Prematurity and respiratory outcomes program (PROP): Study protocol of a prospective multicenter study of respiratory outcomes of preterm infants in the United States

Background With improved survival rates, short- and long-term respiratory complications of premature birth are increasing, adding significantly to financial and health burdens in the United States. In response, in May 2010, the National Institutes of Health (NIH) and the National Heart, Lung, and Blood Institute (NHLBI) funded a 5-year $18.5 million research initiative to ultimately improve strategies for managing the respiratory complications of preterm and low birth weight infants. Using a collaborative, multi-disciplinary structure, the resulting Prematurity and Respiratory Outcomes Program (PROP) seeks to understand factors that correlate with future risk for respiratory morbidity. Methods/Design The PROP is an observational prospective cohort study performed by a consortium of six clinical centers (incorporating tertiary neonatal intensive care units [NICU] at 13 sites) and a data-coordinating center working in collaboration with the NHLBI. Each clinical center contributes subjects to the study, enrolling infants with gestational ages 23 0/7 to 28 6/7 weeks with an anticipated target of 750 survivors at 36 weeks post-menstrual age. In addition, each center brings specific areas of scientific focus to the Program. The primary study hypothesis is that in survivors of extreme prematurity specific biologic, physiologic and clinical data predicts respiratory morbidity between discharge and 1 year corrected age. Analytic statistical methodology includes model-based and non-model-based analyses, descriptive analyses and generalized linear mixed models. Discussion PROP incorporates aspects of NICU care to develop objective biomarkers and outcome measures of respiratory morbidity in the <29 week gestation population beyond just the NICU hospitalization, thereby leading to novel understanding of the nature and natural history of neonatal lung disease and of potential mechanistic and therapeutic targets in at-risk subjects

Current evidence for a modulation of low back pain by human genetic variants

The manifestation of chronic back pain depends on structural, psychosocial, occupational and genetic influences. Heritability estimates for back pain range from 30% to 45%. Genetic influences are caused by genes affecting intervertebral disc degeneration or the immune response and genes involved in pain perception, signalling and psychological processing. This inter-individual variability which is partly due to genetic differences would require an individualized pain management to prevent the transition from acute to chronic back pain or improve the outcome. The genetic profile may help to define patients at high risk for chronic pain. We summarize genetic factors that (i) impact on intervertebral disc stability, namely Collagen IX, COL9A3, COL11A1, COL11A2, COL1A1, aggrecan (AGAN), cartilage intermediate layer protein, vitamin D receptor, metalloproteinsase-3 (MMP3), MMP9, and thrombospondin-2, (ii) modify inflammation, namely interleukin-1 (IL-1) locus genes and IL-6 and (iii) and pain signalling namely guanine triphosphate (GTP) cyclohydrolase 1, catechol-O-methyltransferase, μ opioid receptor (OPMR1), melanocortin 1 receptor (MC1R), transient receptor potential channel A1 and fatty acid amide hydrolase and analgesic drug metabolism (cytochrome P450 [CYP]2D6, CYP2C9)

Topological data analysis reveals genotype-phenotype relationships in primary ciliary dyskinesia

Background: Primary ciliary dyskinesia (PCD) is a heterogeneous inherited disorder caused by mutations in approximately 50 cilia-related genes. PCD genotype-phenotype relationships have mostly arisen from small case series because existing statistical approaches to investigate relationships have been unsuitable for rare diseases. / Methods: We applied a topological data analysis (TDA) approach to investigate genotype-phenotype relationships in PCD. Data from separate training and validation cohorts included 396 genetically defined individuals carrying pathogenic variants in PCD genes. To develop the TDA models, twelve clinical and diagnostic variables were included. TDA-driven hypotheses were subsequently tested using traditional statistics. / Results: Disease severity at diagnosis measured by FEV1 z-score was (i) significantly worse in individuals with CCDC39 mutations compared to other gene mutations and (ii) better in those with DNAH11 mutations; the latter also reported less neonatal respiratory distress. Patients without neonatal respiratory distress had better preserved FEV1 at diagnosis. Individuals with DNAH5 mutations were phenotypically diverse. Cilia ultrastructure and beat pattern defects correlated closely to specific causative gene groups, confirming these tests can be used to support a genetic diagnosis. / Conclusions: This large scale multi-national study presents PCD as a syndrome with overlapping symptoms and variation in phenotype, according to genotype. TDA modelling confirmed genotype-phenotype relationships reported by smaller studies (e.g. FEV1 worse with CCDC39 mutations), and identified new relationships, including FEV1 preservation with DNAH11 mutations and diversity of severity with DNAH5 mutations

Microstructure analysis method for evaluating degenerated intervertebral disc tissue

Degeneration of intervertebral disc (IVD) tissue is characterized by several structural changes that result in variations in disc physiology and loss of biomechanical function. The complex process of degeneration exhibits highly intercorrelated biomechanical, biochemical, and cellular interactions. There is currently some understanding of the cellular changes in degenerated intervertebral disc tissue, but microstructural changes and deterioration of the tissue matrix has previously been rarely explored. In this work, sequestered IVD tissue was successfully characterized using histology, light microscopy, and scanning electron microscopy (SEM) to quantitatively evaluate parameters of interest for intervertebral disc degeneration (IDD) such as delamination of the collagenous matrix, cell density, cell size, and extra cellular matrix (ECM) thickness. Additional qualitative parameters investigated included matrix fibration and irregularity, neovascularization of the IVD, granular inclusions in the matrix, and cell cluster formation. The results of this study corroborated several previously published findings, including those positively correlating female gender and IVD cell density, age and cell size, and female gender and ECM thickness. Additionally, an array of quantitative and qualitative investigations of IVD degeneration could be successfully evaluated using the given methodology, resin-embedded SEM in particular. SEM is especially practical for studying micromorphological changes in tissue, as other microscopy methods can cause artificial tissue damage due to the preparation method. Investigation of the microstructural changes occurring in degenerated tissue provides a greater understanding of the complex process of disc degeneration as a whole. Developing a more complete picture of the degenerative changes taking place in the intervertebral disc is crucial for the advancement and application of regenerative therapies based on the pathology of intervertebral disc degeneration. (C) 2016 Elsevier Ltd. All rights reserved.Peer reviewe

Volcanic and geochemical evolution of the Teno massif, Tenerife, Canary Islands: some repercussions of giant landslides on ocean island magmatism

Large-scale, catastrophic mass wasting is a major process contributing to the dismantling of oceanic intraplate volcanoes. Recent studies, however, have highlighted a possible feedback relationship between flank collapse, or incipient instability, and subsequent episodes of structural rearrangement and/or renewed volcano growth. The Teno massif, located in northwestern Tenerife (Canary Islands), is a deeply eroded Miocene shield volcano that was built in four major eruptive phases punctuated by two lateral collapses, each removing >20–25 km3 of the volcano's north flank. In this paper, we use detailed field observations and petrological and geochemical data to evaluate possible links between large-scale landslides and subsequent volcanism/magmatism during Teno's evolution. Inspection of key stratigraphic sequences reveals that steep angular unconformities, relics of paleolandslide scars, are marked by polymict breccias. Near their base, these deposits typically include abundant juvenile pyroclastic material, otherwise scarce in the region. While some of Teno's most evolved, low-density magmas were produced just before flank collapses, early postlandslide lava sequences are characterized by anomalously high proportions of dense ankaramite flows, extremely rich in clinopyroxene and olivine crystals. A detailed sampling profile shows transitions from low-Mg # lavas relatively rich in SiO2 to lavas with low silica content and comparatively high Mg # after both landslides. Long-term variations in Zr/Nb, normative nepheline, and La/Lu are coupled but do not show a systematic correlation with stratigraphic boundaries. We propose that whereas loading of the growing precollapse volcano promoted magma stagnation and differentiation, the successive giant landslides modified the shallow volcano-tectonic stress field at Teno, resulting in widespread pyroclastic eruptions and shallow magma reservoir drainage. This rapid unloading of several tens of km3 of near-surface rocks appears to have upset magma differentiation processes, while facilitating the remobilization and tapping of denser ankaramite magmas that were stored in the uppermost mantle. Degrees of mantle melting coincidently reached a maximum in the short time interval between the two landslides and declined shortly after, probably reflecting intrinsic plume processes rather than a collapse-induced influence on mantle melting. Our study of Teno volcano bears implications for other oceanic volcanoes where short-term compositional variations may also directly relate to major flank collapse events

Polyurethane scaffold with in situ swelling capacity for nucleus pulposus replacement

Nucleus pulposus (NP) replacement offers a minimally invasive alternative to spinal fusion or total disc replacement for the treatment of intervertebral disc (IVD) degeneration. This study aimed to develop a cytocompatible {NP} replacement material, which is feasible for non-invasive delivery and tunable design, and allows immediate mechanical restoration of the IVD. A bi-phasic polyurethane scaffold was fabricated consisting of a core material with rapid swelling property and a flexible electrospun envelope. The scaffold was assessed in a bovine whole {IVD} organ culture model under dynamic load for 14 days. Nucleotomy was achieved by incision through the endplate without damaging the annulus fibrosus. After implantation of the scaffold and in situ swelling, the dynamic compressive stiffness and disc height were restored immediately. The scaffold also showed favorable cytocompatibility for native disc cells. Implantation of the scaffold in a partially nucleotomized {IVD} down-regulated catabolic gene expression, increased proteoglycan and type {II} collagen intensity and decreased type I collagen intensity in remaining {NP} tissue, indicating potential to retard degeneration and preserve the {IVD} cell phenotype. The scaffold can be delivered in a minimally invasive manner, and the geometry of the scaffold post-hydration is tunable by adjusting the core material, which allows individualized design. Keywords : Intervertebral disc degeneratio

Detection of Greenhouse Gas Precursors from Diesel Engines Using Electrochemical and Photoacoustic Sensors

Atmospheric pollution is one of the worst threats to modern society. The consequences derived from different forms of atmospheric pollution vary from the local to the global scale, with deep impacts on climate, environment and human health. Several gaseous pollutants, even when present in trace concentrations, play a fundamental role in important processes that occur in atmosphere. Phenomena such as global warming, photochemical smog formation, acid rain and the depletion of the stratospheric ozone layer are strongly related to the increased concentration of certain gaseous species in the atmosphere. The transport sector significantly produces atmospheric pollution, mainly when diesel oil is used as fuel. Therefore, new methodologies based on selective and sensitive gas detection schemes must be developed in order to detect and monitor pollutant gases from this source. In this work, CO2 Laser Photoacoustic Spectroscopy was used to evaluate ethylene emissions and electrochemical analyzers were used to evaluate the emissions of CO, NOx and SO2 from the exhaust of diesel powered vehicles (rural diesel with 5% of biodiesel, in this paper called only diesel) at different engine rotation speeds. Concentrations in the range 6 to 45 ppmV for ethylene, 109 to 1,231 ppmV for carbon monoxide, 75 to 868 ppmV for nitrogen oxides and 3 to 354 ppmV for sulfur dioxide were obtained. The results indicate that the detection techniques used were sufficiently selective and sensitive to detect the gaseous species mentioned above in the ppmV range