Mix it-cograzing with cattle reduces broiler losses and increases broiler range use.

Pasture access allows broilers to perform a wide range of behaviors and is a prerequisite in organic poultry production, but exposes broilers to various potential hazards including predators. Co-grazing broilers with cattle can reduce land use and could offer protection from avian predation. Thus, we aimed to assess the effects of co-grazing on broiler losses, range use, performance, contact dermatitis and broilers' manipulation of cow pats. To this end, across 5 replicates we compared each a treatment group of 54 to 61 broilers co-grazing with 10 young cattle and a similar sized control group of broilers on a pasture which had been grazed by cattle 2 weeks prior. Broilers had pasture access during civil daylight and were locked in the coop overnight. Continuous video recordings of the pastures were used to identify the cause when broilers were missing or found dead. On 2 days per week in 4 replicates, broiler distribution in the pasture and maintenance behaviour (i.e. foraging, standing, lying, locomotion) were observed directly using instantaneous scan sampling. Based on the broilers' distance to the coop we calculated a group Ranging Distance Index (RDI). Cow pats were assessed weekly and contact dermatitis was scored before slaughter. Broilers in the treatment groups ranged further (p = 0.003) and higher percentages of birds tended to be outside (p = 0.09) compared to the control groups. Broiler losses due to predatory birds were consistently lower in treatment (median, range: 1, 0 to 3) than in control groups (3, 2 to 5, p = 0.025). Live weight before slaughter was slightly higher (p = 0.035) in treatment groups than in control groups. Feed conversion ratio (p = 0.174), maintenance behaviors and prevalence of contact dermatitis were not affected. No manipulation of cow pats by broilers was found or observed. Overall, co-grazing with cattle positively affected broiler range use, losses due to avian predation and weight gain.

Can a gradual weaning and separation process reduce weaning distress in dam-reared dairy calves? A comparison with the two-step method.

The weaning and separation phase remains one of the biggest challenges for cow-calf-contact systems, but a gradual process that better mimics the naturally occurring reduction in milk intake has not yet been scientifically investigated. Therefore, the aim of our study was to compare behavioral and physiological indicators of distress in 3 mo-old dam-reared dairy calves (with previous full-time cow-calf contact) weaned and separated either via gradual reduction of contact time with the dam (GR, 1 week half day contact, 1 week morning contact, 1 week fence-line contact before complete separation, n = 18) or via 2-step weaning using a nose flap (NF, 2 weeks access to dam with a nose flap, 1 week fence-line contact before complete separation, n = 18). Behavior was recorded 1 week before (or for lying 3 weeks before) weaning start and during the 3 week weaning and separation period with direct observations on 4 d per week or via accelerometers (locomotor play, lying behavior). Blood and fecal samples were taken twice per week from weaning start until 3 weeks after weaning start. Calves were weighed weekly. Statistical analysis was conducted using (generalized) linear mixed models. Over the whole weaning and separation phase, NF calves showed a stronger decrease in the number of lying bouts, amount of locomotor play and average daily weight gains, as well as a higher increase in total mixed ration feeding time compared with GR calves, whereas GR calves vocalized more often and showed more searching behavior than NF calves. Also, the neutrophil:lymphocyte ratio of NF calves was elevated on d 3 after insertion of the nose flaps compared with baseline, but showed no change for GR calves on any sampling day. Overall, results point toward a favorable effect of a gradual weaning strategy on reduction of weaning and separation distress in dam-reared dairy calves, but the method requires further improvement from the protocol used in our study.

Pasture-based fattening does not cause severe nonperforating lesions in veal calves of dairy breeds.

Abomasal damage is a known health issue in intensive veal production and is associated with improper housing and feeding. Grass-based veal production could be an improvement, as access to pasture allows the expression of natural behaviors, such as species-specific foraging, and thus can contribute to calf welfare. However, data on the abomasal health of grazed calves have not yet been reported. As feed composition can affect the severity of mucosal damage, we compared the abomasa of calves that grazed on 2 swards with different plant composition. From 2018 to 2020, 111 calves of 2 dairy breeds, German Holstein and Jersey, were kept in whole-day strip grazing on these swards. Calves were sampled regularly for intestinal parasites and anthelmintic drug use was recorded. The animals were slaughtered at an age of 32 ± 2 wk (mean ± standard deviation) after individually varying grazing periods of 75 ± 22 d. After slaughter, dissection revealed that 104 of the 111 abomasa displayed low-grade nonperforating lesions, which were primarily located in the pyloric part. A more severe nonperforating lesion was registered in one calf only. In 46 abomasa, we observed diffuse inflammation. This inflammation was characterized by normal mucosal rugae but with slight discoloration that varied in the degree of redness and proliferation of the mucosa. Sward composition and breed did not affect the occurrence of abomasal lesions, but treatment with anthelmintics was negatively correlated with diffuse inflammation. Compared with the abomasa of calves fed under intensive conditions, the abomasa of calves kept on pasture in this study were not as severely altered, but completely unaffected abomasa were rarely observed either. This raises the question to what extent the observed changes in the abomasum were caused by husbandry and feeding conditions or whether they correspond to the normal condition of grazing animals.

Fecal cortisol metabolites reflect transport stress in 3-month-old dairy calves pre- and postweaning: A pilot study.

Measurement of fecal cortisol metabolites (FGCM) is a well-established, noninvasive method to assess stress in adult dairy cattle. However, this procedure has not yet been validated for unweaned dairy calves, and it can be expected that the milk proportion of the diet may influence the resulting FGCM concentrations. The aim of this study was therefore to assess whether a peak in FGCM concentrations in response to a stressor can be measured in unweaned dairy calves on a largely milk-based diet. If so, further objectives were to examine whether maximum FGCM concentrations, as well as the time lag until they are reached, are comparable to the values in the same calves on a solid-based diet after weaning. For this study, 5 German Holstein calves of about 3 mo of age (93 to 102 d preweaning) were exposed to a 45 min transport stressor once before and once after weaning, which was 3 wk apart. All voided fecal samples were collected for 24 h after termination of the transport. Fecal cortisol metabolites were analyzed with an 11-oxoetiocholanolone enzyme immunoassay and changes in FGCM concentrations relative to the individual baseline (FGCMrel) were calculated. Results showed a clear peak in FGCM concentrations on both diet types. The peak FGCMrel concentrations tended to be higher when the calves were on the preweaning diet (at peak: +233 ± 25% increase relative to baseline) in comparison to the postweaning diet (+124 ± 23%). Considering the whole 24 h sampling period, the FGCMrel concentrations for all calves were significantly higher on the preweaning diet than on the postweaning diet. There was also a numerical difference in the delay between occurrence of the stressor and appearance of the peak FGCMrel concentrations in feces, as the time lag was 1.5 ± 1.2 h longer when the calves were on the preweaning diet compared with the postweaning diet. In conclusion, our results suggest that FGCM concentrations are a useful stress marker for unweaned dairy calves in the same way they are for older cattle, but that FGCMrel concentrations tend to be higher in unweaned than in weaned calves and are thus not directly comparable.

Incomplete milking before drying off does not impair the udder health of cows infected with minor pathogens.

When implementing the transition from regular milk production to the dry period, drying off is mostly conducted simply by abrupt cessation of milking. Efforts to reduce milk synthesis before cessation of milking aim to reduce stress in cows as well as to lower the risk of mastitis. A previous study demonstrated that incomplete milking during the last ten days of lactation gradually reduced the milk yield of healthy, high-yielding cows. However, a reduction period of ten days might be too long for cows with lower yields. Therefore, a follow-up study was conducted on an organic dairy research farm with a lower average milk yield. We investigated whether automated incomplete milking can reduce milk synthesis within one week without impairing the health status of udder quarters infected with minor pathogens. Before drying off, 15 German-Holstein cows with 58 lactating quarters, 21 of which were infected with minor pathogens (coagulase-negative Staphylococci (CNS) and Corynebacterium bovis), were milked twice daily using the software module AutoDry (GEA Farm Technologies) with the 5%-step-down-per-day-program. The level of udder emptying was gradually reduced over 8-10 milkings beginning at a mean milk yield of 17.2 ± 4.4 kg d-1. During the last three milkings before drying off, milking clusters were automatically removed when a milk flow rate of 0.3 kg min-1 was reached. Quarter fore-milk samples were collected at two time points (14 d before and at the date of the last milking, ie drying off) and were analysed for mastitis pathogens and somatic cell count. The gradual reduced emptying of the udder induced a clear decline in milk yield by 0.8 ± 0.3 kg d-1. Within the reduction period, the somatic cell count of quarter foremilk did not change regardless of the infection status. Furthermore, no cow suffered from clinical mastitis. Thus, a reduction in milk synthesis could be achieved within less than one week before drying off without any impairment in udder health of cows, even when infected with minor mastitis pathogens.

Oligodendrocytes support axonal transport and maintenance via exosome secretion.

Neurons extend long axons that require maintenance and are susceptible to degeneration. Long-term integrity of axons depends on intrinsic mechanisms including axonal transport and extrinsic support from adjacent glial cells. The mechanisms of support provided by myelinating oligodendrocytes to underlying axons are only partly understood. Oligodendrocytes release extracellular vesicles (EVs) with properties of exosomes, which upon delivery to neurons improve neuronal viability in vitro. Here, we show that oligodendroglial exosome secretion is impaired in 2 mouse mutants exhibiting secondary axonal degeneration due to oligodendrocyte-specific gene defects. Wild-type oligodendroglial exosomes support neurons by improving the metabolic state and promoting axonal transport in nutrient-deprived neurons. Mutant oligodendrocytes release fewer exosomes, which share a common signature of underrepresented proteins. Notably, mutant exosomes lack the ability to support nutrient-deprived neurons and to promote axonal transport. Together, these findings indicate that glia-to-neuron exosome transfer promotes neuronal long-term maintenance by facilitating axonal transport, providing a novel mechanistic link between myelin diseases and secondary loss of axonal integrity.

Gentle interactions with restrained and free-moving cows: Effects on the improvement of the animal-human relationship.

The animal-human relationship is essential for farm animal welfare and production. Generally, gentle tactile and vocal interactions improve the animal-human relationship in cattle. However, cows that are fearful of humans avoid their close presence and touch; thus, the animal-human relationship first has to be improved to a point where the animals accept stroking before their perception of the interactions and consequently the animal-human relationship can become positive. We tested whether the animal-human relationship of cows fearful of humans is improved more effectively by gentle interactions during restraint, allowing physical contact from the beginning, or if the gentle interactions are offered while the animals are free to move, giving them more control over the situation and thus probably a higher level of agency and a more positive perception of the interactions. Thirty-six dairy cows (median avoidance distance 1.6 m) were assigned to three treatments (each n = 12): gentle vocal and tactile interactions during restraint in the feeding rack (LOCK); gentle vocal and, if possible, tactile interactions while free in the barn (FREE); routine management without additional interactions (CON). Treatments were applied for 3 min per cow on 10 d per fortnight for 6 weeks (i.e., three periods). Avoidance and approach behaviour towards humans was tested before the start of the treatment period, and then at 2-week intervals. The recorded variables were reduced to one score by Principal Component Analysis. The resulting relationship score (higher values implying a better relationship with humans) increased in all groups; the increase was stronger in FREE than in CON, with the increase in LOCK being not significantly different from the other treatment groups. Thus, we recommend that gentle interactions with cows should take place while they are unrestrained, if possible.

Short- and long-term effects of rearing dairy calves with contact to their mother on their reactions towards humans.

In this Research Communication we address the hypotheses that reduced contact with humans during the first week of life would impair the relationship of dairy calves reared in dam-calf-contact systems to humans in comparison with artificially reared animals, but that this difference would vanish over time. Artificially reared calves (Artificial) that had been separated from their mother within 12 h after birth were bottle-fed with colostrum for 5 d and thereafter sucked milk from an automatic milk feeder. Animals reared with dam-calf contact (Dam-contact) were kept in the calving pen with their dam for 5 d, and then had permanent access to the cow barn and thus to their dam. Calves were weaned at an age of 12 weeks and kept in young stock groups mixed of both treatments until integration into the cow herd. We tested the animals' relationship with humans by assessing the animals' responses towards an unfamiliar person in an avoidance distance (AD) test in the home environment at 4 weeks of age, at 15 months and at 33 months. In calves, we additionally measured AD in a novel arena after a stationary person test. Artificial animals had lower AD, i.e. showed lower level of fear, than Dam-contact calves. However, the AD in Dam-contact calves decreased with increasing number of days they experienced assistance for suckling. Further, there was no significant difference in later ages. In conclusion, gentle human contact in combination with feeding during the first 5 d of life improved calves' relationship to humans leading to differences between the two treatments as well as within the Dam-contact calves. Potential effects under different conditions regarding quantity and quality of human-animal interactions need further research.

Play and social behaviour of calves with or without access to their dam and other cows.

The aim of the study reported in this Research Communication was to compare play behaviour and social interactions of dairy calves either separated from their mother and reared in a calf group (Artificial) or with access to their mother and the cow herd (cow-calf contact: Contact). Contact calves had access to a calf area and also to the cow barn where they could suckle their dam. Artificial calves were fed whole milk up to 16 kg per day via an automatic milk feeder and were only kept in the calf area. We observed the animals on 3 d during the first three months of life. Contact calves showed solitary play, consisting predominantly of locomotor play, for longer than Artificial calves and mainly in the cow barn. This indicates higher welfare in Contact calves. In addition, Artificial calves hardly experienced any agonistic interaction, while Contact calves both initiated and received agonistic interactions, which might contribute to the development of higher social competence.

Methodological terminology and definitions for research and discussion of cow-calf contact systems.

Due to increasing public concern regarding separation of the dairy cow and calf within the first days after birth, alternative systems, where cows and calves stay in contact for an extended period, are receiving increasing interest from a broad array of researchers and other stakeholders. With more research in the area, there is a risk of inconsistencies emerging in the use of terminology. To create a better consensus in further discussions, the aim of this Research Reflection is to provide definitions and propose a common terminology for cow-calf contact in dairy production. We also suggest definitions for various systems allowing cow-calf contact and describe the distinct phases of cow-calf contact systems.

Effects of suckling on milk yield and milk composition of dairy cows in cow-calf contact systems.

In this research communication I show the effect of various cow-calf contact systems on milk yield and milk composition during the periods when calves where allowed to suckle their dams and after the calves were separated in comparison to cows that were only machine milked throughout their lactation. Analyses were based on four different experiments, but conducted at the same research station and under comparable housing and feeding conditions. Nursing dams had contact to their calves during the whole day, during night-time or only twice per day shortly before milking. A control group of cows that had no contact to their offspring was part of every experiment. Data of the regular monthly milk recordings were analysed with linear mixed models. Results showed a significant effect of the suckling system on the machine milk yield over the whole lactation. While cows with night-time contact reached the milk production level of the control cows, cows with whole day or short-time contact still produced less milk after the calves were separated. Fat content was always lower during the suckling period but not afterwards. The significantly higher milk protein content in dams with calf contact requires further investigation. Somatic cell count in milk of nursing dams was slightly increased, probably due to the exposure of the teats to frequent suckling in addition to machine milkings. In conclusion, cow-calf contact systems influence the performance of cows during and after the suckling period but to varying degrees depending on the system adopted.

Methodology for experimental and observational animal studies in cow-calf contact systems.

In this Research Reflection we describe a common standpoint on suitable methodology for controlled and observational studies in cow-calf contact systems in dairy production. Different methods to assess behaviour, health and production in cow-calf contact systems are outlined. Knowledge and experience from researchers working in this field supplement scientific literature whenever relevant. Specific methods including study design, early behaviour of cow and calf, social behaviour relevant to cow-calf contact systems, human-animal relationships and aspects related to management (milking, weaning and separation, health) are reviewed, and recommendations formed. We expect that this paper can contribute to a better understanding of the complexity of cow-calf contact systems and help to advance research in this area of dairy production.

Cell motility and migration as determinants of stem cell efficacy.

BACKGROUND: Stem cells` (SC) functional heterogeneity and its poorly understood aetiology impedes clinical development of cell-based therapies in regenerative medicine and oncology. Recent studies suggest a strong correlation between the SC migration potential and their therapeutic efficacy in humans. Designating SC migration as a denominator of functional SC heterogeneity, we sought to identify highly migrating subpopulations within different SC classes and evaluate their therapeutic properties in comparison to the parental non-selected cells. METHODS: We selected highly migrating subpopulations from mesenchymal and neural SC (sMSC and sNSC), characterized their features including but not limited to migratory potential, trophic factor release and transcriptomic signature. To assess lesion-targeted migration and therapeutic properties of isolated subpopulations in vivo, surgical transplantation and intranasal administration of MSCs in mouse models of glioblastoma and Alzheimer's disease respectively were performed. FINDINGS: Comparison of parental non-selected cells with isolated subpopulations revealed superior motility and migratory potential of sMSC and sNSC in vitro. We identified podoplanin as a major regulator of migratory features of sMSC/sNSC. Podoplanin engineering improved oncovirolytic activity of virus-loaded NSC on distantly located glioblastoma cells. Finally, sMSC displayed more targeted migration to the tumour site in a mouse glioblastoma model and remarkably higher potency to reduce pathological hallmarks and memory deficits in transgenic Alzheimer's disease mice. INTERPRETATION: Functional heterogeneity of SC is associated with their motility and migration potential which can serve as predictors of SC therapeutic efficacy. FUNDING: This work was supported in part by the Robert Bosch Stiftung (Stuttgart, Germany) and by the IZEPHA grant.

Modulating endothelial adhesion and migration impacts stem cell therapies efficacy.

BACKGROUND: Limited knowledge of stem cell therapies` mechanisms of action hampers their sustainable implementation into the clinic. Specifically, the interactions of transplanted stem cells with the host vasculature and its implications for their therapeutic efficacy are not elucidated. We tested whether adhesion receptors and chemokine receptors on stem cells can be functionally modulated, and consequently if such modulation may substantially affect therapeutically relevant stem cell interactions with the host endothelium. METHODS: We investigated the effects of cationic molecule polyethylenimine (PEI) treatment with or without nanoparticles on the functions of adhesion receptors and chemokine receptors of human bone marrow-derived Mesenchymal Stem Cells (MSC). Analyses included MSC functions in vitro, as well as homing and therapeutic efficacy in rodent models of central nervous system´s pathologies in vivo. FINDINGS: PEI treatment did not affect viability, immunomodulation or differentiation potential of MSC, but increased the CCR4 expression and functionally blocked their adhesion receptors, thus decreasing their adhesion capacity in vitro. Intravenously applied in a rat model of brain injury, the homing rate of PEI-MSC in the brain was highly increased with decreased numbers of adherent PEI-MSC in the lung vasculature. Moreover, in comparison to untreated MSC, PEI-MSC featured increased tumour directed migration in a mouse glioblastoma model, and superior therapeutic efficacy in a murine model of stroke. INTERPRETATION: Balanced stem cell adhesion and migration in different parts of the vasculature and tissues together with the local microenvironment impacts their therapeutic efficacy. FUNDING: Robert Bosch Stiftung, IZEPHA grant, EU grant 7 FP Health.

The German MultiCare-study: Patterns of multimorbidity in primary health care - protocol of a prospective cohort study.

BACKGROUND: Multimorbidity is a highly frequent condition in older people, but well designed longitudinal studies on the impact of multimorbidity on patients and the health care system have been remarkably scarce in numbers until today. Little is known about the long term impact of multimorbidity on the patients' life expectancy, functional status and quality of life as well as health care utilization over time. As a consequence, there is little help for GPs in adjusting care for these patients, even though studies suggest that adhering to present clinical practice guidelines in the care of patients with multimorbidity may have adverse effects. METHODS/DESIGN: The study is designed as a multicentre prospective, observational cohort study of 3.050 patients aged 65 to 85 at baseline with at least three different diagnoses out of a list of 29 illnesses and syndromes. The patients will be recruited in approx. 120 to 150 GP surgeries in 8 study centres distributed across Germany. Information about the patients' morbidity will be collected mainly in GP interviews and from chart reviews. Functional status, resources/risk factors, health care utilization and additional morbidity data will be assessed in patient interviews, in which a multitude of well established standardized questionnaires and tests will be performed. DISCUSSION: The main aim of the cohort study is to monitor the course of the illness process and to analyse for which reasons medical conditions are stable, deteriorating or only temporarily present. First, clusters of combinations of diseases/disorders (multimorbidity patterns) with a comparable impact (e.g. on quality of life and/or functional status) will be identified. Then the development of these clusters over time will be analysed, especially with regard to prognostic variables and the somatic, psychological and social consequences as well as the utilization of health care resources. The results will allow the development of an instrument for prediction of the deterioration of the illness process and point at possibilities of prevention. The practical consequences of the study results for primary care will be analysed in expert focus groups in order to develop strategies for the inclusion of the aspects of multimorbidity in primary care guidelines.

Hepatitis C virus RNA replication is resistant to tumour necrosis factor-alpha.

It was demonstrated using self-replicating hepatitis C virus (HCV) RNAs that both types of interferons (IFNs) (in particular IFN-alpha and IFN-gamma) are potent inhibitors of HCV replication in Huh-7 cells. Because IFN-gamma and tumour necrosis factor (TNF)-alpha trigger a partially overlapping set of antiviral defence mechanisms, it is tempting to speculate that TNF-alpha also inhibits HCV replication. However, this study shows that TNF-alpha does not affect HCV protein and RNA synthesis, nor does it synergistically enhance the inhibitory effect of IFN-gamma. Taken together, these results demonstrate that HCV replication in Huh-7 cells is highly resistant to TNF-alpha. It is, therefore, unlikely that the increased production of TNF-alpha, which is seen in many hepatitis C patients, contributes to HCV clearance by inducing antiviral defence mechanisms in infected hepatocytes.

Interferon-gamma inhibits replication of subgenomic and genomic hepatitis C virus RNAs.

Persistent infection with hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. All treatments known so far rely on the antiviral activity of interferon alfa (IFN-alpha) that is given alone or in combination with ribavirin. Unfortunately, only a fraction of the patients clear the virus during therapy and for those who do not respond there is currently no alternative treatment. Selectable subgenomic HCV RNAs (replicons) have been recently used to investigate the effect of IFN-alpha on HCV replication. However, it has not yet been analyzed whether other cytokines also play a role in the innate immune response against HCV. Here we show that IFN-gamma inhibits protein synthesis and RNA replication of subgenomic and genomic HCV replicons. We further show that the inhibitory action of IFN-gamma does not rely on the production of nitric oxide or the depletion of tryptophan. In conclusion, our results suggest that cytotoxic T cells and natural killer cells may contribute to HCV clearance not only by cell killing but also by producing IFN-gamma, thereby enhancing the intracellular inhibition of viral replication.