rather than qualitative descriptors. Given the complex and multifactorial nature of TS and other tic disorders, the selection of animal models that can appropriately capture specific symptomatic aspects of these conditions can pose significant theoretical and methodological challenges. In this article, we will review the state of the art on the available animal models of tic disorders, based on genetic mutations, environmental interventions as well as pharmacological manipulations. Furthermore, we will outline emerging lines of translational research showing how some of these experimental preparations have led to significant progress in the identification of novel therapeutic targets for tic disorders. PMID:25244952
Orme, Ian M
Testing of new vaccines in animal models has certain advantages and disadvantages. As we better understand the complexity of the immune response to vaccines, new information may be complicating the assessment of the efficacy of new candidate vaccines. Four possible complications are discussed here, (i) induction of Foxp3+ T cells; (ii) induction of memory T cell subsets; (iii) location of extracellular organisms in lung necrosis; and (iv) protection against isolates of high/extreme immunopathology.
Godar, Sean C; Mosher, Laura J; Di Giovanni, Giuseppe; Bortolato, Marco
Tics are repetitive, sudden movements and/or vocalizations, typically enacted as maladaptive responses to intrusive premonitory urges. The most severe tic disorder, Tourette syndrome (TS), is a childhood-onset condition featuring multiple motor and at least one phonic tic for a duration longer than 1 year. The pharmacological treatment of TS is mainly based on antipsychotic agents; while these drugs are often effective in reducing tic severity and frequency, their therapeutic compliance is limited by serious motor and cognitive side effects. The identification of novel therapeutic targets and development of better treatments for tic disorders is conditional on the development of animal models with high translational validity. In addition, these experimental tools can prove extremely useful to test hypotheses on the etiology and neurobiological bases of TS and related conditions. In recent years, the translational value of these animal models has been enhanced, thanks to a significant re-organization of our conceptual framework of neuropsychiatric disorders, with a greater focus on endophenotypes and quantitative indices, rather than qualitative descriptors. Given the complex and multifactorial nature of TS and other tic disorders, the selection of animal models that can appropriately capture specific symptomatic aspects of these conditions can pose significant theoretical and methodological challenges. In this article, we will review the state of the art on the available animal models of tic disorders, based on genetic mutations, environmental interventions as well as pharmacological manipulations. Furthermore, we will outline emerging lines of translational research showing how some of these experimental preparations have led to significant progress in the identification of novel therapeutic targets for tic disorders.
Gualandris, L.; Grinfeld, S.; Foulquier, F.; Kan, P.; Duprat, A. M.
Pleurodeles waltl, an Urodele amphibian is proposed as a model for space biology studies. Our laboratory is developing three types of experiments in space using this animal: 1) in vivo fertilization and development (``FERTILE'' project); 2) influence of microgravity and space radiation on the organization and preservation of spacialized structures in the neurons and muscle cells (in vitro; ``CELIMENE'' PROJECT); 3) influence of microgravity on tissue regeneration (muscle, bone, epidermis and spinal cord).
McColl, Bradley; Vadolas, Jim
The structural and functional conservation of hemoglobin throughout mammals has made the laboratory mouse an exceptionally useful organism in which to study both the protein and the individual globin genes. Early researchers looked to the globin genes as an excellent model in which to examine gene regulation – bountifully expressed and displaying a remarkably consistent pattern of developmental activation and silencing. In parallel with the growth of research into expression of the globin genes, mutations within the β-globin gene were identified as the cause of the β-hemoglobinopathies such as sickle cell disease and β-thalassemia. These lines of enquiry stimulated the development of transgenic mouse models, first carrying individual human globin genes and then substantial human genomic fragments incorporating the multigenic human β-globin locus and regulatory elements. Finally, mice were devised carrying mutant human β-globin loci on genetic backgrounds deficient in the native mouse globins, resulting in phenotypes of sickle cell disease or β-thalassemia. These years of work have generated a group of model animals that display many features of the β-hemoglobinopathies and provided enormous insight into the mechanisms of gene regulation. Substantive differences in the expression of human and mouse globins during development have also come to light, revealing the limitations of the mouse model, but also providing opportunities to further explore the mechanisms of globin gene regulation. In addition, animal models of β-hemoglobinopathies have demonstrated the feasibility of gene therapy for these conditions, now showing success in human clinical trials. Such models remain in use to dissect the molecular events of globin gene regulation and to identify novel treatments based upon the reactivation of developmentally silenced γ-globin. Here, we describe the development of animal models to investigate globin switching and the β-hemoglobinopathies, a field
Sugiyama, Naoto; Nishiyama, Eiji; Nishikawa, Yukitoshi; Sasamura, Takashi; Nakade, Shinji; Okawa, Katsumasa; Nagasawa, Tadashi; Yuki, Akane
Patients who have an ischemic stroke are at high risk of swallowing disorders. Aspiration due to swallowing disorders, specifically delayed trigger of the pharyngeal stage of swallowing, predisposes such patients to pneumonia. In the present study, we evaluated swallowing reflex in a rat model of transient middle cerebral artery occlusion (tMCAO), which is one of the most common experimental animal models of cerebral ischemia, in order to develop a novel animal model of dysphagia following ischemic stroke. A swallowing reflex was elicited by a 10-s infusion of distilled water (DW) to the pharyngolaryngeal region in the tMCAO rat model. Swallowing reflex was estimated using the electromyographic activity of the mylohyoid muscle from 1 to 3 weeks after surgery. Two weeks after tMCAO, the number of swallows significantly decreased and the onset latency of the first swallow was prolonged compared with that of the sham group. The number of swallows in rats significantly increased by infusions of 10 mM citric acid and 0.6 μM capsaicin to the pharyngolaryngeal region compared with the number from infusion of DW. It has been reported that sensory stimulation of the pharyngolaryngeal region with citric acid, capsaicin, and L-menthol ameliorates hypofunction of pharyngeal-stage swallowing in dysphagia patients. Therefore, the tMCAO rat model may show some of the symptoms of pharyngeal-stage swallowing disorders, similar to those in patients with ischemic stroke. This rat tMCAO model has the potential to become a novel animal model of dysphagia following stroke that is useful for development of therapeutic methods and drugs.
Debruyn, Adrian M H; Gobas, Frank A P C
Species vary greatly in the degree to which they accumulate dietary contaminants. Bioenergetic processes play a key role in chemical uptake and elimination, and interspecific variation in bioaccumulation can be attributed in large part to variation in how species feed, digest, and allocate energy. We present a quantitative treatment of this relationship for the entire animal kingdom. We derive a model to predict the biomagnification factor for nonmetabolizable, slowly eliminated chemicals, BMF(max). We test the model with observed biomagnification factors and independently derived bioenergetic parameters for a diverse suite of species, including herbivores and carnivores, heterotherms and homeotherms, vertebrates and invertebrates, adults and juveniles, domestic/laboratory animals and wild individuals from freshwater, marine, and terrestrial environments. The model successfully predicts species-specific BMF(max) values across this range of taxa, with values ranging from less than 1 in caterpillars to nearly 100 in some carnivores. In addition, we make novel predictions of BMF(max) for several taxa for which no measured bioaccumulation data are available. Our analysis provides new insights into the role of ecology in chemical dynamics across the animal kingdom, providing a general framework for understanding how characteristics of an organism and its ecological context influence the degree to which that organism accumulates chemicals present in its diet.
Straka, Hans; Zwergal, Andreas; Cullen, Kathleen E
Our knowledge of the vestibular sensory system, its functional significance for gaze and posture stabilization, and its capability to ensure accurate spatial orientation perception and spatial navigation has greatly benefitted from experimental approaches using a variety of vertebrate species. This review summarizes the attempts to establish the roles of semicircular canal and otolith endorgans in these functions followed by an overview of the most relevant fields of vestibular research including major findings that have advanced our understanding of how this system exerts its influence on reflexive and cognitive challenges encountered during daily life. In particular, we highlight the contributions of different animal models and the advantage of using a comparative research approach. Cross-species comparisons have established that the morpho-physiological properties underlying vestibular signal processing are evolutionarily inherent, thereby disclosing general principles. Based on the documented success of this approach, we suggest that future research employing a balanced spectrum of standard animal models such as fish/frog, mouse and primate will optimize our progress in understanding vestibular processing in health and disease. Moreover, we propose that this should be further supplemented by research employing more "exotic" species that offer unique experimental access and/or have specific vestibular adaptations due to unusual locomotor capabilities or lifestyles. Taken together this strategy will expedite our understanding of the basic principles underlying vestibular computations to reveal relevant translational aspects. Accordingly, studies employing animal models are indispensible and even mandatory for the development of new treatments, medication and technical aids (implants) for patients with vestibular pathologies.
Montes, Richard O
Pharmaceutical manufacturing processes consist of a series of stages (e.g., reaction, workup, isolation) to generate the active pharmaceutical ingredient (API). Outputs at intermediate stages (in-process control) and API need to be controlled within acceptance criteria to assure final drug product quality. In this paper, two methods based on tolerance interval to derive such acceptance criteria will be evaluated. The first method is serial worst case (SWC), an industry risk minimization strategy, wherein input materials and process parameters of a stage are fixed at their worst-case settings to calculate the maximum level expected from the stage. This maximum output then becomes input to the next stage wherein process parameters are again fixed at worst-case setting. The procedure is serially repeated throughout the process until the final stage. The calculated limits using SWC can be artificially high and may not reflect the actual process performance. The second method is the variation transmission (VT) using autoregressive model, wherein variation transmitted up to a stage is estimated by accounting for the recursive structure of the errors at each stage. Computer simulations at varying extent of variation transmission and process stage variability are performed. For the scenarios tested, VT method is demonstrated to better maintain the simulated confidence level and more precisely estimate the true proportion parameter than SWC. Real data examples are also presented that corroborate the findings from the simulation. Overall, VT is recommended for setting acceptance criteria in a multi-staged pharmaceutical manufacturing process.
Kloeckner, Frederik; Farkas, Robert; Franken, Tobias; Schmitz-Rode, Thomas
Documentation of research data plays a key role in the biomedical engineering innovation processes. It makes an important contribution to the protection of intellectual property, the traceability of results and fulfilling the regulatory requirement. Because of the increasing digitalization in laboratories, an electronic alternative to the commonly-used paper-bound notebooks could contribute to the production of sophisticated documentation. However, compared to in an industrial environment, the use of electronic laboratory notebooks is not widespread in academic laboratories. Little is known about the acceptance of an electronic documentation system and the underlying reasons for this. Thus, this paper aims to establish a prediction model on the potential preference and acceptance of scientists either for paper-based or electronic documentation. The underlying data for the analysis originate from an online survey of 101 scientists in industrial, academic and clinical environments. Various parameters were analyzed to identify crucial factors for the system preference using binary logistic regression. The analysis showed significant dependency between the documentation system preference and the supposed workload associated with the documentation system (p<0.006; odds ratio=58.543) and an additional personal component. Because of the dependency of system choice on specific parameters it is possible to predict the acceptance of an electronic laboratory notebook before implementation.
Orruño, Estibalitz; Gagnon, Marie Pierre; Asua, José; Ben Abdeljelil, Anis
We examined the main factors affecting the intention of physicians to use teledermatology using a modified Technology Acceptance Model (TAM). The investigation was carried out during a teledermatology pilot study conducted in Spain. A total of 276 questionnaires were sent to physicians by email and 171 responded (62%). Cronbach's alpha was acceptably high for all constructs. Theoretical variables were well correlated with each other and with the dependent variable (Intention to Use). Logistic regression indicated that the original TAM model was good at predicting physicians' intention to use teledermatology and that the variables Perceived Usefulness and Perceived Ease of Use were both significant (odds ratios of 8.4 and 7.4, respectively). When other theoretical variables were added, the model was still significant and it also became more powerful. However, the only significant predictor in the modified model was Facilitators with an odds ratio of 9.9. Thus the TAM was good at predicting physicians' intention to use teledermatology. However, the most important variable was the perception of Facilitators to using the technology (e.g. infrastructure, training and support).
McDonald, Eileen; Lamb, Amanda; Grillo, Barbara; Lucas, Lee; Miesfeldt, Susan
This work examined acceptability of cancer genetic counseling models of service delivery among Maine residents at risk for hereditary cancer susceptibility disorders. Pre-counseling, participants ranked characteristics reflecting models of care from most to least important including: mode-of-communication (in-person versus telegenetics), provider level of training (genetic specialty versus some training/experience), delivery format (one-on-one versus group counseling), and location (local versus tertiary service requiring travel). Associations between models of care characteristic rankings and patient characteristics, including rural residence, perceived cancer risk, and perceived risk for a hereditary cancer risk susceptibility disorder were examined. A total of 149/300 (49.7% response rate) individuals from 11/16 Maine counties responded; 30.8% were from rural counties; 92.2% indicated that an important/the most important model of care characteristic is provider professional qualifications. Among other characteristics, 65.1% ranked one-on-one counseling as important/the most important. In-person and local counseling were ranked the two least important characteristics (51.8% and 52.1% important/the most important, respectively). Responses did not vary by patient characteristics with the exception of greater acceptance of group counseling among those at perceived high personal cancer risk. Cancer telegenetic services hold promise for access to expert providers in a one-on-one format for rurally remote clients.
Masuda, Naoki; O'shea-Wheller, Thomas A; Doran, Carolina; Franks, Nigel R
Collective decision-making is a characteristic of societies ranging from ants to humans. The ant Temnothorax albipennis is known to use quorum sensing to collectively decide on a new home; emigration to a new nest site occurs when the number of ants favouring the new site becomes quorate. There are several possible mechanisms by which ant colonies can select the best nest site among alternatives based on a quorum mechanism. In this study, we use computational models to examine the implications of heterogeneous acceptance thresholds across individual ants in collective nest choice behaviour. We take a minimalist approach to develop a differential equation model and a corresponding non-spatial agent-based model. We show, consistent with existing empirical evidence, that heterogeneity in acceptance thresholds is a viable mechanism for efficient nest choice behaviour. In particular, we show that the proposed models show speed-accuracy trade-offs and speed-cohesion trade-offs when we vary the number of scouts or the quorum threshold.
Moore, V L; Hensley, G T; Fink, J N
This study was devised to produce an animal model of hypersensitivity pneumonitis in order to study both the induction and the elicitation of the disease. Rabbits exposed by aerosol to large quantities of pigeon antigens developed a humoral, but not cellular, immunologic response. Moreover, their lungs were essentially normal histologically. A single i.v. injection of killed BCG in oil permitted the induction of pulmonary cell-medid hypersensitivity to the inhaled antigen, as well as the development of pulmonary lesions which were more severe than that caused by the administration of BCG alone. The humoral immunologic response to the inhaled antigen was not increased after BCG injection. Since many individuals are exposed to the etiologic agents of hypersensitivity pneumonitis for extended periods without developing the disease, these findings in animals suggest that some event may occur to induce cell mediated hypersensitivity in order to initiate the disease process. In addition, we have shown that animals with normal lung histology and circulating complement-fixing antibodies undergo serum complement (CH50) depression after an aerosol challenge with the specific antigen. Animals with circulating, complement-fixing antibodies, and inflamed lungs (BCG-induced failed to undergo a complement depression subsequent to an aerosol challenge with specific antigens. These results re consistent with those seen in symptomatic and asymptomatic pigeon breeders and suggest that antigen distribution through the lung is important in the pathogenesis of hypersensitivity pneumonitis. Images PMID:1099122
Gubellini, P; Kachidian, P
Parkinson's disease (PD) is a progressive neurodegenerative disorder whose etiology, besides a minority of genetic cases, is still largely unknown. Animal models have contributed to elucidate PD etiology and pathogenesis, as well as its cellular and molecular mechanisms, leading to the general hypothesis that this neurological disorder is due to complex interactions between environmental and genetic factors. However, the full understanding of PD is still very far from being achieved, and new potential treatments need to be tested to further improve patients' quality of life and, possibly, slow down the neurodegenerative process. In this context, animal models of PD are required to address all these issues. "Classic" models are based on neurotoxins that selectively target catecholaminergic neurons (such as 6-hydroxydopamine, 1-methyl-1,2,3,6-tetrahydropiridine, agricultural pesticides, etc.), while more recent models employ genetic manipulations that either introduce mutations similar to those find in familial cases of PD (α-synuclein, DJ-1, PINK1, Parkin, etc.) or selectively disrupt nigrostriatal neurons (MitoPark, Pitx3, Nurr1, etc.). Each one of these models has its own advantages and limitations, thus some are better suited for studying PD pathogenesis, while others are more pertinent to test therapeutic treatments. Here, we provide a critical and updated review of the most used PD models.
Zhang, Yu; Prakash, Edmond C.; Sung, Eric
In this paper we propose a new hierarchical 3D facial model based on anatomical knowledge that provides high fidelity for realistic facial expression animation. Like real human face, the facial model has a hierarchical biomechanical structure, incorporating a physically-based approximation to facial skin tissue, a set of anatomically-motivated facial muscle actuators and underlying skull structure. The deformable skin model has multi-layer structure to approximate different types of soft tissue. It takes into account the nonlinear stress-strain relationship of the skin and the fact that soft tissue is almost incompressible. Different types of muscle models have been developed to simulate distribution of the muscle force on the skin due to muscle contraction. By the presence of the skull model, our facial model takes advantage of both more accurate facial deformation and the consideration of facial anatomy during the interactive definition of facial muscles. Under the muscular force, the deformation of the facial skin is evaluated using numerical integration of the governing dynamic equations. The dynamic facial animation algorithm runs at interactive rate with flexible and realistic facial expressions to be generated.
Young, Jared W; Henry, Brook L; Geyer, Mark A
Mania has long been recognized as aberrant behaviour indicative of mental illness. Manic states include a variety of complex and multifaceted symptoms that challenge clear clinical distinctions. Symptoms include over-activity, hypersexuality, irritability and reduced need for sleep, with cognitive deficits recently linked to functional outcome. Current treatments have arisen through serendipity or from other disorders. Hence, treatments are not efficacious for all patients, and there is an urgent need to develop targeted therapeutics. Part of the drug discovery process is the assessment of therapeutics in animal models. Here we review pharmacological, environmental and genetic manipulations developed to test the efficacy of therapeutics in animal models of mania. The merits of these models are discussed in terms of the manipulation used and the facet of mania measured. Moreover, the predictive validity of these models is discussed in the context of differentiating drugs that succeed or fail to meet criteria as approved mania treatments. The multifaceted symptomatology of mania has not been reflected in the majority of animal models, where locomotor activity remains the primary measure. This approach has resulted in numerous false positives for putative treatments. Recent work highlights the need to utilize multivariate strategies to enable comprehensive assessment of affective and cognitive dysfunction. Advances in therapeutic treatment may depend on novel models developed with an integrated approach that includes: (i) a comprehensive battery of tests for different aspects of mania, (ii) utilization of genetic information to establish aetiological validity and (iii) objective quantification of patient behaviour with translational cross-species paradigms. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21410454
Guo, Qinxi; Wang, Zilai; Li, Hongmei; Wiese, Mary; Zheng, Hui
The amyloid precursor protein (APP) has been under intensive study in recent years, mainly due to its critical role in the pathogenesis of Alzheimer's disease (AD). β-Amyloid (Aβ) peptides generated from APP proteolytic cleavage can aggregate, leading to plaque formation in human AD brains. Point mutations of APP affecting Aβ production are found to be causal for hereditary early onset familial AD. It is very likely that elucidating the physiological properties of APP will greatly facilitate the understanding of its role in AD pathogenesis. A number of APP loss- and gain-of-function models have been established in model organisms including Caenorhabditis elegans, Drosophila, zebrafish and mouse. These in vivo models provide us valuable insights into APP physiological functions. In addition, several knock-in mouse models expressing mutant APP at a physiological level are available to allow us to study AD pathogenesis without APP overexpression. This article will review the current physiological and pathophysiological animal models of APP.
Dearman, R J; Kimber, I
Food allergy is an important health issue. With an increasing interest in novel foods derived from transgenic crop plants, there is a growing need for the development of approaches suitable for the characterization of the allergenic potential of proteins. There are methods available currently (such as homology searches and serological testing) that are very effective at identifying proteins that are likely to cross-react with known allergens. However, animal models may play a role in the identification of truly novel proteins, such as bacterial or fungal proteins, that have not been experienced previously in the diet. We consider here the potential benefits, pitfalls and challenges of the selection of various animal models, including the mouse, the rat, the dog and the neonatal swine. The advantages and disadvantages of various experimental end-points are discussed, including the measurement of specific IgE by ELISA, Western blotting or functional tests such as the passive cutaneous anaphylaxis assay, and the assessment of challenge-induced clinical symptoms in previously sensitized animals. The experimental variables of route of exposure to test proteins and the incorporation of adjuvant to increase the sensitivity of the responses are considered also. It is important to emphasize that currently none of these approaches has been validated for the purposes of hazard identification in the context of a safety assessment. However, the available evidence suggests that the judicious use of an accurate and robust animal model could provide important additional data that would contribute significantly to the assessment of the potential allergenicity of novel proteins.
Adel-Patient, K; Wal, J M
Incidence of IgE-mediated allergic reactions to foods is increasing as well as the severity of associated symptoms and numerous foods are now incriminated, probably in relation with modifications of dietary habits and increased exposure to new or modified food ingredients. Therefore, the introduction on the market of food composed of or derived from genetically modified organisms (GMOs) raised the question of their potential allergenicity. Particularly with regards to the allergenicity of a newly expressed protein, it is necessary to obtain, from several steps in the risk assessment process, a cumulative body of evidence which minimises any uncertainty. This may include the use of animal model despite no fully reliable validated model is available yet. Such animal models should allow to address 3 major issues: Is the novel protein a sensitizer, i.e. does it possess intrinsic properties that allow to sensitize a predisposed individual? Is the protein an elicitor i.e. is it able to elicit an allergic reaction in a sensitised individual? And is the protein an adjuvant, i.e. can it facilitate or enhance the sensitisation to an other protein? Animal models under investigation currently include mice, rats and guinea pigs but models such as dogs and swine also appeared a few years ago. The aim is to mimic the mechanism and characteristics of the sensitisation phase and/or the elicitation phase of the allergic reaction as it occurs in atopic humans. They are necessary because sensitisation studies can obviously not be done in human and because in vitro tests cannot reproduce the complexity of the immune system. We propose a mouse model which mimics both phases of the allergic reaction. It has permitted to evidence that biochemical and clinical manifestations occuring during the active phases of the allergic reaction differ according to the structure of the allergen used for the challenge. This may allow to compare the allergenic potential of a genetically modified protein
Fusilier, Marcelline; Durlabhji, Subhash
Purpose: The purpose of this paper is to explore behavioral processes involved in internet technology acceptance and use with a sample in India, a developing country that can potentially benefit from greater participation in the web economy. Design/methodology/approach - User experience was incorporated into the technology acceptance model (TAM)…
The principal objective of this study was to gain insight into attitude changes occurring during IT acceptance from the perspective of elaboration likelihood model (ELM). In particular, the primary target of this study was the process of IT acceptance through an education program. Although the Internet and computers are now quite ubiquitous, and…
Mahdi, Hasan Rebhi
The study aimed at investigating the influence of E-learning Self-Efficacy (ELSE) on the acceptance of e-learning by using the Technology Acceptance Model (TAM). According to the TAM which used as the theoretical basis, both of the Perceived Usefulness (PU) and the Perceived Ease of Use (PEOU) influence directly the end user's Behavioral Intention…
Zhang, Huiying; Cocosila, Mihail; Archer, Norm
Pervasive healthcare support through mobile information technology solutions is playing an increasing role in the attempt to improve healthcare and reduce costs. Despite the apparent attractiveness, many mobile applications have failed or have not been implemented as predicted. Among factors possibly leading to such outcomes, technology adoption is a key problem. This must be investigated early in the development process because healthcare is a particularly sensitive area with vital social implications. Moreover, it is important to investigate technology acceptance using the support of scientific tools validated for relevant information systems research. This article presents an empirical study based on the Technology Acceptance Model 2 in mobile homecare nursing. The study elicited the perceptions of 91 Canadian nurses who used personal digital assistants for 1 month in their daily activities. A partial least squares modeling data analysis revealed that nurse's perception of usefulness is the main factor in the adoption of mobile technology, having subjective norm and image within the organization as significant antecedents. Overall, this study was the first attempt at investigating scientifically, through a pertinent information systems research model, user adoption of mobile systems by homecare nursing personnel.
Morley, P. D.; Chang, Julius
Using cellular automata model, we simulate the British Government Policy (BGP) in the 2001 foot and mouth epidemic in Great Britain. When clinical symptoms of the disease appeared in a farm, there is mandatory slaughter (culling) of all livestock in an infected premise (IP). Those farms in the neighboring of an IP (contiguous premise, CP), are also culled, aka nearest neighbor interaction. Farms where the disease may be prevalent from animal, human, vehicle or airborne transmission (dangerous contact, DC), are additionally culled, aka next-to-nearest neighbor interactions and lightning factor. The resulting mathematical model possesses a phase transition, whereupon if the physical disease transmission kernel exceeds a critical value, catastrophic loss of animals ensues. The nonlocal disease transport probability can be as low as 0.01% per day and the disease can still be in the high mortality phase. We show that the fundamental equation for sustainable disease transport is the criticality equation for neutron fission cascade. Finally, we calculate that the percentage of culled animals that are actually healthy is ≈30%.
Arenaviruses are enveloped, bipartite negative single-stranded RNA viruses that can cause a wide spectrum of disease in humans and experimental animals including hemorrhagic fever. The majority of these viruses are rodent-borne and the arenavirus family can be divided into two groups: the Lassa-Lymphocytic choriomeningitis serocomplex and the Tacaribe serocomplex. Arenavirus-induced disease may include characteristic symptoms ranging from fever, malaise, body aches, petechiae, dehydration, hemorrhage, organ failure, shock, and in severe cases death. Currently, there are few prophylactic and therapeutic treatments available for arenavirus-induced symptoms. Supportive care and ribavirin remain the predominant strategies for treating most of the arenavirus-induced diseases. Therefore, efficacy testing of novel therapeutic and prophylactic strategies in relevant animal models is necessary. Because of the potential for person-to-person spread, the ability to cause lethal or debilitating disease in humans, limited treatment options, and potential as a bio-weapon, the development of prophylactics and therapeutics is essential. This article reviews the current arenavirus animal models and prophylactic and therapeutic strategies under development to treat arenavirus infection.
Cho, A K; Melega, W P; Kuczenski, R; Segal, D S
Although the behavioral consequences of methamphetamine (METH) abuse have been extensively documented, a more precise and thorough understanding of underlying neurobiological mechanisms still requires the use of animal models. To study these biochemical processes in experimental animals requires consideration for the broad range of human METH abuse patterns and the many factors that have been identified to profoundly influence the behavioral and neurochemical effects of exposure to METH-like stimulants. One potentially critical issue relates to pharmacokinetic differences between the species. In this review, METH plasma pharmacokinetic profiles after single and multiple dose intravenous METH administration are compared for the rat and human. Significant differences in elimination half-life between the two species (t1/2: rat-70 min, human-12 h) result in markedly dissimilar profiles of METH exposure. However, the plasma profile of a human METH binge pattern can be approximated in the rat by increasing METH dose frequency. Consideration of METH pharmacokinetics in animal models should permit a closer simulation of the temporal profile of METH exposure in the human CNS and should provide further insight into the mechanisms contributing to the addiciton and psychopathology associated with METH abuse.
Arenaviruses are enveloped, bipartite negative single-stranded RNA viruses that can cause a wide spectrum of disease in humans and experimental animals including hemorrhagic fever. The majority of these viruses are rodent-borne and the arenavirus family can be divided into two groups: the Lassa-Lymphocytic choriomeningitis serocomplex and the Tacaribe serocomplex. Arenavirus-induced disease may include characteristic symptoms ranging from fever, malaise, body aches, petechiae, dehydration, hemorrhage, organ failure, shock, and in severe cases death. Currently, there are few prophylactic and therapeutic treatments available for arenavirus-induced symptoms. Supportive care and ribavirin remain the predominant strategies for treating most of the arenavirus-induced diseases. Therefore, efficacy testing of novel therapeutic and prophylactic strategies in relevant animal models is necessary. Because of the potential for person-to-person spread, the ability to cause lethal or debilitating disease in humans, limited treatment options, and potential as a bio-weapon, the development of prophylactics and therapeutics is essential. This article reviews the current arenavirus animal models and prophylactic and therapeutic strategies under development to treat arenavirus infection. PMID:23170184
Jupp, Bianca; O'Brien, Terence J
The past decade has seen a surge in the utilization of small animal imaging for epilepsy research. In vivo imaging studies have the potential to provide important insights into the structural and functional correlates of the development and progression of epilepsy in these models. However, the small size of the rodent brain means that anatomic resolution is often relatively poor for many imaging modalities, particularly those providing functional information such as positron emission tomography. Coregistration of these images with those of higher structural resolution, such as MRI, provides an attractive approach to this problem, and also allows correlations between structural and functional imaging data. Image coregistration is commonly utilized in clinical research and practice. However, its application for small animal images has been, to date, relatively under utilized and largely unvalidated. The current review aims to provide an overview of image coregistration methods, particularly for MRI and PET, and their application to imaging of small animal models of epilepsy. Methodological advantages and potential traps are highlighted.
A valid animal model of depression was used to explore specific adrenergic receptor differences between rats exhibiting aberrant behavior and control groups. Preliminary experiments revealed a distinct upregulation of hippocampal beta-receptors (as compared to other brain regions) in those animals acquiring a response deficit as a result of exposure to inescapable footshock. Concurrent studies using standard receptor binding techniques showed no large changes in the density of alpha-adrenergic, serotonergic, or dopaminergic receptor densities. This led to the hypothesis that the hippocampal beta-receptor in responses deficient animals could be correlated with the behavioral changes seen after exposure to the aversive stimulus. Normalization of the behavior through the administration of antidepressants could be expected to reverse the biochemical changes if these are related to the mechanism of action of antidepressant drugs. This study makes three important points: (1) there is a relevant biochemical change in the hippocampus of response deficient rats which occurs in parallel to a well-defined behavior, (2) the biochemical and behavioral changes are normalized by antidepressant treatments exhibiting both serotonergic and adrenergic mechanisms of action, and (3) the mode of action of antidepressants in this model is probably a combination of serotonergic and adrenergic influences modulating the hippocampal beta-receptor. These results are discussed in relation to anatomical and biochemical aspects of antidepressant action.
Du, Liang; Zhang, Jingwan; De Meyer, Guido R Y; Flynn, Rowan; Dichek, David A
Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike lesions that develop rapidly in vessels that are amenable to efficient gene delivery. Moreover, because human atherosclerosis develops in normal vessels, gene therapy that prevents atherosclerosis is most logically tested in relatively normal arteries. Similarly, gene therapy that causes atherosclerosis regression requires gene delivery to an existing lesion. Here we report development of three new rabbit models for testing vessel-wall-directed gene therapy that either prevents or reverses atherosclerosis. Carotid artery intimal lesions in these new models develop within 2-7 months after initiation of a high-fat diet and are 20-80 times larger than lesions in a model we described previously. Individual models allow generation of lesions that are relatively rich in either macrophages or smooth muscle cells, permitting testing of gene therapy strategies targeted at either cell type. Two of the models include gene delivery to essentially normal arteries and will be useful for identifying strategies that prevent lesion development. The third model generates lesions rapidly in vector-naïve animals and can be used for testing gene therapy that promotes lesion regression. These models are optimized for testing helper-dependent adenovirus (HDAd)-mediated gene therapy; however, they could be easily adapted for testing of other vectors or of different types of molecular therapies, delivered directly to the blood vessel wall. Our data also supports the promise of HDAd to deliver long
Springer, Matthew L
Therapies that aim to prevent myocardial tissue from dying or to regenerate new myocardium all rely on the preservation or growth of a functional vasculature. The amount of blood that supplies the myocardium is dependent on the number and nature of the microvessels, as well as the ability of the arteries to supply blood and the veins to remove it. All of these factors can be assessed when success of an experimental therapy is being evaluated. Different kinds of information can be obtained from these different parameters, and it is important to understand what each one involves and how it can be misinterpreted. This chapter describes the various approaches to the assessment of vascularity in the heart with a focus on small animal models, dealing both with those approaches that are purely histological endpoint studies and those that are functional measurements in living animals.
Arble, Deanna Marie; Ramsey, Kathryn Moynihan; Bass, Joseph
Social opportunities and work demands have caused humans to become increasingly active during the late evening hours, leading to a shift from the predominantly diurnal lifestyle of our ancestors to a more nocturnal one. This voluntarily decision to stay awake long into the evening hours leads to circadian disruption at the system, tissue, and cellular levels. These derangements are in turn associated with clinical impairments in metabolic processes and physiology. The use of animal models for circadian disruption provides an important opportunity to determine mechanisms by which disorganization in the circadian system can lead to metabolic dysfunction in response to genetic, environmental, and behavioral perturbations. Here we review recent key animal studies involving circadian disruption and discuss the possible translational implications of these studies for human health and particularly for the development of metabolic disease. PMID:21112026
Arble, Deanna Marie; Ramsey, Kathryn Moynihan; Bass, Joseph; Turek, Fred W
Social opportunities and work demands have caused humans to become increasingly active during the late evening hours, leading to a shift from the predominantly diurnal lifestyle of our ancestors to a more nocturnal one. This voluntarily decision to stay awake long into the evening hours leads to circadian disruption at the system, tissue, and cellular levels. These derangements are in turn associated with clinical impairments in metabolic processes and physiology. The use of animal models for circadian disruption provides an important opportunity to determine mechanisms by which disorganization in the circadian system can lead to metabolic dysfunction in response to genetic, environmental, and behavioral perturbations. Here we review recent key animal studies involving circadian disruption and discuss the possible translational implications of these studies for human health and particularly for the development of metabolic disease.
Pita, Lucia; Fraune, Sebastian; Hentschel, Ute
Sponges have a significant impact on marine benthic communities, they are of biotechnological interest owing to their production of bioactive natural compounds, and they promise to provide insights into conserved mechanisms of host–microbe interactions in basal metazoans. The natural variability of sponge-microbe associations across species and environments provides a meaningful ecological and evolutionary framework to investigate animal-microbial symbiosis through experimentation in the field and also in aquaria. In addition, next-generation sequencing technologies have shed light on the genomic repertoire of the sponge host and revealed metabolic capacities and symbiotic lifestyle features of their microbiota. However, our understanding of symbiotic mechanisms is still in its infancy. Here, we discuss the potential and limitations of the sponge-microbe symbiosis as emerging models for animal-associated microbiota. PMID:28066403
Trinkoff, A.M.; Storr, C.L.; Wilson, M.L.; Gurses, A.P.
Summary Background To our knowledge, no evidence is available on health care professionals’ use of electronic personal health records (ePHRs) for their health management. We therefore focused on nurses’ personal use of ePHRs using a modified technology acceptance model. Objectives To examine (1) the psychometric properties of the ePHR acceptance model, (2) the associations of perceived usefulness, ease of use, data privacy and security protection, and perception of self as health-promoting role models to nurses’ own ePHR use, and (3) the moderating influences of age, chronic illness and medication use, and providers’ use of electronic health record (EHRs) on the associations between the ePHR acceptance constructs and ePHR use. Methods A convenience sample of registered nurses, those working in one of 12 hospitals in the Maryland and Washington, DC areas and members of the nursing informatics community (AMIA and HIMSS), were invited to respond to an anonymous online survey; 847 responded. Multiple logistic regression identified associations between the model constructs and ePHR use, and the moderating effect. Results Overall, ePHRs were used by 47%. Sufficient reliability for all scales was found. Three constructs were significantly related to nurses’ own ePHR use after adjusting for covariates: usefulness, data privacy and security protection, and health-promoting role model. Nurses with providers that used EHRs who perceived a higher level of data privacy and security protection had greater odds of ePHR use than those whose providers did not use EHRs. Older nurses with a higher self-perception as health-promoting role models had greater odds of ePHR use than younger nurses. Conclusions Nurses who use ePHRs for their personal health might promote adoption by the general public by serving as health-promoting role models. They can contribute to improvements in patient education and ePHR design, and serve as crucial resources when working with their
Brooks, Elizabeth D.
Glycogen storage diseases (GSD), a unique category of inherited metabolic disorders, were first described early in the 20th century. Since then, the biochemical and genetic bases of these disorders have been determined, and an increasing number of animal models for GSD have become available. At least 7 large mammalian models have been developed for laboratory research on GSDs. These models have facilitated the development of new therapies, including gene therapy, which are undergoing clinical translation. For example, gene therapy prolonged survival and prevented hypoglycemia during fasting for greater than one year in dogs with GSD type Ia, and the need for periodic re-administration to maintain efficacy was demonstrated in that dog model. The further development of gene therapy could provide curative therapy for patients with GSD and other inherited metabolic disorders. PMID:25224826
Brooks, Elizabeth D; Koeberl, Dwight D
Glycogen storage diseases (GSD), a unique category of inherited metabolic disorders, were first described early in the twentieth century. Since then, the biochemical and genetic bases of these disorders have been determined, and an increasing number of animal models for GSD have become available. At least seven large mammalian models have been developed for laboratory research on GSDs. These models have facilitated the development of new therapies, including gene therapy, which are undergoing clinical translation. For example, gene therapy prolonged survival and prevented hypoglycemia during fasting for greater than one year in dogs with GSD type Ia, and the need for periodic re-administration to maintain efficacy was demonstrated in that dog model. The further development of gene therapy could provide curative therapy for patients with GSD and other inherited metabolic disorders.
Perani, C V; Slattery, D A
The post-partum period represents a time during which all maternal organisms undergo substantial plasticity in a wide variety of systems in order to ensure the well-being of the offspring. Although this time is generally associated with increased calmness and decreased stress responses, for a substantial subset of mothers, this period represents a time of particular risk for the onset of psychiatric disorders. Thus, post-partum anxiety, depression and, to a lesser extent, psychosis may develop, and not only affect the well-being of the mother but also place at risk the long-term health of the infant. Although the risk factors for these disorders, as well as normal peripartum-associated adaptations, are well known, the underlying aetiology of post-partum psychiatric disorders remains poorly understood. However, there have been a number of attempts to model these disorders in basic research, which aim to reveal their underlying mechanisms. In the following review, we first discuss known peripartum adaptations and then describe post-partum mood and anxiety disorders, including their risk factors, prevalence and symptoms. Thereafter, we discuss the animal models that have been designed in order to study them and what they have revealed about their aetiology to date. Overall, these studies show that it is feasible to study such complex disorders in animal models, but that more needs to be done in order to increase our knowledge of these severe and debilitating mood and anxiety disorders. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20 PMID:24527704
Human depression or mood disorder is defined as a complex disease, making positional cloning of susceptibility genes a formidable task. We have undertaken genetic analyses of three different animal models for depression, comparing our results with advanced database resources. We first performed quantitative trait loci (QTL) analysis on two mouse models of "despair", namely, the forced swim test (FST) and tail suspension test (TST), and detected multiple chromosomal loci that control immobility time in these tests. Since one QTL detected on mouse chromosome 11 harbors the GABA A receptor subunit genes, we tested these genes for association in human mood disorder patients. We obtained significant associations of the alpha 1 and alpha 6 subunit genes with the disease, particularly in females. This result was striking, because we had previously detected an epistatic interaction between mouse chromosomes 11 and X that regulates immobility time in these animals. Next, we performed genome-wide expression analyses using a rat model of depression, learned helplessness (LH). We found that in the frontal cortex of LH rats, a disease implicated region, the LIM kinase 1 gene (Limk 1) showed greatest alteration, in this case down-regulation. By combining data from the QTL analysis of FST/TST and DNA microarray analysis of mouse frontal cortex, we identified adenylyl cyclase-associated CAP protein 1 (Cap 1) as another candidate gene for depression susceptibility. Both Limk 1 and Cap 1 are key players in the modulation of actin G-F conversion. In summary, our current study using animal models suggests disturbances of GABAergic neurotransmission and actin turnover as potential pathophysiologies for mood disorder.
De Nicola, Alejandro F; Coronel, Florencia; Garay, Laura I; Gargiulo-Monachelli, Gisella; Gonzalez Deniselle, Maria Claudia; Gonzalez, Susana L; Labombarda, Florencia; Meyer, Maria; Guennoun, Rachida; Schumacher, Michael
Substantial evidence supports that progesterone exerts many functions in the central and peripheral nervous system unrelated to its classical role in reproduction. In this review we first discussed progesterone effects following binding to the classical intracellular progesterone receptors A and B and several forms of membrane progesterone receptors, the modulation of intracellular signalling cascades and the interaction of progesterone reduced metabolites with neurotransmitter receptors. We next described our results involving animal models of human neuropathologies to elucidate the protective roles of progesterone. We described: (a) the protective and promyelinating effects of progesterone in experimental spinal cord injury; (b) the progesterone protective effects exerted upon motoneurons in the degenerating spinal cord of Wobbler mouse model of amyotropic lateral sclerosis; (c) the protective and anti-inflammatory effects of progesterone in the murine experimental autoimmune encephalomyelitis model of multiple sclerosis and after lysolecithin demyelination; (d) the progesterone prevention of nociception and neuropathic pain which follow spinal cord injury; and (e) the protective effect of progesterone in experimental ischemic stroke. Whenever available, the molecular mechanisms involved in these progesterone effects were examined. The multiplicity of progesterone beneficial effects has opened new venues of research for neurological disorders. In this way, results obtained in animal models could provide the basis for novel therapeutic strategies and pre-clinical studies.
Glomerulonephritis (GN) encompasses a range of immune-mediated disorders that cause inflammation within the glomerulus of the kidney. The pathogenesis of GN is complex. Intricacy arises from factors such as autoimmunity, cancer and structural abnormalities within the kidney. Studies using animal models have highlighted crucial interaction between inflammatory cells and cells intrinsic to the kidney, both of which are fundamental to the pathogenesis of GN. This review aims to provide insight on a 'suitable' model for nephrotoxic nephritis and glomerulonephritis (NTN GN) and relate its experimental validity to humans. The BALB/c NTN murine model and Wistar Kyoto (WKY) rat have held experimental validity in the study of GN in humans. The chemokine receptor CXCR3 also mediates renal T-cell recruitment and subsequent tissue injury in NTN. It is noteworthy to consider CXCR3 blockade in Th1-mediated renal inflammation as future therapeutic options for patients with GN and subsets thereof. Currently used immunosuppressive therapies for GN are not always uniformly effective and are frequently associated with serious side-effects. Corticosteroids are effective in several types of GN owing to their ability to inhibit the pro-inflammatory effects of cytokines known to promote glomerular inflammation. Differences between experimental and human GN complicate translation of experimental therapies into practice. More research is required to translate animal model research into a better comprehension of human GN disease. However, the complexity of GN research makes findings a challenge to replicate.