Critical Advances for Democratizing Ultrasound Diagnostics in Human and Veterinary Medicine.

The democratization of ultrasound imaging refers to the process of making ultrasound technology more accessible. Traditionally, ultrasound imaging has been predominately used in specialized medical facilities by trained professionals. Advancements in technology and changes in the health-care landscape have inspired efforts to broaden the availability of ultrasound imaging to various settings such as remote and resource-limited areas. In this review, we highlight several key factors that have contributed to the ongoing democratization of ultrasound imaging, including portable and handheld devices, recent advancements in technology, and training and education. Examples of diagnostic point-of-care ultrasound (POCUS) imaging used in emergency and critical care, gastroenterology, musculoskeletal applications, and other practices are provided for both human and veterinary medicine. Open challenges and the future of POCUS imaging are presented, including the emerging role of artificial intelligence in technology development.

Assessing cognitive performance in dairy calves using a modified hole-board test.

The hole-board test has been used to assess working and reference memory in a variety of species, but not in cattle. We developed and applied a modified hole-board test for dairy calves. Fifteen bottles were evenly spaced along three walls of a test arena; 11 of these were empty and 4 were 'baited' with milk. Calves were exposed daily (over an 11-day learning period) to the test arena with the location of the baited bottles held constant; the location of the 4 baited bottles was then changed and calves were re-trained on these new locations (over a 7-day re-learning period). Working memory (no. of revisits to the baited set), general working memory (no. of revisits to the whole set), and reference memory (avoidance of non-baited bottles) were assessed daily. Performance significantly improved during the learning period for reference and general working memory. Working memory tended to improve, albeit non-significantly. The change in bottle location initially reduced all performance measures, but these subsequently improved during the 7-day re-learning period. These results indicate that a modified hole-board test can be used to assess calf cognition, and thus may be helpful in future research designed to investigate the effects of housing and rearing conditions on cognition.

Potential applications of aptamers in veterinary science.

Aptamers are small nucleic acids that fold in a three-dimensional conformation allowing them to bind specifically to a target. This target can be an organic molecule, free or carried in cells or tissues, or inorganic components, such as metal ions. Analogous to monoclonal antibodies, aptamers however have certain advantages over the latter: e.g., high specificity for their target, no to low immunogenicity and easy in vitro selection. Since their discovery more than 30 years ago, aptamers have led to various applications, although mainly restricted to basic research. This work reviews the applications of aptamers in veterinary science to date. First, we present aptamers, how they are selected and their properties, then we give examples of applications in food and environmental safety, as well as in diagnosis and medical treatment in the field of veterinary medicine. Because examples of applications in veterinary medicine are scarce, we explore the potential avenues for future applications based on discoveries made in human medicine. Aptamers may offer new possibilities for veterinarians to diagnose certain diseases-particularly infectious diseases-more rapidly or "at the patient's bedside". All the examples highlight the growing interest in aptamers and the premises of a potential market. Aptamers may benefit animals as well as their owners, breeders and even public health in a "One Health" approach.

Research perspectives on animal health in the era of artificial intelligence.

Leveraging artificial intelligence (AI) approaches in animal health (AH) makes it possible to address highly complex issues such as those encountered in quantitative and predictive epidemiology, animal/human precision-based medicine, or to study host × pathogen interactions. AI may contribute (i) to diagnosis and disease case detection, (ii) to more reliable predictions and reduced errors, (iii) to representing more realistically complex biological systems and rendering computing codes more readable to non-computer scientists, (iv) to speeding-up decisions and improving accuracy in risk analyses, and (v) to better targeted interventions and anticipated negative effects. In turn, challenges in AH may stimulate AI research due to specificity of AH systems, data, constraints, and analytical objectives. Based on a literature review of scientific papers at the interface between AI and AH covering the period 2009-2019, and interviews with French researchers positioned at this interface, the present study explains the main AH areas where various AI approaches are currently mobilised, how it may contribute to renew AH research issues and remove methodological or conceptual barriers. After presenting the possible obstacles and levers, we propose several recommendations to better grasp the challenge represented by the AH/AI interface. With the development of several recent concepts promoting a global and multisectoral perspective in the field of health, AI should contribute to defract the different disciplines in AH towards more transversal and integrative research.

Organoids: a promising new in vitro platform in livestock and veterinary research.

Organoids are self-organizing, self-renewing three-dimensional cellular structures that resemble organs in structure and function. They can be derived from adult stem cells, embryonic stem cells, or induced pluripotent stem cells. They contain most of the relevant cell types with a topology and cell-to-cell interactions resembling that of the in vivo tissue. The widespread and increasing adoption of organoid-based technologies in human biomedical research is testament to their enormous potential in basic, translational- and applied-research. In a similar fashion there appear to be ample possibilities for research applications of organoids from livestock and companion animals. Furthermore, organoids as in vitro models offer a great possibility to reduce the use of experimental animals. Here, we provide an overview of studies on organoids in livestock and companion animal species, with focus on the methods developed for organoids from a variety of tissues/organs from various animal species and on the applications in veterinary research. Current limitations, and ongoing research to address these limitations, are discussed. Further, we elaborate on a number of fields of research in animal nutrition, host-microbe interactions, animal breeding and genomics, and animal biotechnology, in which organoids may have great potential as an in vitro research tool.

Clinical techniques in veterinary dermatology: regional anaesthesia of the canine and feline distal limb.

BACKGROUND: Local anaesthesia for procedures involving the distal limb are a useful component of balanced protocols to achieve effective procedural analgesia for patients. A ring block is an effective and straightforward technique. HYPOTHESIS/OBJECTIVE: To review and describe the ring block technique for local anaesthesia of the canine and feline distal limb. ANIMALS: Images of hospitalized patients were used. These photographs were obtained with owner permission. RESULTS: The clinical technique for the ring block of the canine or feline distal limb is described. CONCLUSIONS AND CLINICAL IMPORTANCE: The ring block can be implemented simply and successfully for a variety of procedures involving the distal limb to provide effective analgesia.

Gas Plasma-Augmented Wound Healing in Animal Models and Veterinary Medicine.

The loss of skin integrity is inevitable in life. Wound healing is a necessary sequence of events to reconstitute the body's integrity against potentially harmful environmental agents and restore homeostasis. Attempts to improve cutaneous wound healing are therefore as old as humanity itself. Furthermore, nowadays, targeting defective wound healing is of utmost importance in an aging society with underlying diseases such as diabetes and vascular insufficiencies being on the rise. Because chronic wounds' etiology and specific traits differ, there is widespread polypragmasia in targeting non-healing conditions. Reactive oxygen and nitrogen species (ROS/RNS) are an overarching theme accompanying wound healing and its biological stages. ROS are signaling agents generated by phagocytes to inactivate pathogens. Although ROS/RNS's central role in the biology of wound healing has long been appreciated, it was only until the recent decade that these agents were explicitly used to target defective wound healing using gas plasma technology. Gas plasma is a physical state of matter and is a partially ionized gas operated at body temperature which generates a plethora of ROS/RNS simultaneously in a spatiotemporally controlled manner. Animal models of wound healing have been vital in driving the development of these wound healing-promoting technologies, and this review summarizes the current knowledge and identifies open ends derived from in vivo wound models under gas plasma therapy. While gas plasma-assisted wound healing in humans has become well established in Europe, veterinary medicine is an emerging field with great potential to improve the lives of suffering animals.

The UK Veterinary Immunological Toolbox Website: promoting vaccine research by facilitating communication and removing reagent barriers.

Using the best animal models to study immune responses against specific pathogens or vaccines can dramatically accelerate our understanding. Veterinary species are well studied, particularly livestock, to reduce their disease burden. They have also proven to be powerful models, especially for zoonotic pathogens and novel vaccination strategies. A prerequisite for any model selection is having the right quality and range of species-specific immunological reagents. To help promote the widest possible use of veterinary species, an open access website (https://www.immunologicaltoolbox.co.uk) has been created as a central community annotated hub for veterinary immunological reagents. The website is also the portal into services offered by the UK Immunological Toolbox project that includes antibody generation, sequencing and recombinant expression. The funding for this effort is linked into sustainable sources, but ultimate success relies on community engagement to continually increase the quality and quantity of information. It is hoped that as more users and reagent owners engage, it will become an essential resource for researchers, veterinarians and clinicians alike by removing barriers that prevent the use of the most informative animal models.

The equine asthma model of airway remodeling: from a veterinary to a human perspective.

Human asthma is a complex and heterogeneous disorder characterized by chronic inflammation, bronchospasm and airway remodeling. The latter is a major determinant of the structure-function relationship of the respiratory system and likely contributes to the progressive and accelerated decline in lung function observed in patients over time. Corticosteroids are the cornerstone of asthma treatment. While their action on inflammation and lung function is well characterized, their effect on remodeling remains largely unknown. An important hindrance to the study of airway remodeling as a major focus in asthma research is the lack of reliable non-invasive biomarkers. In consequence, the physiologic and clinical consequences of airway wall thickening and altered composition are not well understood. In this perspective, equine asthma provides a unique and ethical (non-terminal) preclinical model for hypothesis testing and generation. Severe equine asthma is a spontaneous disease affecting adult horses characterized by recurrent and reversible episodes of disease exacerbations. It is associated with bronchoalveolar neutrophilic inflammation, bronchospasm, and excessive mucus secretion. Severe equine asthma is also characterized by bronchial remodeling, which is only partially improved by prolonged period of disease remission induced by therapy or antigen avoidance strategies. This review will focus on the similarities and differences of airway remodeling in equine and human asthma, on the strengths and limitations of the equine model, and on the challenges the model has to face to keep up with human asthma research.

Precision cut lung slices: a novel versatile tool to examine host-pathogen interaction in the chicken lung.

The avian respiratory tract is a common entry route for many pathogens and an important delivery route for vaccination in the poultry industry. Immune responses in the avian lung have mostly been studied in vivo due to the lack of robust, relevant in vitro and ex vivo models mimicking the microenvironment. Precision-cut lung slices (PCLS) have the major advantages of maintaining the 3-dimensional architecture of the lung and includes heterogeneous cell populations. PCLS have been obtained from a number of mammalian species and from chicken embryos. However, as the embryonic lung is physiologically undifferentiated and immunologically immature, it is less suitable to examine complex host-pathogen interactions including antimicrobial responses. Here we prepared PCLS from immunologically mature chicken lungs, tested different culture conditions, and found that serum supplementation has a detrimental effect on the quality of PCLS. Viable cells in PCLS remained present for ≥ 40 days, as determined by viability assays and sustained motility of fluorescent mononuclear phagocytic cells. The PCLS were responsive to lipopolysaccharide stimulation, which induced the release of nitric oxide, IL-1ß, type I interferons and IL-10. Mononuclear phagocytes within the tissue maintained phagocytic activity, with live cell imaging capturing interactions with latex beads and an avian pathogenic Escherichia coli strain. Finally, the PCLS were also shown to be permissive to infection with low pathogenic avian influenza viruses. Taken together, immunologically mature chicken PCLS provide a suitable model to simulate live organ responsiveness and cell dynamics, which can be readily exploited to examine host-pathogen interactions and inflammatory responses.

Phosphine detection in veterinary samples using headspace gas chromatography/tandem mass spectrometry with multiple reaction monitoring.

RATIONALE: Determination of phosphine exposure from zinc or aluminum phosphide fumigants continues to be a routine analytical requirement in veterinary forensic toxicology. There is a need for a more reliable and specific method than simple gas chromatography/mass spectrometry (GC/MS) analysis of sample solvent extracts, as GC/MS of extracts on capillary columns used for general screens involves significant interference from air peaks. METHODS: GC/MS/MS headspace analysis of acid-generated phosphine gas enabled study of the feasibility of devising multiple reaction monitoring (MRM) approaches to the determination of phosphine with greater specificity. RESULTS: Collision-induced dissociation in GC/MS/MS showed that phosphine generated m/z 34 → 31, 32 and 33 ion transitions by sequential proton release as well as minor transitions m/z 34 → 47, 34 → 63 and 63 → 31.5 by intermolecular collisions and double charging. Study of the formation of these product ions enabled development of MRM settings for a highly useful headspace method for phosphine detection. CONCLUSIONS: The method was validated over a working range of 5-100 ppm of phosphide generating phosphine gas which enabled retention of regular screen capillary columns without necessitating separation from air components. The method should have adequate sensitivity and reliability for veterinary toxicology laboratories confronting specimens from animals poisoned by crop fumigants.

Design of a multiplex quantitative reverse transcription-PCR system to simultaneously detect 16 pathogens associated with bovine respiratory and enteric diseases.

AIM: Bovine respiratory disease (BRD) and bovine enteric disease (BED) are two major diseases in cattle, resulting in severe economic losses in the dairy and beef industries. The two major diseases are associated with several factors such as viruses, bacteria, the health condition of the host and environmental factors. We aimed to design a new efficient diagnostic method, which rapidly detect causative pathogens, minimizing economic loss due to BRD and BED. METHODS AND RESULTS: We designed a multiplex quantitative reverse transcription-PCR (qRT-PCR) system for the simultaneous diagnosis of 16 pathogens, including 12 viruses and 4 bacteria related to BRD and BED, based on single qRT-PCR assays in previous studies. The designed multiplex qRT-PCR was highly sensitive and has minimal detection levels which will be no different from those of single qRT-PCR. Moreover, the multiplex qRT-PCR could more efficiently detect the causative pathogens than conventional RT-PCR in test using a part of BRD and BED clinical samples. Furthermore, our data revealed that the multiplex qRT-PCR had high performance in its specificity and reproducibility tests. CONCLUSIONS: Our system can effectively detect multiple BRD or BED related pathogens from each animal while testing several clinical samples via the multiplex qRT-PCR. It is more time-, cost- and labour-efficient than other diagnostic methods. SIGNIFICANCE AND IMPACT OF THE STUDY: Rapid detection of infected animals from the herd using our system will greatly contribute to infection control and prompt treatment in field.

Development and application of a novel ELISA for detecting antibodies against group I fowl adenoviruses.

Since 2015, outbreaks of hepatitis-hydropericardium syndrome (HPS) caused by a novel genotype of fowl adenovirus 4 (FAdV-4) infection have created serious economic losses in China. Given that other serotypes of hypervirulent FAdVs have also been reported in poultry around the world, a common ELISA for all serotypes within the group I fowl adenoviruses (FAdV-I) is urgently needed, especially for clinical epidemic serotypes. In this study, we used high purity and concentration virions of FAdV-4 and developed a common ELISA for detecting antibodies against 12 FAdV-I serotypes. The developed ELISA was able to distinguish between antibodies against FAdV-I, FAdV-III, and other heterologous viruses without any cross-reaction. Furthermore, the ELISA showed higher sensitivity than the FAdV-1-based ELISA to the novel FAdV-4 found in China. Moreover, since there are no commercial vaccines against FAdVs in China, the ELISA was applied to detect sera samples from specific pathogen-free chickens inoculated with inactivated FAdV-1, FAdV-4, and FAdV-8a. The assay showed high sensitivities for all three detected serotypes within FAdV-I. In conclusion, a novel, common ELISA for FAdV-I was developed in this study and could be a powerful tool for seroepidemiological investigations and FAdVs vaccine development.

Veterinarian barriers to knowledge translation (KT) within the context of swine infectious disease research: an international survey of swine veterinarians.

BACKGROUND: Food animal veterinarians face commodity specific and urgent global challenges yet conditions preventing use of best available knowledge have been sparsely studied. The American Association of Swine Veterinarians (AASV) membership (N = 1289) was surveyed online to benchmark their information priorities and their motivations and sources for keeping current with infectious disease research, and to describe their reported time, skill, access, and process as barriers to knowledge translation (KT). RESULTS: Respondents (n = 80) were mostly from Canada (n = 40) and the U.S.A (n = 31) and demographics approximated the AASV's. Colleagues are the first choice for information on difficult cases (49%, 95%CI: 38-61). Half of respondents (53%, 95%CI: 41-64) spend an hour or less per week keeping up with infectious disease research. The majority reported moderate or less than moderate efficiency (62%, 95%CI: 51-72), and moderate or greater stress (59%, 95%CI: 48-70) with their process for keeping up. Journal article methods sections are commonly not read, almost a third (32%, 95% CI: 22-43) reported either they do not evaluate statistical methods or that they had poor confidence to do so, and half (52, 95%CI: 41-63) could not explain 'confounding bias'. Approximately half (55%, 95%CI: 41-69) with direct oversight of swine herds had full access to 2 or fewer academic journals. Approximately a third of respondents (34%, 95%CI: 24-46) selected only formats involving single research studies (either full text or summaries) as preferred reading materials for keeping current over expert summaries of the body of evidence. CONCLUSION: KT barriers are considerable and a source of stress for many swine veterinarians. Sub-optimal efficiency with keeping up and low confidence to appraise aspects of research are concerns. Results are consistent with previous literature and illustrate need for improved KT infrastructure and for additional training in statistical methods and interpretation of primary research. Further evaluation is warranted of why approximately a third of veterinarians in this study, for the purpose of keeping up, preferentially choose to review individual research studies over choices that would include an expert summary of the body of evidence. Consideration of reasons for this preference will be important in the planning of KT infrastructure improvements.

The use of induced pluripotent stem cells in domestic animals: a narrative review.

Induced pluripotent stem cells (iPSCs) are undifferentiated stem cells characterized by the ability to differentiate into any cell type in the body. iPSCs are a relatively new and rapidly developing technology in many fields of biology, including developmental anatomy and physiology, pathology, and toxicology. These cells have great potential in research as they are self-renewing and pluripotent with minimal ethical concerns. Protocols for their production have been developed for many domestic animal species, which have since been used to further our knowledge in the progression and treatment of diseases. This research is valuable both for veterinary medicine as well as for the prospect of translation to human medicine. Safety, cost, and feasibility are potential barriers for this technology that must be considered before widespread clinical adoption. This review will analyze the literature pertaining to iPSCs derived from various domestic species with a focus on iPSC production and characterization, applications for tissue and disease research, and applications for disease treatment.

Improving decision-making in complicated or rare cases-An approach towards Evidence-based Veterinary Medicine in small animal reproduction.

The concepts of Evidence-based Veterinary Medicine (EBVM) provide a methodological and systematic approach to include the best evidence from research into clinical decision-making. These concepts include steps as the search and assessment of relevant research findings and consideration of individual aspects. In addition, owners and other persons involved in animal health care should be included in shared decision-making. Some breeders have good basic knowledge concerning breeding management and characteristics of diseases and concerning advantages and disadvantages of different therapeutic approaches, while others are notable to understand complex medical interrelations or emergency situations. All these aspects need to be addressed when communicating and discussing different diagnostic, prophylactic and therapeutic options. In special fields, such as small animal reproduction, veterinarians often see animals with rare diseases or complex conditions so that an application of standard therapies and well-established textbook recommendations is not possible. To learn more about cases too rare for successful systematic research, the case collection tool REPROCASES (www.evssar.org/reprocases) is now available. The aim of this project is to gather information from specialists on small animal reproduction in a multicentre approach. If you see rare or not well-investigated cases such as cystic ovarian diseases, cryptorchidism or others, you are more than welcome to share your findings via the database. Even if this approach cannot completely replace standardized clinical trials, the idea is to gather more information on effects, prognosis, side effects and long-term fertility for specific conditions.

Medical-Grade ECG Sensor for Long-Term Monitoring.

The recent trend in electrocardiogram (ECG) device development is towards wireless body sensors applied for patient monitoring. The ultimate goal is to develop a multi-functional body sensor that will provide synchronized vital bio-signs of the monitored user. In this paper, we present an ECG sensor for long-term monitoring, which measures the surface potential difference between proximal electrodes near the heart, called differential ECG lead or differential lead, in short. The sensor has been certified as a class IIa medical device and is available on the market under the trademark Savvy ECG. An improvement from the user's perspective-immediate access to the measured data-is also implemented into the design. With appropriate placement of the device on the chest, a very clear distinction of all electrocardiographic waves can be achieved, allowing for ECG recording of high quality, sufficient for medical analysis. Experimental results that elucidate the measurements from a differential lead regarding sensors' position, the impact of artifacts, and potential diagnostic value, are shown. We demonstrate the sensors' potential by presenting results from its various areas of application: medicine, sports, veterinary, and some new fields of investigation, like hearth rate variability biofeedback assessment and biometric authentication.

Advances in infrared thermography: Surgical aspects, vascular changes, and pain monitoring in veterinary medicine.

One of the main functions of infrared thermography (IRT) consists in detecting temperature changes in organisms caused by variations in surface blood circulation. IRT is a useful tool that has been used mainly as a diagnostic method for various stress-causing pathologies, though recent suggestions indicate that it can be used to assess the block quality of certain body regions. In the field of anaesthesiology, IRT has been applied to brachial and epidural blocks, while in algology, changes in surface blood circulation associated with sympathetic activity have been investigated. Thermography has also been employed to complement pain level scales based on the facial expressions of patients in critical condition, or after surgery. In addition, it has been used as a tool in research designed to evaluate different surgical procedures in human medicine, as in the case of surgical burrs for placing dental implants, where IRT helps assess the degree of heating associated with bone devascularisation, reduction in vascular perfusion as a consequence of stroke, and changes in the autonomous nervous system, or the degree of vascular changes in flaps applied to burn patients. In veterinary medicine, thermography has brought several benefits for animals in terms of evaluating lesions, diseases, and surgical procedures. The aim of this review is to evaluate how IRT can be used as a tool in surgical procedures, cases of vascular change, and pain monitoring in veterinary medicine with an emphasis on small animals.

Diagnosis and treatment of demodicosis in dogs and cats: Clinical consensus guidelines of the World Association for Veterinary Dermatology.

BACKGROUND: Demodicosis is a common disease in small animal veterinary practice worldwide with a variety of diagnostic and therapeutic options. OBJECTIVES: To provide consensus recommendations on the diagnosis, prevention and treatment of demodicosis in dogs and cats. METHODS AND MATERIALS: The authors served as a Guideline Panel (GP) and reviewed the literature available before December 2018. The GP prepared a detailed literature review and made recommendations on selected topics. A draft of the document was presented at the North American Veterinary Dermatology Forum in Maui, HI, USA (May 2018) and at the European Veterinary Dermatology Congress in Dubrovnik, Croatia (September 2018) and was made available via the World Wide Web to the member organizations of the World Association for Veterinary Dermatology for a period of three months. Comments were solicited and responses were incorporated into the final document. CONCLUSIONS: In young dogs with generalized demodicosis, genetic and immunological factors seem to play a role in the pathogenesis and affected dogs should not be bred. In old dogs and cats, underlying immunosuppressive conditions contributing to demodicosis should be explored. Deep skin scrapings are the diagnostic gold standard for demodicosis, but trichograms and tape squeeze preparations may also be useful under certain circumstances. Amitraz, macrocyclic lactones and more recently isoxazolines have all demonstrated good efficacy in the treatment of canine demodicosis. Therapeutic selection should be guided by local drug legislation, drug availability and individual case parameters. Evidence for successful treatment of feline demodicosis is strongest for lime sulfur dips and amitraz baths.