Abstract

Keywords

Introduction

Method

Analyses

Results

Discussion

Conclusion

Acknowledgments

Ethical considerations

Conflict of interest

Appendix. Supplementary materials

References

Abstract

Conservation Detection Dogs (CDDs) are trained to locate biological material from plants and animals relevant to conservation efforts. CDDs can be more effective and more economical than other survey methods, yet financial costs associated with training and maintaining CDDs, while meeting their welfare needs, can prohibit their use. It takes a great deal of time and effort to train operational CDDs, but an important foundational skill is being able to detect a target odor in controlled conditions. In this study we developed and evaluated a program in which community volunteers trained their own companion dog in such a task. Following an initial assessment, 19 dog-handler teams were selected to work with two professional CDD trainers in a 12-week training program. Teams were assessed in Weeks 8 and 12 in scent board and room search activities. Seventeen teams completed the full program and located the target odor in a minimum of 75% of all search trials in which the odor was present. Search performance was re-assessed in 11 teams after a 14-week period without maintenance training, with no significant reduction in performance being found in search time, proportion of correct responses or number of false alerts. These results suggest that companion dogs can be successfully trained to locate a target odor in controlled conditions in 12 weeks and that this skill is retained for at least several months. While this is a far cry from what might be expected of a fully operational CDD, it is an important first step in demonstrating that a volunteer training model may provide one way to help address financial limitations and welfare implications that can be associated with professional CDDs, while engaging community members in important and sustainable conservation work.

Introduction
The use of conservation detection dogs (CDDs), trained to detect targets relevant to conservation efforts, is growing in popularity (Beebe et al., 2017). Evidence suggests that CDDs can be more effective and, in some cases, more economical, than other survey methods, such as camera traps or hair snares, in detecting the presence/absence and relative abundance of plants and wildlife in a non-invasive way (Jenkins et al., 1963; Arnett, 2006; Goodwin et al., 2010; Harrison, 2006; Dematteo et al., 2009). Despite their relative costeffectiveness, the actual cost of training and maintaining CDD dogs and professional handlers remains prohibitive, costing tens to hundreds of thousands of dollars depending on the project requirements (Orkin et al., 2016). This can make them an unrealistic option for many stakeholders, from small community groups through to large not-for-profit organisations.

Highlights

ABSTRACT

Keywords

Introduction

Material and methods

Results

Discussion

Conclusion

Policy and ethics

Conflict of interest

CONTRIBUTORSHIP statement

Uncited References:

Acknowledgements

References

ABSTRACT

Foreign body (FB) ingestion in dogs can threaten the animal’s life and often result in an emergency surgery. The causes of pica (ingestion of non-nutritive substance) remain unexplored, although behavioral conditions including hyperactivity, impulsivity, obsessive-compulsive oral/ingestive disorders, anxiety or attachment related troubles have been implicated. Such behavioral causes of pica were investigated with two grids: Lit’s owner-based questionnaire, which measures inattention and hyperactivity-impulsivity, and Beata’s clinical 4A grid which investigates aggression, anxiety, attachment, and autocontrols of dogs. These grids were fulfilled for 42 FB ingesting dogs and 42 pair-matched control dogs.

The main results show that FB ingestion is rarely related to digestive pain (12% of cases) but is primarily of a behavioural nature (88% of cases). Total Scores from both grids are significantly different between FB and control group (Lit scores: Wilcoxon signed-rank test, W=665.5; p=0.007; 4A: Wilcoxon signed-rank test, W=41; p<0.001). Regular shredding of objects is mainly related to a hyperactivity-impulsivity disorder (Lit total score: Mann-Whitney test, U=99; p=0.02; 4A Autocontrols Scores: Mann-Whitney test, U=35; p<0.001), whereas its absence in FB ingestion suggests anxiety or attachment disorder.

Behavioral pathology should be assessed not only for dogs ingesting non-edible objects, but also for those shredding objects. This exacerbated oral exploration is a sufficient sign for veterinarians to consider a behavioral investigation.

INTRODUCTION

Foreign bodies (FB) ingestion or pica refers to ingestion of non-nutritive, non-food items such as fabric, plastics , sticks or stones (Riva et al., 2008; Overall, 2013). In dogs and cats, intestinal FB are some of the most common causes of obstruction (Papazoglou et al., 2003) and can result in life-threatening complications caused by hypovolemia, toxemia, intestinal necrosis, perforation, or peritonitis (Hayes, 2009; Pratt et al., 2014), especially when the FB are not spherical, i.e., linear or angular (Hobday et al., 2014). The care usually consists in the removal of the FB by endoscopy or surgery and monitoring for possible complications (Lindquist and Lobetti, 2017). Importantly, the causes underlying the FB ingestion are barely investigated or mentioned (Papazoglou et al., 2003; Hayes, 2009; Pratt et al., 2014; Hobday et al., 2014). A recent study indicates that “there are no reports of an apparent underlying reason for the ingestion of the FB” (Lindquist and Lobetti, 2017). Other papers report several causes such as malnutrition, parasites, pancreatic failure, abdominal pain, liver encephalitis, hypothyroidy, anemia, zinc intoxication (Hand et al., 2000) but they do not mention behavioral pathology as possible cause.

Highlights

ABSTRACT

Keywords

Introduction

Materials and methods

Results

Discussion

Conclusions

Uncited References:

Authorship statement

Declaration of Competing Interest

Acknowledgements

References

ABSTRACT

This study evaluated the associations of temperament with body weight (BW) and body condition score (BCS) change, ovarian structures, and inflammatory response in grazing Nellore cows assigned to a fixed-time artificial insemination (FTAI) protocol. Forty multiparous cows were kept on pasture and offered free-choice access to mineral/vitamin supplementation and FTAI on d 0. Individual temperament scores (1-5) were assessed in the squeeze chute on d -30, where 1 are animals extremely calm and 5 extremely excitable. Cows with a chute score ≤ 3 were classified as “calm”, and > 3 as “excitable”. The BW and BCS were evaluated on d -30, 0 and 30, ovarian structures on d 0 and 14, and blood samples collected on d -30, -11, 0, 7, 14, 21 and 30. Excitable animals tended to have less (P = 0.09) BCS and lose more (P = 0.09) BCS from d -30 to 0. Temperament did not affect (P ≥ 0.12) BW and BW change. Excitable animals tended (P ≤ 0.10) to have smaller dominant follicles, corpus luteum (CL) diameters and CL volumes. Temperament did not affect (P ≥ 0.14) plasma concentrations of haptoglobin and ceruloplasmin, but excitable animals had less (P = 0.04) plasma concentrations of progesterone on d 7 and 14. Thus, excitable cows had less plasma progesterone concentrations and tended to have a greater decrease in body condition score and had smaller dominant follicles and corpus luteum size.

Introduction

Several factors may influence the reproductive performance of beef cows, and one of them is temperament (Cooke et al., 2009a, 2011, 2017; Kasimanickam et al., 2014; Rueda et al., 2015). Animal temperament can be defined as a response to environmental or social stimuli (Haskell et al.,2014). Potential causes of the excitable temperament in cattle include genetics, inadequate facilities, and improper handling. According to Rueda et al. (2015), handling excitable cows in the squeeze chute increases the incidence of aggression to the handlers, insemination time, likelihood of accidents, contamination in the perineal region during artificial insemination (AI), and reduces the technician AI efficiency. In addition, excitable cows have less pregnancy percentage following fixed-time AI (FTAI; Cooke et al., 2009a, 2011, 2017; Kasimanickam et al., 2014; Rueda et al., 2015). Temperament can negatively affect reproductive performance by several mechanisms, such as decreasing dry matter intake (DMI) and nutritional status (Bruno et al., 2016), and increasing the stimulation of the hypothalamic-pituitary-adrenal axis leading to greater circulating concentrations of cortisol (Curley Jr et al., 2008) and acute phase proteins (Cooke et al., 2009a, 2012; Francisco et al., 2015). Kasimanickam et al. (2014) observed that temperament also impacts ovarian parameters, and is negatively correlated with follicles number and size of the dominant follicle. We are unaware of studies evaluating the associations of temperament with corpus luteum diameters/volumes in purebred Bos indicus cows. We hypothesized that the excitable temperament in the squeeze chute can mainly reflect in reduction of the size of the corpus luteum and in its production of progesterone. Thus, the objective of this study was to evaluate the associations of temperament with body weight (BW) and body condition score (BCS) change, ovarian structures and inflammatory response of grazing Nellore cows synchronized to FTAI

Highlights

Abstract

Keywords

1. Introduction

2. Materials and methods

3. Results

4. Discussion

5. Conclusions

Declaration of Competing Interest

Acknowledgement

References

Abstract

The objective of this research is to study the feasibility using nanomaterials to prevent and/or repair wear of teeth. Canine teeth have thin enamel prone to dental wear, causing pain, tooth loss, and infection. This research developed a new teeth repair agent based on the tribochemically active nanoparticles. The presence and properties of synthesized repair agents were evaluated after applying the repair agents by rubbing (simulated chewing) between extracted dog teeth. Polyether modified alpha‑zirconium phosphate (α-ZrP) nanoparticles form a strong and durable protective layer on a canine tooth’s enamel surface through chewing. The effectiveness of this protective film generation was enhanced by adding hydroxyapatite (HAp) nanoparticles into the repair agent. This protective film is up to 2 μm thick and has a hardness comparable to the enamel substrate. These results show that by chewing with the repair agent, the teeth are protected. The tomography result shows this repair agent also has the potential to mend cracks on the enamel surface. This research reports a novel approach to protect the wear of teeth. Nanoparticles promoted the generation of a protective film in situ during the chewing process. This nanomaterial can be the base of novel dental protective devices such as chewing toys or gums that preventing or reversing tooth wear and reducing the stress and cost of dental restoration operations.

1. Introduction
Tooth enamel is the hardest and most dense structure in the mammalian body. It serves to protect the interior of the tooth from the normal flora of the oral cavity and other harmful substances [1,2]. Although it is the hardest tissue in humans and animals [3–6], it can suffer damage from mechanical forces [7–12] and acidic solutions [13–16]. In dogs, the enamel layer is significantly thinner than in humans [17] and more prone to excessive wear and damage. This type of wear can result in dentin and pulp exposure causing significant oral pain, tooth loss, or periarticular and pulpal infections [18,19], leading to deterioration in quality of life and, in extreme cases, to be life threatening [13,20,21]. Recently, remineralization of damaged tooth enamel was presented as an alternative method to traditional dental operations [22–24]. These researchers utilized the bio-mineralization process that naturally presented in the dental environment [25–27]. Precursors to the nanoparticle hydroxyapatite were used to form the hard enamel tissue in vitro or in vivo [23,27]. Some examples of the precursors are casein phosphopeptide-stabilized amorphous calcium phosphate [28–30]; amelogenin with fluoride [31], and polydopamine with hydroxyapatite (HAP) [23]. Unlike traditional dental treatments, this method repaired teeth with materials that were almost identical to the teeth themselves. However, like the natural biomineralization process, using the remineralization method required significant time (>24 h) to take effect [22,23,27]. This is a major limitation to the clinical application of this approach.

1- Introduction

2- In vitro studies

3- In vivo studies

4- Conclusion(s)

References

Abstract

Stem cell, one of the most exciting research areas of 21st century, is considered to have broaden the horizons of the field of biology, in general and medicine, in particular. Stem cells, owing to their unique characteristics like self-renewal, multiplication and differentiation are considered to provide an ‘all-in-one-solution’ for diverse clinical problems. Among various stem cell types, mesenchymal stem cells (MSCs) are being made the subject of the most of the studies on their therapeutic applications. It is attributable to their readily available sources, ability to immunemodulate and differentiate into mesodermal and extra-mesodermal tissues. MSCs in contrast to pluripotent stem cells carry minimal risk of teratoma formation and are free from any ethical concern. MSCs have been evaluated under innumerable studies but the definitive applications of these cells are slow, plausibly due to the incomplete understanding of their cellular physiology. Goat MSCs (gMSCs) have been isolated, culture expanded, characterized from various tissue sources and studied for their potential in vivo applications mostly in relation to human translational models. The current review throws some light on gMSC sources, characterization and potential therapeutic applications.

Introduction

The stem cells constitute an important element in the discipline of regenerative medicine that aims to address numerous incurable diseases through tissue regeneration (Gugjoo and Amarpal, 2018; Gugjoo et al. 2019). The specialized properties of selfrenewal, multiplication and differentiation of stem cells make them potential candidates for an all-in-one therapeutic solution to diverse clinical ailments. Among various stem cell types, mesenchymal stem cells (MSCs) make subject of most of the therapeutic applications (Gugjoo et al. 2019). MSCs are available in almost all the tissue types and have easy isolation and culture processes. The cells are plastic in nature, and have immunomodulatory and/ anti-inflammatory properties with minimal risk of teratogenicity and associated ethical issues unlike that of embryonic stem cells (Song et al. 2013; Gugjoo et al. 2019).

1- Introduction

2- Conventional approach to generate genetically engineered livestock

3- Development of genome editing technology

4- Application of genome editing technology in livestock

5- Genetically engineered livestock produced using genome editing technology

6- Future prospective and current limitations

7- Conclusion

References

Abstract

Historically, genetic engineering in livestock proved to be challenging. Without stable embryonic stem cell lines to utilize, somatic cell nuclear transfer (SCNT) had to be employed to produce many of the genetically engineered (GE) livestock models. Through the genetic engineering of somatic cells followed by SCNT, GE livestock models could be generated carrying site-specific modifications. Although successful, only a few GE livestock models were generated because of low efficiency and associated birth defects. Recently, there have been major strides in the development of genome editing tools: Zinc-Finger Nucleases (ZFNs), Transcription activator-like effector nucleases (TALENS), and Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated 9 (Cas9) system. These tools rely on the generation of a double strand DNA break, followed by one of two repair pathways: non-homologous end joining (NHEJ) or homology directed repair (HDR). Compared to the traditional approaches, these tools dramatically reduce time and effort needed to establish a GE animal. Another benefit of utilizing genome editing tools is the application of direct injection into developing embryos to induce targeted mutations, therefore, eliminating side effects associated with SCNT. Emerging technological advancements of genome editing systems have dramatically improved efficiency to generate GE livestock models for both biomedical and agricultural purposes. Although the efficiency of genome editing tools has revolutionized GE livestock production, improvements for safe and consistent application are desired. This review will provide an overview of genome editing techniques, as well as examples of GE livestock models for agricultural and biomedical purposes.

Introduction

54 The ability to engineer the genome has been limited in livestock species, in part due to 55 the lack of stable embryonic stem (ES) cells that can contribute to the germline. In the mouse, 56 targeted disruption of genes can be performed in ES cells, then the ES cells carrying desired 57 genotypes can be introduced into recipient blastocysts to generate chimeric mice that can 58 transmit the desired genotype to the germline [1-3]. This strategy has been effective, thus 59 establishing the mouse as the main model in biomedicine to elucidate the function of target 60 genes. Since true ES cells that can contribute to the germline have not been fully identified in 61 livestock species, the development of somatic cell nuclear transfer (SCNT) technology [4] 62 allowed researchers to generate genetically engineered (GE) livestock. Genetic modification of 63 somatic cells followed by SCNT allowed for the generation of GE livestock with targeted 64 modifications [5]. Although possible, efficiency to produce GE animals through the route is poor; 65 therefore, only selective GE models have been produced [6, 7].

INTRODUCTION

MATERIALS AND METHODS

RESULTS

DISCUSSION

ACKNOWLEDGMENTS

REFERENCES

ABSTRACT

nfectious bursal disease virus (IBDV) is still a vital etiological agent in poultry farms. IBDV outbreaks occasionally occur due to the presence of very virulent, reassortment or variant strains. Vaccine immunization has played crucial roles in IBD control for decades. However, survival pressure of IBDV from the vaccine immunization also increases the reassortments of circulating viruses. In this study, an IBDV strain was isolated from several broiler farms in Henan Province, central part of China, and named IBDV HN strain. Based on the results of RT-PCR, sequencing and phylogenic analyses of VP1 and VP2 genes, the IBDV HN strain is a novel reassortment strain in the Henan region. Segment A of this strain appears to originate from the very virulent IBDV strain, while segment B comes from the other field reassortment strains. This may be the result of natural reassortant of virus circulating in the field. About 60% (6/10) of experimentally infected specific pathogen-free chickens died after 3 to 5 d post-infection with typical symptom and pathological lesions. The IBDV HN strain was prone to horizontal transmission, which poses a serious threat to the chicken industry. Further investigation on the prevalence, virulence, and evolution of HN strain IBDV will provide a foundation for the prevention and control of the disease in this region.

INTRODUCTION

Infectious bursal disease virus (IBDV) is the primary etiological agent of a highly contagious disease among young chickens. The virus damages the immune organs, particularly the bursa of Fabricius, resulting in severe immune suppression and secondary infections with high morbidity and mortality (Rosenberger and Gelb, 1978; Sharma et al., 2000; Ye et al., 2017). As a member of the Birnaviridae family, IBDV contains a doublestranded RNA genome with segments A and B. The 2.8 kb segment B encodes the VP1 protein (879 amino acids (aa)), which is responsible for viral genome replication and RNA synthesis as a RNA-dependent RNA polymerase. The 3.2 kb segment A contains two partially overlapping open reading frames (ORFs), 1 and 2. The smaller ORF1 precedes and overlaps the larger ORF2 and encodes the non-structural protein VP5. The ORF2 encodes a precursor polyprotein (approximately 1012 aa), which is self-processed into three mature proteins: VP2, VP4, and VP3. VP2 is a major structural protein containing the antigen epitope that induces the production of neutralizing antibodies (Alfonso-Morales et al., 2013). Among different strains, the aa sequences of the highly variable region of VP2 are different and commonly affect the virulence of different virus strains (Hoque et al., 2001; Letzel et al., 2007; Lai et al., 2014; Yilmaz et al., 2019). The highly variable region is usually located between the aa residues 206 and 350 and is widely used for molecular epidemiology and phylogenetic studies (Ren et al., 2009; Drissi Touzani et al., 2019).

Introduction

Marek’s disease virus

Avian leukosis virus subgroup J

Influenza A virus

Other viruses

Pathways significantly enriched by the targets of dysregulated miRNAs during viral infection

Conclusions

Acknowledgments

References

Abstract

In poultry, viral infections (e.g., Marek’s disease virus, avian leukosis virus, influenza A virus, and so on) can cause devastating mortality and economic losses. Because viruses are solely dependent on host cells to propagate, they alter the host intracellular microenvironment. Thus, understanding the virus-host interaction is important for antiviral immunity and drug development in the poultry industry. MicroRNAs are crucial posttranscriptional regulators of gene expression in a wide spectrum of biological processes, including viral infection. Recently, microRNAs have been identified as key players in virus-host interactions. In this review, we will discuss the intricacies involved in the virus-host cross-talk mediated by host and viral microRNAs in poultry (i.e., chicken and ducks), as well as recent trends and challenges in this field. These findings may provide some insights into the rapidly developing area of research regarding viral pathogenesis and antiviral immunity in poultry production.

Introduction

Many types of viruses will cause high mortality rates and enormous economic losses to the poultry industry. For example, Marek’s disease virus (MDV) and avian leukosis virus can induce neoplastic diseases in chickens. Moreover, influenza A virus (IAV) is highly variable and can spread across species, thereby resulting in a threat to global public health. Therefore, the cross-talk between the host (i.e., chickens) and viruses during infections is critical to understanding viral pathogenesis and antiviral immunity in chicken production. Over the past decade, studies have attempted to depict the cross-talk between the host and virus from different aspects (e.g., microRNA [miRNAs] perspective) and have made progress in this area (Li et al., 2014a; Skalsky and Cullen, 2010).

miRNAs Are short noncoding 18- to 25-nucleotidelong RNAs that regulate gene expression at the posttranscriptional level. Substantial evidence demonstrates that a single miRNA can have extensive and crucial effects on a range of fundamental biological processes, and miRNA dysregulation can result in biological dysfunction and diseases (Bartel, 2004; Ha and Kim, 2014). Pathogen-induced phenotypic changes in hosts are always accompanied by remarkable alterations at the transcriptional level (Jenner and Young, 2005). The miRNA expression profile is profoundly influenced by viral infection and contributes to the repertoire of virus-host interactions. Differential miRNA expression can be attributed to both host antiviral defenses and alterations in cellular environment that are affected by viral factors (Scaria et al., 2007; Skalsky and Cullen, 2010; tenOever, 2013; Harwig et al., 2014; Powdrill et al., 2016; Nejad et al., 2018). Moreover, miRNAs have been reported to be biomarkers of viral infections (Wang et al., 2014) and have roles in viral reactivation from latency (Hicks et al., 2019). Therefore, the identification of deregulated miRNAs in virally infected chickens will provide novel insight into understanding virus-host interaction. In this review, we will summarize recent advances into the critical role of virally influenced poultry and viral miRNAs in the cross-talk between the host and virus to help understand viral pathogenesis and antiviral immunity in the poultry industry.

1. Introduction

2. Material and methods

3. Results

4. Discussion

5. Conclusions

Acknowledgements

References

Abstract

Marek’s disease (MD) is one of the most devastating diseases of poultry. It’s caused by the highly infectious alphaherpesvirus MD virus serotype 1 (MDV-1). In this study, a rapid and easy-to-use assay based on recombinase polymerase amplification (RPA) was developed for MDV detection. Primer-probe sets targeting the highly conserved region of Meq gene were designed and applied to the RPA assay. The assay was carried out on a real-time thermostatic fluorescence detector at 39 °C for 20 min. As revealed by the results, no cross-reactions were found with the Newcastle disease virus (NDV), chicken infectious anemia virus (CAV), infectious bursal disease virus (IBDV), avian infectious bronchitis virus (IBV), infectious laryngotracheitis virus (ILTV), avain influenza virus (AIV), avian leucosis virus (ALV), avian reovirus (ARV), Marek’s disease virus serotype 2 (MDV-2) and turkey herpes virus (HVT), indicating appropriate specificity of the assay. Plasmid DNA standards were used to determine the sensitivity of the assay and the detection limit was 102 copies/μL. To further evaluate the clinical performance, 94 clinical samples were subjected to the RPA assay and 28 samples were tested MDV positive, suggesting that the real-time RPA assay was sufficient enough for clinical sample detection. Thus, a highly specific and sensitive real-time RPA assay was established and validated as a candidate for MDV diagnosis. Additionally, the portability of real-time RPA assay makes it suitable to be potentially applied in clinical diagnosis in the field, especially in resource-limited settings.

Introduction

Marek’s Disease Virus (MDV) is the causative agent of Marek’s disease (MD) in chickens [1]. It is a highly contagious oncogenic herpesvirus of poultry that can infect chickens, turkeys and pheasant. The virus is shed from feather follicles of infected chicken or birds and contaminates the living environment. Chickens will be infected by inhalation of contaminated air [2,3]. The prevalence of MD in all poultryrearing countries causes huge economic losses every year [4,5]. Isolates of MDV can be classified into three serotypes, only serotype 1 (MDV1) or Gallid herpesvirus 2 (GaHV-2) is pathogenic and oncogenic. The severity of MD varies depending on virus stains, host genotypes and the vaccination status of the infected hosts [6]. Despite the wide use of vaccines, the economic burden of the disease will substantially increase. Therefore, timely and accurate detection of MDV in poultry farms is extremely important.

Conventional methods such as virus isolation and serum neutralization tests are labor-intensive and time-consuming [7]. To date, real-time PCR, GeXP-multiplex PCR assays and xTAG assay have been developed for MDV detection [8–10]. These methods are specific, sensitive and even enable high-throughput detection, which make them perfect choices for laboratory diagnosis. However, the need of expensive equipment such as Luminex-200 reader or GeXP analyser and well-trained technicians limits their applications in poultry farms [11,12].

Birth weight, dystocia, and neonatal survival

Neonatal adaptation

Neonatal immune function

Summary

References

INTRODUCTION

The greatest loss in ruminant production systems occurs during the neonatal period, that is, between birth and 28 days of life. In extensive production systems, neonatal losses are reportedly between 10% and 30% and 6% and 16% for lambs and calves, respectively. With 90% of these offspring born alive, this is considered a preventable welfare issue1 and a high economic burden to the livestock industry. It is well established that in utero environment3 affects ruminant progeny health and welfare. This phenomenon is known as fetal programming and is contingent upon the particularly long gestation period in ruminants during which physiologic systems develop, such that at birth, the ontogeny of these systems is complete. The effects of this fetal programming in the neonate may be mediated by epigenetic modifications that regulate gene expression in both the placenta and the fetus (Fig. 1). These epigenetic modifications may occur as early as embryogenesis through to late gestation. The placenta mediates fetal supply of nutrients, hormones, and oxygen with both the placenta and the fetus responding to maternal perturbations in a sexually dimorphic manner. This dimorphism has significant consequences because survival in the male fetus, during gestation and at birth, is reduced compared with the female fetus. Significantly for this review, many of the contributing factors associated with increased risk of neonatal mortality, that is, premature birth, birth weight, dystocia, and poor adaptation to the postnatal environment, are consequent to the prevailing prenatal environment.

Abstract

During the last decades, the world has witnessed a dramatic increase in allergy prevalence. Epidemiological evidence shows that growing up on a farm is a protective factor, which is partly explained by the consumption of raw cow’s milk. Indeed, recent studies show inverse associations between raw cow’s milk consumption in early life and asthma, hay fever, and rhinitis. A similar association of raw cow’s milk consumption with respiratory tract infections is recently found. In line with these findings, controlled studies in infants with milk components such as lactoferrin, milk fat globule membrane, and colostrum IgG have shown to reduce respiratory infections. However, for ethical reasons, it is not possible to conduct controlled studies with raw cow’s milk in infants, so formal proof is lacking to date. Because viral respiratory tract infections and aeroallergen exposure in children may be causally linked to the development of asthma, it is of interest to investigate whether cow’s milk components can modulate human immune function in the respiratory tract and via which mechanisms. Inhaled allergens and viruses trigger local immune responses in the upper airways in both nasal and oral lymphoid tissue. The components present in raw cow’s milk are able to promote a local microenvironment in which mucosal immune responses are modified and the epithelial barrier is enforced. In addition, such responses may also be triggered in the gut after exposure to allergens and viruses in the nasal cavity that become available in the GI tract after swallowing. However, these immune cells that come into contact with cow’s milk components in the gut must recirculate into the blood and home to the (upper and lower) respiratory tract to regulate immune responses locally. Expression of the tissue homing-associated markers α4β7 and CCR9 or CCR10 on lymphocytes can be influenced by vitamin A and vitamin D3, respectively. Since both vitamins are present in milk, we speculate that raw milk may influence homing of lymphocytes to the upper respiratory tract. This review focuses on potential mechanisms via which cow’s milk or its components can influence immune function in the intestine and the upper respiratory tract. Unraveling these complex mechanisms may contribute to the development of novel dietary approaches in allergy and asthma prevention.

Introduction

In the Western world, the prevalence of chronic inflammatory diseases, including allergies, has increased dramatically in the last few decades, while the number of serious infectious diseases has declined rapidly (1). An inverse correlation, indicating a “protective effect” of infectious diseases against chronic inflammatory diseases (e.g., allergy and asthma), was postulated in 1989 by Strachan, who formulated the hygiene hypothesis (2). The hygiene hypothesis suggests that the exposure to viruses and bacteria is essential to induce a T-helper (Th)1 response, which balances the immune system and protects against Th2-mediated diseases. With the discovery of additional T cell subsets such as Th17 cells and regulatory T cells (Tregs), this paradigm had to be revised. For example, it was demonstrated that suppressive dendritic cells (DCs) induced by helminths restored the disturbed Th1/Th2 balance by induction of Tregs (3). The immune education of DCs was suggested to be an important step toward understanding the complex relation between infectious diseases and allergies (4). Th2 responses are now known to be enhanced by the production of type 2 cytokines (e.g., TSLP, IL-25, IL-33) secreted by group 2 innate lymphoid cells and epithelial cells (5, 6). Thus, different cell types are responsible for Th2-mediated diseases such as allergies. Allergy is initiated as an aberrant immune response towards a harmless antigen (allergen). Via activation of Th2 cells, the allergen triggers the production of allergen-specific IgE by B cells that binds to high-affinity FcεR1 on effector cells like mast cells and basophils. Effector cells release soluble factors (e.g. histamine) upon secondary exposure to the allergen that cause immediate type I allergic symptoms. The term “atopic march” refers to the sequence of IgE responses and clinical symptoms initiated in early life (7).

1. Introduction

Since 1982, the curriculum of the Faculty of Veterinary Medicine in Utrecht (FVM) has changed several times in a relatively short period. Significant changes were made in 1995 and 2001, followed by a fundamental change to an organ-based curriculum within a BachelorMaster (BaMa) structure in 2007. Each time, changes were driven by a need to further improve training in communication, problem-solving capacity and aspects of the profession related to non-clinical areas. The change in 2007 was also driven by a need to conform to the Bologna process in 1999. The main focus in this agreement was: (1) the introduction of a three-cycle system (Bachelor/Master/Doctorate, the latter for example PhD in Academia); (2) strengthened quality assurance; and 3) greater recognition of qualifications and periods of study (http://ec.europa.eu/education/policy/higher-education/bolognaprocess_en). Eysker (2002) discussed the necessity for these changes, and it was noted that teaching of the discipline veterinary parasitology (VP) became more challenging with each curriculum change. This was partly due to the decrease in student contact hours for teaching VP. Within the current BaMa curriculum, a multidisciplinary approach is undertaken, as particularly the Bachelor program is organ-oriented. As if three major curriculum changes over the last two decades were not enough, we now face a new curriculum change proposal to combine the Bachelor of Veterinary and (Bio) medical studies into one common Bachelor, the Life sciences Bachelor. To identify limitations and opportunities in the current and proposed curriculum, we will first present an historical overview. This starts with a short introduction of our Utrecht curriculum of 1995, because that is more similar to the current bi-phasic situation than the 1982 curriculum.

2. The older curricula

2.1. 1995 curriculum

The Netherlands is a small country with a good infrastructure and only one FVM. In this context, older curricula focused on educating Dutch veterinarians for Dutch practices. Students all had the same access to teaching materials, academic staff members and opportunities to witness hospitalised patients as required. The main objective of changing the older curriculum was to improve problem-solving, communication and academic competencies of students (Eysker, 2002). The bi-phasic system then consisted of a so-called general curriculum for all veterinary students, lasting 4 years, followed by a 2-year differentiation program into farm, companion or equine animal health. Improving problem-solving and stronger communication skills was to be achieved with the introduction of (supported) self-study, small working groups of 25 students and group tasks. A core curriculum was supported by elective courses, and the latter were mainly offered to students based on choice of differentiation (from only one, two or up to three differentiations). In the second phase of this curriculum, all students had to carry out a 3-month research assignment to enhance their academic competencies. The total number of contact hours for VP in both phases taken together, was between 72 and 90 h (Eysker, 2002).