Impact of a leptin single nucleotide polymorphism and zilpaterol hydrochloride on growth and carcass characteristics in finishing steers

A total of 4,178 steers (mean initial BW = 403.9 ± 16.04 kg) were used to test the interactive effects, if any, of leptin R25C genotypes (CC, CT, or TT) and zilpaterol hydrochloride (ZH) feeding duration on growth performance and carcass traits. Steers were blocked by arrival at the feed yard, genotyped for the leptin SNP, allotted to genotype-specific pens (90 steers/pen), and assigned randomly within genotype and block to 0 or 21 d of dietary ZH. All pens within a block were slaughtered on the same day (132.1 ± 10.9 d on feed). Final BW of steers fed ZH was 6.0 kg heavier (P = 0.008), and ZH-fed steers had greater (P = 0.003) ADG than steers not fed ZH. Feeding ZH decreased DMI in steers with increased frequency of the T allele (9.67, 9.53, and 9.28 kg/d for CC, CT, and TT, respectively), but DMI increased with the frequency of the T allele (9.68, 9.90, and 10.1 kg for CC, CT, and TT, respectively) when ZH was not fed (leptin genotype × ZH, P = 0.011). At the conclusion of the study, ultrasonic fat was greatest for TT steers (11.4 ± 0.28 mm) and least (P = 0.003) for CC steers (11.0 ± 0.25 mm). Regardless of ZH-feeding duration, TT steers produced a greater (P = 0.006) percentage of USDA yield grade (YG) 4 or higher carcasses (5.4 vs. 2.7%) and a lesser (P = 0.006) percentage of YG 1 carcasses (17.7 vs. 26.8%) than CC steers. In addition, ZH-fed steers produced a greater (P \u3c 0.001) percentage of USDA YG 1 carcasses (25.9 vs. 16.2%) and a lesser (P \u3c 0.001) percentage of YG 4 or higher carcasses (1.6 vs. 6.0%) than steers fed the control diet. Marbling scores and the percentage of carcasses grading USDA Choice and Prime were greater in TT than CC steers when fed diets devoid of ZH, but both marbling and quality grades did not differ among leptin genotypes when fed ZH for 21 d (leptin genotype × ZH, P ≤ 0.03). The amount of HCW gain tended to be less (P = 0.095) for steers of the TT genotype (12.7 kg) than either CC (16.3 kg) or CT (17.0 kg) genotypes. Results indicated that leptin R25C genotype impacted most traits associated with fatness whereas feeding ZH for 21 d affected HCW and ADG positively but impacted feed intake, marbling, and USDA quality grades negatively

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Impact of a leptin single nucleotide polymorphism and zilpaterol hydrochloride on growth and carcass characteristics in finishing steers

A total of 4,178 steers (mean initial BW = 403.9 ± 16.04 kg) were used to test the interactive effects, if any, of leptin R25C genotypes (CC, CT, or TT) and zilpaterol hydrochloride (ZH) feeding duration on growth performance and carcass traits. Steers were blocked by arrival at the feed yard, genotyped for the leptin SNP, allotted to genotype-specific pens (90 steers/pen), and assigned randomly within genotype and block to 0 or 21 d of dietary ZH. All pens within a block were slaughtered on the same day (132.1 ± 10.9 d on feed). Final BW of steers fed ZH was 6.0 kg heavier (P = 0.008), and ZH-fed steers had greater (P = 0.003) ADG than steers not fed ZH. Feeding ZH decreased DMI in steers with increased frequency of the T allele (9.67, 9.53, and 9.28 kg/d for CC, CT, and TT, respectively), but DMI increased with the frequency of the T allele (9.68, 9.90, and 10.1 kg for CC, CT, and TT, respectively) when ZH was not fed (leptin genotype × ZH, P = 0.011). At the conclusion of the study, ultrasonic fat was greatest for TT steers (11.4 ± 0.28 mm) and least (P = 0.003) for CC steers (11.0 ± 0.25 mm). Regardless of ZH-feeding duration, TT steers produced a greater (P = 0.006) percentage of USDA yield grade (YG) 4 or higher carcasses (5.4 vs. 2.7%) and a lesser (P = 0.006) percentage of YG 1 carcasses (17.7 vs. 26.8%) than CC steers. In addition, ZH-fed steers produced a greater (P \u3c 0.001) percentage of USDA YG 1 carcasses (25.9 vs. 16.2%) and a lesser (P \u3c 0.001) percentage of YG 4 or higher carcasses (1.6 vs. 6.0%) than steers fed the control diet. Marbling scores and the percentage of carcasses grading USDA Choice and Prime were greater in TT than CC steers when fed diets devoid of ZH, but both marbling and quality grades did not differ among leptin genotypes when fed ZH for 21 d (leptin genotype × ZH, P ≤ 0.03). The amount of HCW gain tended to be less (P = 0.095) for steers of the TT genotype (12.7 kg) than either CC (16.3 kg) or CT (17.0 kg) genotypes. Results indicated that leptin R25C genotype impacted most traits associated with fatness whereas feeding ZH for 21 d affected HCW and ADG positively but impacted feed intake, marbling, and USDA quality grades negatively

Senescent cells: an emerging target for diseases of ageing

Contains fulltext : 182660.pdf (publisher's version ) (Closed access)Chronological age represents the single greatest risk factor for human disease. One plausible explanation for this correlation is that mechanisms that drive ageing might also promote age-related diseases. Cellular senescence, which is a permanent state of cell cycle arrest induced by cellular stress, has recently emerged as a fundamental ageing mechanism that also contributes to diseases of late life, including cancer, atherosclerosis and osteoarthritis. Therapeutic strategies that safely interfere with the detrimental effects of cellular senescence, such as the selective elimination of senescent cells (SNCs) or the disruption of the SNC secretome, are gaining significant attention, with several programmes now nearing human clinical studies

Assessing the social and environmental determinants of pertussis epidemics in Queensland, Australia: a Bayesian spatio-temporal analysis

Pertussis epidemics have displayed substantial spatial heterogeneity in countries with high socioeconomic conditions and high vaccine coverage. This study aims to investigate the relationship between pertussis risk and socio-environmental factors on the spatio-temporal variation underlying pertussis infection. We obtained daily case numbers of pertussis notifications from Queensland Health, Australia by postal area, for the period January 2006 to December 2012. A Bayesian spatio-temporal model was used to quantify the relationship between monthly pertussis incidence and socio-environmental factors. The socio-environmental factors included monthly mean minimum temperature (MIT), monthly mean vapour pressure (VAP), Queensland school calendar pattern (SCP), and socioeconomic index for area (SEIFA). An increase in pertussis incidence was observed from 2006 to 2010 and a slight decrease from 2011 to 2012. Spatial analyses showed pertussis incidence across Queensland postal area to be low and more spatially homogeneous during 2006–2008; incidence was higher and more spatially heterogeneous after 2009. The results also showed that the average decrease in monthly pertussis incidence was 3·1% [95% credible interval (CrI) 1·3–4·8] for each 1 °C increase in monthly MIT, while average increase in monthly pertussis incidences were 6·2% (95% CrI 0·4–12·4) and 2% (95% CrI 1–3) for SCP periods and for each 10-unit increase in SEIFA, respectively. This study demonstrated that pertussis transmission is significantly associated with MIT, SEIFA, and SCP. Mapping derived from this work highlights the potential for future investigation and areas for focusing future control strategies.W.H. is supported by an ARC future fellowship (FT140101216)

Genetics, structure, and prevalence of FP967 (CDC Triffid) T-DNA in flax

The detection of T-DNA from a genetically modified flaxseed line (FP967, formally CDC Triffid) in a shipment of Canadian flaxseed exported to Europe resulted in a large decrease in the amount of flax planted in Canada. The Canadian flaxseed industry undertook major changes to ensure the removal of FP967 from the supply chain. This study aimed to resolve the genetics and structure of the FP967 transfer DNA (T-DNA). The FP967 T-DNA is thought to be inserted in at single genomic locus. The junction between the T-DNA and genomic DNA consisted of two inverted Right Borders with no Left Border (LB) flanking genomic DNA sequences recovered. This information was used to develop an event-specific quantitative PCR (qPCR) assay. This assay and an existing assay specific to the T-DNA construct were used to determine the genetics and prevalence of the FP967 T-DNA. These data supported the hypothesis that the T-DNA is present at a single location in the genome. The FP967 T-DNA is present at a low level (between 0.01 and 0.1%) in breeder seed lots from 2009 and 2010. None of the 11,000 and 16,000 lines selected for advancement through the Flax Breeding Program in 2010 and 2011, respectively, tested positive for the FP967 T-DNA, however. Most of the FP967 T-DNA sequence was resolved via PCR cloning and next generation sequencing. A 3,720 bp duplication of an internal portion of the T-DNA (including a Right Border) was discovered between the flanking genomic DNA and the LB. An event-specific assay, SAT2-LB, was developed for the junction between this repeat and the LB.Peer reviewed: YesNRC publication: Ye