Bovine telomere dynamics and the association between telomere length and productive lifespan

Average telomere length (TL) in blood cells has been shown to decline with age in a range of vertebrate species, and there is evidence that TL is a heritable trait associated with late-life health and mortality in humans. In non-human mammals, few studies to date have examined lifelong telomere dynamics and no study has estimated the heritability of TL, despite these being important steps towards assessing the potential of TL as a biomarker of productive lifespan and health in livestock species. Here we measured relative leukocyte TL (RLTL) in 1,328 samples from 308 Holstein Friesian dairy cows and in 284 samples from 38 female calves. We found that RLTL declines after birth but remains relatively stable in adult life. We also calculated the first heritability estimates of RLTL in a livestock species which were 0.38 (SE = 0.03) and 0.32 (SE = 0.08) for the cow and the calf dataset, respectively. RLTL measured at the ages of one and five years were positively correlated with productive lifespan (p < 0.05). We conclude that bovine RLTL is a heritable trait, and its association with productive lifespan may be used in breeding programmes aiming to enhance cow longevity

Morbidity and mortality after anaesthesia in early life: results of the European prospective multicentre observational study, neonate and children audit of anaesthesia practice in Europe (NECTARINE)

BACKGROUND: Neonates and infants requiring anaesthesia are at risk of physiological instability and complications, but triggers for peri-anaesthetic interventions and associations with subsequent outcome are unknown. METHODS: This prospective, observational study recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. The primary aim was to identify thresholds of pre-determined physiological variables that triggered a medical intervention. The secondary aims were to evaluate morbidities, mortality at 30 and 90 days, or both, and associations with critical events. RESULTS: Infants (n=5609) born at mean (standard deviation [sd]) 36.2 (4.4) weeks postmenstrual age (35.7% preterm) underwent 6542 procedures within 63 (48) days of birth. Critical event(s) requiring intervention occurred in 35.2% of cases, mainly hypotension (>30% decrease in blood pressure) or reduced oxygenation (SpO2 <85%). Postmenstrual age influenced the incidence and thresholds for intervention. Risk of critical events was increased by prior neonatal medical conditions, congenital anomalies, or both (relative risk [RR]=1.16; 95% confidence interval [CI], 1.04–1.28) and in those requiring preoperative intensive support (RR=1.27; 95% CI, 1.15–1.41). Additional complications occurred in 16.3% of patients by 30 days, and overall 90-day mortality was 3.2% (95% CI, 2.7–3.7%). Co-occurrence of intraoperative hypotension, hypoxaemia, and anaemia was associated with increased risk of morbidity (RR=3.56; 95% CI, 1.64–7.71) and mortality (RR=19.80; 95% CI, 5.87–66.7). CONCLUSIONS: Variability in physiological thresholds that triggered an intervention, and the impact of poor tissue oxygenation on patient's outcome, highlight the need for more standardised perioperative management guidelines for neonates and infants

Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study

BACKGROUND: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. METHODS: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. RESULTS: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1–6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2<90% for 60 s) was reported in 40%. No associated risk factors could be identified among co-morbidities, surgical, or anaesthesia management. Using propensity scoring to adjust for confounders, difficult anaesthesia tracheal intubation did not lead to an increase in 30 and 90 day morbidity or mortality. CONCLUSIONS: The results of the present study demonstrate a high incidence of difficult tracheal intubation in children less than 60 weeks post-conceptual age commonly resulting in severe hypoxaemia. Reassuringly, the morbidity and mortality at 30 and 90 days was not increased by the occurrence of a difficult intubation event

Association analysis of low-phosphorus tolerance in West African pearl millet using DArT markers

Pearl millet [Pennisetum glaucum (L.) R. Br.] is a food security crop in the harshest agricultural regions of the world. While low soil phosphorus (P) availability is a big constraint on its production, especially in West Africa (WA), information on genomic regions responsible for low-P tolerance in pearl millet is generally lacking. We present the first report on genetic polymorphisms underlying several plant P-related parameters, flowering time (FLO) and grain yield (GY) under P-limiting conditions based on 285 diversity array technology markers and 151 West African pearl millet inbred lines phenotyped in six environments in WA under both high-P and low-P conditions. Nine markers were significantly associated with P-related traits, nine markers were associated with FLO, whereas 13 markers were associated with GY each explaining between 5.5 and 15.9 % of the observed variation. Both constitutive and adaptive associations were observed for FLO and GY, with markers PgPb11603 and PgPb12954 being associated with the most stable effects on FLO and GY, respectively, across locations. There were a few shared polymorphisms between traits, especially P-efficiency-related traits and GY, implying possible colocation of genomic regions responsible for these traits. Our findings help bridge the gap between quantitative and molecular methods of studying complex traits like low-P tolerance in WA. However, validation of these markers is necessary to determine their potential applicability in marker-assisted selection programs targeting low-P environments, which are especially important in WA where resource-poor farmers are expected to be the hardest hit by the approaching global P crisis

Triply interlocked covalent organic cages

Interlocked molecules comprise two or more separate components that are joined by ‘mechanical’ rather than covalent bonds. In other words, these molecular assemblies cannot be dissociated without the cleavage of one or more chemical bonds. Although recent progress has enabled the preparation of such topologies through coordination or templating interactions, three-dimensional interlocked covalent architectures remain difficult to prepare. Here, we present a template-free one-pot synthesis of triply interlocked organic cages. These 20-component dimers consist of two tetrahedral monomeric cages each built from four nodes and six linkers. The monomers exhibit axial chirality, which is recognized by their partner cage during the template-free interlocking assembly process. The dimeric cages also include two well-defined cavities per assembly, which for one of the systems studied led to the formation of a supramolecular host–guest chain. These interlocked organic molecules may prove useful as part of a toolkit for the modular construction of complex porous solids and other supramolecular assemblies