Stress can exert long-lasting changes on the brain that contribute to vulnerability to mental illness, yet mechanisms underlying this long-term vulnerability are not well understood. We hypothesized ...that stress may alter the production of oligodendrocytes in the adult brain, providing a cellular and structural basis for stress-related disorders. We found that immobilization stress decreased neurogenesis and increased oligodendrogenesis in the dentate gyrus (DG) of the adult rat hippocampus and that injections of the rat glucocorticoid stress hormone corticosterone (cort) were sufficient to replicate this effect. The DG contains a unique population of multipotent neural stem cells (NSCs) that give rise to adult newborn neurons, but oligodendrogenic potential has not been demonstrated in vivo. We used a nestin-CreER/YFP transgenic mouse line for lineage tracing and found that cort induces oligodendrogenesis from nestin-expressing NSCs in vivo. Using hippocampal NSCs cultured in vitro, we further showed that exposure to cort induced a pro-oligodendrogenic transcriptional program and resulted in an increase in oligodendrogenesis and decrease in neurogenesis, which was prevented by genetic blockade of glucocorticoid receptor (GR). Together, these results suggest a novel model in which stress may alter hippocampal function by promoting oligodendrogenesis, thereby altering the cellular composition and white matter structure.
Pump thrombosis remains an uncommon but potentially catastrophic complication of durable continuous-flow left ventricular assist devices (LVAD). A perceived increase in the incidence of pump ...thrombosis in the HeartMate II (HMII) LVAD (Thoratec, Pleasanton, CA) by clinicians prompted this analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database.
Between 2006 and June 2013, 8,988 United States patients aged older than 18 years received a durable LVAD. Of these, 6,910 adult patients from 132 institutions who received a HMII LVAD were entered in the INTERMACS database and constitute the study group for this analysis.
Overall survival (with censoring at transplant or explant for recovery) with the HMII LVAD was 80% at 1 year and 69% at 2 years and was not significantly different when stratified by era of implant. Freedom from device exchange or death due to thrombosis decreased from 99% at 6 months in 2009 to 94% in 2012 (p < 0.0001). Multivariable hazard function analysis showed risk factors for pump thrombosis included later implant year (p < 0.0001), younger age (p < 0.0001), higher creatinine (p = 0.002), larger body mass index (p = 0.004), white race (p = 0.0004), left ventricular ejection fraction above 20% (p = 0.02), and higher lactate dehydrogenase level at 1 month (p < 0.0001). Survival (p < 0.0001) and freedom from infection (p = 0.008) and cerebrovascular accident (p < 0.0001) were lower after pump exchange than after primary implant.
Pump exchange or death due to pump thrombosis increased during 2011 and 2012, but the magnitude of the increase remained relatively small. Survival remains high (80% at 1 year) with the HMII LVAD. Risk factor analysis suggests that a number of patient-related factors contribute to the risk of thrombosis. Markedly elevated lactate dehydrogenase in the first month is a predictor of pump thrombosis. This analysis could not examine the potential role of technical factors during implant, such as sub-optimal pump or graft positioning, changes in patient management paradigms with pump speed settings, improved recognition and change in the threshold for pump exchange, or design or production changes with the pump, as contributors to the risk of pump thrombosis.
Over the past 50 years, different strategies have been developed for the remediation of polluted air, land and water. Driven by public opinion and regulatory bottlenecks, ecological based strategies ...are preferable than conventional methods in the treatments of chemical effluents. Ecological systems with the application of microbes, fungi, earthworms, plants, enzymes, electrode and nanoparticles have been applied to varying degrees in different media for the remediation of various categories of pollutants. Aquatic macrophytes have been used extensively for the remediation of pollutants in wastewater effluents and aquatic environment over the past 30 years with the common duckweed (L. minor) as one of the most effective macrophytes that have been applied for remediation studies. Duckweed has shown strong potentials for the phytoremediation of organic pollutants, heavy metals, agrochemicals, pharmaceuticals and personal care products, radioactive waste, nanomaterials, petroleum hydrocarbons, dyes, toxins, and related pollutants. This review covers the state of duckweed application for the remediation of diverse aquatic pollutants and identifies gaps that are necessary for further studies as we find pragmatic and sound ecological solutions for the remediation of polluted environment for sustainable development.
•Several tonnes of chemicals are produced annually from the global chemical industry.•Many of these chemicals are released into the environment after their domestic or industrial application.•These chemicals are difficult to remediate using conventional wastewater treatment methods.•Lemna minor is an effective macrophyte for the treatment of chemicals in the environment using constructed wetlands.
The field of mechanical circulatory support has been impacted by the approval of new continuous-flow left ventricular assist devices (LVADs) and changes to the United States heart allocation system.
...Primary isolated continuous-flow LVAD implants in The Society of Thoracic Surgeons Intermacs registry from January 2014 through September 2019 were evaluated. Survival and freedom from major adverse events were compared between axial-flow, centrifugal-flow with hybrid levitation (CF-HL), and centrifugal-flow with full magnetic levitation (CF-FML) devices.
Of 2603 devices implanted in 2014, 1824 (70.1%) were axial flow and 1213 (46.6%) were destination therapy (DT); through September 2019, 1752 devices were implanted, but only 37 (2.1%) were axial flow and 1230 (70.2%) were DT. Implants were performed in 13,016 patients between 2014 and 2018. Patients receiving implants in 2017-2018 compared with 2014-2016 were more likely to be at Intermacs profile 1 (17.1% vs 14.3%, P < .001) and to have preimplant temporary mechanical circulatory support (34.8% vs 29.3%, P < .001). Overall survival and freedom from major adverse events were higher with CF-FML devices. In multivariable analysis of survival between CF-HL and CF-FML, device type was not a significant early hazard, but the use of CF-HL devices had a late hazard ratio for death of 3.01 (P < .001).
Over the past 5 years, centrifugal-flow LVADs have become the dominant technology and DT the most common implant strategy. While outcomes with CF-FML devices are promising, comparisons with other devices from nonrandomized registry studies should be made with caution.
Pump thrombosis in durable continuous-flow pumps is a barrier to long-term mechanical circulatory support. Earlier Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) data ...identified an increasing risk of pump thrombosis in recent years with the HeartMate II (HMII) left ventricular assist device. The current analysis examines pump thrombosis in the patient cohort extended through June 2014.
The INTERMACS identified 9,808 adult patients from 144 institutions receiving a primary HMII implant between April 2008 and June 30, 2014. Pump thrombosis was identified at time of explant, transplant or death. Risk factors for pump thrombosis were examined by multivariable analysis in the hazard function domain. The association between pump thrombosis and implant year was modeled in the hazard domain.
Parametric hazard modeling of thrombosis by year of implant identified an increasing risk of pump thrombosis from 2009 through 2013, followed by a decrease in the risk during the first half of 2014, which was most apparent during the first 3 months post-implant. Risk factors for pump thrombosis included younger age (p < 0.001), higher body mass index (p = 0.02), history of non-compliance (p = 0.004), severe right heart failure (p = 0.02), later date of implant (p < 0.0001), and elevated lactate dehydrogenase during the first month post-implant (p < 0.0001). Subsequent pump thrombosis was more likely if the initial pump exchange indication was pump thrombosis (p < 0.0001).
The small, but progressive increase in the incidence of pump thrombosis observed between 2010 and 2013 with the HMII pump had reversed somewhat in the first half of 2014. Identification of marked elevation of lactate dehydrogenase during the first month offers an opportunity for early intervention strategies.
Continuous-flow left ventricular assist systems increase the rate of survival among patients with advanced heart failure but are associated with the development of pump thrombosis. We investigated ...the effects of a new magnetically levitated centrifugal continuous-flow pump that was engineered to avert thrombosis.
We randomly assigned patients with advanced heart failure to receive either the new centrifugal continuous-flow pump or a commercially available axial continuous-flow pump. Patients could be enrolled irrespective of the intended goal of pump support (bridge to transplantation or destination therapy). The primary end point was a composite of survival free of disabling stroke (with disabling stroke indicated by a modified Rankin score >3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove the device at 6 months after implantation. The trial was powered for noninferiority testing of the primary end point (noninferiority margin, -10 percentage points).
Of 294 patients, 152 were assigned to the centrifugal-flow pump group and 142 to the axial-flow pump group. In the intention-to-treat population, the primary end point occurred in 131 patients (86.2%) in the centrifugal-flow pump group and in 109 (76.8%) in the axial-flow pump group (absolute difference, 9.4 percentage points; 95% lower confidence boundary, -2.1 P<0.001 for noninferiority; hazard ratio, 0.55; 95% confidence interval CI, 0.32 to 0.95 two-tailed P=0.04 for superiority). There were no significant between-group differences in the rates of death or disabling stroke, but reoperation for pump malfunction was less frequent in the centrifugal-flow pump group than in the axial-flow pump group (1 0.7% vs. 11 7.7%; hazard ratio, 0.08; 95% CI, 0.01 to 0.60; P=0.002). Suspected or confirmed pump thrombosis occurred in no patients in the centrifugal-flow pump group and in 14 patients (10.1%) in the axial-flow pump group.
Among patients with advanced heart failure, implantation of a fully magnetically levitated centrifugal-flow pump was associated with better outcomes at 6 months than was implantation of an axial-flow pump, primarily because of the lower rate of reoperation for pump malfunction. (Funded by St. Jude Medical; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755 .).
The Fourth Annual Report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes and analyzes the first 5 years of patient and data collection. With more than ...4,000 patients entered into the database, the evolution of pump technology, strategy at implant, and pre-implant patient profiles are chronicled. A risk factor analysis of the entire adult primary implant population is provided, and the recent composition of patient profiles is examined. Current actuarial survival with continuous-flow pumps exceeds 80% at 1 year and 70% at 2 years.
In this study, we use the approach of geospatial and temporal (GeoST) mapping of urban mobility to evaluate the speed-time-acceleration profile (dynamic status) of passenger cars. We then use a ...pre-developed model, fleet composition and real-world emission factor (EF) datasets to translate vehicles dynamics status into real-urban fuel consumption (FC) and exhaustive (CO2 and NOx) emissions with high spatial (15 m) and temporal (2 h) resolutions. Road transport in the West Midlands, UK, for 2016 and 2018 is the spatial and temporal scope of this study. Our approach enables the analysis of the influence of factors such as road slope, non-rush/rush hour and weed days/weekends effects on the characteristics of the transport environment. The results show that real-urban NOx EFs reduced by more than 14 % for 2016–18. This can be attributed to the increasing contribution of Euro 6 vehicles by 63 %, and the increasing contribution of diesel vehicles by 13 %. However, the variations in the real-urban FC and CO2 EFs are less significant (±2 %). We found that the FC estimated for driving under the NEDC (National European Driving Cycle) is a qualified benchmark for evaluating real-urban FCs. Considering the role of road slope increases the estimated real-urban FC, and NOx, and CO2 EFs by a weighted average of 4.8 %, 3.9 %, and 3.0 %, respectively. Time of travel (non-rush/rush hour or weed days/weekends) has a profound effect on vehicle fuel consumption and related emissions, with EFs increasing in more free-flowing conditions.
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•We use GeoSTMUM here to estimate vehicle dynamics with high spatiotemporal resolution.•Telematics data were collected from the West Midlands in the UK for 2016 and 2018.•Real-urban FC and EFs are estimated by vehicle dynamics and real-world measurements.•Fleet renovation reduces real-urban NOx EFs by over 14 % for the studied period.•Road slope has an increasing impact of 2–5 % on the estimated real-urban FC and EFs.
Anthropogenic noise is a pervasive pollutant that decreases environmental quality by disrupting a suite of behaviors vital to perception and communication. However, even within populations of ...noise-sensitive species, individuals still select breeding sites located within areas exposed to high noise levels, with largely unknown physiological and fitness consequences. We use a study system in the natural gas fields of northern New Mexico to test the prediction that exposure to noise causes glucocorticoid-signaling dysfunction and decreases fitness in a community of secondary cavity-nesting birds. In accordance with these predictions, and across all species, we find strong support for noise exposure decreasing baseline corticosterone in adults and nestlings and, conversely, increasing acute stressor-induced corticosterone in nestlings. We also document fitness consequences with increased noise in the form of reduced hatching success in the western bluebird (Sialia mexicana), the species most likely to nest in noisiest environments. Nestlings of all three species exhibited accelerated growth of both feathers and body size at intermediate noise amplitudes compared with lower or higher amplitudes. Our results are consistent with recent experimental laboratory studies and show that noise functions as a chronic, inescapable stressor. Anthropogenic noise likely impairs environmental risk perception by species relying on acoustic cues and ultimately leads to impacts on fitness. Our work, when taken together with recent efforts to document noise across the landscape, implies potential wide-spread, noise-induced chronic stress coupled with reduced fitness for many species reliant on acoustic cues.
Abstract Optimal healing of damaged tissue following myocardial infarction (MI) requires a coordinated cellular response that can be divided into three phases: inflammatory, proliferative/reparative, ...and maturation. The inflammatory phase, characterized by rapid influx of cytokines, chemokines, and immune cells, is critical to the removal of damaged tissue. The onset of the proliferative/reparative phase is marked by increased proliferation of myofibroblasts and secretion of collagen to replace dead tissue. Lastly, crosslinking of collagen fibers and apoptosis of immune cells marks the maturation phase. Excessive inflammation or fibrosis has been linked to increased incidence of arrhythmia and other MI-related pathologies. This review describes the roles of inflammation and fibrosis in arrhythmogenesis and prospective therapies for anti-arrhythmic treatment.
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