Methylotrophic methanogenesis is often proposed to be responsible for methane production in sulfate-rich environments, yet the magnitude of this process remains elusive. In this study, we incubated ...sediment from Aarhus Bay (Denmark) with 13C labeled CH₄ to measure total methane turnover by isotope dilution, and with 14C-radiotracers to measure specifically the gross hydrogenotrophic and acetoclastic methane production. Highest CH₄ production rates (> 200 pmol cm-3 d-1) were found in the top 0–2 cm. Most of this production was via methylotrophic pathways. Methanogenesis via the hydrogenotrophic pathway accounted for less than 20 pmol cm-3 d-1 throughout the surface sediment (0–10 cm), and there was no apparent contribution from acetoclastic methanogenesis. To further assess potentials for methanogenesis from hydrogen, acetate, or trimethylamine (TMA), sediment slurry incuabtions with excess substrate addition were performed. A high and accelarating CH₄ production was only detected in incubations amended with TMA. Our results show that methylotrophic methanogenesis dominated the CH₄ production in these sulfate-rich marine surface sediments.
Summary
Cable bacteria have been reported in sediments from marine and freshwater locations, but the environmental factors that regulate their growth in natural settings are not well understood. Most ...prominently, the physiological limit of cable bacteria in terms of oxygen availability remains poorly constrained. In this study, we investigated the presence, activity and diversity of cable bacteria in relation to a natural gradient in bottom water oxygenation in a depth transect of the Eastern Gotland Basin (Baltic Sea). Cable bacteria were identified by FISH at the oxic and transiently oxic sites, but not at the permanently anoxic site. Three species of the candidate genus Electrothrix, i.e. marina, aarhusiensis and communis were found coexisting within one site. The highest filament density (33 m cm−2) was associated with a 6.3 mm wide zone depleted in both oxygen and free sulphide, and the presence of an electric field resulting from the electrogenic sulphur oxidizing metabolism of cable bacteria. However, the measured filament densities and metabolic activities remained low overall, suggesting a limited impact of cable bacteria at the basin level. The observed bottom water oxygen levels (< 5 μM) are the lowest so far reported for cable bacteria, thus expanding their known environmental distribution.
BACKGROUND AND PURPOSE—Loss of cerebral autoregulation in the acute phase of ischemic stroke leaves patients vulnerable to blood pressure (BP) changes. Effective BP management after endovascular ...thrombectomy may protect the brain from hypoperfusion or hyperperfusion. In this observational study, we compared personalized, autoregulation-based BP targets to static systolic BP thresholds.
METHODS—We prospectively enrolled 90 patients undergoing endovascular thrombectomy for stroke. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy–derived tissue oxygenation (a cerebral blood flow surrogate) in response to changes in mean arterial pressure. The resulting autoregulatory index was used to trend the BP range at which autoregulation was most preserved. Percent time that mean arterial pressure exceeded the upper limit of autoregulation or decreased below the lower limit of autoregulation was calculated for each patient. Time above fixed systolic BP thresholds was computed in a similar fashion. Functional outcome was measured with the modified Rankin Scale at 90 days.
RESULTS—Personalized limits of autoregulation were successfully computed in all 90 patients (age 71.6±16.2, 47% female, mean National Institutes of Health Stroke Scale 13.9±5.7, monitoring time 28.0±18.4 hours). Percent time with mean arterial pressure above the upper limit of autoregulation associated with worse 90-day outcomes (odds ratio per 10% 1.84 95% CI, 1.3–2.7 P=0.002), and patients with hemorrhagic transformation spent more time above the upper limit of autoregulation (10.9% versus 16.0%, P=0.042). Although there appeared to be a nonsignificant trend towards worse outcome with increasing time above systolic BP thresholds of 140 mm Hg and 160 mm Hg, the effect sizes were smaller compared with the personalized approach.
CONCLUSIONS—Noninvasive determination of personalized BP thresholds for stroke patients is feasible. Deviation from these limits may increase risk of further brain injury and poor functional outcome. This approach may present a better strategy compared with the classical approach of maintaining systolic BP below a predetermined value, though a randomized trial is needed to determine the optimal approach for hemodynamic management.
BACKGROUND AND PURPOSE—Optimal blood pressure (BP) management during the early stages of aneurysmal subarachnoid hemorrhage remains uncertain. Observational studies have found worse outcomes in ...patients with increased hemodynamic variability, suggesting BP optimization as a potential neuroprotective strategy. In this study, we calculated personalized BP targets at which cerebral autoregulation was best preserved. We analyzed how deviation from these limits correlates with functional outcome.
METHODS—We prospectively enrolled 31 patients with aneurysmal subarachnoid hemorrhage. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy (NIRS)-derived tissue oxygenation—a surrogate for cerebral blood flow—as well as intracranial pressure (ICP) in response to changes in mean arterial pressure using time-correlation analysis. The resulting autoregulatory indices were used to identify the upper and lower limit of autoregulation. Percent time that mean arterial pressure exceeded limits of autoregulation was calculated for each patient. Functional outcome was assessed using the modified Rankin Scale at discharge and 90 days. Associations with outcome were analyzed using ordinal multivariate logistic regression.
RESULTS—Personalized limits of autoregulation were computed in all patients (age 57.5±13.4, 23F, mean World Federation of Neurological Surgeons 2±1, monitoring time 67.8±50.8 hours). Optimal BP and limits of autoregulation were calculated on average for 89.5±6.7% of the total monitoring period. ICP- and NIRS-derived optimal pressures strongly correlated with one another (P<0.0001). Percent time that mean arterial pressure deviated from limits of autoregulation significantly associated with worse functional outcome at discharge (NIRS, P=0.001; ICP, P=0.004) and 90 days (NIRS, P=0.002; ICP, P=0.003), adjusting separately for age, World Federation of Neurological Surgeons, vasospasm, and delayed cerebral ischemia.
CONCLUSIONS—Both invasive (ICP) and noninvasive (NIRS) determination of personalized BP targets after aneurysmal subarachnoid hemorrhage is feasible, and these 2 approaches revealed significant collinearity. Furthermore, exceeding individualized limits of autoregulation was associated with poor functional outcomes.
Reported associations between air pollution and pulmonary and cardiovascular diseases prompted studies on the effects of gold nanoparticles (Au NP) on pulmonary surfactant function. Low levels ...(3.7mol % Au/lipid, 0.98% wt/wt) markedly inhibited adsorption of a semisynthetic pulmonary surfactant (dipalmitoyl-phosphatidylcholine (DPPC)/palmitoyl-oleoyl-phosphatidylglycerol/surfactant protein B (SP-B); 70:30:1wt %). Au NP also impeded the surfactant's ability to reduce surface tension (γ) to low levels during film compression and to respread during film expansion. Transmission electron microscopy showed that Au NP generated by a seed-growth method were spherical with diameters of ∼15nm. Including palmitoyl-oleoyl-phosphatidylglycerol appeared to coat the NP with at least one lipid bilayer but did not affect NP shape or size. Similar overall observations occurred with dimyristoyl phosphatidylglycerol. Dipalmitoyl-phosphatidylglycerol was less effective in NP capping, although similar sized NP were formed. Including SP-B (1% wt/wt) appears to induce the formation of elongated strands of interacting threads with the fluid phosphatidylglycerols (PG). Including DPPC resulted in formation of aggregated, less spherical NP with a larger size distribution. With DPPC, strand formation due to SP-B was not observed. Agarose gel electrophoresis studies demonstrated that the aggregation induced by SP-B blocked migration of PG-coated NP. Migration was also influenced by the fluidity of the PGs. It is concluded that Au NP can interact with and sequester pulmonary surfactant phospholipids and, if inhaled from the atmosphere, could impede pulmonary surfactant function in the lung.
Hemorrhagic transformation remains a potentially catastrophic complication of reperfusion therapies for the treatment of large-vessel occlusion ischemic stroke. Observational studies have found an ...increased risk of hemorrhagic transformation in patients with elevated blood pressure as well as a high degree of blood pressure variability, suggesting a link between hemodynamics and hemorrhagic transformation. Current society-endorsed guidelines recommend maintaining blood pressure below a fixed threshold of 180/105 mmHg regardless of thrombolytic or endovascular intervention. However, given the high recanalization rates with mechanical thrombectomy, it is unclear if the same hemodynamic goals from the pre-thrombectomy era apply. Also, individual patient factors such as the degree of reperfusion, infarct size, and collateral status likely need to be considered. In this review, we will discuss current evidence linking hemodynamics to hemorrhagic transformation after mechanical thrombectomy. In addition, we will review the clinical relevance of cerebral autoregulation in stroke, highlighting recent studies that have harnessed autoregulatory physiology to define and trend individualized limits of autoregulation. This review will go on to emphasize the translatability of this approach to stroke management. Finally, we will discuss novel statistical approaches like trajectory analysis to post-thrombectomy hemodynamics.
Gold nanoparticles (GNPs) have been applied as diagnostic and therapeutic agents because they can be targeted, localized, and be heated to cause cell death. However, their use has been limited by ...their relatively low biocompatibility. In this work, we coated the GNPs' surface by a biocompatible phospholipid bilayer composed of 1-stearoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (SOPG). We tested their interaction with A549 cells to investigate their uptake and intracellular fate as well as the response of the cells to the presence of the GNPs. We used flow cytometry and confocal microscopy to show that the SOPG coated GNPs were readily taken up by the A549 cells. Transmission electron microscopy (TEM) images and fluorescence images further showed that the number of granular structures in the cells was increased following exposure to the lipid coated GNPs. Co-localization experiments demonstrated that SOPG coated GNPs localize in acidic compartments in a time dependent manner and that the number of these increase as the cells are exposed to the GNPs suggesting that they induce formation of lamellar bodies (LBs) which in A549 cells in turn can serve as a means of exporting the GNPs.
Display omitted
► Lipid coated gold nanoparticles are readily taken up by A549 cells. ► The lipid coated gold nanoparticles exclusively locate in the acidic compartments of A549 cells. ► The lipid coated gold nanoparticles promote the formation of lamellar bodies (LBs) in A549 cells.
Interactions of monomeric alpha-synuclein (αS) with lipid membranes have been suggested to play an important role in initiating aggregation of αS. We have systematically analyzed the distribution and ...self-assembly of monomeric αS on supported lipid bilayers. We observe that at protein/lipid ratios higher than 1:10, αS forms micrometer-sized clusters, leading to observable membrane defects and decrease in lateral diffusion of both lipids and proteins. An αS deletion mutant lacking amino-acid residues 71–82 binds to membranes, but does not observably affect membrane integrity. Although this deletion mutant cannot form amyloid, significant amyloid formation is observed in the wild-type αS clusters. These results suggest that the process of amyloid formation, rather than binding of αS on membranes, is crucial in compromising membrane integrity.
BACKGROUND:Anecdotal reports suggest fewer patients with stroke symptoms are presenting to hospitals during the coronavirus disease 2019 (COVID-19) pandemic. We quantify trends in stroke code calls ...and treatments at 3 Connecticut hospitals during the local emergence of COVID-19 and examine patient characteristics and stroke process measures at a Comprehensive Stroke Center (CSC) before and during the pandemic.
METHODS:Stroke code activity was analyzed from January 1 to April 28, 2020, and corresponding dates in 2019. Piecewise linear regression and spline models identified when stroke codes in 2020 began to decline and when they fell below 2019 levels. Patient-level data were analyzed in February versus March and April 2020 at the CSC to identify differences in patient characteristics during the pandemic.
RESULTS:A total of 822 stroke codes were activated at 3 hospitals from January 1 to April 28, 2020. The number of stroke codes/wk decreased by 12.8/wk from February 18 to March 16 (P=0.0360) with nadir of 39.6% of expected stroke codes called from March 10 to 16 (30% decrease in total stroke codes during the pandemic weeks in 2020 versus 2019). There was no commensurate increase in within-network telestroke utilization. Compared with before the pandemic (n=167), pandemic-epoch stroke code patients at the CSC (n=211) were more likely to have histories of hypertension, dyslipidemia, coronary artery disease, and substance abuse; no or public health insurance; lower median household income; and to live in the CSC city (P<0.05). There was no difference in age, sex, race/ethnicity, stroke severity, time to presentation, door-to-needle/door-to-reperfusion times, or discharge modified Rankin Scale.
CONCLUSIONS:Hospital presentation for stroke-like symptoms decreased during the COVID-19 pandemic, without differences in stroke severity or early outcomes. Individuals living outside of the CSC city were less likely to present for stroke codes at the CSC during the pandemic. Public health initiatives to increase awareness of presenting for non-COVID-19 medical emergencies such as stroke during the pandemic are critical.
PDF
