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EC Directive 2001/93 requires that all pigs have access to proper investigation and manipulation materials. Intensively farmed pigs in Europe are frequently provided with a short metal chain with or without an indestructible object attached to the chain. To date authorities are regarding this as proper enrichment, perhaps with (in)direct reference to the RICHPIG model as a justification. However, it has become increasingly clear that the chains do not provide proper enrichment, and that adding an indestructible object to the end of the chain may even reduce rather than improve pig welfare. To test this hypothesis an expert survey was conducted containing 26 more or less compound questions. On a scale from 0 to 10 experts specified their level of agreement with the hypothesis, the prevalence and welfare scores of nine indestructible enrichment materials. In total 36 experts, mostly pig-welfare scientists, responded (response rate: 39%). Indestructible objects are less prevalent in countries that provide straw (like Sweden and the UK) and outside the EU (US). They are more prevalent in the Netherlands, Belgium, France and Finland, while the prevalence seems to be low in Spain. Balls, wood and pipes were provided most frequently: hard wood especially in the UK (as specified in farm assurance); indestructible balls and pipes in Germany and the Netherlands. The experts' score for agreement with the hypothesis was only 4.6 on average (scale 0-10; n = 25). Enrichment materials, ranked from high to low welfare score, were grouped in 5 significance levels as indicated by different superscripts based on Wilcoxon signed rank tests: Branched chains (5.1a), Chain on the floor (4.4b), Hard wood (3.7bc), Pipe (3.5c), Bare chain (3.3c), Short chain (3.1d), Small ball (2.8d), Big ball (2.5d), and Chain hanging too high (1.3e). Branched chains scored significantly better than all other indestructible materials and its welfare score (5.1 on average) was close to the pre-defined level of acceptability (5.5 on a scale from 0, worst, to 10, best). The welfare benefits of adding balls, pipes or hard wood to the metal chain were marginal, and well below what the experts considered acceptable enrichment. The branched-chains design, by contrast, appears to be the most viable alternative. It involves providing a longer chain, i.e. with the free end reaching to floor level, adding 'branches', i.e. several short chains ending at the nose height of the pigs, and providing more chains per pen (i.e. 1 branched chain per 5 pigs). Branched chains should be implemented widely and in the short term as a first step towards, and benchmark for, providing proper enrichment to intensively-farmed pigs.

A 'meta-analysis' was performed to determine effects of post-hatch food and water deprivation (PHFWD) on chicken development, performance and welfare (including health). Two types of meta-analysis were performed on peer-reviewed scientific publications: a quantitative 'meta-analysis' (MA) and a qualitative analysis (QA). Previously reported effects of PHFWD were quantified in the MA, for variables related to performance, mortality and relative yolk sac weight. The QA counted the number of studies reporting (non-)significant effects when five or more records were available in the data set (i.e. relative heart, liver and pancreas weight; plasma T3, T4 and glucose concentrations; relative duodenum, jejunum and ileum weight; duodenum, jejunum and ileum length; and villus height and crypt depth in duodenum, jejunum and ileum). MA results indicated that 24 hours of PHFWD (i.e. ≥12-36 hours) or more resulted in significantly lower body weights compared to early-fed chickens up to six weeks of age. Body weights and food intake were more reduced as durations of PHFWD (24, 48, 72, ≥84 hours) increased. Feed conversion rate increased in chickens up to 21 and 42 days of age after ≥84 hours PHFWD in comparison with chickens fed earlier. Total mortality at day 42 was higher in chickens after 48 hours PHFWD compared to early fed chickens or chickens after 24 hours PHFWD. First week mortality was higher in chickens after ≥84 hours PHFWD than in early fed chickens. The MA for relative yolk sac weight was inconclusive for PHFWD. The QA for plasma T3, T4 and glucose concentrations indicated mainly short-term decreases in T3 and glucose in PHFWD chickens compared to early fed chickens, and no effects of PHFWD on T4 concentrations. Relative weights of liver, pancreas and heart were lower after PHFWD, but only in the first week of life. A retarded development of gut segments (duodenum, jejunum and ileum) was found in the first week of life, measured as shorter, lower relative weight, and lower villus height and crypt depth. It is concluded that 48 hours (≥36-60 hours) PHFWD leads to lower body weights and higher total mortality in chickens up to six weeks of age, the latter suggesting compromised chicken welfare, but effects of PHFWD on organ development and physiological status appear to be mainly short-term.

In order to support decision making on how to most effectively improve broiler welfare an innovative expert survey was conducted based on principles derived from semantic modelling. Twenty-seven experts, mainly broiler welfare scientists (n = 20; and 7 veterinarians), responded (response rate 38%) by giving welfare scores (GWS, scale 0-10) to 14 benchmarking housing systems (HSs), and explaining these overall scores by selecting, weighing and scoring main welfare parameters, including both input and output measures. Data exploration followed by REML (Linear Mixed Model) and ALM (Automatic Linear Modelling) analyses revealed 6 clusters of HSs, sorted from high to low welfare, i.e. mean GWS (with superscripts indicating significant differences): 1. (semi-natural backyard) Flock (8.8a); 2. Nature (7.7ab), Label Rouge II (7.4ab), Free range EU (7.2ab), Better Life (7.2ab); 3. Organic EU (7.0bc), Freedom Food (6.2bc); 4. Organic US (5.8bcd), Concepts NL (5.6abcdef), GAP 2 (4.9bcd); 5. Conventional EU (3.7de), Conventional US (2.9ef), Modern cage (2.9abcdef); 6. Battery cage (1.3f). Mean weighting factors (WF, scale 0-10) of frequently (n> = 15) scored parameters were: Lameness (8.8), Health status (8.6), Litter (8.3), Density (8.2), Air quality (8.1), Breed (8.0), Enrichment (7.0) and Outdoor (6.6). These did not differ significantly, and did not have much added value in explaining GWS. Effects of Role (Scientist/Vet), Gender (M/F) and Region (EU/non-EU) did not significantly affect GWS or WF, except that women provided higher WF than men (7.2 vs 6.4, p<0.001). The contribution of welfare components to overall welfare has been quantified in two ways: a) using the beta-coefficients of statistical regression (ALM) analyses, and b) using a semantic-modelling type (weighted average) calculation of overall scores (CalcWS) from parameter level scores (PLS) and WF. GWS and CalcWS were highly correlated (R = ~0.85). CalcWS identified Lameness, Health status, Density, Breed, Air quality and Litter as main parameters contributing to welfare. ALM showed that the main parameters which significantly explained the variance in GWS based on all PLS, were the output parameter Health status (with a beta-coefficient of 0.38), and the input parameters (stocking) Density (0.42), Litter (0.14) and Enrichment (0.27). The beta-coefficients indicated how much GWS would improve from 1 unit improvement in PLS for each parameter, thus the potential impact on GWS ranged from 1.4 welfare points for Litter to 4.2 points for Density. When all parameters were included, 81% of the variance in GWS was explained (77% for inputs alone; 39% for outputs alone). From this, it appears that experts use both input and output parameters to explain overall welfare, and that both are important. The major conventional systems and modern cages for broilers received low welfare scores (2.9-3.7), well below scores that may be considered acceptable (5.5). Also, several alternatives like GAP 2 (4.9), Concepts NL (5.6), Organic US (5.8) and Freedom Food (6.2) are unacceptable, or at risk of being unacceptable due to individual variation between experts and farms. Thus, this expert survey provides a preliminary semi-quantified decision-support tool to help determine how to most effectively improve broiler welfare in a wide range of HSs.

This is a comprehensive review on the pigs’ normal eliminatory behaviour (i.e., defaecation and urination) and pen soiling. This review is aimed primarily at solving issues with pen soiling in current systems, and ultimately at the future design of a well-functioning pig toilet, which we intend to elaborate on in a subsequent publication. In this paper, first, normal elimination is described in relation to what is known about its phylogeny, ontogeny, causation, and function, i.e., according to Tinbergen’s four why questions concerning animal behaviour. Then, pen soiling is described as if it were a medical disorder, highlighting its importance, aetiology, symptoms, diagnosis, pathogenesis, treatment, and prevention. Due to its negative consequences in terms of animal welfare, health, workload, and environmental emissions, possible methods to address pen soiling in current systems are described. Probably, pigs do not choose a specific place to eliminate but rather choose the most comfortable place for resting, and avoid eliminating there. We identified four main strategies to reduce pen soiling: (1) reducing the suitability of the designated elimination area to be used for other functions, especially resting or thermoregulation; (2) improving the suitability of other functional areas in the pen to be used for their specific function, such as resting and activity; (3) reducing the suitability of other functional areas to be used for elimination; and (4) improving the suitability of the elimination area for elimination. These prevention strategies and the encompassing disease framework provide a structured approach to deal with pen soiling in existing systems and to support the future design, development, and implementation of a well-functioning pig toilet that can help to achieve some of the main goals of modern pig production, namely reducing environmental emissions as well as substantially improving pig welfare.

Roughly one in five patients with colorectal cancer develops peritoneal minimal residual disease after surgical resection, and about one in seven patients develops peritoneal carcinomatosis. By contrast with the vast body of research addressing haematogenous metastasis, little is known about the biology of peritoneal spread of colorectal cancer. The development of peritoneal carcinomatosis involves well-defined steps including cell shedding and transport, adhesion to the mesothelial layer, invasion of and proliferation into the submesothelial stroma, and potential access to the systemic circulation. In this Review, we summarise the molecular mechanisms and potential preventive measures associated with each step of the peritoneal metastatic cascade.

Despite an enormous interest in the role of extracellular vesicles, including exosomes, in cancer and their use as biomarkers for diagnosis, prognosis, drug response and recurrence, there is no consensus on dependable isolation protocols. We provide a comparative evaluation of 4 exosome isolation protocols for their usability, yield and purity, and their impact on downstream omics approaches for biomarker discovery. OptiPrep density gradient centrifugation outperforms ultracentrifugation and ExoQuick and Total Exosome Isolation precipitation in terms of purity, as illustrated by the highest number of CD63-positive nanovesicles, the highest enrichment in exosomal marker proteins and a lack of contaminating proteins such as extracellular Argonaute-2 complexes. The purest exosome fractions reveal a unique mRNA profile enriched for translation, ribosome, mitochondrion and nuclear lumen function. Our results demonstrate that implementation of high purification techniques is a prerequisite to obtain reliable omics data and identify exosome-specific functions and biomarkers.

Lack of environmental enrichment and high stocking densities in growing-finishing pigs can lead to adverse social behaviors directed to pen mates, resulting in skin lesions, lameness, and tail biting. The objective of the study was to improve animal welfare and prevent biting behavior in an experiment with a 2 × 2 × 2 factorial design on exploration feeding, stocking density, and sex. We kept 550 pigs in 69 pens from 63 days to 171 days of life. Pigs were supplemented with or without exploration feeding, kept in groups of seven (1.0 m2/pig) or nine animals (0.8 m2/pig) and separated per sex. Exploration feeding provided small amounts of feed periodically on the solid floor. Skin lesion scores were significantly lower in pens with exploration feeding (p = 0.028, p < 0.001, p < 0.001 for front, middle, and hind body), in pens with high compared to low space allowance (p = 0.005, p = 0.006, p < 0.001 for front, middle and hind body), and in pens with females compared to males (p < 0.001, p = 0.005, p < 0.001 for front, middle and hind body). Males with exploration feeding had fewer front skin lesions than females with exploration feeding (p = 0.022). Pigs with 1.0 m2 compared to 0.8 m2 per pig had a higher daily gain of 27 g per pig per day (p = 0.04) and males compared to females had a higher daily gain of 39 g per pig per day (p = 0.01). These results indicate that exploration feeding might contribute to the development of a more welfare-friendly pig husbandry with intact tails in the near future.

The role of the human microbiome on cancer progression remains unclear. Therefore, in this study, we investigated the influence of some quorum sensing peptides, produced by diverse commensal or pathogenic bacteria, on breast cancer cell invasion and thus cancer outcome. Based on microscopy, transcriptome and Chick Chorioallantoic Membrane (CAM) analyses, four peptides (PhrG from B. subtilis, CSP from S. mitis and EDF from E. coli, together with its tripeptide analogue) were found to promote tumour cell invasion and angiogenesis, thereby potentially influencing tumour metastasis. Our results offer not only new insights on the possible role of the microbiome, but also further opportunities in cancer prevention and therapy by competing with these endogenous molecules and/or by modifying people's life style.

Background Recent scientific developments have shed more light on the importance of the host-microbe interaction, particularly in the gut. However, the mechanistic study of the host-microbe interplay is complicated by the intrinsic limitations in reaching the different areas of the gastrointestinal tract (GIT) in vivo . In this paper, we present the technical validation of a new device - the Host-Microbiota Interaction (HMI) module - and the evidence that it can be used in combination with a gut dynamic simulator to evaluate the effect of a specific treatment at the level of the luminal microbial community and of the host surface colonization and signaling. Results The HMI module recreates conditions that are physiologically relevant for the GIT: i) a mucosal area to which bacteria can adhere under relevant shear stress (3 dynes cm −2 ); ii) the bilateral transport of low molecular weight metabolites (4 to 150 kDa) with permeation coefficients ranging from 2.4 × 10 −6 to 7.1 × 10 −9  cm sec −1 ; and iii) microaerophilic conditions at the bottom of the growing biofilm (PmO 2 = 2.5 × 10 −4  cm sec −1 ). In a long-term study, the host’s cells in the HMI module were still viable after a 48-hour exposure to a complex microbial community. The dominant mucus-associated microbiota differed from the luminal one and its composition was influenced by the treatment with a dried product derived from yeast fermentation. The latter - with known anti-inflammatory properties - induced a decrease of pro-inflammatory IL-8 production between 24 and 48 h. Conclusions The study of the in vivo functionality of adhering bacterial communities in the human GIT and of the localized effect on the host is frequently hindered by the complexity of reaching particular areas of the GIT. The HMI module offers the possibility of co-culturing a gut representative microbial community with enterocyte-like cells up to 48 h and may therefore contribute to the mechanistic understanding of host-microbiome interactions.

Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer.