Impact of early inoculation of probiotics to suckling piglets on postweaning diarrhoea - A challenge study with Enterotoxigenic E. Coli F18.

Postweaning diarrhoea caused by Enterotoxigenic Escherichia coli (ETEC) is a threat to the pig industry. With an intensified focus on finding alternatives to the use of medical zinc oxide and antibiotics in newly weaned pigs, the objective of this study was to investigate the effect of early inoculation of probiotics to suckling piglets on subsequently ETEC faecal shedding and immune parameters in ETEC F18-challenged weaned piglets. Sixty pigs weaned on day 28 of age were assigned to three treatment groups: (i) Negative Control (non-challenged), (ii) Positive Control (challenged) and (iii) Probiotic (challenged and inoculated with a multi-species probiotic product during suckling). On days 1 and 2 postweaning, pigs in the Positive Control and Probiotic groups were challenged with 5 × 108 colony-forming unit ETEC F18/pig/day, whereas pigs in the Negative Control group were provided with NaCl. Growth and diarrhoea incidence were not significantly affected by ETEC challenge or probiotic administration. ETEC F18 shedding and C-reactive protein concentration in plasma were significantly lower in the Negative Control group, confirming a successful challenge model. Pigs in the Probiotic group had a significantly reduced number of pigs shedding ETEC F18 and STb toxin in faeces compared with the Positive Control group. Probiotic application did not significantly impact the concentration of C-reactive protein, haptoglobin and cytokines in plasma nor haematology numbers. In conclusion, weaned pigs administered with a multi-species probiotic product early in life had a more rapid response towards the pathogen challenge and a faster clearance of ETEC compared with the Positive Control group. Administration of a multi-species probiotic to newborn piglets may thus promote resilience in the newly weaned pig. However, further studies with pigs subjected to a more severe pathogen challenge are needed to confirm these results and to investigate the mechanism of action of the probiotic intervention.

Human sperm cells can form paracetamol metabolite AM404 that directly interferes with sperm calcium signalling and function through a CatSper-dependent mechanism.

STUDY QUESTION: Do paracetamol (N-acetyl-para-aminophenol (APAP) or acetaminophen) and/or its metabolites affect human sperm Ca2+-signalling and function? SUMMARY ANSWER: While APAP itself does not interact with Ca2+-signalling in human sperm, its metabolite N-arachidonoyl phenolamine (AM404), produced via fatty acid amide hydrolase (FAAH), interferes with human sperm Ca2+-signalling and function through a suggested CatSper channel-dependent action. WHAT IS KNOWN ALREADY: Studies have shown that adult men with high urinary levels of over-the-counter mild analgesic APAP have impaired sperm motility and increased time-to-pregnancy. STUDY DESIGN, SIZE, DURATION: This study consists of (i) an in vivo human pharmaceutical APAP exposure experiment to understand to what degree APAP reaches the sperm cells in the seminal fluid; (ii) in vitro calcium imaging and functional experiments in freshly donated human sperm cells to investigate CatSper channel-dependent activation by APAP and its metabolites; and (iii) experiments to understand the in situ capabilities of human sperm cells to form APAP metabolite AM404. PARTICIPANTS/MATERIALS, SETTING, METHODS: Three healthy young males participated in the in vivo human exposure experiment after prior consent. Human semen samples were provided by healthy young volunteer donors after prior consent on the day of the in vitro experiments. MAIN RESULTS AND THE ROLE OF CHANCE: Pharmaceutical APAP exposure reaches the seminal plasma in high micromolar concentrations and accumulates in the seminal plasma between 3 and 5 days of exposure (P-value 0.023). APAP and its primary metabolite 4-aminophenol (4AP) do not interact with human sperm Ca2+-signalling. Instead, the APAP metabolite AM404 produced via FAAH interferes with human sperm Ca2+-signalling through a CatSper-dependent action. Also, AM404 significantly increases sperm cell penetration into viscous mucous (P-value of 0.003). FAAH is functionally expressed in human sperm cells in the neck/midpiece region, as evidenced by immunohistochemical staining and the ability of human sperm cells to hydrolyse the fluorogenic FAAH substrate arachidonyl 7-amino, 4-methyl coumarin amide in an FAAH-dependent manner. Importantly, human sperm cells have the capacity to form AM404 in situ after exposure to 4AP (P-value 0.0402 compared to vehicle-treated sperm cells). LIMITATIONS, REASONS FOR CAUTION: The experiments were conducted largely in vitro. Future studies are needed to test whether APAP can disrupt human sperm function in vivo through the action of AM404. WIDER IMPLICATIONS OF THE FINDINGS: We hypothesize that these observations could, at least in part, be responsible for the negative association between male urinary APAP concentrations, sperm motility and time-to-pregnancy. STUDY FUNDING/COMPETING INTEREST(S): D.M.K. is funded by the Lundbeck Foundation, grant number R324-2019-1881, and the Svend Andersen Foundation. A.R. is funded by a BRIDGE-Translational Excellence Programme grant funded by the Novo Nordisk Foundation, grant agreement number: NNF18SA0034956. All authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

The impact of two commonly used neutralizing agents in water sampling bottles on legionella and pseudomonas bacteria recovery.

BACKGROUND: Microbiological monitoring may be indicated by the local risk assessment of hospital water systems. When water sampling is carried out, it is imperative that the activity of any residual biocide is completely neutralized. Sodium thiosulphate pentahydrate (Na2S2O3·5H2O) is commonly used to neutralize oxidizing biocides in water samples for microbiological testing. Ethylenediaminetetraacetic acid dihydrate (Na2EDTA.2H2O) is recommended to neutralize silver-copper ionization treated water samples. However, there are inconsistencies in the recommended effective concentration. Furthermore, sampling bottles dosed with Na2EDTA.2H2O are not commercially available. AIM: To investigate the efficacy of Na2EDTA.2H2O as a neutralizing agent compared with sodium thiosulphate (Na2S2O3·5H2O) on water samples treated with silver and copper ions and to assess the biocidal activity in water samples. METHODS: An interlaboratory investigation was carried out using simulated water samples spiked with Legionella pneumophila or Pseudomonas aeruginosa with and without silver and copper ions. Bacterial recovery was determined in sterile sampling bottles dosed with either 50 mg/L Na2EDTA.2H2O or 180 mg/L Na2S2O3·5H2O as the chemical biocide neutralizing agent. FINDINGS: Na2S2O3·5H2O effectively complexed both silver and copper ions and inhibited biocidal activity. The 50 mg/L of Na2EDTA.2H2O continued to demonstrate significant biocidal activity in the spiked samples. CONCLUSION: This study demonstrated that Na2EDTA.2H2O is not an efficacious neutralizing agent on water samples treated with silver and copper ions. Sample bottles dosed with 180 mg/L Na2S2O3·5H2O were more effective in neutralizing silver and copper ions generated in water that had been treated by silver-copper ionization systems.

Dairy goats adjust their meal patterns to the fibre content of the diet.

Few studies have investigated how meal patterns of ruminants are affected by diet fibre content. Dairy goats (N = 32) in late lactation and early gestation were housed in eight groups of four goats, with all combinations of breed (Alpine and Saanen) and lactation number (1 and 2) represented in each group. Each goat had access to its own individual feed trough placed on a weigh scale with data logged automatically. All goats were fed the same total mixed ration (TMR; 30% concentrate and 44.6% NDF in DM) ad libitum for a control period of 22 days. Using the same feed ingredients, half of the groups were then offered a High fibre diet (20% concentrate; 47.3% NDF), and the other half a Low fibre diet (40% concentrate; 41.5% NDF) for a treatment period of 16 days. Daily meal patterns (meal frequency, duration and size, feeding rate, daily feed intake and daily feeding time) were computed for each animal using a meal criterion of 8 min. The last 10 days for each period (control and treatment) were used to calculate individual period means and individual differences between the two periods. During the control period, the goats ate on average 12.1 ± 0.49 meals/day, consuming 4.2 ± 0.10 kg fresh TMR daily. When the ration changed, all measures of feeding behaviour except meal size changed asymmetrically for the goats on the two diets. Goats fed the High fibre diet reduced their meal frequency by 10%, and the first meal after feed distribution lasted 11% longer, leading to a 9% reduction in feeding rate and no significant changes in daily feed intake and daily feeding time. Goats on the Low fibre diet did not significantly change their meal frequency or meal size, but the combined changes nevertheless led to a 9% increase in daily feed intake. On the Low fibre diet, goats were able to increase their feeding rate by a third, leading to a reduction in meal durations, thus reducing daily feeding time by 13%. Goats adapt their feeding behaviour to the fibre proportion of the offered diet, with more changes when fibre content is lowered, which needs to be taken into account when comparing phenotypes and adaptability of small ruminants to different diets.

Screening of probiotic candidates in a simulated piglet small intestine in vitro model.

The CoMiniGut in vitro model mimicking the small intestine of piglets was used to evaluate four probiotic strains for their potential as a preventive measure against development of diarrhea in weaned pigs. In the in vitro system, piglet digesta was inoculated with pathogenic enterotoxigenic Escherichia coli F4 (ETEC F4), and the short-chain fatty acid profile and the gut microbiota composition were assessed. A total of four probiotic strains were evaluated: Enterococcus faecium (CHCC 10669), Lactobacillus rhamnosus (CHCC 11994), Bifidobacterium breve (CHCC 15268) and Faecalibacterium prausnitzii (CHCC 28556). The significant differences observed in metabolite concetration and bacterial enumeration were attributed to variation in inoculating material or pathogen challenge rather than probiotic treatment. Probiotic administration influenced the microbiota composition to a small extend. Learnings from the present study indicate that the experimental setup, including incubation time and choice of inoculating material, should be chosen with care.

Functional in vitro screening of probiotic strains for inoculation of piglets as a prophylactic measure towards Enterotoxigenic Escherichia coli infection.

Enterotoxigenic Escherichia coli (ETEC), being the major cause of post-weaning diarrhoea (PWD) in newly weaned piglets, induces poor performance and economic losses in pig production. This functional in vitro screening study investigated probiotic strains for use in suckling piglets as a prophylactic strategy towards PWD. Nine strains were evaluated based on their ability to: enhance intestinal epithelial barrier function, reduce adherence of ETEC F18 to intestinal cells, inhibit growth of ETEC F18, and grow on porcine milk oligosaccharides. Strains included in the screening were of the species Lactobacillus, Enterococcus, Bifidobacterium and Bacillus. Our in vitro screening demonstrated genus-, species and strain-specific differences in the mode of action of the tested probiotic strains. Some of the tested bifidobacteria were able to grow on the two porcine milk oligosaccharides, 3'-sialyllactose sodium salt (3'SL) and Lacto-N-neotetraose (LNnT), whereas most lactic acid bacteria strains and both Bacillus subtilis strains failed to do so. All probiotic strains inhibited growth of ETEC F18 on agar plates. All but the bifidobacteria reduced binding of ETEC F18 to Caco-2 cell monolayers, with the Enterococcus faecium strain having the most profound effect. All three lactic acid bacteria and Bifidobacterium animalis subsp. lactis counteracted the ETEC F18-induced permeability across Caco-2 cell monolayers with the E. faecium strain exhibiting the most pronounced protective effect. The findings from this in vitro screening study indicate that, when selecting probiotic strains for suckling piglets as a prophylactic strategy towards PWD, it would be advantageous to choose a multi-species product including strains with different modes of action in order to increase the likelihood of achieving beneficial effects in vivo.

Prevalence of muscle dysfunction concomitant with osteoporosis in a home-dwelling Danish population aged 65-93 years - The Copenhagen Sarcopenia Study.

INTRODUCTION: As life expectancy increases, a growing percentage of older individuals with age-related diseases such as osteoporosis and sarcopenia are expected. Patients with both conditions, i.e. patient with osteosarcopenia, are suggested to have a higher risk of fall and fracture compared to individuals with either condition. AIM: To investigate the potential relationship between low bone mineral density (BMD) and muscle dysfunction in a Danish cohort of older home-dwelling individuals. Furthermore, to examine the prevalence of osteosarcopenia and alterations in prevalence depending on cut-off values chosen. METHOD: Measures of BMD, relative appendicular lean mass and hand grip strength were assessed in 529 individuals aged 65+ from the population-based cross-sectional Copenhagen Sarcopenia Study (CSS). Osteoporosis was diagnosed according to the World Health Organization guidelines. Sarcopenia was diagnosed in accordance with the guidelines from the European Working Group on Sarcopenia in Older People (EWGSOP2) with application of cut-off values from the EWGSOP2 paper compared to cut-off values derived from a local cohort (CSS). RESULTS: 19.2% had osteoporosis (66 women and 35 men), whereas 2.7% (6 women and 8 men) and 4.2% (7 women and 15 men) had sarcopenia with application of EWGSOP2 and CSS cut-off values, respectively. Using the EWGSOP2 cut-off values, 1.5% (4 women and 4 men) were diagnosed with osteosarcopenia compared to 1.4% (4 women and 3 men) using CSS cut-off values. In the osteoporosis sub-population, 8% (EWGSOP2) and 7% (CSS) had sarcopenia and within the sarcopenia sub-population, 61.5% (EWGSOP2) and 33.3% (CSS) had osteoporosis. At all sites, BMD was lower among individuals with sarcopenia and sarcopenia increased the risk of osteoporosis (odds ratios: EWGSOP2: 7.3 (p < 0.001) and CSS: 2.2 (ns)). CONCLUSION: Osteosarcopenia was present in 1.5% of a group of healthy home-dwelling older individuals. Notably, individuals with sarcopenia had lower BMD and a higher risk of osteoporosis, whereas the opposite (prevalence of sarcopenia in individuals with osteoporosis) was not as frequent. Our data indicate that screening for sarcopenia and osteoporosis should be performed simultaneously in older individuals at high risk of falls and fractures. However, further studies with outcome-related results are needed to identify optimal measures of osteosarcopenia and cut-off values for sarcopenia.

Marked reduction in fertility among African women with urogenital infections: A prospective cohort study.

BACKGROUND: There is paucity of data on risk factors for reduced fertility in low-income countries. OBJECTIVE: To investigate factors associated with fertility among women in rural north eastern Tanzania. SUBJECTS AND METHODS: A cohort of 1248 non-pregnant women was followed with urine pregnancy testing every third month or more regularly if they reported a missed menstrual period. Pregnancy was confirmed with trans-abdominal ultrasound. Information regarding general health, socioeconomic status and obstetric-gynaecological history was collected. Factors associated with conceiving within 180 days were identified using multivariate logistic regression analyses. RESULTS: Among the 1248 women, 736 were followed for 180 days and 209 of these had an ultrasound confirmed pregnancy. During the follow-up period, 169/736 women were diagnosed with urogenital infections, including suspected sexually transmitted or reproductive tract infections, urinary tract infection, and vaginal candidiasis. Urogenital infections were significantly associated with reduced odds of conceiving within 180 days (adjusted OR (AOR) 0.21, 95% CI 0.11-0.36). Being above 30 years of age was also negatively associated with odds of conceiving (AOR 0.45, 95% CI 0.26-0.77). In contrast, women who recently stopped using hormonal contraceptives (AOR 2.86, 95% CI 1.45-5.70) and women with low socioeconomic status (AOR 1.56, 95% CI 1.04-2.33) were significantly more likely to become pregnant within 180 days. CONCLUSION: Urogenital infection seems to be a major health factor associated with reduced chances of conceiving. Considering the availability of effective treatment options for these diseases, public health authorities should increase awareness of diagnostic tools in settings with limited resources in order to improve fertility.

Perspectives and unmet needs in polymyalgia rheumatica. Providing the fundamental framework for the development of new treatment regimes in polymyalgia rheumatica.

Polymyalgia rheumatica is effectively treated with glucocorticoids. However, glucocorticoid treatment can cause numerous and potentially serious side effects. Therefore, lowest effective dose and shortest duration to control disease is aimed for and glucocorticoid-sparing treatments are needed. Nevertheless, development of treatment regimens in PMR has been hampered by the lack of reliable classification criteria and evidence-based outcome measures. In this editorial, we discuss the need for valid classification criteria in PMR, the strengths and limitations of the ACR/EULAR 2012 provisional classification criteria for PMR and the need of validation and possible refining of the criteria.

Effects of age and diet on glucose and insulin dynamics in the horse.

BACKGROUND: Age and diet may affect insulin sensitivity (SI) but these factors have received limited investigation in horses. OBJECTIVES: To measure minimal model parameters during an insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT) after adaptation to a forage only diet (HAY) or forage supplemented with either starch/sugar-rich (SS) or oil/fibre-rich (FF) concentrate feeds; and to assess glucose and insulin responses to a standardised meal challenge (SMC, 4 g/kg BW of SS) after diet adaptation in adult and aged mares. STUDY DESIGN: Latin square design with eight adult (5-12 years) and nine aged (>19 years) healthy mares. METHODS: Diets were fed for 6 weeks, and the FSIGTT and SMC were performed after 31-32 and 41 days on each diet respectively. Data were analysed by a mixed ANOVA for repeated measures. RESULTS: Acute insulin response to glucose (AIRg) was greater and SI was lower in aged horses, compared with adults, regardless of diet. Both AIRg and SI were greater in aged mares after adaptation to SS, as compared with HAY. Similar trends, although not statistically significant, were observed after adaptation to SS in adult mares. Peak insulin concentration and area under the insulin vs. time curve during the SMC were greater in aged than adult mares with all diets. Furthermore, area under the glucose vs. time curve was lower after adaptation to SS, when compared with other diets, in both groups. MAIN LIMITATIONS: Transient weight loss occurred at the beginning of the study and only one sex was included. Incomplete ingestion of the SMC by four mares was another limitation. CONCLUSIONS: Insulin responses to i.v. and enteral nonstructural carbohydrate challenge increase with age in healthy horses, regardless of diet fed.

Effect of locally tailored labour management guidelines on intrahospital stillbirths and birth asphyxia at the referral hospital of Zanzibar: a quasi-experimental pre-post study (The PartoMa study).

OBJECTIVE: To evaluate effect of locally tailored labour management guidelines (PartoMa guidelines) on intrahospital stillbirths and birth asphyxia. DESIGN: Quasi-experimental pre-post study investigating the causal pathway through changes in clinical practice. SETTING: Tanzanian low-resource referral hospital, Mnazi Mmoja Hospital. POPULATION: Facility deliveries during baseline (1 October 2014 until 31 January 2015) and the 9th to 12th intervention month (1 October 2015 until 31 January 2016) [corrected]. METHODS: Birth outcome was extracted from all cases of labouring women during baseline (n = 3690) and intervention months (n = 3087). Background characteristics and quality of care were assessed in quasi-randomly selected subgroups (n = 283 and n = 264, respectively). MAIN OUTCOME MEASURES: Stillbirths and neonates with 5-minute Apgar score ≤5. RESULTS: Stillbirth rate fell from 59 to 39 per 1000 total births (RR 0.66, 95% CI 0.53-0.82), and subanalyses suggest that this was primarily due to reduction in intrahospital stillbirths. Apgar scores between 1 and 5 fell from 52 to 28 per 1000 live births (RR 0.53, 95% CI 0.41-0.69). Median time from last fetal heart assessment till delivery (or fetal death diagnosis) fell from 120 minutes (IQR 60-240) to 74 minutes (IQR 30-130) (Mann-Whitney test for difference, P < 0.01). Oxytocin augmentation declined from 22% to 12% (RR 0.54, 95% CI 0.37-0.81) and timely use improved. CONCLUSION: Although low human resources and substandard care remain major challenges, PartoMa guidelines were associated with improvements in care, leading to reductions in stillbirths and birth asphyxia. Findings furthermore emphasise the central role of improved fetal surveillance and restricted intrapartum oxytocin use in safety at birth. TWEETABLE ABSTRACT: #PartoMa guidelines aided in reducing stillbirths and birth asphyxia at a Tanzanian low-resource hospital PLAIN LANGUAGE SUMMARY: PartoMa guidelines help birth attendants in Tanzania to save lives Every year, 3 million babies die on the day of birth. The vast majority of these deaths occur in the poorest countries. If their mothers had received better care during birth, most babies would have survived. At Mnazi Mmoja Hospital, an East African referral hospital, the PartoMa study shows that use of locally developed guidelines helps birth attendants to deliver better quality of care, which has led to improved survival at birth. At the hospital studied, resources are scarce. Each birth attendant assists four to six birthing women simultaneously, and many have less than 1 year of professional experience. International guidelines are available, but they are often unachievable and seldom applied. The PartoMa guidelines were developed in close collaboration with the birth attendants and approved by seven international experts. The result is an 8-page pocket booklet providing locally achievable and simple decision support for care during birth. Use of the PartoMa guidelines began in February 2015. As the staff group frequently changes, quarterly seminars are conducted where birth attendants are welcomed after working hours to learn about the guidelines. The guidelines have been positively received, and seminar attendance remains high. Use of the PartoMa guidelines is associated with: A decrease by one-third in stillbirths (59 to 39 per 1000 total births) A nearly halving in the number of babies born in immediate poor medical condition (52 to 28 per 1000 live births) The results presented here derive from a comparison of births before using the PartoMa guidelines and during the 9th-12th month of use. Such a 'before-after' study cannot exclude the possibility of other causes of better survival at birth. However, the improved survival is consistent with improved care during birth, which is in line with the PartoMa guidelines.

Transport of valine across the small intestinal epithelium in pigs fed different valine levels and Bacillus subtilis.

Mutants of Bacillus subtilis overproducing valine (B. subtilis VAL) could be an approach to supply pigs dietary valine (Val). In the study, 18 gilts were fed: (i) negative diet with a standardized ileal digestible (SID) Val:Lys of 0.63:1 (Neg); (ii) Neg added B. subtilis VAL (1.28 × 1011  cfu/kg as-fed) or; (iii) Neg added L-Val to a Val:Lys of 0.69:1. Using the Ussing chamber method, the study aimed to investigate whether (i) the diets affect intestinal transport of additions of 0, 5, 10 or 20 mmol Val/L from the mucosal to the serosal side and (ii) the B. subtilis VAL contributes to a net transport of Val produced in situ. The results showed that the Isc (ΔIscVal ) and release of Val to the serosal side solution (Srel ; µmol cm-2  min-1 ) increased with Val addition (linear and quadratic, p < .0001) but was similar for 5, 10 or 20 mmol Val/L and not affected by diet. No net transport of in situ produced Val by B. subtilis VAL was detected. In conclusion, feeding a Val-deficient diet with or without B. subtilis VAL or a Val sufficient diet did not affect the Val transport across intestinal epithelia. No in situ Val production by B. subtilis VAL was observed in the Ussing chambers.

Joint analysis of longitudinal feed intake and single recorded production traits in pigs using a novel Horizontal model.

A novel Horizontal model is presented for multitrait analysis of longitudinal traits through random regression analysis combined with single recorded traits. Weekly ADFI on test for Danish Duroc, Landrace, and Yorkshire boars were available from the national test station and were collected from 30 to 100 kg BW. Single recorded production traits of ADG from birth to 30 kg BW (ADG30), ADG from 30 to 100 kg BW (ADG100), and lean meat percentage (LMP) were available from breeding herds or the national test station. The Horizontal model combined random regression analysis of feed intake (FI) with single recorded traits of ADG100, LMP, and ADG30. In the Horizontal model, the FI data were horizontally structured with FI on each week as a "trait." The additive genetic and litter effects were modeled to be common across different FI records by reducing the rank of the covariance matrices using second- and first-order Legendre polynomials of age on test, respectively. The fixed effect and random residual variance were estimated for each weekly FI trait. Residual feed intake (RFI) was derived from the conditional distribution of FI given the breeding values of ADG100 and LMP. The heritability of FI varied by week on test in Duroc (0.12 to 0.19), Landrace (0.13 to 0.22), and Yorkshire (0.21 to 0.23). The heritability of RFI was lowest and highest in wk 6 (0.03) and 10 (0.10), respectively, in Duroc and wk 7 (0.04 and 0.02) and 1 (0.09 and 0.20), respectively, in Landrace and Yorkshire. The proportion of FI genetic variance explained by RFI ranged from 20 to 75% in Duroc, from 19 to 75% in Landrace, and from 11 to 91% in Yorkshire. Average daily gain from 30 to 100 kg BW and ADG30 heritabilities were moderate in Duroc (0.24 and 0.22, respectively), Landrace (0.34 and 0.25, respectively), and Yorkshire (0.34 and 0.22, respectively). Lean meat percentage heritability was moderate in Duroc (0.37) and large in Landrace (0.62) and Yorkshire (0.60). The genetic correlation of FI with ADG100 increased by week on test followed by a 32% decrease from wk 7 in Duroc and a 7% decrease in dam line breeds. Defining RFI as genetically independent of production traits leads to consistent and easy interpretable breeding values. The genetic parameters of traits in the feed efficiency complex and their dynamics over the test period showed breed differences that could be related to the fatness and growth potential of the breeds. The Horizontal model can be used to simultaneously analyze repeated and single recorded traits through proper modeling of the environmental variances and covariances.

A National Needs Assessment to Identify Technical Procedures in Vascular Surgery for Simulation Based Training.

OBJECTIVES AND BACKGROUND: Practical skills training in vascular surgery is facing challenges because of an increased number of endovascular procedures and fewer open procedures, as well as a move away from the traditional principle of "learning by doing." This change has established simulation as a cornerstone in providing trainees with the necessary skills and competences. However, the development of simulation based programs often evolves based on available resources and equipment, reflecting convenience rather than a systematic educational plan. The objective of the present study was to perform a national needs assessment to identify the technical procedures that should be integrated in a simulation based curriculum. DESIGN AND METHODS: A national needs assessment using a Delphi process was initiated by engaging 33 predefined key persons in vascular surgery. Round 1 was a brainstorming phase to identify technical procedures that vascular surgeons should learn. Round 2 was a survey that used a needs assessment formula to explore the frequency of procedures, the number of surgeons performing each procedure, risk and/or discomfort, and feasibility for simulation based training. Round 3 involved elimination and ranking of procedures. RESULTS: The response rate for round 1 was 70%, with 36 procedures identified. Round 2 had a 76% response rate and resulted in a preliminary prioritised list after exploring the need for simulation based training. Round 3 had an 85% response rate; 17 procedures were eliminated, resulting in a final prioritised list of 19 technical procedures. CONCLUSION: A national needs assessment using a standardised Delphi method identified a list of procedures that are highly suitable and may provide the basis for future simulation based training programs for vascular surgeons in training.

Recombinant porcine factor VIII for high-risk surgery in paediatric congenital haemophilia A with high-titre inhibitor.

INTRODUCTION: High-titre factor VIII (FVIII) inhibitors complicate peri-operative haemostasis. Recombinant porcine FVIII (r-pFVIII) may provide an alternative haemostatic agent for high-risk procedures and allow FVIII activity monitoring. AIM: Devise an effective haemostatic plan for repair of a progressively symptomatic aortic coarctation in a 5-year-old male with immune tolerance induction (ITI) refractory high-titre FVIII inhibitors. METHODS: Preprocedure human FVIII inhibitor titre was 58 Bethesda Units mL-1 (BU) and cross-reacted to neutralize porcine FVIII at 30 BU. Daily ITI with plasma-derived FVIII concentrate was supplemented with anti-B-cell and anti-plasma cell immunotherapy to reduce FVIII inhibitor titres. Potential haemostatic agents were evaluated in comparative ex vivo thrombin generation assays (TGA). RESULTS: Four weeks after immunosuppression, human and porcine inhibitor titres declined to 16 and 2 BU respectively. TGA with r-pFVIII was less robust than with activated prothrombin complex concentrate (aPCC); however, r-pFVIII was selected for cardiac surgery to secure the ability to assay FVIII levels throughout this high-bleeding risk procedure. Haemostasis with r-pFVIII was excellent; initial trough FVIII activity levels ranged from 0.81-1.17 IU mL-1 . On postoperative day 3, peak and trough levels markedly declined suggesting a rising porcine inhibitor titre. Postprocedure prophylaxis was transitioned to aPCC, informed by TGA. CONCLUSIONS: R-pFVIII provided effective peri-procedural haemostasis with no adverse events. Rapid neutralization of r-pFVIII after the first 60 hours, despite intensive immune suppression, accentuates the importance of careful monitoring. Use of TGA can support bypassing agent selection for convalescence. The comparative cost of r-pFVIII may limit its use to high morbidity clinical scenarios.

Short communication: Calving site selection of multiparous, group-housed dairy cows is influenced by site of a previous calving.

A calving cow and her newborn calf appear to have an attracting effect on periparturient cows, which may potentially influence the functionality of future motivation-based calving pen designs. In this pilot study we examined whether calving site selection of group-housed Holstein dairy cows was affected by the site of a previous calving. Ten multiparous cows moved to 1 of 2 group pens 11 (range = 4-27) d before calving were included. Each pen consisted of an open area (9 × 9 m) connected to 6 secluded areas (4.5 × 3 m each), where cows could move freely between all areas. Time of calving, location of the breaking of the amniotic sac, as well as the place of birth were recorded. In all but 1 case cows calved within a distance of 1 cow length from where the previous calving took place, suggesting that the cows did not select calving site at random. These preliminary observations indicate that choice of calving site may be affected by the site of a previous calving, potentially explained by the presence of amniotic fluids.

Review: Drinking water for liquid-fed pigs.

Liquid feeding has the potential to provide pigs with sufficient water to remain hydrated and prevent prolonged thirst. However, lack of permanent access to fresh water prevents animals from drinking when they are thirsty. Moreover, individual differences between pigs in a pen may result in uneven distribution of the water provided by the liquid feed, leading to some pigs being unable to meet their water requirements. In this review, we look at the need for and provision of water for liquid-fed pigs in terms of their production performance, behaviour, health and welfare. We highlight factors which may lead to water ingestion above or below requirements. Increases in the need for water may be caused by numerous factors such as morbidity, ambient temperature or competition within the social group, emphasising the necessity of permanent access to water as also prescribed in EU legislation. The drinkers can be the target of redirected behaviour in response to feed restriction or in the absence of rooting materials, thereby generating water losses. The method of water provision and drinker design is critical to ensure easy access to water regardless of the pig's physiological state, and to limit the amount of water used, which does not benefit the pig.

Selective complexation of divalent cations by a cyclic α,ß-peptoid hexamer: a spectroscopic and computational study.

We describe the qualitative and quantitative analysis of the complexation properties towards cations of a cyclic peptoid hexamer composed of alternating α- and ß-peptoid monomers, which bear exclusively chiral (S)-phenylethyl side chains (spe) that have no noticeable chelating properties. The binding of a series of monovalent and divalent cations was assessed by 1H NMR, circular dichroism, fluorescence and molecular modelling. In contrast to previous studies on cations binding by 18-membered α-cyclopeptoid hexamers, the 21-membered cyclopeptoid cP1 did not complex monovalent cations (Na+, K+, Ag+) but showed selectivity for divalent cations (Ca2+, Ba2+, Sr2+ and Mg2+). Hexacoordinated C-3 symmetrical complexes were demonstrated for divalent cations with ionic radii around 1 Å (Ca2+ and Ba2+), while 5-coordination is preferred for divalent cations with larger (Ba2+) or smaller ionic radii (Mg2+).