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Knowing PRRSV status is essential to design herd management protocols. For this, weaning-age pigs are a key subpopulation. In the last years, several alternatives to blood sampling have been tested because of easier, welfare friendly and cost saving tools. Moreover, most of them allow to test more animals and then, seem to be more sensitive in case of low prevalence scenario. However, these studies have been implemented mainly in PRRSV-2 infected herds. The first objective of our study was to compare the rate of detection of PRRSV-1 by RT-qPCR in individual serum samples, family oral fluid samples (FOF) and udder wipes (UW) collected the day before weaning. The second objective was to evaluate the interest of pooling. The study was performed on a 200-sows farrow-to-finish farm, PRRSV-1 infected and unstable. 119 litters were sampled (one sample type per litter). The rate of detection of PRRSV-1 in blood samples, FOF and UW was 10.9%, 7.6% and 0.8%, respectively. The agreement between sera and FOF was almost perfect even if detection capacity of sera was numerically superior to FOF. The Ct values on sera were statistically lower than FOF ones. Two modalities of pooling (1/3 and 1/5) were tested for sera and FOF. They showed that both modalities did not impact the qualification neither of the litter not of the batch PRRSV classification. On the other hand, even pooled by 3, most of the FOF pools gave negative results misclassifying many litters and batches. In the conditions of our study, in a PRRSV-1 infected scenario, FOF seemed to be a good alternative to blood sampling only when analysed individually and so a more costly alternative.

Mycoplasma suis (M. suis) is an haemotropic Mycoplasma that adheres and invades erythrocytes and is responsible for infectious anaemia of pigs. Infections with M. suis have been reported worldwide. Clinical signs after M. suis infection can be significant particularly for the breeding herd in the period around farrowing but consequences are highly variable with some infected pigs never exhibiting clinical disease. The study aimed to determine the clinical relevance of Giemsa-stained blood smear for the diagnosis of M. suis compared with qPCR results. In our study, the comparison of qPCR results with microscopic investigation of Giemsa-stained blood smears revealed a lower sensitivity of the microscopic method: only 33 out of 102 qPCR positive blood samples were microscopically positive (M. suis visualised). No relationship between mean qPCR loads and microscopic observation was observed. Although more costly, qPCR is probably the best diagnostic tool available today for M. suis diagnosis.

Background Microbial colonisation of piglets' intestines starts at birth, especially from contact with sow's faeces. Piglet microbiota could therefore be influenced by the sow's diet. The objective of this study was to evaluate whether the microbiological flora of liquid feed for sows can be associated with the development of neonatal diarrhoea. Methods This study was carried out on 10 case farms with neonatal diarrhoea and 10 control farms without neonatal diarrhoea. On each farm, a microbiological analysis of gestating and lactating liquid feed was performed. A generalised linear model was used to study the impact of the liquid feed microbiological counts and pH on the probability of neonatal diarrhoea developing. Results For thermotolerant coliforms, sulphite-reducing bacteria, heterotrophic bacteria and lactic-acid bacteria counts, there was no significant difference between case and control farms. The higher the count of total coliforms, enterococci and yeasts in sow non-fermented liquid feed, the greater the probability of observing neonatal diarrhoea. Moreover, taking into account total coliforms and yeasts counts together is highly predictive of neonatal diarrhoea risk. Conclusion This study offers new perspectives of investigation and understanding of neonatal diarrhoea in breeding farms feeding sows with a non-fermented liquid feed.

Background Changes in haematological values occur during the reproductive cycle. In veterinary swine practice, haematological reference intervals for this period are scarce. Over past decades, there has been a remarkable increase in reproductive prolificacy, possibly making previously established haematological reference intervals for sows outdated. Objectives The aim of this study was to provide updated haematological reference intervals for sows at end-gestation, to study the influence of parity on those haematological parameters and to evaluate the impact of haemoglobin levels on production performance. Methods The data presented in this article were obtained using blood samples from 198 apparently healthy and conventionally managed group-housed sows at end-gestation from ten breeding herds located in France. The samples were analysed for haematological variables using impedance technique on Horiba ABX analyser (Horiba, Kyoto, Japan). The reference intervals were calculated according to the guidelines of The American Society for Veterinary Clinical Pathology using SUMMARY procedure in R Studio. Analysis of variance (ANOVA) models were used to evaluate the influence of parity on each haematological parameter and the impact of haemoglobin values on production performances at farrowing. Differences were considered as significant if p Results Reference intervals produced in this study were similar to previously published references but we noticed marked differences in white blood cell values. The study of the impact of parity revealed significant changes for gilts and parity 5 + sows regarding haematological values. Gilts had higher red and white blood cells counts, haemoglobin values and haematocrit values. Regarding haemoglobin values, the higher the number of liveborn and weaned piglets per litter, the lower the haemoglobin value at end-gestation. For sows of fifth or higher gestation, we found that the higher the percentage of stillborn piglets, the lower the haemoglobin value at end-gestation. Conclusions This study provides haematological reference intervals for sows at end-gestation. These will be useful for swine veterinarians and researchers for a better understanding of the influence of parity on haematological parameters and haemoglobin values and their relation to reproductive performance.

Background Mycoplasma hyopneumoniae and Porcine circovirus type 2 are two economically important pathogens affecting growing pigs. Control and prevention of both diseases can be accomplished by vaccination, together with biosecurity and good management practices. Many commercial vaccines are available. The aim of this study was to assess the efficacy of Hyogen® and Circovac® administered mixed at weaning and to compare this protocol with a competitor ready-to-use (RTU) vaccine. Case presentation A randomised field trial was designed in a commercial farrow-to-finish farm located in France. A total of 641 pigs born from 54 different sows were included in this study. Piglets at weaning were allocated into three groups: the first one vaccinated with Hyogen® and Circovac® combined (group A), the second one vaccinated with a competitor RTU vaccine (group B) and the last one unvaccinated. Only minor local reactions for both vaccination groups could be observed which revealed a good safety of both protocols. Both vaccination schemes in this trial didn’t improve wean-to-slaughter growth performances but significantly reduced lung lesions, lung fissures and pleurisy at slaughter, produced a seroconversion for both M. hyopneumoniae and PCV-2 and significantly reduced the PCV-2 viral load in blood. When we compared groups A and B, we observed no significant differences in growth performances, mortality, clinical signs, percentages of affected lungs at slaughter, lung fissures and pleurisy, and no difference in pathogens detection. However, two statistical differences were observed between both vaccines: the mean lung lesion score and the percentage of extensive lung lesions were lower in group A. This is consistent with lower M. hyopneumoniae loads in the lower respiratory tract in pigs from group A but this difference was not statistically significant. Conclusions Results reported in this case study must be considered with caution since it was done in only one farm. In this trial, Hyogen® and Circovac® mixed together under field conditions offered a successful protection of growing pigs and significantly decreased the extension of lung lesions during a natural field challenge when compared with a competitor RTU vaccine.

Highlights • Maternally-derived neutralizing antibodies impair PRRS vaccination immune responses in piglets. • Maternally-derived neutralizing antibodies reduce PRRS vaccine efficacy in piglets. • IFNa may also interfere with PRRS vaccination., Modified live virus (MLV) vaccines are commonly used to reduce the impact of porcine reproductive and respiratory syndrome (PRRS) but limited efficacy is achieved in field conditions. Here, we evaluated the impact of maternally-derived neutralizing antibodies (MDNAs) on vaccine efficacy after PRRS virus (PRRSV) challenge. Piglets with low (A−) or high (A+) MDNA levels derived from a commercial pig herd were moved to experimental facilities to be vaccinated (V+) or not (V−) with a PRRSV-1 MLV vaccine at 3 weeks of age (woa). Because of unexpectedly low vaccine detection in A−V+ piglets post-vaccination (pv), all V+ piglets received a second vaccination at 4 woa. Five weeks (W5) pv, piglets were inoculated with a PRRSV-1 field strain to evaluate vaccine protection, and were mingled 24 h later with non-inoculated piglets of similar immune status to assess viral transmission. Vaccine strain was detected at W2 pv in 69% and 6% of A−V+ and A+V+ piglets, and at W5 pv in 50% and 25% of A−V+ and A+V+ piglets, respectively. At W5 pv, 94% of A−V+ and 44% of A+V+ piglets seroconverted, with a significant IFNg response induction in the A−V+ group only. After challenge, compared to the V− inoculated group, viremia was 100-fold lower at 10 days post-infection in A−V+ whereas viremia was not significantly reduced in A+V+ piglets. A lower transmission rate was estimated for the A−V+ group: 0.15 [0.07–0.29] versus 0.44 [0.18–1.76] and 0.32 [0.14–0.68] for the A+V+ and V− groups, respectively. Investigations about the low vaccine strain detection after the first vaccination suggested a relationship between IFNa levels and vaccine strain detection in A−V+ piglets. We showed that MDNAs impair vaccine efficacy against PRRSV both in inoculated and contact piglets, probably by reducing vaccine replication. IFNa may also interfere with PRRSV vaccination. These new data could help improving vaccination protocols.

In the last two decades, in France, Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) stabilization protocols have been implemented using mass vaccination with a modified live vaccine (MLV), herd closure and biosecurity measures. Efficient surveillance for PRRSV is essential for generating evidence of absence of viral replication and transmission in pigs. The use of processing fluid (PF) was first described in 2018 in the United States and was demonstrated to provide a higher herd-level sensitivity compared with blood samples (BS) for PRRSV monitoring. In the meantime, data on vertical transmission of MLV viruses are rare even as it is a major concern. Therefore, veterinarians usually wait for several weeks after a sow mass vaccination before starting a stability monitoring. This clinical study was conducted in a PRRSV-stable commercial 1000-sow breed-to-wean farm. This farm suffered from a PRRS outbreak in January 2018. After implementing a stabilisation protocol, this farm was controlled as stable for more than 9 months before the beginning of the study. PF and BS at weaning were collected in four consecutive batches born after a booster sow mass MLV vaccination. We failed to detect PRRSV by qPCR on PF and BS collected in a positive-stable breeding herd after vaccination with ReproCyc® PRRS EU (Boehringer Ingelheim, Ingelheim, Germany).

Highlights • Pooled oral fluid (OF) sampling from piglets is achievable pre-weaning using a cotton rope. • OF collection was successful for 62–100% of the litters depending on age and pre-exposure. • 84.7 and 95% of naïve pigs interacted spontaneously with a rope at 21 and 28 days age, respectively. • Latency to interact with the rope highly varied between piglets within litters., Collection of pooled oral fluid (OF) by allowing pigs to chew on a cotton rope is an alternative to blood sampling. However, little is known about the applicability of this method to suckling piglets. The objectives of the present study were to describe the spontaneous interaction of suckling piglets with a rope and to investigate the influence of a rope pre-exposure on the success rate of sampling. We studied the interaction dynamics of 21 and 28 days-old suckling piglets with a cotton rope presented for 30 min. Ropes were manually wrung out inside plastic bags to release the oral fluid. A total of 49 litters were included. Percentages of success of pooled OF collection for 28-day-old, 21-day-old and 21-day-old pre-exposed litters were 82%, 62% and 100%, respectively. The mean volume collected did not differ between groups. Without pre-exposure, 84.7% and 95% of piglets interacted spontaneously with the rope at 21 and 28 days of age, respectively. The latency between rope presentation and interaction was highly variable between piglets within litters: from < 10 s to 30 min. Among piglets having interacted with the rope, the interaction lasted for at least 60 s for 90% and 91.4% of 21 and 28-day-old piglets, respectively. Pooled OF collection is achievable prior to weaning in piglets of at least 21 days of age. Pooled OF sampling is representative at litter level if collection is successful. In order to improve the success rate of collection, pre-exposing the piglets with a rope one day prior to sampling is effective.

In Europe, modified live vaccines (MLV) are commonly used to control porcine reproductive and respiratory syndrome virus (PRRSV) infection. However, they have been associated with safety issues such as reversion to virulence induced by mutation and/or recombination. On a French pig farm, we identified a field recombinant strain derived from two PRRSV-1 MLV (MLV1). As a result, we aimed to evaluate its clinical, virological, and transmission parameters in comparison with both parental strains. Three groups with six pigs in each were inoculated with either one of the two MLV1s or with the recombinant strain, six contact pigs were then added into each inoculated group. The animals were monitored daily for 35 days post-inoculation (dpi) for clinical symptoms, blood samples and nasal swabs were collected twice a week. PRRS viral load in inoculated pigs of recombinant group was higher in serum, nasal swabs, and tonsils in comparison with both vaccine groups. The first viremic contact pig was detected as soon as 2 dpi in the recombinant group compared to 10 and 17 dpi for vaccine groups. Estimation of transmission parameters revealed fastest transmission and longest duration of infectiousness for recombinant group. Our in vivo study showed that the field recombinant strain derived from two MLV1s demonstrated high viremia, shedding and transmission capacities.

Background Defining shedding and exposure status for PRRSV is essential in herd stabilisation protocols and weaning-age pigs is a key subpopulation. Oral fluid (OF) sampling is a welfare-friendly and cost saving promising alternative to blood sampling. The first objective of our study was to compare the rate of detection of PRRSV-1 in individual serum sample, individual OF sample, litter-based OF sample, collected the day before weaning. The second objective was to evaluate the interest of pooling samples. Results The study was performed on a 210-sows, PRRSV-1 exposed, with confirmed shedding, non-vaccinated against PRRSV, herd. 80 litters were sampled and 26 were viropositive and therefore included. The rate of detection of PRRSV-1 with RT-qrtPCR in blood samples, iOF and cOF was 67, 23 and 77%, respectively. The Ct values from RT-qrtPCR on collective OF were statistically lower if the serum of the piglet of the litter was positive. The lower the Cycle threshold (Ct) value of RT-qrtPCR on collective OF, the higher the probability that the serum sampled in the same litter was positive. Ability to detect PRRSV RNA after pooling was 67% for sera and 58% for cOF. Conclusions The rate of detection of PRRSV-1 was about the same in cOF and blood samples. Virus sequencing, if required, should be performed on individual serum samples. The smaller the Ct of a cOF sample from a litter, the greater the likelihood that the serum sample from a piglet of that litter is positive. A cost-effective and representative sampling protocol to monitor sow herds stabilisation of a sow batch could be: to collect both cOF and one serum sample per litter; to perform firstly RT-qrtPCR on pooled cOF; in case of negative results to consider the batch negative; in case of positive results in a unvaccinated herd or a killed vaccine vaccinated one to consider the batch positive; in case of positive result in a herd vaccinated with a modified live vaccine serum samples of litters with positive cOF should be tested for sequencing (selecting the litters with the lowest Ct for cOF).

We conducted a meta-analysis of pharmacogenomic substudies of three randomized trials conducted in patients with decompensated heart failure (HF) that were led by National Heart Lung and Blood Institute (NHLBI)-funded HF Network to test the hypothesis that candidate genes modulate net fluid loss and weight change in patients with decompensated HF treated with a furosemide-based diuretic regimen. Although none of the genetic variants previously shown to modulate the effects of loop diuretics in healthy individuals were associated with net fluid loss after 72 h of treatment, a set of rare variants in the APOL1 gene, which codes for apolipoprotein L1 (P=0.0005 in the random effects model), was associated with this end point. Moreover, a common variant in the multidrug resistance protein-4 coding gene (ABCC4, rs17268282) was associated with weight loss with furosemide use (P=0.0001). Our results suggest that both common and rare genetic variants modulate the response to a furosemide-based diuretic regimen in patients with decompensated HF.

Aim: To evaluate the impact of AGTR1 A1166C (rs5186) on the response to candesartan in patients with heart failure. Materials & methods: Prospective, multicentre, open-label study. We studied 299 symptomatic patients with heart failure presenting a left ventricular ejection fraction ≤40%. Results: Reductions in the primary end points of natriuretic peptides were not significantly associated with AGTR1 A1166C. Nevertheless, carrying the 1166C allele was associated with a greater compensatory increase in renin activity (p = 0.037) after 16 weeks of treatment with candesartan and a more modest effect on aldosterone concentrations (p = 0.022). Conclusion: AGTR1 1166C carriers may experience a greater long-term compensatory renin–angiotensin–aldosterone system activation following treatment with candesartan. Whether these associations ultimately influence clinical outcomes requires investigation. Clinicaltrials.gov : NCT00400582

The presence of pneumoviruses in pigs is poorly documented. In this study, we used the published sequence of the nucleoprotein (N) of the recently identified Swine Orthopneumovirus (SOV) to express and purify SOV N as a recombinant protein in Escherichia coli. This protein was purified as nanorings and used to set up an enzyme-linked immunosorbent assay, which was used to analyse the presence of anti-pneumovirus N antibodies in swine sera. Sera collected from different pig farms in the West of France and from specific pathogen free piglets before colostrum uptake showed indirectly that a pneumovirus is circulating in pig populations with some variations between animals. Piglets before colostrum uptake were sero-negative for anti-pneumovirus antibodies while most of the other pigs showed positivity. Interestingly, in two farms presenting respiratory clinical signs and negative or under control for some common respiratory pathogens, pigs were detected positive for anti-pneumovirus antibodies. Globally, anti-pneumovirus N antibody concentrations were variable between and within farms. Further studies will aim to isolate the circulating virus and determine its potential pathogenicity. SOV could potentially become a new member of the porcine respiratory complex, important on its own or in association with other viral and bacterial micro-organisms. Electronic supplementary material The online version of this article (10.1186/s13567-018-0615-x) contains supplementary material, which is available to authorized users.

Pharmacogenomic markers in the HLA coding genes have been associated with drug hypersensitivity of multiple drugs, including allopurinol. In this systematic review, we summarize the pharmacogenomic evidence available regarding allopurinol-induced cutaneous adverse drug reactions (cADRs). We found that the HLA-B*5801 allele was significantly associated with the risk of severe cADRs in the Han Chinese, Korean, Thai, Japanese and European populations. The association between less severe cADRs and HLA-B*5801 was less consistent. All SNPs identified in genome-wide association studies of common variants were also located in or nearby HLA-B*5801. Future studies should focus on more common but less severe allopurinol-induced cADRs, as well as the potential role of rare variants as predictors of these cADRs.

This paper provides information on the complete genome sequence of a porcine reproductive and respiratory syndrome virus (PRRSV) strain isolated on a French pig farm which was identified as a recombinant strain from two commercial modified live virus vaccine strains of genotype 1 (VP-046BIS and DV strains).

Background Porcine reproductive and respiratory syndrome virus (PRRSV) is responsible for reproductive disorders in sows and respiratory problems in pigs, and has a major economic impact. Controlling PRRSV is therefore a priority for the swine industry. Stabilization of a herd, defined as the production of PRRSV-negative pigs at weaning from seropositive sows, is a common method of control, and different protocols have been described in the literature to achieve this stabilization. Context and purpose The objective of this study was to evaluate wether the combination of mass vaccination of sows and their piglets with a Genotype I modified live virus (MLV) vaccine, with temporal closure to the introduction of replacement animals and unidirectional pig and human flow can result in the production of PRRSV-negative pigs at weaning. The study took place in French farrow-to-finish farms located in a high-density swine area where the disease concerns over 60% of farms and only closely related strains of genotype I have been reported. Twenty-three 100-to-700 sow farrow-to-finish farms were selected prospectively between 2005 and 2014, regardless of their biosecurity level. Those farms adopted a stabilization protocol characterized by the following standardized measures: vaccination of sows, gilts, and piglets with the Genotype I MLV vaccine PORCILIS®PRRS, temporary herd closure, and strict internal biosecurity measures. Monitoring of herd status was then performed using a combination of 3 diagnostic tools: Real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and Open reading frame (ORF) 5 and ORF7 sequencing. The status of finishing units (either active or inactive, meaning PRRSV-positive or PRRSV-negative, respectively) was not considered in this study. Results and conclusions At the end of the monitoring period, considering the results of all the analyses, clinical signs, and epidemiology, 19 farms were considered stable and 1 remained unstable. In 3 farms it was commonly agreed to extend the number of vaccinated batches of piglets, which enabled them to be considered stable at the end of a second round of monitoring. The combination of vaccination of sows and their piglets with a Genotype I MLV vaccine, together with the closure of the farm and a unidirectional pig and human flow, seems to be effective for farrow–to-finish farms even in high-density swine area, even with French PRRSV strains closely related to one another. This research is the first European study examining such a large number of farms, and increased confidence in the results stems from the added value of using the ORF7 and ORF5 sequencing tool.

The influence of maternally-derived antibodies (MDAs) on the post-vaccination humoral and cellular immune responses in piglets vaccinated against PRRS was studied. The piglets came from a vaccinated breeding herd. Thirty piglets with a low (A-) or high level (A+) of PRRSV-neutralizing MDAs were vaccinated (V+) with a modified live vaccine at 3 weeks of age. Blood samples were collected before vaccination and then at 2, 4, 8 and 14 weeks post-vaccination (WPV). The samples were analysed to detect the vaccine viraemia (RT-PCR) and quantify the post-vaccination humoral (ELISA and virus neutralisation test) and cellular (ELISPOT IFNγ) immune responses. PRRSV vaccine strain was detected in 60%, 64%, 36% and 0% of A-V+ piglets 2, 4, 8 and 14 WPV respectively. No virus was detected in A+V+ piglets during the first four WPV but 32% and 6% of A+V+ piglets were PCR-positive at 8 and 14 WPV. Eighty-five percent of A-V+ piglets and 0% of A+V+ piglets seroconverted (ELISA) between 2 and 4 WPV. Neutralising antibodies appeared 4 WPV in the A-V+ piglets and 14 WPV in the A+V+ piglets. The number of PRRSV-specific IFNγ-secreting cells was significantly higher in A-V+ piglets at 2 and 4 WPV than in A+V+ piglets. These results show that MDAs can affect both post-vaccination humoral and cellular immune responses in piglets. Further studies are required to assess the impact of MDAs on vaccine efficacy following a PRRSV challenge and its ability to reduce viral transmission.

OBJECTIVES Single nucleotide polymorphisms (SNPs) in the transforming growth factor-β1 gene (TGFB1) have been inconsistently associated with calcineurin inhibitor (CNI)-induced renal dysfunction following cardiac transplantation. The impact of genetic variants related to the renin-angiotensin-aldosterone system (RAAS) and natriuretic peptides, which are implicated in CNI nephrotoxicity, is unknown. The primary objective of this study was to validate the association between two common variants in TGFB1 (rs1800470, rs1800471) and postcardiac transplant renal function. The secondary objective was to investigate the effect of candidate genes related to the RAAS, natriuretic peptides, and other elements involved in the intracellular signaling of these pathways. METHODS We conducted a retrospective cohort study of 158 heart transplant recipients treated with CNIs, and evaluated the association between select SNPs and the estimated glomerular filtration rate as calculated by the Modification of Diet in Renal Disease simplified formula. A total of 273 SNPs distributed in 44 genes were tested. RESULTS No association was observed between TGFB1 variants and renal function. One polymorphism in the protein kinase C-β gene (PRKCB; rs11074606), which is implicated in the RAAS intracellular signaling, was significantly associated with post-transplant estimated glomerular filtration rate after adjusting for possible confounders (P=0.00049). This marker is in linkage disequilibrium with two variants located in putative regulatory regions of the gene (rs2283541, rs1013316). CONCLUSION Our results suggest that PRKCB may be a potential predictor of CNI-induced nephrotoxicity in heart transplant recipients, and could therefore be a promising candidate to identify patients who are most susceptible to this adverse drug reaction.

The effect of luminal gastrin on the secretion of pancreatic juice was studied in seven conscious preruminant calves employing luminal infusions of gastrin and cholecystokinin (CCK)-9 and pharmacological CCK1 and CCK2 receptor blocks with antagonists. The study was performed in the preprandial and prandial states. Pharmacological blocking of the CCK2 receptor, like that of the CCK1 receptor, resulted in reduction of pancreatic postprandial secretion and increased the duration of the prandial pattern of duodenal electrical activity. Exogenous luminal gastrin, like luminal CCK-9, enhanced the secretion of pancreatic juice proteins, though the overall effect of gastrin was weaker than that of CCK-9. The effect was inhibited by infusion of CCK2 but also by CCK1 receptor antagonist. In conclusion, duodenal luminal gastrin can stimulate exocrine pancreatic secretion by a mechanism that depends on CCK2 receptors in calves. Involvement of the CCK1 receptor in this mechanism needs further investigation. Prandial pancreatic secretory and duodenal motility cycles can be regulated by endogenous gastrin release.

Background— Statins (HMG-CoA reductase inhibitors) are the most prescribed class of lipid-lowering drugs for the treatment and prevention of cardiovascular disease. Creatine kinase (CK) is a commonly used biomarker to assist in the diagnosis of statin-induced myotoxicity but the normal range of CK concentrations is wide, which limits its use as a diagnostic biomarker. Methods and Results— We conducted a genome-wide association study of serum CK levels in 3412 statin users. Patients were recruited in Quebec, Canada, and genotyped on Illumina Human610-Quad and an iSelect panel enriched for lipid homeostasis, hypertension, and drug metabolism genes. We found a strong association signal between serum levels of CK and the muscle CK ( CKM ) gene (rs11559024: P =3.69×10 −16 ; R 2 =0.02) and with the leukocyte immunoglobulin-like receptor subfamily B member 5 ( LILRB5 ) gene (rs2361797: P =1.96×10 −10 ; R 2 =0.01). Genetic variants in those 2 genes were independently associated with CK levels in statin users. Results were successfully replicated in 5330 participants from the Montreal Heart Institute Biobank in statin users for CKM (rs11559024: P =4.32×10 −16 ; R 2 =0.02) and LILRB5 (rs12975366 P =4.45×10 −10 ; R 2 =0.01) and statin nonusers ( P =4.08×10 −7 , R 2 =0.01; P =3.17×10 −9 , R 2 =0.02, respectively). Conclusions— This is the first genome-wide study to report on the underlying genetic determinants of CK variation in a population of statin users. We found statistically significant association for variants in the CKM and LILRB5 genes.

We conducted a meta-analysis of pharmacogenomic substudies of three randomized trials conducted in patients with decompensated heart failure (HF) which were led by National Heart Lung and Blood Institute (NHLBI)-funded HF Network to test the hypothesis that candidate genes modulate net fluid loss and weight change in patients with decompensated HF treated with a furosemide-based diuretic regimen. Although none of the genetic variants previously shown to modulate the effects of loop diuretics in healthy individuals were associated with net fluid loss after 72 hours of treatment, a set of rare variants in the APOL1 gene, which codes for apolipoprotein L1 (P= 0.0005 in the random effects model) was associated with this endpoint. Moreover, a common variant in the multidrug resistance protein-4 coding gene (ABCC4, rs17268282) was associated with weight loss with furosemide use (P = 0.0001). Our results suggest that both common and rare genetic variants modulate the response to a furosemide-based diuretic regimen in patients with decompensated HF.

This chapter examines Nagoya Protocol's innovations over the Convention on Biological Diversity (CBD) and some of the contributions it makes to advancing international environmental law. It provides a short primer on access and benefit-sharing (ABS) and the CBD including the process leading to the adoption of the Protocol. The chapter reviews the Protocol's innovative provisions in relation to those of the CBD, highlighting how they respond to outstanding implementation challenges, and thereby advance international environmental law addressing ABS. It also examines some of the other international instruments and intergovernmental processes influenced by the ABS concept and their relationship with the Protocol, and provide some thoughts on the way forward for the implementation of the Protocol. The ongoing work of the World Intellectual Property Organisation (WIPO), particularly the IGC, is another forum whose work influenced the Protocol's negotiation and may be itself influenced by the Protocol. Keywords:access and benefit-sharing (ABS); Convention on Biological Diversity (CBD); international environmental law; Nagoya Protocol; World Intellectual Property Organisation (WIPO)

Campylobacter is recognized as one of the leading cause of gastroenteritis worldwide, and is frequently isolated from the small intestines and ceca microflora of chickens. Twenty-one out of 81 Campylobacter-positive poultry flocks were selected to evaluate the genetic diversity of Campylobacter isolates and to study the distribution of genotypes among flocks. Campylobacter isolates recovered from chicken carcasses and ceca were analyzed by pulsed-field gel electrophoresis (PFGE). Little diversity was found among Campylobacter strains isolated from a given carcass, with a maximum of 2 different genotypes being present. However, at flock level, as many as 4 different profiles were observed. Typing of strains showed that most strains isolated from ceca were similar to those isolated from corresponding broiler carcasses. A total of 39 different macrorestriction profiles were observed, with evidence of Campylobacter cross-contamination among broiler flocks in Quebec slaughterhouses. Surprisingly, some flocks shared related genotypes both with and without sharing similar rearing practices. Existence of such cross-contamination must be considered to in developing strategies to control Campylobacter in chickens, and to avoid bacteria contamination of noncolonized flocks. Further typing studies of Campylobacter found in hatcheries, farm environment, and crates or trucks in Quebec might be helpful in elucidating the kinetics of broiler chicken Campylobacter contamination.

We conducted an observational study to estimate prevalence and risk factors for Salmonella spp. and Campylobacter spp. caecal colonization in poultry. Eighty-one broiler chicken and 59 turkey flocks selected among flocks slaughtered in the province of Quebec, Canada, were included in the study. Flock status was evaluated by culturing pooled caecal contents from about 30 birds per flock. Exposure to potential risk factors was evaluated with a questionnaire. Odds ratios were computed using multivariable logistic regression. The prevalence of Salmonella-positive flocks was 50% (95% CI: 37, 64) for chickens and 54% (95% CI: 39, 70) for turkeys, respectively. Odds of Salmonella colonization were 2.6 times greater for chicken flocks which failed to lock the chicken house permanently. In turkeys, odds of Salmonella colonization were 4.8-7.7 times greater for flocks which failed to be raised byor=2 producers with no other visitors allowed onto the premises, or origin from a hatchery. The prevalence of Campylobacter-positive flocks was 35% (95% CI: 22, 49) for chickens and 46% (95% CI: 30, 62) for turkeys. Odds of colonization were 4.1 times higher for chicken flocks raised on farms with professional rodent control and 5.2 times higher for flocks with manure heap200m from the poultry house, and also increased with the number of birds raised per year on the farm and with the age at slaughter. For turkeys, odds of Campylobacter flock colonization were 3.2 times greater in flocks having a manure heap at/=200m from poultry house and 4.2 times greater in flocks drinking unchlorinated water.