Kleinphillips5638

The glucose portal sensor informs the brain of changes in glucose inflow through vagal afferents that require an activated glucagon-like peptide 1 receptor (GLP-1r). The GLP-1 system is known to be impaired in insulin-resistant conditions, and we sought to understand the consequences of GLP-1 resistance on glucose portal signaling. GLP-1-dependent portal glucose signaling was identified, in vivo, using a novel 68Ga-labeled GLP-1r positron-emitting probe that supplied a quantitative in situ tridimensional representation of the portal sensor with specific reference to the receptor density expressed in binding potential units. It also served as a map for single-neuron electrophysiology driven by an image-based abdominal navigation. We determined that in insulin-resistant animals, portal vagal afferents failed to inhibit their spiking activity during glucose infusion, a GLP-1r-dependent function. This reflected a reduction in portal GLP-1r binding potential, particularly between the splenic vein and the entrance of the liver. We propose that insulin resistance, through a reduction in GLP-1r density, leads to functional portal desensitization with a consequent suppression of vagal sensitivity to portal glucose.

Pneumonia is the largest cause of child deaths in low-income countries. Lack of availability of oxygen in small rural hospitals results in avoidable deaths and unnecessary and unsafe referrals.

We evaluated a programme for improving reliable oxygen therapy using oxygen concentrators, pulse oximeters and sustainable solar power in 38 remote health facilities in nine provinces in Papua New Guinea. The programme included a quality improvement approach with training, identification of gaps, problem solving and corrective measures. Admissions and deaths from pneumonia and overall paediatric admissions, deaths and referrals were recorded using routine health information data for 2-4 years prior to the intervention and 2-4 years after. Using Poisson regression we calculated incidence rates (IRs) preintervention and postintervention, and incidence rate ratios (IRR).

There were 18 933 pneumonia admissions and 530 pneumonia deaths. Pneumonia admission numbers were significantly lower in the postintervention era than in the preintervention era. The IRs for pneumonia deaths preintervention and postintervention were 2.83 (1.98-4.06) and 1.17 (0.48-1.86) per 100 pneumonia admissions the IRR for pneumonia deaths was 0.41 (0.24-0.71, p<0.005). selleck compound There were 58 324 paediatric admissions and 2259 paediatric deaths. The IR for child deaths preintervention and postintervention were 3.22 (2.42-4.28) and 1.94 (1.23-2.65) per 100 paediatric admissions IRR 0.60 (0.45-0.81, p<0.005). In the years postintervention period, an estimated 348 lives were saved, at a cost of US$6435 per life saved and over 1500 referrals were avoided.

Solar-powered oxygen systems supported by continuous quality improvement can be achieved at large scale in rural and remote hospitals and health care facilities, and was associated with reduced child deaths and reduced referrals. Variability of effectiveness in different contexts calls for strengthening of quality improvement in rural health facilities.

ACTRN12616001469404.

ACTRN12616001469404.

To determine if administration of oral prednisolone to preschool children with acute wheeze alters respiratory outcomes.

Double-blind, randomised, placebo-controlled equivalence trial.

Three hospitals in New Zealand.

477 children aged 24-59 months with acute wheeze associated with respiratory illness.

2 mg/kg (maximum 40 mg) oral prednisolone or similar placebo, once daily for 3 days.

Primary outcome was change in Preschool Respiratory Assessment Measure (PRAM) score 24 hours after intervention. Secondary outcomes included PRAM score at 4 hours, length of emergency department and inpatient stays, admission and representation rates, time to return to normal activities and use of additional oral prednisolone or intravenous medications. Analysis was by intention-to-treat.

There was no difference between groups for change in PRAM score at 24 hours (difference between means -0.39, 95% CI -0.84 to 0.06, p=0.09). Absolute PRAM score was lower in the prednisolone group at 4 hours (median (IQR) 1 (0-2) vs 2 (0-3), p=0.01) and 24 hours (0 (0-1) vs 0 (0-1), p=0.01), when symptoms had resolved for most children regardless of initial treatment. Admission rate, requirement for additional oral prednisolone and use of intravenous medication were lower in the prednisolone group, although there were no differences between groups for time taken to return to normal activities or rates of representation within 7 days.

Oral prednisolone does not alter respiratory outcomes at 24 hours or beyond in preschool children presenting with acute wheeze.

Oral prednisolone does not alter respiratory outcomes at 24 hours or beyond in preschool children presenting with acute wheeze.Genomic selection (GS) is a breeding approach which exploits genome-wide information and whose unprecedented success has shaped several animal and plant breeding schemes through delivering their genetic progress. This is the first study assessing the potential of GS in apricot (Prunus armeniaca) to enhance postharvest fruit quality attributes. Genomic predictions were based on a F1 pseudo-testcross population, comprising 153 individuals with contrasting fruit quality traits. They were phenotyped for physical and biochemical fruit metrics in contrasting climatic conditions over two years. Prediction accuracy (PA) varied from 0.31 for glucose content with the Bayesian LASSO (BL) to 0.78 for ethylene production with RR-BLUP, which yielded the most accurate predictions in comparison to Bayesian models and only 10% out of 61,030 SNPs were sufficient to reach accurate predictions. Useful insights were provided on the genetic architecture of apricot fruit quality whose integration in prediction models improved their performance, notably for traits governed by major QTL. Furthermore, multivariate modeling yielded promising outcomes in terms of PA within training partitions partially phenotyped for target traits. This provides a useful framework for the implementation of indirect selection based on easy-to-measure traits. Thus, we highlighted the main levers to take into account for the implementation of GS for fruit quality in apricot, but also to improve the genetic gain in perennial species.