Noninvasive Cardiorespiratory Signals Analysis for Asthma Evolution Monitoring in Preschool Children

OBJECTIVE: Despite its increasing prevalence, diagnosis of asthma in children remains problematic due to their difficulties in producing repeatable spirometric maneuvers. Moreover, low adherence to inhaled corticosteroids (ICS) treatment could result in permanent airway remodeling. The growing interest in a noninvasive and objective way for monitoring asthma, together with the apparent role of autonomic nervous system (ANS) in its pathogenesis, have attracted interest towards heart rate variability (HRV) and cardiorespiratory coupling (CRC) analyses. METHODS: HRV and CRC were analyzed in 70 children who were prescribed ICS treatment due to recurrent obstructive bronchitis. They underwent three different electrocardiogram and respiratory signals recordings, during and after treatment period. After treatment completion, they were followed up during 6 months and classified attending to their current asthma status. RESULTS: Vagal activity, as measured from HRV, and CRC, were reduced after treatment in those children at lower risk of asthma, whereas it kept unchanged in those with a worse prognosis. CONCLUSION: Results suggest that HRV analysis could be useful for the continuous monitoring of ANS anomalies present in asthma, thus contributing to evaluate the evolution of the disease, which is especially challenging in young children. SIGNIFICANCE: Noninvasive ANS assessment using HRV analysis could be useful in the continuous monitoring of asthma in children

Prediction of Solar Proton Event Fluence spectra from their Peak flux spectra

Solar Proton Events (SPEs) are of great importance and significance for the study of Space Weather and Heliophysics. These populations of protons are accelerated at high energies ranging from a few MeVs to hundreds of MeVs and can pose a significant hazard both to equipment on board spacecrafts as well as astronauts as they are ionizing radiation. The ongoing study of SPEs can help to understand their characteristics, relative underlying physical mechanisms, and help in the design of forecasting and nowcasting systems which provide warnings and predictions. In this work, we present a study on the relationships between the Peak Flux and Fluence spectra of SPEs. This study builds upon existing work and provides further insights into the characteristics and the relationships of SPE Peak flux and Fluence spectra. Moreover it is shown how these relationships can be quantified in a sound manner and exploited in a simple methodology with which the Fluence spectrum of an SPE can be well predicted from its given Peak spectrum across two orders of magnitude of proton energies, from 5 MeV to 200 MeV. Finally it is discussed how the methodology in this work can be easily applied to forecasting and nowcasting systems

A Genotype-First Approach for the Molecular and Clinical Characterization of Uncommon De Novo Microdeletion of 20q13.33

Background: Subtelomeric deletions of the long arm of chromosome 20 are rare, with only 11 described in the literature. Clinical features of individuals with these microdeletions include severe limb malformations, skeletal abnormalities, growth retardation, developmental and speech delay, mental retardation, seizures and mild, non-specific dysmorphic features. Methodology/Principal Findings: We characterized microdeletions at 20q13.33 in six individuals referred for genetic evaluation of developmental delay, mental retardation, and/or congenital anomalies. A comparison to previously reported cases of 20q13.33 microdeletion shows phenotypic overlap, with clinical features that include mental retardation, developmental delay, speech and language deficits, seizures, and behavior problems such as autistic spectrum disorder. There does not appear to be a clinically recognizable constellation of dysmorphic features among individuals with subtelomeric 20q microdeletions. Conclusions/Significance: Based on genotype-phenotype correlation among individuals in this and previous studies, we discuss several possible candidate genes for specific clinical features, including ARFGAP1, CHRNA4 and KCNQ2 and neurodevelopmental deficits. Deletion of this region may play an important role in cognitive development

Association between promoter -1607 polymorphism of MMP1 and Lumbar Disc Disease in Southern Chinese

<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteinases (MMPs) are involved in the degradation of the extracellular matrix of the intervertebral disc. A SNP for guanine insertion/deletion (G/D), the -1607 promoter polymorphism, of the <it>MMP1 </it>gene was found significantly affecting promoter activity and corresponding transcription level. Hence it is a good candidate for genetic studies in DDD.</p> <p>Methods</p> <p>Southern Chinese volunteers between 18 and 55 years were recruited from the population. DDD in the lumbar spine was defined by MRI using Schneiderman's classification. Genomic DNA was isolated from the leukocytes and genotyping was performed using the Sequenom^®platform. Association and Hardy-Weinberg equilibrium checking were assessed by Chi-square test and Mann-Whitney U test.</p> <p>Results</p> <p>Our results showed substantial evidence of association between -1607 promoter polymorphism of <it>MMP1 </it>and DDD in the Southern Chinese subjects. D allelic was significantly associated with DDD (p value = 0.027, odds ratio = 1.41 with 95% CI = 1.04–1.90) while Genotypic association on the presence of D allele was also significantly associated with DDD (p value = 0.046, odds ratio = 1.50 with 95% CI = 1.01–2.24). Further age stratification showed significant genotypic as well as allelic association in the group of over 40 years (genotypic: p value = 0.035, odds ratio = 1.617 with 95% CI = 1.033–2.529; allelic: p value = 0.033, odds ratio = 1.445 with 95% CI = 1.029–2.029). Disc bulge, annular tears and the Schmorl's nodes were not associated with the D allele.</p> <p>Conclusion</p> <p>We demonstrated that individuals with the presence of D allele for the -1607 promoter polymorphism of <it>MMP1 </it>are about 1.5 times more susceptible to develop DDD when compared with those having G allele only. Further association was identified in individuals over 40 years of age. Disc bulge, annular tear as well as Schmorl's nodes were not associated with this polymorphism.</p

In Situ Data and Effect Correlation During September 2017 Solar Particle Event

Solar energetic particles are one of the main sources of particle radiation seen in space. In the first part of September 2017 the most active solar period of cycle 24 produced four large X-class flares and a series of (interplanetary) coronal mass ejections, which gave rise to radiation storms seen over all energies and at the ground by neutron monitors. This paper presents comprehensive cross comparisons of in situ radiation detector data from near-Earth satellites to give an appraisal on the state of present data processing for monitors of such particles. Many of these data sets have been the target of previous cross calibrations, and this event with a hard spectrum provides the opportunity to validate these results. As a result of the excellent agreement found between these data sets and the use of neutron monitor data, this paper also presents an analytical expression for fluence spectrum for the event. Derived ionizing dose values have been computed to show that although there is a significant high-energy component, the event was not particularly concerning as regards dose effects in spacecraft electronics. Several sets of spacecraft data illustrating single event effects are presented showing a more significant impact in this regard. Such a hard event can penetrate thick shielding; human dose quantities measured inside the International Space Station and derived through modeling for aircraft altitudes are also presented. Lastly, simulation results of coronal mass ejection propagation through the heliosphere are presented along with data from Mars-orbiting spacecraft in addition to data from the Mars surface

Simulated-Physiological Loading Conditions Preserve Biological and Mechanical Properties of Caprine Lumbar Intervertebral Discs in Ex Vivo Culture

Low-back pain (LBP) is a common medical complaint and associated with high societal costs. Degeneration of the intervertebral disc (IVD) is assumed to be an important causal factor of LBP. IVDs are continuously mechanically loaded and both positive and negative effects have been attributed to different loading conditions

Genetic susceptibility of intervertebral disc degeneration among young Finnish adults

<p>Abstract</p> <p>Background</p> <p>Disc degeneration (DD) is a common condition that progresses with aging. Although the events leading to DD are not well understood, a significant genetic influence has been found. This study was undertaken to assess the association between relevant candidate gene polymorphisms and moderate DD in a well-defined and characterized cohort of young adults. Focusing on young age can be valuable in determining genetic predisposition to DD.</p> <p>Methods</p> <p>We investigated the associations of existing candidate genes for DD among 538 young adults with a mean age of 19 belonging to the 1986 Northern Finland Birth Cohort. Nineteen single nucleotide polymorphisms (SNP) in 16 genes were genotyped. We evaluated lumbar DD using the modified Pfirrmann classification and a 1.5-T magnetic resonance scanner for imaging.</p> <p>Results</p> <p>Of the 538 individuals studied, 46% had no degeneration, while 54% had DD and 51% of these had moderate DD. The risk of DD was significantly higher in subjects with an allele G of <it>IL6 </it>SNPs rs1800795 (OR 1.45, 95% CI 1.07-1.96) and rs1800797 (OR 1.37, 95% CI 1.02-1.85) in the additive inheritance model. The role of <it>IL6 </it>was further supported by the haplotype analysis, which resulted in an association between the GGG haplotype (SNPs rs1800797, rs1800796 and rs1800795) and DD with an OR of 1.51 (95% CI 1.11-2.04). In addition, we observed an association between DD and two other polymorphisms, <it>SKT </it>rs16924573 (OR 0.27 95% CI 0.07-0.96) and <it>CILP </it>rs2073711 in women (OR 2.04, 95% CI 1.07-3.89).</p> <p>Conclusion</p> <p>Our results indicate that <it>IL6</it>, <it>SKT </it>and <it>CILP </it>are involved in the etiology of DD among young adults.</p

The human COL9A3 gene:structure of the gene for the α3 chain of type IX collagen and its role in human cartilage and intervertebral disc diseases

Abstract The nucleotide sequence of the entire COL9A3 gene, coding for the human α3(IX) chain, was determined. The gene was approximately 23 kb in length and consisted of 32 exons. The polymerase chain reaction (PCR)-based procedure of conformation-sensitive gel electrophoresis (CSGE) was used to screen the gene for sequence variations and mutations in 83 unrelated patients with generalized primary osteoarthritis (OA), 31 with rheumatoid arthritis (RA), 171 with intervertebral disc disease (IDD), and 50 with various osteochondrodysplasias. The frequencies of certain sequence variations in healthy individuals were also determined. The COL9A3 gene was analyzed for mutations in two unrelated families with multiple epiphyseal dysplasia (MED). The analysis revealed a splice site mutation leading to skipping of exon 3 and an in-frame loss of 12 amino acid residues in the COL3 domain, the first diseasecausing mutation to be identified in the COL9A3 gene. Sequencing also indicated a 9 bp deletion in one allele in the second MED family that removed a Gly-Pro-Pro triplet. Surprisingly, the deletion did not co-segregate with the MED phenotype in the family. A similar 9 bp deletion, was also found in an unrelated family with no obvious phenotype, suggesting that the two 9 bp deletions represent neutral sequence variants. A construct with the deletion was then made in order to produce a recombinant protein, and the mutant type IX collagen was analyzed under reducing conditions by SDS-PAGE. The results indicated that the recombinant type IX collagen proteins consisted of three α chains, α1(IX), α2(JX), α3(IX), in a 1:1:1 ratio. To study the triple helix stability, pepsin treatment followed by SDS-PAGE was performed on normally folded and denatured recombinant type IX collagen samples. The results demonstrated that the recombinant type IX collagen containing the Gly-X-Y deletion in the a3(IX) chain is secreted as a correctly folded triple-helical molecule. CSGE analysis of exon 5 of the COL9A3 gene identified two nucleotide variations in the same codon, and thus three alleles: CGG (Arg), CAG (Gln), and TGG (Trp). The frequency of the Trp for Arg substitution, the Trp3 allele, was 0.244 among the probands with the IDD, while its overall frequency in the combined group of all non-IDD cases was 0.093. This difference was significant, with a p-value of 0.000013. The Trp3 allele increases the relative risk of IDD by a factor of 2.6 (95 percent confidence interval, 1.6 to 4.3). COL9A3 mutations are shown to be associated with mild cartilage and intervertebral disc diseases