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Background: Cysteinyl leukotrienes (Cys-LTs) and isoprostanes are inflammatory metabolites derived from arachidonic acid whose levels are increased in the airways of asthmatic patients. Isoprostanes are relatively stable and specific for lipid peroxidation, which makes them potentially reliable biomarkers for oxidative stress. A study was undertaken to evaluate the effect of a course of oral steroids on Cys-LT and 8-isoprostane levels in exhaled breath condensate of children with an asthma exacerbation.Methods: Exhaled breath condensate was collected and fractional exhaled nitric oxide (FE(NO)) and spirometric parameters were measured before and after a 5 day course of oral prednisone (1 mg/kg/day) in 15 asthmatic children with an asthma exacerbation. Cys-LT and 8-isoprostane concentrations were measured using an enzyme immunoassay. FE(NO) was measured using a chemiluminescence analyser. Exhaled breath condensate was also collected from 10 healthy children.Results: Before prednisone treatment both Cys-LT and 8-isoprostane concentrations were higher in asthmatic subjects (Cys-LTs, 12.7 pg/ml (IQR 5.4-15.6); 8-isoprostane, 12.0 pg/ml (9.4-29.5)) than in healthy children (Cys-LTs, 4.3 pg/ml (2.0-5.7), p=0.002; 8-isoprostane, 2.6 pg/ml (2.1-3.0), p<0.001). After prednisone treatment there was a significant decrease in both Cys-LT (5.2 pg/ml (3.9-8.8), p=0.005) and 8-isoprostane (8.4 pg/ml (5.4-11.6), p=0.04) concentrations, but 8-isoprostane levels remained higher than in controls (p<0.001). FE(NO) levels, which fell significantly after prednisone treatment (p<0.001), did not correlate significantly with either Cys-LT or 8-isoprostane concentrations.Conclusion: After a 5 day course of oral prednisone there is a reduction in Cys-LT and 8-isoprostane levels in EBC of children with an asthma exacerbation, although 8-isoprostane levels remain higher than in controls. This finding suggests that corticosteroids may not be fully effective in reducing oxidative stress in children with an exacerbation of asthma. [ABSTRACT FROM AUTHOR]

A systematic review and a meta-analysis of data of literature were performed to evaluate the efficacy of clodronate in the reduction of risk of fractures in patients with osteoporosis or tumour diseases. A systematic review was conducted to identify original articles, reviews, and any other literature report suitable for the purposes of the meta-analysis, limited to prospective randomized trials that included a placebo or an untreated control arm. The search has identified 18 trials, 13 of which in patients with cancer diseases (breast cancer and multiple myeloma were prevalent), 4 in patients with osteoporosis/low BMD, and 1 in elderly women living in community. A placebo control arm was used in 13 trials. Treatment and follow-up duration ranged from 3 months to 5 years. The meta-analysis showed that treatment with clodronate was associated with a reduction of the probability of new fractures compared with controls (OR = 0.572, 95 % CI 0.465-0.704 for new vertebral fractures; OR = 0.668, 95 % CI 0.494-0.905 for new non-vertebral fractures; and OR = 0.744, 95 % CI 0.635-0.873 for new overall fractures in those articles where vertebral and non-vertebral new fractures were not considered separately). Similar findings were observed in the separate analysis in patients with cancer forms or osteoporosis. The results of the meta-analysis have demonstrated that clodronate is effective in reducing the risk of vertebral, non-vertebral, and overall fractures in patients with skeletal fragility. [ABSTRACT FROM AUTHOR]

To cite this article: van der Valk RJP, Baraldi E, Stern G, Frey U, de Jongste JC. Daily exhaled nitric oxide measurements and asthma exacerbations in children. Allergy 2012; 67: 265-271. Abstract Background: Fractional exhaled Nitric Oxide (FeNO) is a biomarker for eosinophilic airway inflammation and can be measured at home on a daily basis. A short-term increase in FeNO may indicate a higher risk of future asthma exacerbations. Objective: To assess changes in FeNO before and after asthma exacerbations compared to a stable control period. Methods: A post hoc analysis was performed on daily FeNO measurements over 30 weeks in children with asthma ( n = 77). Moderate exacerbations were defined by an increase in symptom scores and severe exacerbations by prescription of prednisone. Individual mean and maximum FeNO, the variability of FeNO assessed by the coefficient of variation (CV), and slopes of FeNO in time were all quantified in 3-week blocks. Cross-correlation of FeNO with symptoms and autocorrelation of FeNO were assessed in relation to exacerbations and examined as predictors for exacerbations compared to reference periods using logistic regression. Results: Fractional exhaled nitric oxide could be assessed in relation to 25 moderate and 12 severe exacerbations. The CV, slope, cross-correlation, and autocorrelation of daily FeNO increased before moderate exacerbations. Increases in slope were also randomly seen in 19% of 2-week blocks of children without exacerbations. At least 3-5 FeNO measurements in the 3 weeks before an exacerbation were needed to calculate a slope that could predict moderate exacerbations. No specific pattern of FeNO was seen before severe exacerbations. Conclusion: Fractional exhaled nitric oxide monitoring revealed changes in FeNO prior to moderate exacerbations. Whether this can be used to prevent loss of asthma control should be further explored. [ABSTRACT FROM AUTHOR]

Background: Asthmatic patients have high exhaled nitric oxide (NO) levels. NO-mediated inflammatory actions are mainly due to NO conversion into reactive nitrogen species, which can lead to nitrotyrosine formation. The aim of this study was to assess 3-nitrotyrosine (3-NT) levels in exhaled breath condensate (EBC) of asthmatic and healthy children and to investigate whether there is any relationship with exhaled NO (FENO) and lung function. Methods: The study included 20 asthmatic children (10 steroid-naive with intermittent asthma, 10 steroid-treated with unstable persistent asthma) and 18 healthy controls. They underwent FENO measurement, EBC collection and spirometry. 3-NT was measured by a new liquid chromatography–tandem mass spectrometry (LC-MS/MS) method in isotopic dilution. Results: The median EBC concentration of 3-NT (expressed as nitrotyrosine/tyrosine ratio × 100) in asthmatic children was fivefold higher than in healthy subjects [0.23% (0.12–0.32) vs 0.04% (0.02–0.06), P < 0.001] with no difference between steroid-naive and unstable steroid-treated asthmatic patients. FENO levels were higher in asthmatic [44.6 ppb (36.0–66.0)] than in healthy children [7.5 ppb (6.0–8.8), P < 0.001]. No correlation was found among 3-NT, FENO and lung function parameters. Conclusion: Nitrotyrosine is high in EBC of asthmatic children and could be considered as a noninvasive marker of nitrosative events in the airways. [ABSTRACT FROM AUTHOR]

Isolates of Penicillium expansum recovered from stored pears were scored for resistance to the fungicide thiabendazole (TBZ) and for pathogenic fitness. Out of 50 isolates, nine were sensitive (S) and 41 resistant (R or RR). Seven of these resistant isolates (RR) germinated with a higher percentage on TBZ-amended medium than on unamended medium. Six S isolates and six RR isolates were chosen at random for further analysis. S and RR isolates had similar in vitro growth fitness, although RR isolates were characterized by higher infection severity on fruits. Laboratory-induced resistant isolates were generated by UV-irradiating S strains, and a similar correlation between the induced TBZ resistance and pathogenic fitness was observed. The β-tubulin gene of RR and S isolates was amplified and sequenced; mutations correlating with TBZ resistance were identified at residues Phe 167 and Glu 198. Analogous mutations were detected in the laboratory-induced resistant isolates. [ABSTRACT FROM AUTHOR]

Abstract The effects on Botrytis cinerea of prolonged exposures to CO2 -enriched atmospheres were studied in vitro and in vivo at 0°C. Mycelial growth on potato dextrose agar decreased linearly with increasing CO2 concentrations from 5, 10, 15 and 20% CO2 . The growth reduction was greater after 30–40 days of incubation. A reduced production of sclerotia in air by the colonies formerly exposed to various CO2 concentrations was also detected. Conidial germination was delayed and the amount of germinated conidia decreased with increased CO2 and at 20% CO2 it was inhibited. Germ tube elongation was affected in the same way. In artificially inoculated red chicory, lesion area caused by B. cinerea decreased with increasing concentrations of CO2 up to 60 days storage, later only 10 and 15% CO2 were really effective, while in the final inspection after 120 days all the concentration tested showed a low efficacy. Similar results were obtained in naturally infected chicory where the severity of the disease decreased by increasing CO2 from 5 to 10%, higher values did not improve the suppressive effect or determined, after 150 days of storage, an increased vulnerability of the tissues to disease due to the phytotoxic effects of the gas. An atmosphere enriched with 10% CO2 is advised to suppress Botrytis rot during storage at 0°C of red chicory. [ABSTRACT FROM AUTHOR]

Abstract Ninety isolates of Botrytis cinerea collected from kiwi fruit in orchards and in cold storage were compared phenotypically and genetically. The phenotypic characters evaluated were conidia germination, germ tube length and mycelial growth at 0∘ and 20∘ C. At 20∘ C the two populations showed slight differences but, at 0∘ C, isolates from cold storage appeared to grow significantly faster than isolates from orchards. Isolates were then scored with six genetic markers with the aim of investigating population, genetic structure and the mode of reproduction. We detected no genetic differentiation between isolates from orchards and those from cold storage. This suggests that low temperature adaptation of B. cinerea isolates does not have a genetic basis. By contrast, we found great intra-population genetic diversity, observations suggesting the occurrence of genetic recombination which follows sexual reproduction or alternatively of parasexuality. [ABSTRACT FROM AUTHOR]

We followed the clinical course of 21 infants with bronchopulmonary dysplasia enrolled in a prospective home O[sub 2] therapy programme during a 4-year-period. Mean gestational age was 28.5 weeks (range, 25–36 weeks) and mean birth weight 1093 g (range 630–2750 g). Infants were regularly monitored to maintain pulse oximeter O[sub 2] saturation over 94%–95%. The source of O[sub 2] was liquid oxygen and was delivered by nasal cannula. During the follow up oxygenation was assessed by SatO[sub 2] measurement, cardiac function by Doppler echocardiography and respiratory function by the occlusion technique. All patients had an ophthalmological follow up. The mean age of the infants at discharge was 3.7 months (range 1.7–8.6) and mean weight 2830 g (range 2150–3780 g). At discharge 8 infants had right ventricular hypertrophy (RVH) and four of them had pulmonary hypertension. Mean duration of home O[sub 2] therapy was 97 days (range 15–320 days) and the mean age of discontinuation of O[sub 2] was 6.9 months (range 3–14.7 months). The cardiological follow up was benign: the ECG signs of RVH disappeared by 12 months of age in six out of eight infants and the right ventricular pulmonary pressure, as measured by the Doppler method, normalised in the four patients in whom it was detected. No relationship was found between respiratory mechanics and the duration of O[sub 2] therapy. Weight gain was poor with mean growth at the 3rd percentile for females and just below the 3rd percentile for males. Twelve of the 21 infants required 25 rehospitalizations. No one presented deterioration of retinopathy of prematurity that was present in 16 infants at discharge; at 12 months retinopathy was resolved in 14 infants. A total of 2025 hospital days were saved, representing a significant financial saving.Conclusion Home O[sub 2] therapy permits the safe early discharge of O[sub 2] -dependent BPD infants and it reduces significantly the... [ABSTRACT FROM AUTHOR]

Determines the safety and feasibility of the exhaled breath condensate procedure in a group of asthmatic children with varying levels of severity. Pulmonary function and fractional exhaled nitric oxide measurement; Analysis of pertinent topics and relevant issues; Implications on pediatrics.

In the May 1, 2001 issue of the journal "Thorax," researchers suggest that it is possible to distinguish different patterns of difficult childhood asthma by measuring exhaled nitrogen oxide (NO). The knowledge that severe asthma may have different phenotypes with different types of airway inflammation is not new and has been clearly shown by bronchoalveolar lavage and airway biopsy studies in adult patients. The potential importance of these data lies in the classification of different patterns by using a non-invasive instantaneous measurement such as NO. Exhaled NO levels are known to be increased in atopic asthma, to increase during an exacerbation, to decrease with anti-inflammatory therapy, and to rise as the dose of inhaled steroids is reduced.

The article offers information on study related to poor response of wheezing children with tracheobronchomalacia to asthma therapy. It observed the trend of wheezing children under three years of age, collected from the clinical database and found that several children underwent flexible bronchoscopy. It highlights that main cause of poor response to asthma therapy was tracheobronchomalacia.

Background: International guidelines recommend regular treatment with inhaled glucocorticoids for children with frequent wheezing; however, prn inhaled bronchodilator alone or in combination with glucocorticoid is also often used in practice. We aimed to evaluate whether regular nebulized glucocorticoid plus a prn bronchodilator or a prn nebulized bronchodilator/glucocorticoid combination is more effective than prn bronchodilator alone in preschool children with frequent wheeze. Methods: Double-blind, double-dummy, randomized, parallel-group trial. After a 2-week run-in period, 276 symptomatic children with frequent wheeze, aged 1–4 years, were randomly assigned to three groups for a 3-month nebulized treatment: (1) 400 μg beclomethasone bid plus 2500 μg salbutamol prn; (2) placebo bid plus 800 μg beclomethasone/1600 μg salbutamol combination prn; (3) placebo bid plus 2500 μg salbutamol prn. The percentage of symptom-free days was the primary outcome measure. Secondary outcomes included symptom scores, use of relief medication and exacerbation frequency. Results: As compared with prn salbutamol (61.0 ± 24.83 [SD]), the percentage of symptom-free days was higher with regular beclomethasone (69.6%, SD 20.89; P = 0.034) but not with prn combination (64.9%, SD 24.74). Results were no different in children with or without risk factors for developing persistent asthma. The effect of prn combination was no different from that of regular beclomethasone on the primary and on several important secondary outcomes. Conclusions: Regular inhaled glucocorticoid is the most effective treatment for frequent wheezing in preschool children. However, prn bronchodilator/glucocorticoid combination might be an alternative option, but it requires further study. [ABSTRACT FROM AUTHOR]

Neofabraea vagabunda, causing bull's eye rot, produces notable loss during cold storage of apples growing in cool humid regions. The infection initiates in the orchard, but the pathogen lives quiescently in fruit for some months before causing the symptoms of the disease. In vivo and in vitro assays were carried out to gain knowledge on the influence of fruit volatile organic compounds (VOCs) in N. vagabunda development and define volatile markers for pathogen detection, using SPME/GC‐MS, PTR‐ToF‐MS analysis and light microscopic observations. This study reports that: (i) the main VOCs of Cripps Pink apple (highly susceptible to bull's eye rot) are degraded during the conidial germination of N. vagabunda, stimulating pathogen hyphal growth towards the host; (ii) first disease symptoms appear when fruit releases VOCs related to senescence, which also stimulate pathogen hyphal growth; (iii) VOCs typical of ripe‐senescent fruit are also emitted by infected fruit during N. vagabunda quiescence, and methanol and ethanol are the earliest markers of bull's eye rot; and (iv) the in vitro volatile metabolism of Botrytis cinerea, Penicillium expansum and Colletotrichum fioriniae has similarities with that of N. vagabunda, but the volatile profile of each pathogen is distinguishable. Overall, this study provides novel knowledge on fruit–fungus interaction and insights for the development of tools for early disease detection in packing houses. [ABSTRACT FROM AUTHOR]

Bull's eye rot is a typical quiescent postharvest apple disease in major fruit‐growing areas. The susceptibility of different apple cultivars to Neofabraea spp. (N. vagabunda and N. malicorticis) was assessed, with Granny Smith showing the most resistance and Cripps Pink the most susceptibility. To assess the factors involved in conidial germination, Neofabraea spp. were grown on crude protein extracts (CPEs) collected from apple fruits at different storage periods. Fungal germ tube growth rate and pathogenic enzyme (cellulase and xylanase) activity were assessed. Results showed that CPEs collected after 2 and 4 months of storage progressively stimulated conidial germination and germ tube elongation, while a lesser effect was observed from CPEs after 1 month of storage. Xylanase proved to be the main degrading enzyme secreted by all the isolates, while cellulase was produced only by N. vagabunda isolates. Overall, the isolate ID02 was the most virulent, based on more rapid germ tube elongation and greater activity of the lytic enzymes. [ABSTRACT FROM AUTHOR]

• Neofusicoccum parvum is representing an emerging problem for apple productions. • L1 and L8 strains are able to completely inhibit pathogen sporification in wood. • Both strains reduced by 70% pathogen mycelial growth through non volatile compounds. • L8 was able to increase cellulose content in wood preventing a fast fungal attack. Aureobasidium pullulans strains L1 and L8 were used as an alternative strategy against Neofusicoccum parvum , pathogen of apple wood and fruit. Both strains displayed a great ability to reduce pathogen conidia germination of almost 50% and totally stop its sporification in wood of 'Gala' and 'Fuji' apple cultivars. In addition, by in vitro tests the antagonistic activity displayed by non-volatile metabolites produced by both yeasts was highlighted by 70% of reduction of the pathogen mycelial growth. On apple fruit, the pathogen severity was reduced by 66% and 50% in 'Gala', and 70% and 60% in 'Fuji' by L1 and L8 respectively. In wood, no statistical differences were observed between L1, L8 and the control, except for 'Fuji' wood, where L8 strain displayed a wood lesion reduction of 23% with respect to the untreated control. Infrared analysis showed how the presence of both strains on woody tissues helped preserving cellulose content, preventing in this way the faster wood degradation by the pathogen. In addition, L1 and L8 simply colonized the wood surface, probably displaying an endophytic attitude, an essential requirement for controlling N. parvum in field. [ABSTRACT FROM AUTHOR]

Kiwifruit, wounded at the equator or by pedicel removal, to simulate the stem end wound, were treated with Aureobasidium pullulans (L1 and L8 strains) and subsequently inoculated with conidia of Botrytis cinerea . Fruits were stored at -1 °C in normal refrigeration (NR) or in controlled atmosphere (CA) (2% O 2 ; 4.5% CO 2 ). After 4 months, both antagonists significantly reduced the disease in all experiments, L1 better than L8. In NR, their efficacy was higher than 80%. In CA, the disease reduction was lower: between 30% (L1) and 60% (L8). The ability of both strains to compete with the pathogen for nutrients was tested in kiwifruit juice (0.5%) by in vitro experiments. Antagonists significantly reduced pathogen conidia germination in water and in juice. An HPLC analysis was performed to define the amino acid composition of kiwifruit juice upon L1 and L8 treatment. L1 and L8 greatly increased the concentration of both glutamic and aspartic acids and stimulated the production of new amino acids, although at low concentrations. Each amino acid displayed an antifungal effect against mycelium growth of B. cinerea. Finally, L1 and L8, cold tolerant and active strains in CA, can be effectively applied to control the stem end rot of kiwifruit in long storage. [ABSTRACT FROM AUTHOR]

Summary: The diagnosis of asthma is currently based on clinical history, physical examination and lung function, and to date, there are no accurate objective tests either to confirm the diagnosis or to discriminate between different types of asthma. This consensus exercise reviews the state of the art in asthma diagnosis to identify opportunities for future investment based on the likelihood of their successful development, potential for widespread adoption and their perceived impact on asthma patients. Using a two‐stage e‐Delphi process and a summarizing workshop, a group of European asthma experts including health professionals, researchers, people with asthma and industry representatives ranked the potential impact of research investment in each technique or tool for asthma diagnosis and monitoring. After a systematic review of the literature, 21 statements were extracted and were subject of the two‐stage Delphi process. Eleven statements were scored 3 or more and were further discussed and ranked in a face‐to‐face workshop. The three most important diagnostic/predictive tools ranked were as follows: “New biological markers of asthma (eg genomics, proteomics and metabolomics) as a tool for diagnosis and/or monitoring,” “Prediction of future asthma in preschool children with reasonable accuracy” and “Tools to measure volatile organic compounds (VOCs) in exhaled breath.” [ABSTRACT FROM AUTHOR]

Antimicrobial prescriptions in neonatal intensive care units (NICUs) represent a point of concern for the emergence of MDROs and for morbidity associated with prolonged antibiotic exposure (e.g., invasive candidiasis, necrotizing enterocolitis, and late-onset sepsis). Antimicrobial stewardship programs (ASPs) have shown to be a valuable tool for the prevention of resistance with the goals of optimizing clinical outcomes while decreasing unnecessary prescribing. The most frequent ASP strategies include the correct collection and interpretation of microbiological specimens, prescription of the narrowest-spectrum antibiotic appropriate for a particular case, and de-escalation or discontinuation of therapy in defined situations. A robust ASP requires everyday multidisciplinary collaboration between ID physicians, neonatologist, clinical pharmacists, clinical microbiologists, infection control professionals, hospital epidemiologists, and information services specialists. Education and clinical pathways (e.g., sepsis or surgical prophylaxis pathways) are an excellent starting point if followed by proactive interventions such as prospective audits and feedback and formulary restriction with prior antimicrobial authorization. The current review outlines the problems faced in NICU antimicrobial prescribing and presents various solutions from the literature. [ABSTRACT FROM AUTHOR]

Background Isocyanate-induced asthmatic reactions are associated with delayed increase in fractional exhaled nitric oxide measured at expiratory flow of 50 mL/s (Fe NO50), a biomarker of airway inflammation. The time course of Fe NO increase is compatible with the activation of NO synthase, but the origin of NO production in the lung is undetermined. Objective The aim of this study was to define the dynamics of airway and alveolar NO during specific inhalation challenge ( SIC) with isocyanates and the role of asymmetric dimethylarginine ( ADMA), an endogenous inhibitor of NO synthase. Methods Spirometry, exhaled NO parameters (Fe NO50, bronchial wall NO concentration, NO airway diffusing capacity, NO flux to luminal space, alveolar NO) and ADMA levels in exhaled breath condensate were measured before and at intervals up to 24 h after exposure to isocyanates. The results were compared between 17 SIC-positive and eight SIC-negative subjects. Results A significant Fe NO50 increase in SIC-positive subjects was detected 24 h after exposure and was associated with the augmented NO flux from airway wall to the lumen, whereas airway NO diffusion and alveolar NO were not affected. The changes in NO dynamics were specific for the subjects who developed an asthmatic reaction, but were independent from the pattern and magnitude of bronchoconstriction. There was no evidence that exhaled NO is modulated by the changes in ADMA concentration. Conclusions and Clinical Relevance Because isocyanate-induced increase in Fe NO50 was almost exclusively determined by the increase in NO flux, the use of Fe NO50 appears adequate to monitor the exhaled NO dynamics during SIC. Fe NO50 measurement may provide additional information to spirometry, because bronchoconstriction and airway inflammatory responses are dissociated. [ABSTRACT FROM AUTHOR]

Introduction This study aimed to verify the association between the JAK2 46/1 haplotype (V617F positive) and some hematological parameters in BCR- ABL-negative chronic myeloproliferative neoplasms ( cMPNs) in our population. Methods The blood samples obtained from the patients with cMPN were genotyped for the JAK2 V617F mutation and JAK2 rs10974944 SNP screening using a PCR- RFLP assay. Results The JAK2 V617F mutation was detected in 80.15% of patients. The G variant of rs10974944 was more frequent in all MPNs, especially those that were JAK2 V617F positive, than in the control population. We also compared the 46/1 haplotype status in each MPN disease entity, polycythemia vera ( PV), essential thrombocythemia ( ET), primary myelofibrosis ( PMF), and MPNu with controls. The G allele frequency relative to controls was significantly enriched in patients with PV and ET, but not in those with PMF and MPNu. PV and ET patients especially, all of whom had the JAK2 V617F mutation, showed significant excess of the G allele. The frequency of JAK2 V617F mutation was associated with elevated hematological parameters, but when we analyze the occurrence of the mutation and the presence of the G allele, just the high hemoglobin was significantly. Conclusion In agreement with previous reports, JAK2 46/1 haplotype for JAK2 V617F was associated with cMPN positive in Brazilian patients. [ABSTRACT FROM AUTHOR]

This paper presents the case of an 8-year-old boy who developed an anaphylactic reaction after skin-prick testing (SPT). The tests were performed with commercial extracts and were strongly positive for dog and grass. The boy had no incidence of anaphylaxis reported in his history. At the time tests were performed, he had been admitted to the hospital because of persistent wheezing and had a dog at home for a few days. Although anaphylaxis is very rare after SPTs, these tests should always be peformed in a place equipped to treat anaphylaxis. [ABSTRACT FROM AUTHOR]

• Organic essential oils (EOs) can control apple pathogens aggressiveness on apple. • Essential oils used as biofumigant, completely inhibited apple pathogens. • The chemical composition is strictly connected to the EOs efficacy. Fusarium avenaceum, Botrytis cinerea, Penicillium expansum, and Neofabraea vagabunda , represent postharvest diseases which cause significant apple losses. The aim of this study was therefore to evaluate the effects of organic essential oils (EOs) (Thymus vulgaris, Lavandula angustifolia, Rosmarinus officinalis) against apple pathogens both in vitro and in vivo, as an integrated management tool. By GC–MS analysis a total of 101 compounds principally belonging to the groups of terpenes and terpenoids were detected in the extracted EOs. In vitro results showed T. vulgaris as the most active EO, both as agar infusion or biofumigant. Through agar infusion, starting from the lowest concentration (0.2 mL L −1), T. vulgaris reduced by 74.9%, 86.1%, 66.9%, and 45.7% F. avenaceum, B. cinerea, P. expansum, and N. vagabunda mycelial growth, respectively; as biofumigant, it completely inhibited the growth of all the tested mycelial pathogens. Application of EOs on apples through dipping treatment displayed some potential to inhibit the above-mentioned pathogens, especially by T. vulgaris and L. angustifolia. The efficacy of these organic EOs is probably strictly correlated to the chemical composition. [ABSTRACT FROM AUTHOR]

The genome of Vitis vinifera contains 79 defensin-like ( DEFL) gene sequences, classified in four groups based on peptide sequence similarity. Group-2 DEFL proteins are highly conserved peptides with 10 cysteine residues, and include VvAMP2, a defensin active against the fungal pathogen Botrytis cinerea. Here, quantitative reverse transcription- PCR (q RT- PCR) analysis was used to show that group-2 DEFLs are specifically expressed in grapevine inflorescences, with the highest level in pollen/stamen, and weak expression in calyptrae and carpels. Immunofluorescence microscopy showed that the protein accumulates in pollen grains and in specific areas of the ovary parenchyma, suggesting a role in grapevine fertilization. Antimicrobial tests showed that VvAMP2 inhibits the growth of B. cinerea, but not of other fungal pathogens, nor bacteria. Fluorescence microscopy analysis of B. cinerea cells treated with VvAMP2 revealed that this defensin is first internalized and then leads to membrane permeabilization, suggesting that membrane damage is a secondary effect of this plant defensin. To identify possible intracellular targets of VvAMP2, its inhibitory action was tested on 54 B. cinerea mutants, with deletions in key signalling genes. The ΔBcATF1 transcription factor mutant, impaired in regulation of cell wall and oxidative stress genes, completely lost sensitivity to VvAMP2. Mutants lacking the Rho-type GTPase BcCDC42, the G protein-coupled receptor BcGPR3 and the putative scaffold protein BcBEM1, showed very low sensitivity. [ABSTRACT FROM AUTHOR]

Ppdfn1 is a defensin gene previously identified in peach ( Prunus persica). The biological role of Ppdfn1 was investigated by analysing its expression profile in leaves, flowers and fruits, either inoculated with the Monilinia laxa fungal pathogen or mock-inoculated. Ppdfn1 expression was highest in flowers and, in fruits, did not vary upon M. laxa inoculation. To characterize the PpDFN1 antifungal activity, the recombinant mature peptide was expressed in Escherichia coli and purified; recombinant PpDFN1 displays antifungal activity against Botrytis cinerea, M. laxa and Penicillium expansum, with IC50 values of 15·1, 9·9 and 1·1 μg mL−1, respectively. Treatment of fungal hyphae with FITC-labelled PpDFN1 indicated that the peptide is not internalized by fungal hyphae, but localizes on their external cell surface. At this site, PpDFN1 is capable of membrane destabilization and permeabilization, as demonstrated by SYTOX Green fluorescence uptake by the treated mycelia. Using artificial lipid monolayers, it was shown that PpDFN1 interacts with sphingolipid-containing membranes; however the strongest interaction occurs with monolayers composed of lipids extracted from sensitive fungi, such as P. expansum. These data suggest that the lipid composition of fungal membranes is of key relevance for defensin specificity. [ABSTRACT FROM AUTHOR]

Background Asthma is a heterogeneous disease and its different phenotypes need to be better characterized from a biochemical-inflammatory standpoint. This study aimed to apply the metabolomic approach to exhaled breath condensate (breathomics) to discriminate different asthma phenotypes, with a particular focus on severe asthma in children. Methods In this cross-sectional study, we recruited 42 asthmatic children (age, 8-17 years): 31 with nonsevere asthma (treated with inhaled steroids or not) and 11 with severe asthma. Fifteen healthy children were enrolled as controls. Children performed exhaled nitric oxide measurement, spirometry, exhaled breath condensate ( EBC) collection. Condensate samples were analyzed using a metabolomic approach based on mass spectrometry. Results A robust Bidirectional- Orthogonal Projections to Latent Structures- Discriminant Analysis (O2 PLS- DA) model was found for discriminating both between severe asthma cases and healthy controls ( R2 = 0.93; Q2 = 0.75) and between severe asthma and nonsevere asthma ( R2 = 0.84; Q2 = 0.47). The metabolomic data analysis leads to a robust model also when the 3 groups of children were considered altogether ( K = 0.80), indicating that each group is characterized by a specific metabolomic profile. Compounds related to retinoic acid, adenosine and vitamin D ( Human Metabolome Database) were relevant for the discrimination between groups. Conclusion The metabolomic profiling of EBC could clearly distinguish different biochemical-metabolic profiles in asthmatic children and enabled the severe asthma phenotype to be fully discriminated. The breathomics approach may therefore be suitable for discriminating between different asthma metabolic phenotypes. [ABSTRACT FROM AUTHOR]

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (i CAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on ( ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved. [ABSTRACT FROM AUTHOR]

To cite this article: Bozzetto S, Carraro S, Giordano G, Boner A, Baraldi E. Asthma, allergy, and respiratory infections: the vitamin D hypothesis. Allergy 2012; 67: 10-17. Abstract The recent discovery that every tissue in the human body has vitamin D receptors and that vitamin D has pleiotropic effects has prompted an increased interest in this hormone. Vitamin D deficiency is widespread and on the increase. There is no consensus on the serum vitamin D levels to consider appropriate for global health, the cutoffs for its deficiency, or the doses to use for its supplementation. Vitamin D seems to correlate closely with host reactions against various respiratory infections. Epidemiological studies have shown that low serum 25-hydroxyvitamin D levels are associated with a higher risk of upper and lower respiratory infections in children and a shortage of vitamin D may contribute to asthmatic patients' symptoms and morbidity rates. There are studies highlighting associations between childhood asthma, fetal lung and/or immune development, and maternal vitamin D intake. An insufficiency of this vitamin also seems to be implicated in the onset of childhood atopy and food allergies. The hypothesis is that vitamin D could have a central role in these pathological situations and that it may represent a novel preventive and/or therapeutic strategy. This article reviews and discusses published data on the relationship between vitamin D and asthma and allergy, emphasizing the need for controlled, prospective studies on vitamin D supplementation to clarify whether it has a role in the prevention of and treatment for asthma and allergic conditions. [ABSTRACT FROM AUTHOR]

Microscopic investigations were conducted into the interaction of Colletotrichum acutatum on white and red strawberry (Fragaria ・ananassa) fruit surfaces. The results showed that, whilst the early interaction events were similar in both white and red fruits, after 24 h fungal colonization dramatically varied: in white fruits C. acutatum became quiescent as melanized appressoria, but on red fruits it displayed subcuticular necrotrophic invasion. A microarray analysis of white and red strawberries after 24 h of interaction with C. acutatum was performed, in order to reveal differences in gene expression possibly related to the different susceptibility of unripe and ripe fruits. Epi ⁄ catechin related genes and fatty acid metabolism genes, involved in the production of quiescence-related molecules such as flavan-3-ols, proanthocyanidins and antifungal dienes, were found to be regulated during strawberry ripening, supporting a role for these molecules as preformed defence mechanisms. Besides several genes commonly regulated upon pathogen interaction, different genes were specifically transcribed only in white or red challenged fruits; a number of these, such as those coding for lectin and polyphenol oxidase, possibly account for specific pathogen-induced responses. The putative biological role of these genes in the different susceptibility of fruits to C. acutatum is discussed. [ABSTRACT FROM AUTHOR]

Prediction of assisted reproduction treatment outcome has been the focus of clinical research for many years, with a variety of prognostic models describing the probability of an ongoing pregnancy or a live birth. This study assessed whether serum anti-Müllerian hormone (AMH) concentrations may be incorporated into a model to enhance the prediction of a live birth in women undergoing their first IVF cycle, by analysing a database containing clinical and laboratory information on IVF cycles carried out between 2005 and 2008 at the Mother-Infant Department of University Hospital, Modena. Logistic regression was used to examine the association of live birth with baseline patient characteristics. Only AMH and age were demonstrated in regression analysis to predict live birth, so a model solely based on these two criteria was generated. The model permitted the identification of live birth with a sensitivity of 79.2% and a specificity of only 44.2%. In the prediction of a live birth following IVF, a distinction, however moderate, can be made between couples with a good and a poor prognosis. The success of IVF was found to mainly depend on maternal age and serum AMH concentrations, one of the most relevant and valuable markers of ovarian reserve. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the prescription rate of respiratory drugs (ATC code R03) in an Italian community setting and to estimate the extent of off-label use by both age and indication. Methods: A cohort study aimed at evaluating prescriptions of drugs with ATC code R03 was conducted for the period 2002–2006. Data source was the PEDIANET Database. Results: Ninety percent of R03 prescriptions are covered by 11 active substances or combinations, corresponding to 67 medicinal products. Inhaled corticosteroids are the most prescribed anti-asthmatic agents, followed by short-acting β2 mimetics. The mean off-label rate is 19 and 56%, by age and indication respectively. The majority of off-label uses is among children under the age of 2. Five active substances are used at dosages not supported by adequate dose-finding studies. Conclusion: In Italy, many respiratory drugs are approved for the treatment of paediatric respiratory diseases, but a remarkable percentage of their prescriptions is off-label. This pharmaco-utilization study demonstrates that there is a need to perform clinical studies aimed at increasing the current knowledge on marketed paediatric drugs, and to revise and re-label the existing regulatory documents to reduce their off-label uses. [ABSTRACT FROM AUTHOR]

BACKGROUND In women, anti-Müllerian hormone (AMH) levels may represent the ovarian follicular pool and could be a useful marker of ovarian reserve. The clinical application of AMH measurement has been proposed in the prediction of quantitative and qualitative aspects in assisted reproductive technologies (ART). In men AMH is secreted in both the serum and seminal fluid. Its measurement may be useful in clinical evaluation of the infertile male. METHODS The PubMed database was systematically searched for studies published until the end of January 2009, search criteria relevant to AMH, ovarian reserve, ovarian response to gonadotrophin stimulation, spermatogenesis and azoospermia were used. RESULTS AMH seems to be a better marker in predicting ovarian response to controlled ovarian stimulation than age of the patient, FSH, estradiol and inhibin B. A similar performance for AMH and antral follicular count has been reported. In clinical practice, AMH measurement may be useful in the prediction of poor response and cycle cancellation and also of hyper-response and ovarian hyperstimulation syndrome. In the male, the wide overlap of AMH values between controls and infertile men precludes this hormone from being a useful marker of spermatogenesis. CONCLUSIONS As AMH may permit the identification of both the extremes of ovarian stimulation, a possible role for its measurement may be in the individualization of treatment strategies in order to reduce the clinical risk of ART along with optimized treatment burden. It is fundamental to clarify the cost/benefit of its use in ovarian reserve testing. Regarding the role of AMH in the evaluation of infertile men, AMH as single marker of spermatogenesis does not seem to reach a satisfactory clinical utility. [ABSTRACT FROM PUBLISHER]

The article focuses on the hazelnut allergy in children predicted by COR a 14-specific immunoglobin IgE. Topics discussed include Hazelnut allergy demonstrated by open oral food challenge (OFC); larger wheals after skin pricking with hazelnut extract; and prick-to-prick test with native hazelnut as more accurate in diagnosing symptomatic allergy.

Background: The Childhood Asthma Control Test (C-ACT) has been proposed as a tool in assessing the level of disease control in asthmatic children. To evaluate the position of C-ACT in the clinical management of asthmatic children, in relationship to the level of airway inflammation as assessed by fractional exhaled nitric oxide (FeNO) and with lung function. Methods: A total of 200 asthmatic children were included in the study: 47 children with newly diagnosed asthma (‘New’) and without any regular controller therapy; and 153 children with previously diagnosed asthma, treated according to GINA guidelines, and evaluated during a scheduled follow-up visit (‘Follow-up’). Childhood Asthma Control Test, FeNO and lung function [forced expiratory volume 1 (FEV1) and forced vital capacity (FVC)] were evaluated. Results: In New vs Follow-up participants, C-ACT score ( P < 0.001), FVC ( P < 0.005) and FEV1 ( P < 0.05) were significantly lower, and FeNO ( P = 0.011) were significantly higher. In New, but not in Follow-up participants, significant correlations were observed between C-ACT score and FeNO ( r = −0.51; P < 0.001), FEV1 ( r = 0.34; P = 0.022) and FEV1/FVC ( r = 0.32; P = 0.03). This lack of correlation in Follow-up visits seemed attributable to dissociation between inadequately controlled asthma by C-ACT ratings with normalization of other measures such as FeNO levels. Conclusions: This study confirms and expands the concept that C-ACT is complementary to, but not a substitute for, other markers of disease control in asthmatic children, especially in the context of follow-up visits. [ABSTRACT FROM AUTHOR]

The dysregulation of airway pH control may have a role in asthma pathophysiology. The measurement of exhaled breath condensate (EBC) pH and ammonia levels may be used as a noninvasive method to study acid–base status in the airway of asthmatics.Exhaled breath condensate from 29 allergic stable asthmatic children and 13 healthy controls was collected by cooling exhaled air during tidal breathing. Ammonia was measured by high-performance liquid chromatography with fluorescence detection. pH was measured after deaeration of EBC samples by bubbling with argon. The children also underwent FENO measurement.Both pH and ammonia values in EBC were significantly lower in the asthmatics than in the control group [pH: ICS-treated (median and interquartile range) 7.70 (7.62–7.74), steroid-naïve 7.53 (7.41–7.68), controls 7.85 (7.80–7.90),P < 0.01 andP < 0.001, respectively; ammonia: ICS-treated 476.17 μM (282.50–594.80), steroid-naïve 253.24 μM (173.43–416.08), controls 788.30 μM (587.29–1310.39),P < 0.05 andP < 0.001, respectively]. Both pH and ammonia values were higher in ICS-treated than in steroid-naïve asthmatic children. There was a significant correlation between EBC pH and ammonia concentrations.These data show that EBC pH values of stable asthmatic children are lower compared with those of healthy controls and positively correlated with ammonia concentrations, supporting the hypothesis that airway acidification may have a role in the pathobiology of allergic asthma. [ABSTRACT FROM AUTHOR]

Montelukast has been shown to be effective in controlling the increase in exhaled NO in asthmatic children re-exposed to house dust mite (HDM). This study compared the effect of low dose inhaled budesonide and oral montelukast in preventing the expected relapse of airway inflammation and reactivity in a group of 24 mild asthmatic children allergic to HDM after a brief period of exposure to relevant allergens.Lung function, bronchial hyperresponsiveness (BHR) to methacholine (PC20), fractional exhaled nitric oxide (FeNO) levels and sputum eosinophilia were evaluated.Pulmonary function remained stable. The BHR was unchanged after exposure in the group treated with budesonide, whereas a significant increase (P = 0.028) was observed in the patients receiving montelukast. No significant difference was observed in FeNO levels after exposure to mite antigen in the two groups. In both the groups of asthmatic children we observed a significant increase in sputum eosinophil % after the exposure to mite antigen.The significant increase in BHR level observed in the group of children receiving montelukast suggests a more comprehensive effect as disease controller by inhaled steroids than by leukotriene antagonist in allergic asthmatic children re-exposed to relevant allergens. [ABSTRACT FROM AUTHOR]

Background. Severely immunocompromised individuals are highly susceptible to Candida infection of the esophagus. This randomized, double-blind study assessed the dose-response relationship of the new echinocandin antifungal, micafungin, compared with that of standard fluconazole treatment. Methods. A total of 245 patients (age,&ges;18 years) with a prior diagnosis of acquired immunodeficiency syndrome/human immunodeficiency virus (HIV) infection and esophageal candidiasis, confirmed by endoscopy and culture, were randomized to receive micafungin (50, 100, or 150 mg per day) or fluconazole (200 mg per day). Both agents were administered once per day by a 1-h intravenous infusion for 14-2 1 days. The primary efficacy end point was endoscopic cure rate, defined as endoscopy grade of 0 at the end of therapy. Results. The endoscopic cure rate (grade 0) was dose-dependent with 50, 100, and 150 mg of micafungin per day at 68.8%, 77.4%, and 89.8%, respectively. Symptoms improved or resolved rapidly (3-7 days of treatment in the majority of patients). The endoscopic cure rate for 100 and 150 mg of micafungin per day (83.5%) was comparable to that for 200 mg of fluconazole per day (86.7%; 95% confidence interval for the difference in endoscopic cure rate, -14.0% to 7.7%). The overall safety and tolerability was acceptable, with no important differences between micafungin (all doses) and fluconazole. Conclusions. The dose-response findings demonstrate a greater efficacy with micafungin at 100 and 150 mg per day than at 50 mg per day. This study also indicates that the efficacy of micafungin (at dosages of 100 and 150 mg per day) was comparable to that of fluconazole, suggesting that micafungin represents a valuable new treatmen option for esophageal candidiasis in HIV-positive patients. [ABSTRACT FROM AUTHOR]

Bodini A, Peroni D, Vicentini L, Loiacono A, Baraldi E, Ghiro L, Corradi M, Alinovi R, Boner AL, Piacentini GL. Exhaled breath condensate eicosanoids and sputum eosinophils in asthmatic children: A pilot study. Pediatr Allergy Immunol 2004: 15: 26–31. © 2004 Blackwell Munksgaard Cysteinyl leukotrienes (cys-LTs), LTB4 and 8-isoprostane are increased in the exhaled breath condensate (EBC) from asthmatic patients. The aim of this study was to investigate whether the measurement of cys-LTs, LTB4 and 8-isoprostane in EBC can reflect the level of airway inflammation assessed by induced sputum in asthmatic children sensitized to house dust mite (HDM) during natural avoidance of HDM allergens. Twelve children were evaluated at the time of admission (T0) and after 3 months of stay (T1) at the Istituto Pio XII (Misurina, Italian Dolomites 1756 m). Sputum eosinophil percentage and measurement of cys-LTs, LTB4 and 8-isoprostanes in the breath condensate at T0 and T1 were evaluated. Eosinophil percentage in induced sputum was 8.5 ± 1.1% at T0 and 3.5 ± 0.4% at T1 (p = 0.011). Neutrophil percentage in sputum was 1.1 ± 0.5% at T0 and 1.5 ± 1.0% at T1 (ns). Cys-LTs mean level was 14.24 ± 4.53 pg/ml at T0 and 4.65 ± 0.68 pg/ml at T1 (p = 0.0125). LTB4 level was 2.36 ± 0.19 pg/ml at T0 and 2.41 ± 0.23 pg/ml at T1 (ns). 8-Isoprostane level reduced from 17.47 ± 3.18 pg/ml at T0 to 7.36 ± 3.26 pg/ml at T1 (p = 0.003). This study show that exhaled cys-LTs and 8-isoprostane, as well as eosinophil percentage in induced sputum, are reduced after allergen avoidance in asthmatic children suggesting a potential application of EBC for the non-invasive evaluation of airway inflammation in asthma in allergic asthmatic children. [ABSTRACT FROM AUTHOR]

Aureobasidium strains isolated from diverse unconventional environments belonging to the species A. pullulans, A. melanogenum, and A. subglaciale were evaluated for Volatile Organic Compounds (VOCs) production as a part of their modes of action against Botrytis cinerea of tomato and table grape. By in vitro assay, VOCs generated by the antagonists belonging to the species A. subglaciale showed the highest inhibition percentage of the pathogen mycelial growth (65.4%). In vivo tests were conducted with tomatoes and grapes artificially inoculated with B. cinerea conidial suspension, and exposed to VOCs emitted by the most efficient antagonists of each species (AP1, AM10, AS14) showing that VOCs of AP1 (A. pullulans) reduced the incidence by 67%, partially confirmed by the in vitro results. Conversely, on table grape, VOCs produced by all the strains did not control the fungal incidence but were only reducing the infection severity (< 44.4% by A. pullulans; < 30.5% by A. melanogenum, and A. subglaciale). Solid-phase microextraction (SPME) and subsequent gas chromatography coupled to mass spectrometry identified ethanol, 3-methyl-1-butanol, 2-methyl-1-propanol as the most produced VOCs. However, there were differences in the amounts of produced VOCs as well as in their repertoire. The EC50 values of VOCs for reduction of mycelial growth of B. cinerea uncovered 3-methyl-1-butanol as the most effective compound. The study demonstrated that the production and the efficacy of VOCs by Aureobasidium could be directly related to the specific species and pathosystem and uncovers new possibilities for searching more efficient VOCs producing strains in unconventional habitats other than plants. [ABSTRACT FROM AUTHOR]

The article presents a study regarding the biological and clinical response of children with food allergy. It mentions that the research aims to study the urinary concentrations of kids with food allergy. According to the authors, there is an increase of inflammatory mediators in children with food allergy.

Exhaled nitric oxide (FENO) is a surrogate marker of eosinophilic airway inflammation. The measurement of this gas can be easily performed in children and the result is immediately available. Because of these characteristics, measurement of FENO is slowly becoming part of the routine clinical evaluation of an asthmatic patient. FENO measurement may have a role both in the diagnosis of asthma and as a guide in therapy algorithms. For example when FENO levels are persistently normal and the asthmatic child is asymptomatic, the steroid therapy may be decreased or even stopped. In patients with acute or chronic rhinosinusitis the levels of nasal nitric oxide (nNO) are significantly decreased, while they rise up after a course of antibiotics. The measurement of nasal NO has been proposed as a functional test to evaluate sinus ventilation. Nasal NO is significantly reduced also in primary ciliary dyskinesia and can be used as a screening tool to identify patients affected by this condition. [ABSTRACT FROM AUTHOR]

The article discusses the case of a three-year-old boy with mild intermittent asthma, who developed life-threatening status asthmaticus refractory to maximal conventional treatment and required extracorporeal membrane oxygenation support for survival. His past medical history was notable for two mild wheezing episodes, with no recurrence in the last 12 months.

A response by P. Baiardi and colleagues to a letter to the editor about their article related to the use of off-label R05 drugs in young children published in a previous issue is presented.