Partial Meal Replacement for Weight Loss after Stroke: Results of a Pilot Clinical Trial.

INTRODUCTION: Over half of patients with acute ischemic stroke are overweight or obese as defined by a body mass index (BMI) ≥25 kg/m2. Professional and government agencies recommend weight management for these persons to improve risk factors for cardiovascular disease, including hypertension, dyslipidemia, vascular inflammation, and diabetes. However, approaches to weight loss have not been adequately tested specifically in patients with stroke. In anticipation of a larger trial with vascular or functional outcomes, we tested the feasibility and safety of a 12-week partial meal replacement (PMR) intervention for weight loss in overweight or obese patients with a recent ischemic stroke. METHODS: This randomized open-label trial enrolled participants from December 2019 to February 2021 (with hiatus from March to August 2020 due to COVID-19 pandemic restrictions on research). Eligible patients had a recent ischemic stroke and BMI 27-49.9 kg/m2. Patients were randomized to a PMR diet (OPTAVIA® Optimal Weight 4 & 2 & 1 Plan®) plus standard care (SC) or SC alone. The PMR diet consisted of four meal replacements supplied to participants, two meals with lean protein and vegetables (self-prepared or supplied), and a healthy snack (also self-prepared or supplied). The PMR diet provided 1,100-1,300 calories per day. SC consisted of one instructional session on a healthy diet. Co-primary outcomes were ≥5% weight loss at 12 weeks and to identify barriers to successful weight loss among participants assigned to PMR. Safety outcomes included hospitalization, falls, pneumonia, or hypoglycemia requiring treatment by self or others. Due to the COVID-19 pandemic, study visits after August 2020 were by remote communication. RESULTS: We enrolled 38 patients from two institutions. Two patients in each arm were lost and could not be included in outcome analyses. At 12 weeks, 9/17 patients in the PMR group and 2/17 patients in the SC group achieved ≥5% weight loss (52.9% vs. 11.9%; Fisher's exact p = 0.03). Mean percent weight change in the PMR group was -3.0% (SD 13.7) and -2.6% (SD 3.4) in the SC group (Wilcoxon rank-sum p = 0.17). No adverse events were attributed to study participation. Some participants had difficulty completing home monitoring of weight. In the PMR group, participants reported that food cravings and dislike for some food products were barriers to weight loss. CONCLUSION: A PMR diet after ischemic stroke is feasible, safe, and effective for weight loss. In future trials, in-person or improved remote outcome monitoring may reduce anthropometric data variation.

Diagnosis, Workup, Risk Reduction of Transient Ischemic Attack in the Emergency Department Setting: A Scientific Statement From the American Heart Association.

At least 240 000 individuals experience a transient ischemic attack each year in the United States. Transient ischemic attack is a strong predictor of subsequent stroke. The 90-day stroke risk after transient ischemic attack can be as high as 17.8%, with almost half occurring within 2 days of the index event. Diagnosing transient ischemic attack can also be challenging given the transitory nature of symptoms, often reassuring neurological examination at the time of evaluation, and lack of confirmatory testing. Limited resources, such as imaging availability and access to specialists, can further exacerbate this challenge. This scientific statement focuses on the correct clinical diagnosis, risk assessment, and management decisions of patients with suspected transient ischemic attack. Identification of high-risk patients can be achieved through use of comprehensive protocols incorporating acute phase imaging of both the brain and cerebral vasculature, thoughtful use of risk stratification scales, and ancillary testing with the ultimate goal of determining who can be safely discharged home from the emergency department versus admitted to the hospital. We discuss various methods for rapid yet comprehensive evaluations, keeping resource-limited sites in mind. In addition, we discuss strategies for secondary prevention of future cerebrovascular events using maximal medical therapy and patient education.

Expedited and Comprehensive Management of Low-Risk TIA Patients in the Emergency Department is Safe and Less Costly.

OBJECTIVES: Transient ischemic attack (TIA) can be a warning sign of an impending stroke. The objective of our study is to assess the feasibility, safety, and cost savings of a comprehensive TIA protocol in the emergency room for low-risk TIA patients. MATERIALS AND METHODS: This is a retrospective, single-center cohort study performed at an academic comprehensive stroke center. We implemented an emergency department-based TIA protocol pathway for low-risk TIA patients (defined as ABCD2 score < 4 and without significant vessel stenosis) who were able to undergo vascular imaging and a brain MRI in the emergency room. Patients were set up with rapid outpatient follow-up in our stroke clinic and scheduled for an outpatient echocardiogram, if indicated. We compared this cohort to TIA patients admitted prior to the implementation of the TIA protocol who would have qualified. Outcomes of interest included length of stay, hospital cost, radiographic and echocardiogram findings, recurrent neurovascular events within 30 days, and final diagnosis. RESULTS: A total of 138 patients were assessed (65 patients in the pre-pathway cohort, 73 in the expedited, post-TIA pathway implementation cohort). Average time from MRI order to MRI end was 6.4 h compared to 2.3 h in the pre- and post-pathway cohorts, respectively (p < 0.0001). The average length of stay for the pre-pathway group was 28.8 h in the pre-pathway cohort compared to 7.7 h in the post-pathway cohort (p < 0.0001). There were no differences in neuroimaging or echocardiographic findings. There were no differences in the 30 days re-presentation for stroke or TIA or mortality between the two groups. The direct cost per TIA admission was $2,944.50 compared to $1,610.50 for TIA patients triaged through the pathway at our institution. CONCLUSIONS: This study demonstrates the feasibility, safety, and cost-savings of a comprehensive, emergency department-based TIA protocol. Further study is needed to confirm overall benefit of an expedited approach to TIA patient management and guide clinical practice recommendations.

Stroke Code Presentations, Interventions, and Outcomes Before and During the COVID-19 Pandemic.

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.

Presentation and outcomes of carotid endarterectomy in active smokers.

OBJECTIVE: Smoking is a significant modifiable risk factor in the pathogenesis of carotid artery disease and has been shown to be a predictor of worse outcomes after vascular surgery. However, the effect of active smoking on outcomes of patients undergoing carotid endarterectomy is unknown. This study analyzed the outcomes of carotid endarterectomy by smoking status in a large national database. METHODS: The American College of Surgeons National Surgical Quality Improvement Program targeted carotid endarterectomy files (2011-2017) were reviewed. Patients were stratified according to smoking status, and outcomes were compared using propensity score matching (1:1) based on preoperative characteristics. RESULTS: During the study period, 26,293 patients underwent carotid endarterectomy, with 19,282 (73.34%) nonsmokers and 7011 (26.66%) smokers. Smokers were more likely to be younger, to have chronic obstructive pulmonary disease, to have a symptomatic presentation, and to have higher anatomic risk (P < .05). Smokers were also more likely to have emergent surgery, to have general anesthesia, and to be reintubated (P < .05). After propensity matching, 5354 nonsmokers were matched with 5354 smokers who underwent carotid endarterectomy. Smokers were at significantly higher risk for death, with an odds ratio of 1.93 (confidence interval, 1.18-3.13). CONCLUSIONS: Smokers are at increased risk for death after carotid endarterectomy compared with matched counterparts. Smoking should be considered an important risk factor for worse outcomes, and patients should be strongly counseled on the importance of smoking cessation before undergoing carotid endarterectomy.

Pathophysiologic mechanisms, neuroimaging and treatment in wake-up stroke.

Wake-up stroke (WUS) or ischemic stroke occurring during sleep accounts for 14%-29.6% of all ischemic strokes. Management of WUS is complicated by its narrow therapeutic time window and attributable risk factors, which can affect the safety and efficacy of administering intravenous (IV) tissue plasminogen activator (t-PA). This manuscript will review risk factors of WUS, with a focus on obstructive sleep apnea, potential mechanisms of WUS, and evaluate studies assessing safety and efficacy of IV t-PA treatment in WUS patients guided by neuroimaging to estimate time of symptom onset. The authors used PubMed (1966 to March 2018) to search for the term "Wake-Up Stroke" cross-referenced with "pathophysiology," ''pathogenesis," "pathology," "magnetic resonance imaging," "obstructive sleep apnea," or "treatment." English language Papers were reviewed. Also reviewed were pertinent papers from the reference list of the above-matched manuscripts. Studies that focused only on acute Strokes with known-onset of symptoms were not reviewed. Literature showed several potential risk factors associated with increased risk of WUS. Although the onset of WUS is unknown, a few studies investigated the potential benefit of magnetic resonance imaging (MRI) in estimating the age of onset which encouraged conducting clinical trials assessing the efficacy of MRI-guided thrombolytic therapy in WUS.

Decreases in Blood Pressure During Thrombectomy Are Associated With Larger Infarct Volumes and Worse Functional Outcome.

Background and Purpose- After large-vessel intracranial occlusion, the fate of the ischemic penumbra, and ultimately final infarct volume, largely depends on tissue perfusion. In this study, we evaluated whether blood pressure reduction and sustained relative hypotension during endovascular thrombectomy are associated with infarct progression and functional outcome. Methods- We identified consecutive patients with large-vessel intracranial occlusion ischemic stroke who underwent mechanical thrombectomy at 2 comprehensive stroke centers. Intraprocedural mean arterial pressure (MAP) was monitored throughout the procedure. ΔMAP was calculated as the difference between admission MAP and lowest MAP during endovascular thrombectomy until recanalization. Sustained hypotension was measured as the area between admission MAP and continuous measurements of intraprocedural MAP (aMAP). Final infarct volume was measured using magnetic resonance imaging at 24 hours, and functional outcome was assessed using the modified Rankin Scale at discharge and 90 days. Associations with outcome were analyzed using linear and ordinal multivariable logistic regression. Results- Three hundred ninety patients (mean age 71±14 years, mean National Institutes of Health Stroke Scale score of 17) were included in the study; of these, 280 (72%) achieved Thrombolysis in Cerebral Infarction 2B/3 reperfusion. Eighty-seven percent of patients experienced MAP reductions during endovascular thrombectomy (mean 31±20 mm Hg). ΔMAP was associated with greater infarct growth ( P=0.036) and final infarct volume ( P=0.035). Mean ΔMAP among patients with favorable outcomes (modified Rankin Scale score, 0-2) was 20±21 mm Hg compared with 30±24 mm Hg among patients with poor outcome ( P=0.002). In the multivariable analysis, ΔMAP was independently associated with higher (worse) modified Rankin Scale scores at discharge (adjusted odds ratio per 10 mm Hg, 1.17; 95% CI, 1.04-1.32; P=0.009) and at 90 days (adjusted odds ratio per 10 mm Hg, 1.22; 95% CI, 1.07-1.38; P=0.003). The association between aMAP and outcome was also significant at discharge ( P=0.002) and 90 days ( P=0.001). Conclusions- Blood pressure reduction before recanalization is associated with larger infarct volumes and worse functional outcomes for patients affected by large-vessel intracranial occlusion stroke. These results underscore the importance of BP management during endovascular thrombectomy and highlight the need for further investigation of blood pressure management after large-vessel intracranial occlusion stroke.

Risk of Acute Ischemic Stroke in Patients With Monocular Vision Loss of Vascular Etiology.

BACKGROUND: To evaluate the risk of concurrent acute ischemic stroke and monocular vision loss (MVL) of vascular etiology. DESIGN: Retrospective, cross-sectional study. SUBJECTS: Patients aged 18 or older diagnosed with MVL of suspected or confirmed vascular etiology who had no other neurologic deficits and who received brain MRI within 7 days of onset of visual symptoms were included. METHODS: A medical record review was performed from 2013 to 2016 at Yale New Haven Hospital. Patients were included if vision loss was unilateral and due to transient monocular vision loss (TMVL), central retinal artery occlusion (CRAO), or branch retinal artery occlusion (BRAO). Any patients with neurologic deficits other than vision loss were excluded. Other exclusion criteria were positive visual phenomena, nonvascular intraocular pathology, and intracranial pathology other than ischemic stroke. MAIN OUTCOME MEASURES: The presence or absence of acute stroke on diffusion-weighted imaging (DWI) on brain MRI. RESULTS: A total of 641 records were reviewed, with 293 patients found to have MVL. After excluding those with focal neurologic deficits, there were 41 patients who met the inclusion criteria and received a brain MRI. Eight of the 41 subjects (19.5%) were found to have findings on brain MRI positive for acute cortical strokes. The proportion of lesion positive MRI was 1/23 (4.3%) in TMVL subjects, 4/12 (33.3%) in CRAO subjects, and 2/5 (40%) in BRAO subjects. Brain computed tomography (CT) scans were not able to identify the majority of acute stroke lesions in this study. CONCLUSIONS: Patients with MVL of vascular etiology such as TMVL, CRAO, or BRAO may have up to 19.5% risk of concurrent ischemic stroke, even when there are no other neurologic deficits. These strokes were detected acutely with brain MRI using DWI but were missed on CT.

On- versus Off-Hour Patient Cohorts at a Primary Stroke Center: Onset-to-Treatment Duration and Clinical Outcomes after IV Thrombolysis.

BACKGROUND: The symptom onset-to-treatment (OTT) duration predicts symptomatic intracerebral hemorrhage (sICH) and adverse outcomes after ischemic stroke. Previous studies found disparities in OTT durations and clinical outcomes between stroke patients with symptom onset during on-hours versus off-hours, which led to the initiation of nationwide efforts to provide consistent 24-hour stroke care. GOAL: Our objective is to compare OTT durations and clinical outcomes in ischemic stroke patients whose symptoms originated during on- versus off-hours at a primary stroke center. METHODS: We analyzed clinical data from 210 consecutive patients receiving intravenous recombinant tissue plasminogen activator therapy between January 2009 and December 2013 at Yale-New Haven Stroke Center, a primary stroke center. Stroke severity was assessed by baseline National Institutes of Health Stroke Scale (NIHSS) scores. Clinical outcomes were assessed by presence of sICH and by stroke-related fatalities. OTT durations and clinical outcomes were compared using Mann-Whitney tests, 2-sample tests of proportions, and 2-sample t-tests after testing for equal variance. FINDINGS: We found no significant differences in OTT durations between on-hour and off-hour patient cohorts (137 minutes versus 145 minutes, P = .53). There were also no differences in stroke severity (mean NIHSS score 12.4 versus 11.3, P = .27), sICH rates (4.6% versus 6.5%, P = .56), or stroke fatality rates (9.2% versus 9.8%, P = .89) between the 2 cohorts. CONCLUSIONS: Our results represent progress in emergency response and acute stroke care, and reinforce ongoing nationwide efforts to increase stroke awareness and provide consistent quality care for patients with acute stroke.

Comparison of 8 scores for predicting symptomatic intracerebral hemorrhage after IV thrombolysis.

BACKGROUND: Intracerebral hemorrhage is a feared complication of IV thrombolytic (rt-PA) therapy. In recent years, at least 8 clinical scores have been proposed to predict either adverse outcome or symptomatic intracerebral hemorrhage (sICH) in patients undergoing rt-PA therapy. The purpose of this study was to evaluate the ability of these 8 scores to predict sICH in an independent clinical dataset. METHODS: Clinical data was analyzed from consecutive patients (n = 210) receiving IV rt-PA therapy from January 2009 to December 2013 at Yale-New Haven Hospital. Eight scores were calculated for each patient: Stroke-TPI, DRAGON, SPAN-100, ASTRAL, PRS, HAT, SEDAN, and SITS-ICH. sICH was defined according to the NINDS study criteria. Univariate logistic regression was performed using each score as an independent variable and sICH as the dependent variable. Goodness of fit was tested by Receiver operating characteristic (ROC) analysis and by Hosmer-Lemeshow statistics. RESULTS: sICH occurred in 12 patients (5.71 %) after IV rt-PA treatment. Only 4 scores predicted sICH with good accuracy (ROC area >0.7): DRAGON 0.76 (0.63, 0.89); Stroke-TPI 0.74 (0.61, 0.87); ASTRAL 0.72 (0.59, 0.86); and HAT 0.70 (0.55, 0.85), with odds ratios as follows: Stroke-TPI, 1.91 (1.26, 2.90); HAT, 1.67 (1.06, 2.62); DRAGON, 1.66 (1.21, 2.30); and ASTRAL, 1.10 (1.03, 1.16). CONCLUSIONS: Three scores showed good agreement with sICH: DRAGON, Stroke-TPI, and HAT with odds ratios substantially greater than 1. Stroke-TPI and HAT additionally benefited from low computational complexity and therefore performed best overall. Our results demonstrate the utility of clinical scores as predictors of sICH in acute ischemic stroke patients undergoing IV thrombolytic therapy.

TURN: A Simple Predictor of Symptomatic Intracerebral Hemorrhage After IV Thrombolysis.

BACKGROUND: IV Thrombolysis (rt-PA) for ischemic stroke treatment carries a substantial risk for symptomatic intracerebral hemorrhage (sICH). Our purpose was to develop a computationally simple and accurate sICH predictor METHODS : Our derivation dataset consisted of 210 ischemic stroke patients receiving IV rt-PA from January 2009 until July 2013 at Yale-New Haven Hospital. Our validation dataset included 303 patients who received IV rt-PA during the NINDS rt-PA trial. Independent sICH predictors were identified by logistic regression and combined to form the TURN score. Predictive ability and goodness of fit were quantified by odds ratios (OR) and areas under the receiver operating characteristic curve (AUROC). RESULTS: 3 out of 17 clinical parameters were identified as independent predictors of sICH: prestroke mRS score (OR 1.54, P = 0.02), baseline NIHSS score (OR 1.13, P = 0.002), and platelet count (OR 0.99, P = 0.04). We combined these three parameters to form the TURNP score. For added simplicity, prestroke mRS score and baseline NIHSS score alone were also combined to form the TURN score, and predicted sICH without a significant drop in OR or AUROC. CONCLUSIONS: We developed a new score for predicting sICH after IV thrombolysis. Our score is simple and with acceptable accuracy, making it ideal for use in the hyperacute stroke setting.

Cohort-Based Identification of Predictors of Symptomatic Intracerebral Hemorrhage After IV Thrombolysis.

INTRODUCTION: Symptomatic intracranial hemorrhage (sICH) is a serious complication of IV rt-PA therapy after acute ischemic stroke. Independent sICH predictors have been previously derived using case-control studies. Here we utilized a novel cohort-based comparison to identify additional independent predictors of sICH. METHODS: We included 210 patients receiving IV rt-PA therapy from January 2009 through December 2013 at the Yale-New Haven Stroke Center. Clinical parameters were compared using Mann-Whitney tests, two-sample tests of proportions and two-sample t tests. Logistic regression was performed using sICH as the dependent variable. Predictive ability was assessed using areas under the receiver operating characteristic (ROC) curve. RESULTS: sICH rates were lowest from 2010 to 2012 and comprised the low sICH cohort (2.0 % sICH), compared to the high sICH cohort from 2009 to 2013 (9.2 % sICH, P = 0.025). Patients in the low sICH cohort had significantly more visual field deficits (38.6 vs. 24.8 %, P = 0.03) and decreased levels of consciousness (62.4 vs. 39.4 %, P < 0.001), but fewer hyperdense MCA signs (5 vs. 13.8 %, P = 0.03) and early CT hypodensities (14.9 vs. 29.4 %, P = 0.01). These four parameters together predicted sICH modestly (area under ROC curve 0.66, odds ratio 2.72, P = 0.03) CONCLUSIONS: Using a novel cohort-based approach, we identified two new independent predictors of sICH after IV rt-PA therapy: the presence of the hyperdense MCA sign and early CT hypodensities. Novel methods are needed to reduce the risk of sICH for patients receiving antithrombolytic therapy for ischemic stroke.

Modest association between the discharge modified Rankin Scale score and symptomatic intracerebral hemorrhage after intravenous thrombolysis.

BACKGROUND: Thirty- and 90-day modified Rankin Scale (mRS) scores are used to monitor adverse outcome or symptomatic intracerebral hemorrhage (sICH) in ischemic stroke patients after intravenous (IV) thrombolytic therapy. Discharge mRS scores are more readily available and could serve as a proxy for 30- or 90-day mRS data. Our goal was to evaluate agreement between the discharge mRS score and sICH. Additionally, we tested for correlations between the discharge mRS score and 8 clinical scores developed to predict sICH or adverse outcomes based on 90-day mRS data. METHODS: Clinical data were analyzed from 210 patients receiving IV thrombolysis from January 2009 till December 2013 at the Yale New Haven Hospital. Agreement between sICH and the discharge mRS score was assessed using linear kappa. Eight clinical scores were calculated for each patient and compared with the discharge mRS score by univariate logistic regression. Goodness of fit was tested by receiver operating characteristic (ROC) analysis and by Hosmer-Lemeshow statistics. RESULTS: We found only modest agreement between sICH and unfavorable discharge mRS scores (mRS ≥ 5), with kappa .22, P = .0001. All 8 clinical scores tested showed good agreement with discharge mRS score of 5 or more (ROC area >.7). CONCLUSIONS: The discharge mRS score shows only modest agreement with sICH and therefore cannot be recommended as a proxy for 30- or 90-day mRS data. However, the discharge mRS score correlates strongly with clinical scores predicting long-term adverse outcome; therefore, assessment of discharge mRS scores may be of some clinical benefit.

A lipidated TLR7/8 adjuvant enhances the efficacy of a vaccine against fentanyl in mice.

Opioid use disorders (OUD) and opioid-related fatal overdoses are a public health concern in the United States. Approximately 100,000 fatal opioid-related overdoses occurred annually from mid-2020 to the present, the majority of which involved fentanyl or fentanyl analogs. Vaccines have been proposed as a therapeutic and prophylactic strategy to offer selective and long-lasting protection against accidental or deliberate exposure to fentanyl and closely related analogs. To support the development of a clinically viable anti-opioid vaccine suitable for human use, the incorporation of adjuvants will be required to elicit high titers of high-affinity circulating antibodies specific to the target opioid. Here we demonstrate that the addition of a synthetic TLR7/8 agonist, INI-4001, but not a synthetic TLR4 agonist, INI-2002, to a candidate conjugate vaccine consisting of a fentanyl-based hapten, F1, conjugated to the diphtheria cross-reactive material (CRM), significantly increased generation of high-affinity F1-specific antibody concentrations, and reduced drug distribution to the brain after fentanyl administration in mice.

Effect of bark beetle infestation on secondary organic aerosol precursor emissions.

Bark beetles are a potentially destructive force in forest ecosystems; however, it is not known how insect attacks affect the atmosphere. The emissions of volatile organic compounds (VOCs) were sampled i.) from bark beetle infested and healthy lodgepole pine (Pinus contorta var. latifolia) trees and ii.) from sites with and without active mountain pine beetle infestation. The emissions from the trunk and the canopy were collected via sorbent traps. After collection, the sorbent traps were extracted with hexane, and the extracts were separated and detected using gas chromatography/mass spectroscopy. Canister samples were also collected and analyzed by a multicolumn gas chromatographic system. The samples from bark beetle infested lodgepole pine trees suggest a 5- to 20-fold enhancement in total VOCs emissions. Furthermore, increases in the ß-phellandrene emissions correlated with bark beetle infestation. A shift in the type and the quantity of VOC emissions can be used to identify bark beetle infestation but, more importantly, can lead to increases in secondary organic aerosol from these forests as potent SOA precursors are produced.

Acute central retinal artery occlusion treated with intravenous recombinant tissue plasminogen activator.

Central retinal artery occlusion (CRAO) causes ischemic stroke of the eye. We report a case of CRAO that was successfully treated with intravenous recombinant tissue plasminogen activator (rt-PA) and review the current literature. A 64-year-old right-handed man presented to the emergency department with acute left eye amaurosis. An ophthalmologic assessment revealed a left afferent pupillary defect, minimal visual acuity, macular edema with a cherry red spot, and multiple emboli in the inferotemporal arcade of the left eye. A neurologic examination was otherwise nonfocal; neuroimaging was normal. Acute CRAO was diagnosed, and rt-PA was administered intravenously 185 minutes after symptom onset. A repeat examination 4.5 hours after treatment found improved vision, reduced macular edema, and no emboli. An ophthalmologic evaluation 10 days later found a visual acuity of 20/200 in the left eye and bilateral arterial sclerosis without evidence of retinal emboli or macular edema. This case illustrates that intravenous rt-PA may be an effective therapeutic option for CRAO in select patients. Given the current literature and the recommended established safety window for thrombolytics in acute ischemic cerebral stroke, it is reasonable to administer intravenous treatment for CRAO within 4.5 hours after symptom onset. Nevertheless, it is critical that a prospective clinical trial confirm the efficacy, safety, and time window for treatment.

Portable, low-field magnetic resonance imaging enables highly accessible and dynamic bedside evaluation of ischemic stroke.

Brain imaging is essential to the clinical management of patients with ischemic stroke. Timely and accessible neuroimaging, however, can be limited in clinical stroke pathways. Here, portable magnetic resonance imaging (pMRI) acquired at very low magnetic field strength (0.064 T) is used to obtain actionable bedside neuroimaging for 50 confirmed patients with ischemic stroke. Low-field pMRI detected infarcts in 45 (90%) patients across cortical, subcortical, and cerebellar structures. Lesions as small as 4 mm were captured. Infarcts appeared as hyperintense regions on T2-weighted, fluid-attenuated inversion recovery and diffusion-weighted imaging sequences. Stroke volume measurements were consistent across pMRI sequences and between low-field pMRI and conventional high-field MRI studies. Low-field pMRI stroke volumes significantly correlated with stroke severity and functional outcome at discharge. These results validate the use of low-field pMRI to obtain clinically useful imaging of stroke, setting the stage for use in resource-limited environments.

Current Progress on the Genomics of Schistosomiasis for Drug Discovery and Diagnostics.

For a number of decades, schistosomiasis has remained a public threat and an economic burden in a number of countries, directly impacting over 200 million people. The past 15 years have seen tremendous progress in the development of high-throughput methods for targeting or compound selection that are vital to early-stage schistosome drug discovery research. Genomewide approaches to analyze gene expression at the transcriptional and other -omic levels have helped immensely for gaining insight into the pathways and mechanisms involved in the schistosomiasis and it is expected to revolutionize the drug discovery as well as related diagnostics. This review discusses the most recent progress of pharmacology and genomics concerning schistosomiasis with a focus on drug discovery and diagnostic tools. It also provides chemical structural insights of promising targets along with available in vitro and/or in vivo data. Although significant research has been done to identify new molecules for the treatment and new methods for diagnosis, the necessity of new options for the sustainable control of schistosomiasis remains a great challenge.

Combinatory interpretation of protein corona and shear stress for active cancer targeting of bioorthogonally clickable gelatin-oleic nanoparticles.

Nanoparticle-protein interactions under conditions mimicking physiology determine how nanoparticles (NPs) will behave inside blood vessels and, therefore, the overall outcome of the drug-delivery system. Here, for the first time, we explore the effects of bio-mimicking shear stress and protein corona conditions on novel active targeting of clickable fattigation nanoparticles (NPs) for cancer therapy. Active targeting dibenzocyclooctyne-functionalized biocompatible gelatin-oleic NPs (GON-DBCOs) via a bioorthogonal click reaction were prepared by the desolvation method for delivery of docetaxel (DTX) to lung and breast cancer models. The effect of shear stress (5 dyne/cm2) and human serum albumin (HSA) protein corona on the cellular behavior of NPs was explored under a dynamic microfluidic system in lung (A549) and breast (MCF-7) cancer cell lines. The developed drug-loaded NPs had a particle size of 300 nm, a narrow size distribution, positive zeta potential, high encapsulation efficacy (72.4%), and spherical morphology. The particle size of the protein corona-coated NPs increased to 341 nm with a negative zeta potential. The inhibitory dose (IC50) increased approximately 3- and 42-fold in A549 and MCF-7 cells, respectively, under dynamic microfluidic conditions compared to static conditions. Cellular uptake was significantly decreased in the presence of shear stress and a protein corona, compared with static conditions, in both lung (A549, **p < 0.01) and breast (MCF-7, *p < 0.05) cancer cell lines. Clathrin-and energy-dependent pathways were found to be involved in the cellular uptake of NPs. This study could serve as a vital tool for the evaluation of NPs under aggressive bio-mimicking conditions comprising shear stress and a protein corona to predict the in vivo performance of NPs and support the preclinical and clinical translation of NP drug delivery systems.