Selected anthropometric variables and aerobic fitness as predictors of cardiovascular disease risk in children

The aim of this study was to assess the suitability of body mass index, waist circumference, waist-to-height ratio and aerobic fitness as predictors of cardiovascular risk factor clustering in children. A cross-sectional study was conducted with 290 school boys and girls from 6 to 10 years old, randomly selected. Blood was collected after a 12-hour fasting period. Blood pressure, waist circumference (WC), height and weight were evaluated according to international standards. Aerobic fitness (AF) was assessed by the 20-metre shuttle-run test. Clustering was considered when three of these factors were present: high systolic or diastolic blood pressure, high low-density lipoprotein (LDL) cholesterol, high triglycerides, high plasma glucose, high insulin concentrations and low high-density lipoprotein (HDL) cholesterol. A ROC curve identified the cut-off points of body mass index (BMI), WC, waist-to-height ratio (WHtR) and AF as predictors of risk factor clustering. BMI, WC and WHR resulted in significant areas under the ROC curves, which was not observed for AF. The anthropometric variables were good predictors of cardiovascular risk factor clustering in both sexes, whereas aerobic fitness should not be used to identify cardiovascular risk factor clustering in these children.     

Cytokine profile of autologous conditioned serum for treatment of osteoarthritis, <Emphasis Type="Italic">in vitro</Emphasis>effects on cartilage metabolism and intra-articular levels after injection

Introduction  

Intraarticular administration of autologous conditioned serum (ACS) recently demonstrated some clinical effectiveness in treatment of osteoarthritis (OA). The current study aims to evaluate the in vitro effects of ACS on cartilage proteoglycan (PG) metabolism, its composition and the effects on synovial fluid (SF) cytokine levels following intraarticular ACS administration.     

A pharmacological investigation of the biphasic nature of the contractile response of rabbit and rat vas deferens to field stimulation

It has been demonstrated previously with the vas deferens of the guinea-pig that the first and second phases of the contractile response to motor nerve stimulation are preferentially antagonized by the P₂-purinoceptor antagonist arylazido aminopropionyl ATP (ANAPP₃), and the α₁-adrenoceptor antagonist prazosin, respectively. We have now investigated the effect of the two antagonists on the biphasic contraction in the vas deferens of two other species; rabbit and rat. ANAPP₃, in a concentration which antagonized responses to exogenously applied ATP but not those to exogenous norepinephrine, preferentially reduced the initial phasic response of the rabbit vas deferens to motor nerve stimulation without significantly reducing the secondary, tonic phase of the response. Prazosin had the opposite effect; antagonizing the response to norepinephrine but not to ATP and reducing the tonic response to motor nerve stimulation without significantly reducing the initial phasic response. Results obtained with the rat vas deferens were similar. The present results combined with previous findings suggest that ATP and norepinephrine act as cotransmitters in the vas deferens of several species.     

Neuropeptide Y inhibition of calcium channels in PC-12 pheochromocytoma cells

We previouslydemonstrated, using rat PC-12 pheochromocytoma cells differentiated toa sympathetic neuronal phenotype with nerve growth factor (NGF), thatneuropeptide Y (NPY) inhibits catecholamine synthesis as well asrelease. Inquiry into the mechanisms of these inhibitions implicateddistinct pathways involving reduction ofCa²⁺ influx throughvoltage-activated Ca²⁺ channels.In the present investigation the effects of NPY on whole cellBa²⁺ currents were examined toobtain direct evidence supporting the mechanisms suggested by thosestudies. NPY was found to inhibit the voltage-activatedBa²⁺ current in NGF-differentiatedPC-12 cells in a reversible fashion with anEC₅₀ of 13 nM. This inhibition waspertussis toxin sensitive and resulted from NPY modulation of L- andN-type Ca²⁺ channels. Theinhibition of L-type channels was not seen with <1 nM freeintracellular Ca²⁺ or when proteinkinase C (PKC) was inhibited by chelerythrine or PKC-(1931).Furthermore, the effect of NPY on L-type channels was mimicked by thePKC activator phorbol 12-myristate 13-acetate. These studiesdemonstrate that, in addition to inhibition of N-type Ca²⁺ channels, inNGF-differentiated PC-12 cells NPY inhibits L-type Ca²⁺ channels via an intracellularCa²⁺- and PKC-dependent pathway.

     

Cell Signaling-Based Classifier Predicts Response to Induction Therapy in Elderly Patients with Acute Myeloid Leukemia

Single-cell network profiling (SCNP) data generated from multi-parametric flow cytometry analysis of bone marrow (BM) and peripheral blood (PB) samples collected from patients >55 years old with non-M3 AML were used to train and validate a diagnostic classifier (DX_SCNP) for predicting response to standard induction chemotherapy (complete response [CR] or CR with incomplete hematologic recovery [CRi] versus resistant disease [RD]). SCNP-evaluable patients from four SWOG AML trials were randomized between Training (N = 74 patients with CR, CRi or RD; BM set = 43; PB set = 57) and Validation Analysis Sets (N = 71; BM set = 42, PB set = 53). Cell survival, differentiation, and apoptosis pathway signaling were used as potential inputs for DX_SCNP. Five DX_SCNP classifiers were developed on the SWOG Training set and tested for prediction accuracy in an independent BM verification sample set (N = 24) from ECOG AML trials to select the final classifier, which was a significant predictor of CR/CRi (area under the receiver operating characteristic curve AUROC = 0.76, p = 0.01). The selected classifier was then validated in the SWOG BM Validation Set (AUROC = 0.72, p = 0.02). Importantly, a classifier developed using only clinical and molecular inputs from the same sample set (DX_CLINICAL2) lacked prediction accuracy: AUROC = 0.61 (p = 0.18) in the BM Verification Set and 0.53 (p = 0.38) in the BM Validation Set. Notably, the DX_SCNP classifier was still significant in predicting response in the BM Validation Analysis Set after controlling for DX_CLINICAL2 (p = 0.03), showing that DX_SCNP provides information that is independent from that provided by currently used prognostic markers. Taken together, these data show that the proteomic classifier may provide prognostic information relevant to treatment planning beyond genetic mutations and traditional prognostic factors in elderly AML.     

Role of Maternal Dietary Peanut Exposure in Development of Food Allergy and Oral Tolerance

Background

The impact of maternal ingestion of peanut during pregnancy and lactation on an offspring’s risk for peanut allergy is under debate.

Objective

To investigate the influence of maternal dietary peanut exposure and breast milk on an offspring’s allergy risk.

Methods

Preconceptionally peanut-exposed C3H/HeJ females were either fed or not fed peanut during pregnancy and lactation. The offsprings’ responses to peanut sensitization or oral tolerance induction by feeding antigen prior to immunization were assessed. We also assessed the impact of immune murine milk on tolerance induction pre- or post-weaning. For antigen uptake studies, mice were gavaged with fluorescent peanut in the presence or absence of immune murine milk; Peyer’s patches were harvested for immunostaining.

Results

Preconceptional peanut exposure resulted in the production of varying levels of maternal antibodies in serum (and breast milk), which were transferred to the offspring. Despite this, maternal peanut exposure either preconceptionally or during pregnancy and lactation, when compared to no maternal exposure, had no impact on peanut allergy. When offspring were fed peanut directly, dose-dependent tolerance induction, unaltered by maternal feeding of peanut, was seen. Although peanut uptake into the gut-associated lymphoid tissues was enhanced by immune milk as compared to naïve milk, tolerance induction was not affected by the co-administration of immune milk either pre- or post-weaning.

Conclusion

Maternal peanut exposure during pregnancy and lactation has no impact on the development of peanut allergy in the offspring. Tolerance to peanut can be induced early, even pre-weaning, by giving moderate amounts of peanut directly to the infant, and this is neither enhanced nor impaired by concurrent exposure to immune milk.     

Multiple McNemar Tests

Summary Methods for performing multiple tests of paired proportions are described. A broadly applicable method using McNemar's exact test and the exact distributions of all test statistics is developed; the method controls the familywise error rate in the strong sense under minimal assumptions. A closed form (not simulation‐based) algorithm for carrying out the method is provided. A bootstrap alternative is developed to account for correlation structures. Operating characteristics of these and other methods are evaluated via a simulation study. Applications to multiple comparisons of predictive models for disease classification and to postmarket surveillance of adverse events are given.     

Comparative ultrastructure of Clara cells in neonatal and older cattle

Calf lungs were fixed with glutaraldehyde and examined by scanning (SEM) and transmission (TEM) electron microscopy to compare the ultrastructure of Clara cells in terminal bronchioles of neonatal calves and older cattle. In the neonatal calf, SEM revealed numerous smooth-surfaced Clara cells protruding above a similar number of ciliated cells, whereas in older animals the surface of Clara cells was lobulated. Thin sections examined by TEM revealed numerous cuboidal to columnar Clara cells with indented nuclei and a pale cytoplasm filled with faintly granular glycogen in the neonatal calf. Some cells were characterized by apical dense and/or pale membrane-bound granules or secretory droplets. Many cells had an apical tubular network of cisternae that were partly smooth and partly decorated with ribosomes. Ultrastructural comparison of Clara cells in a 2-day-old calf with those of 14- and 19-day-old, 4- and 5. 5-month-old, and 3.5-year-old cattle revealed a striking reduction in the amount of glycogen per cell after 14 days. The number of cells with apical granules was small at all ages, and the density of the secretory granules varied greatly in different cells. A variable amount of smooth endoplasmic reticulum (SER) was present but was less prominent than cisternae of ribosomal endoplasmic reticulum (RER). In older cattle, the limited amount of SER compared to the RER and secretory granules suggests that bovine Clara cells are more likely to be secretory than detoxifying.     

A two-generation analysis of pollen pool genetic structure in flowering dogwood, Cornus florida (Cornaceae), in the Missouri Ozarks

Anthropogenic landscape change can disrupt gene flow. As part of the Missouri Ozark Forest Ecosystem Project, this study examined whether silvicultural practices influence pollen-mediated gene movement in the insect-pollinated species, Cornus florida L., by comparing pollen pool structure (Φ(st)) among clear-cutting, selective cutting, and uncut regimes with the expectation that pollen movement should be least in the uncut regime. Using a sample of 1500 seedlings-10 each from 150 seed parents (43 in clear-cut, 74 in selective, and 33 in control sites) from six sites (each ranging from 266 to 527 ha), eight allozyme loci were analyzed with a pollen pool structure approach known as TwoGener (Smouse et al., 2001; Evolution 55: 260-271). This analysis revealed that pollen pool structure was less in clear-cut (Φ(C) = 0.090, P < 0.001) than in uncut areas (Φ(U) = 0.174, P < 0.001), with selective-cut intermediate (Φ(S) = 0.125, P < 0.001). These estimates translate into more effective pollen donors (N(ep)) in clear-cut (N(ep) = 5.56) and selective-cut (N(ep) = 4.00) areas than in uncut areas (N(ep) = 2.87). We demonstrate that Φ(C) ≤ Φ(S) ≤ Φ(U), with Φ(C) significantly smaller than Φ(U) (P < 0.034). The findings imply that, as long as a sufficiently large number of seed parents remain to provide adequate reproduction and to avoid a genetic bottleneck in the effective number of mothers, silvicultural management may not negatively affect the effective number of pollen parents, and hence subsequent genetic diversity in Cornus florida.