Background and purpose
The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion‐weighted magnetic ...resonance imaging (DWI‐MRI) and whether ischaemic core size affects this rate remain to be investigated.
Methods
This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI‐MRI that was categorized into three groups: small Diffusion‐Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI‐ASPECTS) (8–10), moderate (5–7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0–2). The interaction between onset‐to‐groin puncture time (OTP) and DWI‐ASPECTS categories regarding functional outcomes was investigated.
Results
Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI‐ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction = 0.06). Every 60‐min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity = 0.15).
Conclusions
Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI‐ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.
Roxadustat (FG‐4592), an oral hypoxia‐inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis, was evaluated in a phase 1b study in patients with end‐stage renal disease with ...anemia on hemodialysis. Seventeen patients, on epoetin‐alfa maintenance therapy with stable hemoglobin levels ≥10 g/dL, had epoetin‐alfa discontinued on day 3 and were enrolled in this double‐blind placebo‐controlled study. Two cohorts were randomized 3:1 (roxadustat: placebo). Patients received single doses of roxadustat (1 or 2 mg/kg) or placebo 1 hour after hemodialysis on day 1 and 2 hours before dialysis on day 8. Maximum plasma concentration and area under the plasma concentration–time curve for patients receiving roxadustat were slightly more than dose proportional and elimination half‐life ranged from 14.7 to 19.4 hours. Roxadustat was highly protein bound (99%) in plasma, and dialysis contributed a small fraction of the total clearance: only 4.56% and 3.04% of roxadustat recovered from the 1 and 2 mg/kg dose groups, respectively. Roxadustat induced transient elevations of endogenous erythropoietin that peaked between 7 and 14 hours after dosing and returned to baseline by 48 hours after dosing. Peak median endogenous erythropoietin levels were 96 mIU/mL and 268 mIU/mL for the 1‐ and 2‐mg/kg doses, respectively, within physiologic range of endogenous erythropoietin responses to hypoxia at high altitude or after blood loss. No serious adverse events were reported, and there were no treatment‐ or dose‐related trends in adverse event incidence.
Although they show potential to improve ultrasound image quality, plane wave (PW) compounding and synthetic aperture (SA) imaging are computationally demanding and are known to be challenging to ...implement in real-time. In this work, we have developed a novel beamformer architecture with the real-time parallel processing capacity needed to enable fast realization of PW compounding and SA imaging. The beamformer hardware comprises an array of graphics processing units (GPUs) that are hosted within the same computer workstation. Their parallel computational resources are controlled by a pixel-based software processor that includes the operations of analytic signal conversion, delay-and-sum beamforming, and recursive compounding as required to generate images from the channel-domain data samples acquired using PW compounding and SA imaging principles. When using two GTX-480 GPUs for beamforming and one GTX-470 GPU for recursive compounding, the beamformer can compute compounded 512 × 255 pixel PW and SA images at throughputs of over 4700 fps and 3000 fps, respectively, for imaging depths of 5 cm and 15 cm (32 receive channels, 40 MHz sampling rate). Its processing capacity can be further increased if additional GPUs or more advanced models of GPU are used.
Aims
This study aimed synergistic effects of three herbs in Salmonella via increased membrane permeability and apoptosis.
Methods and Results
Using high‐performance liquid chromatography, four types ...of phenylethyl glycosides and a lignan were detected in the herb mixture (Brassica juncea, Forsythia suspensa, and Inula britannica). During treatment with the herb mixture (1×, 2×, or 4× the MIC), viable cells decreased to 1·87 log CFU per ml (Salmonella Gallinarum) and 2·33 log CFU per ml (Salmonella Enteritidis) after 12 h of incubation according to inhibition of tricarboxylic acid cycle (P < 0·01). In addition, N‐phenyl‐1‐naphthylamine uptake increased from 229·00 to 249·67 AU in S. Gallinarum and from 232·00 to 250·67 AU in S. Enteritidis (P < 0·05), whereas membrane potential decreased from 8855·00 to 3763·25 AU and from 8703·67 to 4300·38 AU, respectively. Apoptotic Salmonella cells were observed by confocal laser scanning microscopy and flow cytometry. Transmission electron microscopy observations with negative staining showed protein leakage from damaged Salmonella.
Conclusions
These results showed the synergistic effect of the three herbs against avian pathogenic Salmonella induced by membrane damage and apoptosis.
Significance and Impact of the Study
Salmonella causes enormous economic losses in the poultry industry. These results indicated that potency of natural antimicrobial agents due to apoptosis in Salmonella.
The recent focus on topological insulators is due to the scientific interest in the new state of quantum matter as well as the technology potential for a new generation of THz optoelectronics, ...spintronics and quantum computations. It is important to elucidate the dynamics of the Dirac fermions in the topologically protected surface state. Hence we utilized a novel ultrafast optical pump mid-infrared probe to explore the dynamics of Dirac fermions near the Dirac point. The femtosecond snapshots of the relaxation process were revealed by the ultrafast optics. Specifically, the Dirac fermion-phonon coupling strength in the Dirac cone was found to increase from 0.08 to 0.19 while Dirac fermions were away from the Dirac point into higher energy states. Further, the energy-resolved transient reflectivity spectra disclosed the energy loss rate of Dirac fermions at room temperature was about 1 meV/ps. These results are crucial to the design of Dirac fermion devices.
Background and purpose
We analyzed the incidence and causes of oral anticoagulant (OAC) cessation and subsequent stroke after OAC withdrawal in a cohort of Korean stroke patients with atrial ...fibrillation.
Methods
The Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke patients (K‐ATTENTION) is a multicenter cohort study, merging stroke registries from 11 tertiary centers in Korea. The number of OAC interruption episodes and the reasons were reviewed from hospital records. Stroke after OAC withdrawal was defined when a patient experienced ischaemic stroke within 31 days after OAC withdrawal. Clinical variables were compared between patients who experienced stroke recurrence during OAC interruption and those who did not experience recurrence.
Results
Among 3213 stroke patients with atrial fibrillation, a total of 329 episodes of OAC interruption were detected in 229 patients after index stroke (mean age 72.9 ± 8.3 years, 113 female patients). The most frequent reason for OAC withdrawal was poor compliance 103 episodes (31.3%) followed by extracranial bleeding 96 episodes (29.2%). Stroke after OAC withdrawal was noted in 13 patients. Mean age, vascular risk factor profile and mean CHA2DS2‐VASc score were not significantly different between patients with and without recurrent stroke.
Conclusions
A considerable number of stroke patients with atrial fibrillation experienced temporary interruption of OAC after index stroke, which was associated with stroke recurrence of 4.0 cases per 100 interruption episodes.
Background and purpose
Immune system dysfunction and inflammatory dysregulation have been shown in several animal models of fragile X syndrome (FXS). However, the phenotypical implications of this ...dysregulation have not been systematically evaluated in a large patient cohort.
Methods
Five thousand seven hundred thirty‐six FXS patients from a nationwide health insurance database were identified and compared to 573 600 age‐ and sex‐matched controls. The phenome‐wide association studies codes of FXS patients and those without FXS were compared and the false discovery rate was controlled at 0.05 using the Benjamini–Hochberg procedure.
Results
In addition to the commonly reported comorbidities of FXS, an over‐representation of infectious diseases, including otitis media, cellulitis and abscess of fingers or toes, viral enteritis, candidiasis and pneumonia, was discovered. In addition, there was an under‐representation of autoimmune disorders in FXS patients.
Conclusions
Our systematic comorbidity analyses identified immunologically‐based phenotypes associated with FXS. Our findings align with previous observations of compromised immunity and phagocytic defects in animal models of FXS. These results suggest the importance of immune‐related pathways in FXS patients and their relevance to the FMR1 gene.
This randomized trial compared the rates of delayed xerostomia between two-dimensional radiation therapy (2DRT) and intensity-modulated radiation therapy (IMRT) in the treatment of early-stage ...nasopharyngeal carcinoma (NPC).
Between November 2001 and December 2003, 60 patients with T1-2bN0-1M0 NPC were randomly assigned to receive either IMRT or 2DRT. Primary end point was incidence of observer-rated severe xerostomia at 1 year after treatment based on Radiotherapy Oncology Group /European Organisation for the Research and Treatment of Cancer late radiation morbidity scoring criteria. Parallel assessment with patient-reported outcome, stimulated parotid flow rate (SPFR), and stimulated whole saliva flow rate (SWSFR) were also made.
At 1 year after treatment, patients in IMRT arm had lower incidence of observer-rated severe xerostomia than patients in the 2DRT arm (39.3% v 82.1%; P = .001), parallel with a higher fractional SPFR (0.90 v 0.05; P < .0001), and higher fractional SWSFR (0.41 v 0.20; P = .001). As for patient's subjective feeling, although a trend of improvement in patient-reported outcome was observed after IMRT, recovery was incomplete and there was no significant difference in patient-reported outcome between the two arms.
IMRT is superior to 2DRT in preserving parotid function and results in less severe delayed xerostomia in the treatment of early-stage NPC. Incomplete improvement in patient's subjective xerostomia with parotid-sparing IMRT reflects the need to enhance protection of other salivary glands.
This study aimed to evaluate endogenous metabolic markers of hepatic cytochrome P450 (CYP)3A activity in healthy subjects using a metabolomics approach. Twenty‐four subjects received the following ...medication during the following three study periods: 1 mg of i.v. midazolam alone (control phase), 1 mg of i.v. midazolam after 4 days of pretreatment with 400 mg of ketoconazole once daily (CYP3A‐inhibited phase), and 2.5 mg of i.v. midazolam after 10 days of pretreatment with 600 mg of rifampicin once daily (CYP3A‐induced phase). During each study period, 24 h before and after the administration of midazolam, urine samples were collected at 12‐h intervals for metabolomic analyses. We derived an equation to predict midazolam clearance (CL) based on several of these markers. We demonstrated that a combination of the concentrations and ratios of several endogenous metabolites and the CYP3A5*3 genotype is a reliable predictive marker of hepatic CYP3A activity as assessed by i.v. administration of midazolam.
Clinical Pharmacology & Therapeutics (2013); 94 5, 601–609. doi:10.1038/clpt.2013.128
China has been experiencing fine particle (i.e., aerodynamic diameters ≤ 2.5 μm; PM2.5) pollution and acid rain in recent decades, which exert adverse impacts on human health and the ecosystem. ...Recently, ammonia (i.e., NH₃) emission reduction has been proposed as a strategic option to mitigate haze pollution. However, atmospheric NH₃ is also closely bound to nitrogen deposition and acid rain, and comprehensive impacts of NH₃ emission control are still poorly understood in China. In this study, by integrating a chemical transport model with a high-resolution NH₃ emission inventory, we find that NH₃ emission abatement can mitigate PM2.5 pollution and nitrogen deposition but would worsen acid rain in China. Quantitatively, a 50% reduction in NH₃ emissions achievable by improving agricultural management, along with a targeted emission reduction (15%) for sulfur dioxide and nitrogen oxides, can alleviate PM2.5 pollution by 11−17% primarily by suppressing ammonium nitrate formation. Meanwhile, nitrogen deposition is estimated to decrease by 34%, with the area exceeding the critical load shrinking from 17% to 9% of China’s terrestrial land. Nevertheless, this NH₃ reduction would significantly aggravate precipitation acidification, with a decrease of as much as 1.0 unit in rainfall pH and a corresponding substantial increase in areas with heavy acid rain. An economic evaluation demonstrates that the worsened acid rain would partly offset the total economic benefit from improved air quality and less nitrogen deposition. After considering the costs of abatement options, we propose a region-specific strategy for multipollutant controls that will benefit human and ecosystem health.
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