Perfusion profile evaluated by severity-weighted multiple Tmax strata predicts early neurological deterioration in minor stroke with large vessel occlusion.

Minor stroke due to large vessel occlusion (LVO) is associated with poor outcomes. Hypoperfused tissue fate may be more accurately predicted by severity-weighted multiple perfusion strata than by a single perfusion threshold. We investigated whether poor perfusion profile evaluated by multiple Tmax strata is associated with early neurological deterioration (END) in patients with minor stroke with LVO. Ninety-four patients with a baseline National Institute of Health Stroke Scale score ≤5 and anterior circulation LVO admitted within 24 hours of onset were included. Tmax strata proportions (Tmax 2-4 s, 4-6 s, 6-8 s, 8-10 s, and >10 s) against the entire hypoperfusion volume (Tmax >2 s) were measured. The perfusion profile was defined as the shift of the distribution of the Tmax strata proportions towards worse hypoperfusion severity compared with that of the entire cohort using the Wilcoxon-Mann-Whitney generalised odds ratio (OR); its performance to predict END was tested. The area under the curve of perfusion profile was 0.785 (95% confidence interval [CI]: 0.691-0.878, p < 0.001). Poor perfusion profile (generalised OR >1.052) was independently associated with END (adjusted OR 13.42 [95% CI: 4.38-41.15], p < 0.001). Thus, perfusion profile with severity-weighted multiple Tmax strata may predict END in minor stroke and LVO.

Perfusion and Diffusion Variables Predict Early Neurological Deterioration in Minor Stroke and Large Vessel Occlusion.

BACKGROUND AND PURPOSE: Patients with acute large vessel occlusion (LVO) presenting with mild stroke symptoms are at risk of early neurological deterioration (END). This study aimed to identify the optimal imaging variables for predicting END in this population. METHODS: We retrospectively analyzed 94 patients from the prospectively maintained institutional stroke registry admitted between January 2011 and May 2019, presenting within 24 hours after onset, with a baseline National Institutes of Health Stroke Scale score ≤5 and anterior circulation LVO. Patients who underwent endovascular therapy before END were excluded. Volumes of Tmax delay (at >2, >4, >6, >8, and >10 seconds), mismatch (Tmax >4 seconds - diffusion-weighted imaging [DWI] and Tmax >6 seconds - DWI), and mild hypoperfusion lesions (Tmax 2-6 and 4-6 seconds) were measured. The association of each variable with END was examined using receiver operating characteristic curves. The variables with best predictive performance were dichotomized at the cutoff point maximizing Youden's index and subsequently analyzed using multivariable logistic regression. RESULTS: END occurred in 39.4% of the participants. The optimal variables were identified as Tmax >6 seconds, Tmax >6 seconds - DWI, and Tmax 4-6 seconds with cut-off points of 53.73, 32.77, and 55.20 mL, respectively. These variables were independently associated with END (adjusted odds ratio [aOR], 12.78 [95% confidence interval (CI), 3.36 to 48.65]; aOR, 5.73 [95% CI, 2.04 to 16.08]; and aOR, 9.13 [95% CI, 2.76 to 30.17], respectively). CONCLUSIONS: Tmax >6 seconds, Tmax >6 seconds - DWI, and Tmax 4-6 seconds could identify patients at high risk of END following minor stroke due to LVO.

Modification of Acute Stroke Pathway in Korea After the Coronavirus Disease 2019 Outbreak.

Background: Since the global pandemic of coronavirus disease 2019 (COVID-19), the process of emergency medical services has been modified to ensure the safety of healthcare professionals as well as patients, possibly leading to a negative impact on the timely delivery of acute stroke care. This study aimed to assess the impact of the COVID-19 pandemic on the acute stroke care processes and outcomes in tertiary COVID-19-dedicated centers in South Korea. Methods: We included 1,213 patients with acute stroke admitted to three centers in three cities (Seoul, Seongnam, and Daegu) through the stroke critical pathway between September 2019 and May 2020 (before and during the COVID-19 pandemic). In all three centers, we collected baseline characteristics and parameters regarding the stroke critical pathway, including the number of admitted patients diagnosed with acute stroke through the stroke critical pathway, door to brain imaging time, door to intravenous recombinant tissue plasminogen activator time, door to groin puncture time, and door to admission time. We performed an interrupted time series analysis to determine the impact of the COVID-19 outbreak on outcomes and critical pathway parameters. Results: Three centers modified the protocol of the stroke critical pathway during the COVID-19 pandemic. There was an immediate decrease in the number of patients admitted with acute ischemic stroke after the outbreak of COVID-19 in Korea, especially in the center of Daegu, an epicenter of the COVID-19 outbreak. However, the number of patients with stroke soon increased to equal that before the Covid-19 outbreak. In several critical pathway parameters, door to imaging time showed a temporary increase, and door to admission was transiently decreased after the COVID-19 outbreak. However, there was no significant effect on the timely trend. Moreover, there was no significant difference in the baseline characteristics and clinical outcomes between the periods before and during the COVID-19 pandemic. Conclusion: This study demonstrated that the COVID-19 outbreak immediately affected the management process. However, it did not have a significant overall impact on the trends of stroke treatment processes and outcomes. The stroke management process should be modified according to changing situations for optimal acute management.

Adjustable and Versatile 3D Tumor Spheroid Culture Platform with Interfacial Elastomeric Wells.

Three-dimensional (3D) cell culture platforms have recently received a great deal of attention, as these systems are able to recapitulate the in vivo microenvironment of tissues or tumors. Herein, we describe adjustable and versatile elastomeric well structures for spheroid formation and their use for in situ analyses as a tunable 3D cell culture platform. Elastomeric spherical wells are fabricated using a one-step interfacial reaction between aqueous droplets on immiscible liquid polydimethylsiloxane (PDMS) without any template or expensive equipment. Because of their differing surface tensions, spherical wells are spontaneously formed on liquid PDMS with various sizes and curvatures that are easily controlled. Using arrays of these optimized wells, single tumor spheroids within each well were successfully formed at high efficiency (up to 97%) by coculturing tumor cells and fibroblasts to reflect the complex microenvironment of cancer tissue. Moreover, the tumor spheroids formed within the interfacial wells were directly applied for observing drug responses and monitoring reactive oxygen species (ROS) to investigate tumor cell responses to drugs or their 3D microenvironment. We believe that our proposed platform provides a significant contribution to the multimodal analyses of anticancer therapeutics and the tumor microenvironment.

Photothermally Enhanced Molecular Delivery and Cellular Positioning on Patterned Plasmonic Interfaces.

Photothermal conversion effect of plasmonic nanostructures is considered as a promising technique for cellular and molecular manipulations owing to controllability of local temperature. Therefore, this technique has been extensively applied to biological studies such as controlling cellular behavior, delivery of biologics, and biomolecular detection. Herein, we propose a novel method for directed cell positioning and photothermally modulated molecular delivery to the cells using patterned plasmonic interfaces. Plasmonic substrates with gold nanorods (GNRs) and cell adhesion molecules fabricated by microcontact printing are optimized for cellular positioning on designated patterns. Through the photothermal conversion effect of GNRs on the pattern, we further demonstrate on-demand, light-induced delivery of drug molecules to the target cells. We expect that this approach will provide a new way to study single cellular behaviors and enhance molecular delivery to the target cells.

Controlled drug release with surface-capped mesoporous silica nanoparticles and its label-free in situ Raman monitoring.

Mesoporous silica nanoparticles (MSNs) have drawn attention as efficient nanocarriers for drug delivery systems owing to their unique physiochemical properties. However, systemically controlling the kinetics of drug release from the nanocarriers and in situ monitoring of the drug release are still challenging. Here, we report surface-capped MSNs used for controlled drug release and demonstrate label-free in situ Raman monitoring of released drugs based on the molecule-specific spectral fingerprints. By capping the surface of MSNs with amine moieties, gold nanoparticles, and albumin, we achieved high loading efficiencies (up to 97%) of doxorubicin and precisely controlled drug release stimulated by changing pH value. Moreover, we monitored in real-time drug release profile and visualized cellular distribution of the delivered drug at nanoscale based on its intrinsic Raman peak. Finally, we evaluated drug responses in cancer cells and normal cells to investigate whether capped-dMSNs exhibit selective drug release. Our findings would be beneficial for designing smart drug carriers and directly monitoring the release behavior of drugs in actual cellular environments.

Facile Fabrication of Large-Scale Porous and Flexible Three-Dimensional Plasmonic Networks.

Assembling metallic nanoparticles and trapping target molecules within the probe volume of the incident light are important in plasmonic detection. Porous solid structures with three-dimensionally integrated metal nanoparticles would be very beneficial in achieving these objectives. Currently, porous inorganic oxides are being prepared under stringent conditions and further subjected to either physical or chemical attachment of metal nanoparticles. In this study, we propose a facile method to fabricate large-scale porous and flexible three-dimensional (3D) plasmonic networks. Initially, uncured polydimethylsiloxane (PDMS), in which metal ions are dissolved, diffuses spontaneously into the simple sugar crystal template via capillary action. As PDMS is cured, metal ions are automatically reduced to form a dense array of metal nanoparticles. After curing, the sugar template is easily removed by water treatment to obtain porous 3D plasmonic networks. We controlled the far-field scattering and near-field enhancement of the network by changing either the metal ion precursor or its concentration. To demonstrate the key advantages of our 3D plasmonic networks, such as simple fabrication, optical signal enhancement, and molecular trapping, we conducted sensitive Raman detection of several important molecules, including adenine, humidifier disinfectants, and volatile organic compounds.

Tunable Plasmonic Cavity for Label-free Detection of Small Molecules.

Owing to its high sensitivity and high selectivity along with rapid response time, plasmonic detection has gained considerable interest in a wide variety of sensing applications. To improve the fieldwork applicability and reliability of plasmonic detection, the integration of plasmonic nanoparticles into optical devices is desirable. Herein, we propose an integrated label-free detection platform comprising a plasmonic cavity that allows sensitive molecular detection via either surface-enhanced Raman scattering (SERS) or plasmon resonance energy transfer (PRET). A small droplet of metal ion solution spontaneously produces a plasmonic cavity on the surface of uncured poly(dimethylsiloxane) (PDMS), and as PDMS is cured, the metal ions are reduced to form a plasmonic antennae array on the cavity surface. Unique spherical feature and the integrated metallic nanoparticles of the cavity provide excellent optical functions to focus the incident light in the cavity and to rescatter the light absorbed by the nanoparticles. The optical properties of the plasmonic cavity for SERS or PRET are optimized by controlling the composition, size, and density of the metal nanoparticles. By using the cavity, we accomplish both 1000-fold sensitive detection and real-time monitoring of reactive oxygen species secreted by live cells via PRET. In addition, we achieve sensitive detection of trace amounts of toxic environmental molecules such as 5-chloro-2-methyl-4-isothiazolin-3-one/2-methyl-4-isothiazol-3-one (CMIT/MIT) and bisphenol A, as well as several small biomolecules such as glucose, adenine, and tryptophan, via SERS.

Rapid and high-throughput colorimetric screening for anti-aggregation reagents of protein conformational diseases by using gold nanoplasmonic particles.

Cellular deposition of destabilized proteins and their aggregates is considered one of the most indisputable factors implicated in protein conformational diseases. Here, we report an innovative high-throughput screening method for discovering anti-aggregation reagents out of numerous potential candidates by using gold nanoplasmonic particles. In our method, nanoparticles act as catalytic activators to accelerate protein aggregation and simultaneously exhibit a colorimetric response according to their embedded shape on the protein aggregates. Using this principle, we observed the colorimetric response to the anti-aggregation effect of amyloid ß (Aß) with the naked eye within a few minutes. Investigation of the anti-aggregation effects of select candidates under three different protein aggregation stages showed that the anti-aggregation efficiency could relate to disease progression. Finally, results obtained with spiked samples in cerebrospinal fluid as well as under various denaturation conditions and different Aß compositions show the feasibility of future personalized medicine considering individual patient's disease progression.