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Introduction: Lung clearance index (LCI) is a very sensitive marker of early lung disease in Cystic Fibrosis (CF). In Cystic Fibrosis Screen Positive Inconclusive Diagnosis (CFSPID) and in compound heterozygotes carrying at least one mutation with indefinite clinical liability (CH), respiratory symptoms are often more mild and they might begin in adulthood. In childhood usually these patients have normal spirometric values. Aims and objectives: Compare LCI among three groups of patients: CFSPID-CH, CF and controls. We wanted to find out whether it is true that CFSPID-CH have normal LCI as healthy controls. Methods: We perform and compare Spirometry test and N2-Multiple Breath Wash Out (N2-MBW, Exhalyzer D, Ecomedix) in a group of CFSPID-CH, a group of CF and a control group. Results: 9 healthy controls (mean age: 5.4 yrs), 17 CFSPID-CH (mean age: 10.4 yrs) and 37 CF patients (mean age: 7.5 yrs) were tested. Basal FEV1 was normal in all groups and it was not statistically different between them. CF had significantly higher mean LCI than CFSPID-CH (9.68 versus 7.23; p=0.004). CFSPID-CH9s LCI was higher than healthy controls but without statistical significance. Conclusions: Our data show that CFSPID-CH have a pattern of LCI that is different from the one of CF patients and is similar to the one of healthy control. LCI could be a promising technique to study pulmonary function of CFSPID-CH and could be use in the follow-up of these patients.

INTRODUCTION Over the last decade the study of pulmonary function by multiple breath washout technique (MBW) has been widely used to detect early pulmonary changes in Cystic Fibrosis. On the contrary there are only few studies that use Lung Clearance Index (LCI) in other chronic lung diseases like asthma. Moreover data regarding bronchodilator response on LCI are contradictory. AIMS AND OBJECTIVES To find out whether LCI was able to detect any early involvement of small airways in stable asthmatic children and if was more sensitive than spirometry to detect bronchoreversibility after salbutamol administration. METHODS We performed spirometry and N2-Multiple Breath Wash Out (N2-MBW, Exhalyzer D, Ecomedix) in a group of stable asthmatic patients and in a group of healthy children. In the first group we repeated spirometry and N2-MBW after administration of 400μg of salbutamol RESULTS 12 asthmatic children (mean age: 6.0 yrs) and 9 healthy controls (mean age: 5.4 yrs) were tested. Basal FEV 1 and basal LCI were no statistically different between the 2 groups. After the administration of Salbutamol the increase of FEV 1 was of 5%. Among the asthmatic group LCI after the administration of salbutamol showed a statistically significant decrease (p=0.009) CONCLUSIONS Our data showed that basal LCI was not different between the two groups. In asthmatic patients it could be more sensitive then spirometry in detecting bronchoreversibility.

We sought to assess the glucose disposition index using an oral glucose tolerance test (OGTT; oDI) compared with the glucose disposition index measured from the combination of the euglycemic-hyperinsulinemic and hyperglycemic clamps (cDI) in obese pediatric subjects spanning the range of glucose tolerance.Overweight/obese adolescents (n = 185) with varying glucose tolerance (87 normal, 54 impaired, 31 with type 2 diabetes, and 13 with type 1 diabetes) completed an OGTT and both a hyperinsulinemic-euglycemic and a hyperglycemic clamp study. Indices of insulin sensitivity and β-cell function were calculated, and 4 different oDI estimates were calculated as the products of insulin and C-peptide-based sensitivity and secretion indices.Mirroring the differences across groups by cDI, the oDI estimates were greatest in normal glucose tolerance adolescents and lowest in type 2 diabetes mellitus and obese with type 1 diabetes mellitus adolescents. The insulin-based oDI estimates correlated with cDI overall (r ≥ 0.74, P.001) and within each glucose tolerance group (r ≥ 0.40, P.001). Also, oDI and cDI predicted 2-hour OGTT glucose similarly.The oDI is a simple surrogate estimate of β-cell function relative to insulin sensitivity that can be applied to obese adolescents with varying glucose tolerance in large-scale epidemiological studies where the applicability of clamp studies is limited due to feasibility, cost, and labor intensiveness.

In epidemiological studies of childhood obesity, simple and reliable surrogate estimates of insulin sensitivity are needed because the gold standard, the hyperinsulinemic-euglycemic clamp, is not feasible on a large scale.To examine the correlation of fasting and oral glucose tolerance test (OGTT)-derived surrogate indices of insulin sensitivity with the hyperinsulinemic-euglycemic clamp in obese adolescents with normal glucose tolerance, prediabetes, and diabetes.A total of 188 overweight/obese adolescents (10 to20 yr old) who completed a standard 2-h OGTT and 3-h hyperinsulinemic-euglycemic clamp were included. Fasting-derived surrogates [fasting glucose (G(F)), fasting insulin (I(F)), 1/I(F), G(F)/I(F), homeostasis model assessment and quantitative insulin sensitivity check index] and OGTT-derived surrogates [whole-body insulin sensitivity index and the ratio of glucose and insulin areas under the curve (Gluc(AUC)/Ins(AUC))] were calculated.We evaluated the correlations between the clamp-measured insulin sensitivity and the surrogate estimates and area under the receiver operating characteristic curves.Fasting indices (1/I(F), G(F)/I(F), homeostasis model assessment of insulin sensitivity, and quantitative insulin sensitivity check index) correlated significantly with clamp insulin sensitivity (r = 0.82, 0.78, 0.81, and 0.80, respectively), with lower correlations between the OGTT surrogates and clamp (whole-body insulin sensitivity index, r = 0.77; Gluc(AUC)/Ins(AUC), r = 0.62). The area under the receiver operating characteristic curves was more than or equal to 0.94 for all surrogates except Gluc(AUC)/Ins(AUC.) Across quartiles of clamp-measured insulin sensitivity, there was a significant overlap in individual values of I(F), 1/I(F), and G(F)/I(F).In obese adolescents with normal or impaired glucose tolerance or diabetes, OGTT-derived surrogates do not offer any advantage over the simpler fasting indices, which correlate strongly with clamp insulin sensitivity. Surrogate indices of insulin sensitivity could be used in epidemiological studies but not to define insulin resistance in individual patients or research subjects.

The authors detail their multidisciplinary collaboration of cardiologists, physiologists, neurologists, psychologists, engineers, and statisticians in researching the effects of hypnosis on the cardiovascular system and their additions to that incomplete literature. The article details their results and provides guidelines for researchers interested in replicating their research on hypnosis' effect on the cardiovascular system.

Both low and high iron levels have been associated with cardiovascular outcome. The aim of this study was to determine if dietary iron intake is a cardiovascular predictor in women at a population level.A 138-item food frequency questionnaire (FFQ) was administered to 906 women aged 61.1±17.1 years from an unselected general population followed for 10 years. The mass of dietary items was calculated, and each food was resolved into its chemical components according to food composition tables conceived for Italian food.An inverse association between iron intake and cardiovascular morbidity was found. Incident nonfatal cerebrovascular events were 10 of 302 (3.3%), 4 of 302 (1.3%), and 2 of 302 (0.7%) in the first, second, and third tertiles of nonheme iron intake (p for trend0.01), respectively; fatal cerebrovascular events were 20 of 302 (6.6%), 13 of 302 (4.3%), and 5 of 302 (1.7%), respectively (p0.01); nonfatal coronary events were 24 of 302 (7.9%), 13 of 302 (4.3%), and 10 of 302 (3.3%), respectively, and fatal coronary events were 20 of 302 (6.6%), 15 of 302 (5.0%), and 10 of 302 (3.3%), respectively (p0.01). Independenly of confounders, hazard ratios (HR) and 95% confidence intervals (CI) of being the first rather than third tertile of nonheme iron intake were 5.00 (1.08-23.26), 3.18 (1.41-10.12), and 3.25 (1.39-7.59), respectively, for cerebrovascular and 2.48 (1.17-5.25), 2.25 (1.03-4.80), and 2.51 (1.39-4.53), respectively, for coronary events. Heme iron intake was not a predictor.Based on a longitudinal population analysis, low iron intake seems to be an independent predictor of cerebrovascular and coronary morbidity and mortality in women.

Obesity is clearly associated with insulin resistance and chronic low-grade inflammation.1,2 Macrophages appear to be especially important in this relationship, as they infiltrate adipose tissue and produce a variety of inflammatory cytokines.1 Exploring the contribution of other immune cells to the development of obesity, Liu, et al., described a role for mast cells in the development of obesity and diabetes in mice.3 Using genetically modified mice and pharmacologic stabilizers of mast cells, they demonstrated that mast cells and mast cell-mediated protease expression may promote the growth of white adipose tissue (WAT). Importantly, the idea that mast cells may function in a similar manner in human obesity was suggested by the finding of increased numbers of mast cells in human WAT from obese compared to lean subjects in their study. Furthermore, mean serum tryptase levels were higher in obese (13.1 ng/ml) than lean (7.7 ng/ml) individuals using an in-house tryptase assay. We attempted to replicate this data by comparing serum tryptase levels in obese, overweight, and lean individuals from a pediatric population. As the serum total tryptase level, comprised primarily of α and β protryptases, seems to correlate with the total-body burden of mast cells,4 we measured the level of this protein in individuals 8–18 years old, recruited through newspaper advertisement for research participation. The cohort contained a diverse group of children and adolescents with and without obesity, impaired glucose tolerance, and/or diabetes mellitus (see Figure 1A and Tables E1 and E2). As the body mass index (BMI) is age- and gender-specific in children and teens,5 we divided the subjects based on the BMI percentiles by age and sex into those of healthy weight (BMI ≥5th–