Fraction of Exhaled Nitric Oxide and Asthma Predictive Index in Infants Less Than Two Years-Old

IntroductionThe fraction of exhaled nitric oxide (FE_NO) is considered an indirect marker of eosinophilic inflammation of the airway. In cooperative children, the usual method is a single breath. The impossibility of performing this in uncooperative children has led to the development of the online and offline tidal breathing technique. The objective of the study has been to analyse the relationship between the multiplebreath online FE_NO and the asthma predictive index (API) in children under the age of two.Material and methodsAn observational and cross-sectional study on a consecutive sample of boys and girls between 2 months and 2 years of age, over a period of 4 months. The post-prandial multiple breaths online FE_NO and flow spirometry between 40 and 60 ml/s, using a stationary chemiluminescence analyser (CLD 88 sp). The quantitative variables were: age, weight, IgE, eosinophilia, FE_NO, flow spirometry. The qualitative variables were: gender, atopic dermatitis, allergic rhinitis, food and medical allergies, family history of asthma and atopy, diagnosis and treatment. The relationship between API and FE_NO was analysed using the exact Fisher and Student t tests and the level of agreement between API and FE_NO using Cohen's Kappa. The relationship between eosinophilia, IgE, atopic dermatitis and FE_NO was also studied (exact Fisher and Student t tests).ResultsThe cohort consisted of 38 patients. The determinations were successfully carried out on 32 (84.21) of the cases. The mean age was 10.9 ± 5.06 months. The cases with a positive API had significantly higher FE_NO values than those with a negative API, with a level of agreement between API and FE_NO of 0.71.ConclusionsThere is a significant relationship and a good level of agreement between the online tidal breathing FE_NO and the API.     

Mutant A53T α-Synuclein Improves Rotarod Performance Before Motor Deficits and Affects Metabolic Pathways

The protein α-synuclein (α-Syn) interferes with glucose and lipid uptake and also activates innate immune cells. However, it remains unclear whether α-Syn or its familial mutant forms contribute to metabolic alterations and inflammation in synucleinopathies, such as Parkinson’s disease (PD). Here, we address this issue in transgenic mice for the mutant A53T human α-Syn (α-SynA53T), a mouse model of synucleinopathies. At 9.5 months of age, mice overexpressing α-SynA53T (homozygous) had a significant reduction in weight, exhibited improved locomotion and did not show major motor deficits compared with control transgenic mice (heterozygous). At 17 months of age, α-SynA53T overexpression promoted general reduction in grip strength and deficient hindlimb reflex and resulted in severe disease and mortality in 50 % of the mice. Analysis of serum metabolites further revealed decreased levels of cholesterol, triglycerides and non-esterified fatty acids (NEFA) in α-SynA53T—overexpressing mice. In fed conditions, these mice also showed a significant decrease in serum insulin without alterations in blood glucose. In addition, assessment of inflammatory gene expression in the brain showed a significant increase in TNF-α mRNA but not of IL-1β induced by α-SynA53T overexpression. Interestingly, the brain mRNA levels of Sirtuin 2 (Sirt2), a deacetylase involved in both metabolic and inflammatory pathways, were significantly reduced. Our findings highlight the relevance of the mechanisms underlying initial weight loss and hyperactivity as early markers of synucleinopathies. Moreover, we found that changes in blood metabolites and decreased brain Sirt2 gene expression are associated with motor deficits.     

Evidence of loss of heterozygosity of the PTCH gene in orthokeratinized odontogenic cyst

J Oral Pathol Med (2011) 40 : 277–280 The orthokeratinized odontogenic cyst (OOC) is an odontogenic cyst of unknown etiology. Clinical, histological, and biological differences are reported between keratocystic odontogenic tumor (KOT) and OOC. PTCH is a tumor suppressor gene related to sonic hedgehog (SHH) pathway important in embryological development. Considering that alterations in this pathway have been described in sporadic and nevoid basal cell syndrome‐associated KOT, we tested the hypothesis that OOC is also associated with loss of heterozygosity (LOH) of the PTCH gene. Seven samples of OOC and seven of KOT were included in the study. D9S287, D9S196, and D9S127 microsatellite markers located in the region of PTCH gene, at chromosome 9q, were investigated for LOH. There was loss in at least one locus in 5/7 KOT and in 4/7 OOC samples. The present finding demonstrates that, despite the existence of clinical, morphological, immunohistochemical, and biological behavior differences between OOC and KOT, both harbor similar genetic alterations at 9q.     

Thigh and buttock exertional pain for the diagnosis of peripheral arterial disease

ObjectivesTo evaluate the prevalence of both non-calf intermittent claudication (IC) and classic IC in patients with no known atherosclerotic disease, and their accuracy to detect peripheral arterial disease (PAD).DesignCross sectional, observational study conducted at 96 internal medicine services.Materials and methods1487 outpatients with no known atherosclerotic disease, and either diabetes or a SCORE risk estimation of at least 3% were enrolled. IC was assessed using the Edinburgh Claudication Questionnaire and PAD was confirmed by an ankle-brachial index (ABI) < 0.9.ResultsOverall, 7.2% met criteria of classic and 5.8% of non-calf IC. PAD was diagnosed in 393 cases (26.4%). In these PAD patients, 17.8% exhibited classic and 13.2% non-calf IC. Both calf and non-calf IC had similar overall accuracy for detecting PAD. Considering both categories as a whole, the sensitivity of IC to predict a low ABI was 31% and the specificity 93%.ConclusionsNon-calf IC is comparable to classic IC for the diagnosis of PAD in patients with no known arterial disease. The systematic implementation of Edinburgh Claudication Questionnaire could be a valuable call-to-action to improve clinical evaluation of PAD, bearing in mind that PAD detected by either non-calf or classic IC must be confirmed by ABI testing.