'Xenia', a new pear cultivar from Moldava, first results in the Netherlands

The pear cultivar `Xenia¿ (synonym `Noiabriskaia¿) from Moldova is a selection from a cross between `Triomphe de Vienne¿ and `Nicolai Krier¿. In The Netherlands, `Xenia¿ has been tested since 2001. So far, trees have given early and high yields and required little thinning. Up to now, a very low to moderate susceptibility to scab (Venturia pirinia) and a very low susceptibility to fruit tree canker (Nectria galligena) have been observed. The trees showed a medium vigour and there was a low tendency to biennial bearing. With the relatively young trees, the average fruit size of `Xenia¿ fruits at full crop was 250-300 g. The harvest window was wide. Fruits of `Xenia¿ had a green ground colour at harvest and were moderately bronzed. `Xenia¿ had a spherical pear shape. The fruits had a strong fruit skin. The firmness was higher than that of `Conference¿. The juiciness varied from juicy to very juicy, depending on the maturity stage. `Xenia¿ had a good eating quality: fresh, slightly aromatic with a typical aroma. The storability of the fruits was very good and the shelf life of `Xenia¿ proved to be much better than of `Conference¿. Summarizing, the first results show a good potential for commercial fruit growing

Pharmacokinetics and sputum penetration of azithromycin during once weekly dosing in cystic fibrosis patients

In this study we examined pharmacokinetics, systemic exposure and sputum penetration of azithromycin (AZM) in CF patients on chronic daily AZM therapy after changing to a once weekly dosing scheme. Eight adult CF patients using AZM 500 mg/day were changed to a once weekly dose of 1000 mg during 3 months. Once per month sputum and blood samples were collected. AZM was quantified in blood plasma and polymorphonuclear neutrophils. The cumulative weekly dose was reduced with a factor of 3.5 (7x500 mg vs. 1x1000 mg weekly). This led to a reduction in area under the curve (AUC+/-S.D.) with a factor of 2.5+/-0.8 in plasma, 2.8+/-0.9 in blood, 2.2+/-1.1 in PMNNs and to a reduction in average sputum concentration with a factor of 3.0 (+/-1.5). At 1000 mg once weekly reduced but still substantial concentrations were achieved in PMNNs and in sputum. Although not significant, a tendency towards less than linear reduction was found. In order to calculate and propose an optimal dosing scheme we need to establish a relation between exposure levels and clinical efficacy

Concept studie autonoom oogsten van appels en peren

Bij de oogst van appels en peren is in een korte periode veel arbeid nodig. Het vraagt een forse inspanning om voldoende kwalitatief juiste arbeid te krijgen op het juiste moment tegen de juiste prijs, de kosten voor arbeid zijn hoog. Voor NFO en het PT hebben initiatief genomen om te komen tot robotisering van deze handeling te automatiseren. Doelstelling van dit project is één of meerdere concepten te ontwerpen voor het automatisch oogsten van appels en peren, waarbij kritische deelfuncties op eerste haalbaarheid zijn getoetst om de drempel te verlagen om een vervolg te starten. Aansluitend is het doel ontwikkelingstraject te starten dat binnen een afzienbare periode zal leiden tot implementatie. In het rapport zijn enkele perspectiefvolle concepten uitgewerkt. Verschillende deelfuncties zijn ontworpen en getest op haalbaarheid zoals: het sensorconcept globaal (waar zitten de appels); het sensorconcept lokaal (Is de appel voldoende rijp); manipulatie en end-effector en logistiek en buffering. Voor de verschillende functies zijn goede oplossingen voorhanden. De studie betreft met name een papieren studie. In een vervolg zal moeten blijken of het ook daadwerkelijk technisch haalbaar is. De focus in een vervolg dient te liggen bij de plukhandeling zelf en de daarbij horende sensoriek (de ogen, de arm en het handje). Het afvoeren van de geoogste appels, het bufferen en het transport door de boomgaard lijkt niet het probleem te zijn. Aan het einde heeft een herijking van de businesscase plaatsgevonden. De NFO/PT acht het project voldoende perspectiefvol om te starten met een initiatief voor verdere implementatie als vervolg op de conceptontwikkeling

Targeted exhaled breath analysis for detection of Pseudomonas aeruginosa in cystic fibrosis patients

Background Pseudomonas aeruginosa (PA) is an important respiratory pathogen for cystic fibrosis (CF) patients. Routine microbiology surveillance is time-consuming, and is best performed on expectorated sputum. As alternative, volatile organic compounds (VOCs) may be indicative of PA colonisation. In this study, we aimed to identify VOCs associated with PA in literature and perform targeted exhaled breath analysis to recognize PA positive CF patients non-invasively. Methods This study consisted of 1) a literature review to select VOCs of interest, and 2) a cross-sectional CF study. Definitions used: A) PA positive, PA culture at visit/chronically; B) PA free, no PA culture in ≥12 months. Exhaled VOCs were identified via quadrupole MS. The primary endpoint was the area under the receiver operating characteristics curve (AUROCC) of individual VOCs as well as combined VOCs against PA culture. Results 241 VOCs were identified in literature, of which 56 were further evaluated, and 13 could be detected in exhaled breath in our cohort. Exhaled breath of 25 pediatric and 28 adult CF patients, PA positive (n=16) and free (n=28) was available. 3/13 VOCs were significantly (p<0.05) different between PA groups in children; none were in adults. Notably, a composite model based on 5 or 1 VOC(s) showed an AUROCC of 0.86 (CI 0.71–1.0) and 0.87 (CI 0.72–1.0) for adults and children, respectively. Conclusions Targeted VOC analysis appears to discriminate children and adults with and without PA positive cultures with clinically acceptable sensitivity values

Clinical effects of the three CFTR potentiator treatments curcumin, genistein and ivacaftor in patients with the CFTR-S1251N gating mutation

Contains fulltext : 229853.pdf (Publisher’s version ) (Closed access)BACKGROUND: The natural food supplements curcumin and genistein, and the drug ivacaftor were found effective as CFTR potentiators in the organoids of individuals carrying a S1251N gating mutation, possibly in a synergistic fashion. Based on these in vitro findings, we evaluated the clinical efficacy of a treatment with curcumin, genistein and ivacaftor, in different combinations. METHODS: In three multi-center trials people with CF carrying the S1251N mutation were treated for 8 weeks with curcumin+genistein, ivacaftor and ivacaftor+genistein. We evaluated change in lung function, sweat chloride concentration, CFQ-r, BMI and fecal elastase to determine the clinical effect. We evaluated the pharmacokinetic properties of the compounds by evaluating the concentration in plasma collected after treatment and the effect of the same plasma on the intestinal organoids. RESULTS: A clear clinical effect of treatment with ivacaftor was observed, evidenced by a significant improvement in clinical parameters. In contrast we observed no clear clinical effect of curcumin and/or genistein, except for a small but significant reduction in sweat chloride and airway resistance. Plasma concentrations of the food supplements were low, as was the response of the organoids to this plasma. CONCLUSIONS: We observed a clear clinical effect of treatment with ivacaftor, which is in line with the high responsiveness of the intestinal organoids to this drug. No clear clinical effect was observed of the treatment with curcumin and/or genistein, the low plasma concentration of these compounds emphasizes that pharmacokinetic properties of a compound have to be considered when in vitro experiments are performed

Impact of Enhanced Staphylococcus DNA Extraction on Microbial Community Measures in Cystic Fibrosis Sputum

Staphylococcus aureus is a common constituent of the bacterial community inhabiting the airways of persons with cystic fibrosis (CF). Culture-independent studies have shown that this species is often present in relatively high abundance and would therefore be expected to exert a pronounced effect on measures of CF airway bacterial community structure. We investigated the impact of DNA extraction method on pyrosequencing-based measures of Staphylococcus abundance and bacterial community structure in 17 sputum samples from five CF patients. Staphylococcus was detected in fewer samples when DNA was extracted using a standard bacterial lysis method compared to when DNA was extracted using a lysis buffer amended with lysostaphin and lysozyme. The standard lysis method resulted in significantly lower measures of Staphylococcus relative abundance and higher levels of community diversity, richness, and evenness compared to the lysostaphin-lysozyme modified method. Measures of community dynamics in serial sputum samples from the same individual were nevertheless highly concordant between the two DNA extraction methods. These results illustrate the impact of DNA preparation method on measures of Staphylococcus abundance and bacterial community structures in studies of the airways microbiota in CF

Mechanisms of the noxious inflammatory cycle in cystic fibrosis

Multiple evidences indicate that inflammation is an event occurring prior to infection in patients with cystic fibrosis. The self-perpetuating inflammatory cycle may play a pathogenic part in this disease. The role of the NF-κB pathway in enhanced production of inflammatory mediators is well documented. The pathophysiologic mechanisms through which the intrinsic inflammatory response develops remain unclear. The unfolded mutated protein cystic fibrosis transmembrane conductance regulator (CFTRΔF508), accounting for this pathology, is retained in the endoplasmic reticulum (ER), induces a stress, and modifies calcium homeostasis. Furthermore, CFTR is implicated in the transport of glutathione, the major antioxidant element in cells. CFTR mutations can alter redox homeostasis and induce an oxidative stress. The disturbance of the redox balance may evoke NF-κB activation and, in addition, promote apoptosis. In this review, we examine the hypotheses of the integrated pathogenic processes leading to the intrinsic inflammatory response in cystic fibrosis