Delayed cerebral ischemia (DCI) is the leading complication of subarachnoid hemorrhage (SAH). Because DCI was traditionally thought to be caused by large vessel vasospasm, transcranial Doppler ...ultrasounds (TCDs) have been the standard of care. Continuous EEG has emerged as a promising complementary monitoring modality and predicts increased DCI risk. Our objective was to determine whether combining EEG and TCD data improves prediction of DCI after SAH. We hypothesize that integrating these diagnostic modalities improves DCI prediction.
We retrospectively assessed patients with moderate to severe SAH (2011-2015; Fisher 3-4 or Hunt-Hess 4-5) who had both prospective TCD and EEG acquisition during hospitalization. Middle cerebral artery (MCA) peak systolic velocities (PSVs) and the presence or absence of epileptiform abnormalities (EAs), defined as seizures, epileptiform discharges, and rhythmic/periodic activity, were recorded daily. Logistic regressions were used to identify significant covariates of EAs and TCD to predict DCI. Group-based trajectory modeling (GBTM) was used to account for changes over time by identifying distinct group trajectories of MCA PSV and EAs associated with DCI risk.
We assessed 107 patients; DCI developed in 56 (51.9%). Univariate predictors of DCI are presence of high-MCA velocity (PSV ≥200 cm/s, sensitivity 27%, specificity 89%) and EAs (sensitivity 66%, specificity 62%) on or before day 3. Two univariate GBTM trajectories of EAs predicted DCI (sensitivity 64%, specificity 62.75%). Logistic regression and GBTM models using both TCD and EEG monitoring performed better. The best logistic regression and GBTM models used both TCD and EEG data, Hunt-Hess score at admission, and aneurysm treatment as predictors of DCI (logistic regression: sensitivity 90%, specificity 70%; GBTM: sensitivity 89%, specificity 67%).
EEG and TCD biomarkers combined provide the best prediction of DCI. The conjunction of clinical variables with the timing of EAs and high MCA velocities improved model performance. These results suggest that TCD and cEEG are promising complementary monitoring modalities for DCI prediction. Our model has potential to serve as a decision support tool in SAH management.
This study provides Class II evidence that combined TCD and EEG monitoring can identify delayed cerebral ischemia after SAH.
Laboratory and field studies have indicated that anaerobic ammonium oxidation (anammox) is an important process in the marine nitrogen cycle. In this study 11 additional anoxic marine sediment and ...water column samples were studied to substantiate this claim. In a combined approach using the molecular methods, polymerase chain reaction (PCR), qualitative and quantitative fluorescence in situ hybridization (FISH), as well as ¹⁵N stable isotope activity measurements, it was shown that anammox bacteria were present and active in all samples investigated. The anammox activity measured in the sediment samples ranged from 0.08 fmol cell⁻¹ day⁻¹ N₂ in the Golfo Dulce (Pacific Ocean, Costa Rica) sediment to 0.98 fmol cell⁻¹ day⁻¹ N₂ in the Gullmarsfjorden (North Sea, Sweden) sediment. The percentage of anammox cell of the total population (stained with DAPI) as assessed by quantitative FISH was highest in the Barents Sea (9% ± 4%) and in most of the samples well over 2%. Fluorescence in situ hybridization and phylogenetic analysis of the PCR products derived from the marine samples indicated the exclusive presence of members of the Candidatus'Scalindua' genus. This study showed the ubiquitous presence of anammox bacteria in anoxic marine ecosystems, supporting previous observations on the importance of anammox for N cycling in marine environments.
Surgical and catheter-based cardiovascular procedures and adjunctive pharmacology have an inherent risk of neurological complications. The current diversity of neurological endpoint definitions and ...ascertainment methods in clinical trials has led to uncertainties in the neurological risk attributable to cardiovascular procedures and inconsistent evaluation of therapies intended to prevent or mitigate neurological injury. Benefit-risk assessment of such procedures should be on the basis of an evaluation of well-defined neurological outcomes that are ascertained with consistent methods and capture the full spectrum of neurovascular injury and its clinical effect. The Neurologic Academic Research Consortium is an international collaboration intended to establish consensus on the definition, classification, and assessment of neurological endpoints applicable to clinical trials of a broad range of cardiovascular interventions. Systematic application of the proposed definitions and assessments will improve our ability to evaluate the risks of cardiovascular procedures and the safety and effectiveness of preventive therapies.
The NAST force field is a popular tool for modeling RNA and is typical of low-resolution approaches. Unfortunately, some combinations of bond and dihedral angles can reach cliffs on the energy ...landscape which lead to numerical disasters. We describe changes to the formulation (NAST improved, NASTI) which smooth the dihedral energy term when neighboring angles become flat. We also improved the fit to experimental structures by replacing the harmonic term for the backbone angles with spline functions and using a more sophisticated approach to calculate energies for fragments that span both helix and loop regions. A newer, larger set of structures was used for the parametrization. The new formulation can be run for millions of steps without a thermostat, whereas NAST routinely suffers numerical catastrophes. Simulations with NASTI showed no decrease in the quality of the structures as reflected by slightly better GDT-TS scores and, in three of the five cases, marginally better RMSD values when compared to the crystal structures.
Increased blood pressure variability (BPV) is linked to cardiovascular disease and mortality, yet few modifiable BPV risk factors are known. We aimed to assess the relationship between sleep quality ...and activity level on longitudinal BPV in a cohort of community-dwelling adults (age ≥18) from 17 countries. Using Withings home measurement devices, we examined sleep quality and physical activity over one year, operationalized as mean daily step count and number of sleep interruptions, both transformed into tertiles. The primary study outcome was high BPV, defined as the top tertile of systolic blood pressure standard deviation. Our cohort comprised 29,375 individuals (mean age = 58.6 years) with 127.8±90.1 mean days of measurements. After adjusting for age, gender, country, body mass index, measurement days, mean blood pressure, and total time in bed, the odds ratio of having high BPV for those in the top tertile of sleep interruptions (poor sleep) was 1.37 (95% CI, 1.28-1.47) and 1.44 (95% CI, 1.35-1.54) for those in the lowest tertile of step count (physically inactive). Combining these exposures revealed a significant excess relative risk of 0.20 (95% CI, 0.04-0.35, p = 0.012), confirming their super-additive effect. Comparing individuals with the worst exposure status (lowest step count and highest sleep interruptions, n = 2,690) to those with the most optimal status (highest step count and lowest sleep interruptions, n = 3,531) yielded an odds ratio of 2.01 (95% CI, 1.80-2.25) for high BPV. Our findings demonstrate that poor sleep quality and physical inactivity are associated with increased BPV both independently and super-additively.
Some bacteria are capable of extracellular electron transfer, thereby enabling them to use electron acceptors and donors without direct cell contact. Beyond the micrometre scale, however, no firm ...evidence has previously existed that spatially segregated biogeochemical processes can be coupled by electric currents in nature. Here we provide evidence that electric currents running through defaunated sediment couple oxygen consumption at the sediment surface to oxidation of hydrogen sulphide and organic carbon deep within the sediment. Altering the oxygen concentration in the sea water overlying the sediment resulted in a rapid (<1-h) change in the hydrogen sulphide concentration within the sediment more than 12 mm below the oxic zone, a change explicable by transmission of electrons but not by diffusion of molecules. Mass balances indicated that more than 40% of total oxygen consumption in the sediment was driven by electrons conducted from the anoxic zone. A distinct pH peak in the oxic zone could be explained by electrochemical oxygen reduction, but not by any conventional sets of aerobic sediment processes. We suggest that the electric current was conducted by bacterial nanowires combined with pyrite, soluble electron shuttles and outer-membrane cytochromes. Electrical communication between distant chemical and biological processes in nature adds a new dimension to our understanding of biogeochemistry and microbial ecology.
To test the hypothesis that admission hemoglobin levels are associated with outcome in primary, nontraumatic intracerebral hemorrhage.
Individual patient data meta-analysis of three studies of ...intracerebral hemorrhage.
Two randomized clinical trials and one multiethnic observational study.
Patients with spontaneous, nontraumatic intracerebral hemorrhage.
None.
Our exposure of interest was admission hemoglobin levels and the primary outcome was 3-month postintracerebral hemorrhage-dichotomized modified Rankin Scale (0-3 vs 4-6). Intermediate outcomes were admission hematoma volume and hematoma expansion defined as 6 mL or 33% increase in hemorrhage size on repeat CT. A total of 4,172 intracerebral hemorrhage patients were included in the study (mean age 63 sd = 14; female sex 1,668 40%). Each additional g/dL of admission hemoglobin was associated with 14% (odds ratio, 0.86; 95% CI, 0.82-0.91) and 7% (odds ratio, 0.93; 95% CI, 0.88-0.98) reductions in the risk of poor outcome in unadjusted and adjusted analyses, respectively. Dose-response analyses indicated a linear relationship between admission hemoglobin levels and poor outcome across the entire evaluated range (test-for-trend p < 0.001). No consistent associations were found between the admission hemoglobin levels and hematoma volume or hematoma expansion.
Higher hemoglobin levels are associated with better outcome in intracerebral hemorrhage. Further research is needed to evaluate admission hemoglobin levels as both a therapeutic target and predictor of outcome.
Pre-fibrillar oligomers of α-synuclein are thought to be pathogenic molecules leading to neurotoxicity associated with Parkinson's disease and other neurodegenerative disorders. However, small ...oligomers are difficult to isolate for study. To gain better insight into the properties of small α-synuclein oligomers, we investigated engineered oligomers of specific size (dimers, tetramers, and octamers) linked head-to-tail in tandem, comparing the behavior of the oligomers to monomeric α-synuclein. All oligomeric constructs remained largely disordered in solution, as determined from dynamic light scattering and size-exclusion chromatography. Electron microscopy revealed that each construct could aggregate to form fibrils similar to those formed by monomeric α-synuclein. The interactions with large unilamellar vesicles (LUVs) composed of negatively-charged lipids differed depending on size, with smaller oligomers forming more extensive helical structure as determined by CD spectroscopy. Monitoring the influx of a fluorescence bleaching agent into vesicles showed that larger oligomers were somewhat more effective at degrading vesicular integrity and inducing membrane permeabilization.
A transition toward sustainable bio-based chemical production is important for green growth. However, productivity and yield frequently decrease as large-scale microbial fermentation progresses, ...commonly ascribed to phenotypic variation. Yet, given the high metabolic burden and toxicities, evolutionary processes may also constrain bio-based production. We experimentally simulate large-scale fermentation with mevalonic acid-producing Escherichia coli. By tracking growth rate and production, we uncover how populations fully sacrifice production to gain fitness within 70 generations. Using ultra-deep (>1000×) time-lapse sequencing of the pathway populations, we identify multiple recurring intra-pathway genetic error modes. This genetic heterogeneity is only detected using deep-sequencing and new population-level bioinformatics, suggesting that the problem is underestimated. A quantitative model explains the population dynamics based on enrichment of spontaneous mutant cells. We validate our model by tuning production load and escape rate of the production host and apply multiple orthogonal strategies for postponing genetically driven production declines.
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