156 research outputs found
Pulmonary Hypertension in Patients with Chronic Fibrosing Idiopathic Interstitial Pneumonias
Background Pulmonary hypertension (PH) is a common finding in patients with chronic fibrosing idiopathic interstitial pneumonias (IIP). Little is known about the response to pulmonary vasodilator therapy in this patient population. COMPERA is an international registry that prospectively captures data from patients with various forms of PH receiving pulmonary vasodilator therapies. Methods We retrieved data from COMPERA to compare patient characteristics, treatment patterns, response to therapy and survival in newly diagnosed patients with idiopathic pulmonary arterial hypertension (IPAH) and PH associated with IIP (PH-IIP). Results Compared to patients with IPAH (n = 798), patients with PH-IIP (n = 151) were older and predominantly males. Patients with PH-IIP were treated predominantly with phosphodiesterase-5 inhibitors (88% at entry, 87% after 1 year). From baseline to the first follow-up visit, the median improvement in 6MWD was 30 m in patients with IPAH and 24.5 m in patients with PH-IIP (p = 0.457 for the difference between both groups). Improvements in NYHA functional class were observed in 22.4% and 29.5% of these patients, respectively (p = 0.179 for the difference between both groups). Survival rates were significantly worse in PH-IIP than in IPAH (3-year survival 34.0 versus 68.6%; p<0.001). Total lung capacity, NYHA class IV, and mixed-venous oxygen saturation were independent predictors of survival in patients with PH-IIP. Conclusions Patients with PH-IIP have a dismal prognosis. Our results suggest that pulmonary vasodilator therapy may be associated with short-term functional improvement in some of these patients but it is unclear whether this treatment affects survival
Assessing Pulmonary Perfusion in Emphysema Automated Quantification of Perfused Blood Volume in Dual-Energy CTPA
Objectives: The objective of this study was to determine whether automated quantification of lung perfused blood volume (PBV) in dual-energy computed tomographic pulmonary angiography (DE-CTPA) can be used to assess the severity and regional distribution of pulmonary hypoperfusion in emphysema. Materials and Methods: We retrospectively analyzed 40 consecutive patients (mean age, 67 13] years) with pulmonary emphysema, who have no cardiopulmonary comorbidities, and a DE-CTPA negative for pulmonary embolism. Automated quantification of global and regional pulmonary PBV was performed using the syngo Dual Energy application (Siemens Healthcare). Similarly, the global and regional degrees of parenchymal hypodensity were assessed automatically as the percentage of voxels with a computed tomographic density less than -900 Hounsfield unit. Emphysema severity was rated visually, and pulmonary function tests were obtained by chart review, if available. Results: Global PBV generated by automated quantification of pulmonary PBV in the DE-CTPA data sets showed a moderately strong but highly significant negative correlation with residual volume in percentage of the predicted residual volume (r = -0.62; P = 0.002; n = 23) and a positive correlation with forced expiratory volume in 1 second in percentage of the predicted forced expiratory volume in 1 second (r = 0.67; P < 0.001; n = 23). Global PBV values strongly correlated with diffusing lung capacity for carbon monoxide (r = 0.80; P < 0.001; n = 15). Pulmonary PBV values decreased with visual emphysema severity (r = -0.46, P = 0.003, n = 40). Moderate negative correlations were found between global PBV values and parenchymal hypodensity both in a per-patient (r = -0.63; P G 0.001; n = 40) and per-region analyses (r = -0.62; P < 0.001; n = 40). Conclusions: Dual-energy computed tomographic pulmonary angiography allows simultaneous assessment of lung morphology, parenchymal density, and pulmonary PBV. In patients with pulmonary emphysema, automated quantification of pulmonary PBV in DE-CTPA can be used for a quick, reader-independent estimation of global and regional pulmonary perfusion, which correlates with several lung function parameters
Evidence of two-electron tunneling interference in Nb/InAs junctions
The impact of junction transparency in driving phase-coherent charge transfer
across diffusive semiconductor-superconductor junctions is demonstrated. We
present conductivity data for a set of Nb-InAs junctions differing only in
interface transparency. Our experimental findings are analyzed within the
quasi-classical Green-function approach and unambiguously show the physical
processes giving rise to the observed excess zero-bias conductivity.Comment: 10 pages (RevTex), 4 figures (PostScript), accepted for pubblication
in Physical Review
Causes and Risk Factors for Absenteeism among Medical Staff in German Specialized Lung Clinics during the COVID Pandemic
Nonequilibrium Josephson effect in mesoscopic ballistic multiterminal SNS junctions
We present a detailed study of nonequilibrium Josephson currents and
conductance in ballistic multiterminal SNS-devices. Nonequilibrium is created
by means of quasiparticle injection from a normal reservoir connected to the
normal part of the junction. By applying a voltage at the normal reservoir the
Josephson current can be suppressed or the direction of the current can be
reversed. For a junction longer than the thermal length, , the
nonequilibrium current increases linearly with applied voltage, saturating at a
value equal to the equilibrium current of a short junction. The conductance
exhibits a finite bias anomaly around . For symmetric
injection, the conductance oscillates -periodically with the phase
difference between the superconductors, with position of the minimum
( or ) dependent on applied voltage and temperature. For
asymmetric injection, both the nonequilibrium Josephson current and the
conductance becomes -periodic in phase difference. Inclusion of barriers
at the NS-interfaces gives rise to a resonant behavior of the total Josephson
current with respect to junction length with a period . Both
three and four terminal junctions are studied.Comment: 21 pages, 19 figures, submitted to Phys. Rev.
Chronic thromboembolic pulmonary hypertension and impairment after pulmonary embolism: the FOCUS study
AIMS: To systematically assess late outcomes of acute pulmonary embolism (PE) and to investigate the clinical implications of post-PE impairment (PPEI) fulfilling prospectively defined criteria.
METHODS AND RESULTS: A prospective multicentre observational cohort study was conducted in 17 large-volume centres across Germany. Adult consecutive patients with confirmed acute symptomatic PE were followed with a standardized assessment plan and pre-defined visits at 3, 12, and 24 months. The co-primary outcomes were (i) diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH), and (ii) PPEI, a combination of persistent or worsening clinical, functional, biochemical, and imaging parameters during follow-up. A total of 1017 patients (45% women, median age 64 years) were included in the primary analysis. They were followed for a median duration of 732 days after PE diagnosis. The CTEPH was diagnosed in 16 (1.6%) patients, after a median of 129 days; the estimated 2-year cumulative incidence was 2.3% (1.2-4.4%). Overall, 880 patients were evaluable for PPEI; the 2-year cumulative incidence was 16.0% (95% confidence interval 12.8-20.8%). The PPEI helped to identify 15 of the 16 patients diagnosed with CTEPH during follow-up (hazard ratio for CTEPH vs. no CTEPH 393; 95% confidence interval 73-2119). Patients with PPEI had a higher risk of re-hospitalization and death as well as worse quality of life compared with those without PPEI.
CONCLUSION: In this prospective study, the cumulative 2-year incidence of CTEPH was 2.3%, but PPEI diagnosed by standardized criteria was frequent. Our findings support systematic follow-up of patients after acute PE and may help to optimize guideline recommendations and algorithms for post-PE care
A review of bronchiolitis obliterans syndrome and therapeutic strategies
Lung transplantation is an important treatment option for patients with advanced lung disease. Survival rates for lung transplant recipients have improved; however, the major obstacle limiting better survival is bronchiolitis obliterans syndrome (BOS). In the last decade, survival after lung retransplantation has improved for transplant recipients with BOS. This manuscript reviews BOS along with the current therapeutic strategies, including recent outcomes for lung retransplantation
The surfactant protein C mutation A116D alters cellular processing, stress tolerance, surfactant lipid composition, and immune cell activation
<p>Abstract</p> <p>Background</p> <p>Surfactant protein C (SP-C) is important for the function of pulmonary surfactant. Heterozygous mutations in <it>SFTPC</it>, the gene encoding SP-C, cause sporadic and familial interstitial lung disease (ILD) in children and adults. Mutations mapping to the BRICHOS domain located within the SP-C proprotein result in perinuclear aggregation of the proprotein. In this study, we investigated the effects of the mutation A116D in the BRICHOS domain of SP-C on cellular homeostasis. We also evaluated the ability of drugs currently used in ILD therapy to counteract these effects.</p> <p>Methods</p> <p>SP-C<sup>A116D </sup>was expressed in MLE-12 alveolar epithelial cells. We assessed in vitro the consequences for cellular homeostasis, immune response and effects of azathioprine, hydroxychloroquine, methylprednisolone and cyclophosphamide.</p> <p>Results</p> <p>Stable expression of SP-C<sup>A116D </sup>in MLE-12 alveolar epithelial cells resulted in increased intracellular accumulation of proSP-C processing intermediates. SP-C<sup>A116D </sup>expression further led to reduced cell viability and increased levels of the chaperones Hsp90, Hsp70, calreticulin and calnexin. Lipid analysis revealed decreased intracellular levels of phosphatidylcholine (PC) and increased lyso-PC levels. Treatment with methylprednisolone or hydroxychloroquine partially restored these lipid alterations. Furthermore, SP-C<sup>A116D </sup>cells secreted soluble factors into the medium that modulated surface expression of CCR2 or CXCR1 receptors on CD4<sup>+ </sup>lymphocytes and neutrophils, suggesting a direct paracrine effect of SP-C<sup>A116D </sup>on neighboring cells in the alveolar space.</p> <p>Conclusions</p> <p>We show that the A116D mutation leads to impaired processing of proSP-C in alveolar epithelial cells, alters cell viability and lipid composition, and also activates cells of the immune system. In addition, we show that some of the effects of the mutation on cellular homeostasis can be antagonized by application of pharmaceuticals commonly applied in ILD therapy. Our findings shed new light on the pathomechanisms underlying SP-C deficiency associated ILD and provide insight into the mechanisms by which drugs currently used in ILD therapy act.</p
International collaborative follow - up investigation of graduating high school students’ understandings of the nature of scientific inquiry: is progress Being made?
Understandings of the nature of scientific inquiry (NOSI), as opposed to engaging students in inquiry learning experiences, are included in science education reform documents around the world. However, little is known about what students have learned about NOSI during their pre-college school years. The purpose of this large-scale follow-up international project (i.e. 32 countries and regions, spanning six continents and including 3917 students for the high school sample) was to collect data on what exiting high school students have learned about NOSI. Additionally, the study investigated changes in 12th grade students’ NOSI understandings compared to seventh grade (i.e. 20 countries and regions) students’ understandings from a prior investigation [Lederman et al. (2019). An international collaborative investigation of beginning seventh grade students’ understandings of scientific inquiry: Establishing a baseline. Journal of Research in Science Teaching, 56(4), 486–515. https://doi.org/10.1002/tea.21512]. This study documents and discusses graduating high school students’ understandings and compares their understandings to seventh grade students’ understandings of the same aspects of scientific inquiry for each country. It is important to note that collecting data from each of the 130+ countries globally was not feasible. Similarly, it was not possible to collect data from every region of each country. A concerted effort was made, however, to provide a relatively representative picture of each country and the world
SMC complexes differentially compact mitotic chromosomes according to genomic context
Structural maintenance of chromosomes (SMC) protein complexes are key determinants of chromosome conformation. Using Hi-C and polymer modelling, we study how cohesin and condensin, two deeply conserved SMC complexes, organize chromosomes in the budding yeast Saccharomyces cerevisiae. The canonical role of cohesin is to co-align sister chromatids, while condensin generally compacts mitotic chromosomes. We find strikingly different roles for the two complexes in budding yeast mitosis. First, cohesin is responsible for compacting mitotic chromosome arms, independently of sister chromatid cohesion. Polymer simulations demonstrate that this role can be fully accounted for through cis-looping of chromatin. Second, condensin is generally dispensable for compaction along chromosome arms. Instead, it plays a targeted role compacting the rDNA proximal regions and promoting resolution of peri-centromeric regions. Our results argue that the conserved mechanism of SMC complexes is to form chromatin loops and that distinct SMC-dependent looping activities are selectively deployed to appropriately compact chromosomes
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