Mimicking natural deterrent strategies in plants using adhesive spheres.

With a continuous increase in world population and food production, chemical pesticide use is growing accordingly, yet unsustainably. As chemical pesticides are harmful to the environment and developmental resistance in pests is increasing, a sustainable and effective pesticide alternative is needed. Inspired by nature, we mimic one defense strategy of plants, glandular trichomes, to shift away from using chemical pesticides by moving toward a physical immobilization strategy via adhesive particles. Through controlled oxidation of a biobased starting material, triglyceride oils, an adhesive material is created while monitoring the reactive intermediates. After being milled into particles, nanoindentation shows these particles to be adhesive even at low contact forces. A suspension of particles is then sprayed and found to be effective at immobilizing a target pest, thrips, Frankliniella occidentalis. Small arthropod pests, like thrips, can cause crop damage through virus transfer, which is prevented by their immobilization. We show that through a scalable fabrication process, biosourced materials can be used to create an effective, sustainable physical pesticide.

Migraine-Associated Common Genetic Variants Confer Greater Risk of Posterior vs. Anterior Circulation Ischemic Stroke☆.

OBJECTIVE: To examine potential genetic relationships between migraine and the two distinct phenotypes posterior circulation ischemic stroke (PCiS) and anterior circulation ischemic stroke (ACiS), we generated migraine polygenic risk scores (PRSs) and compared these between PCiS and ACiS, and separately vs. non-stroke control subjects. METHODS: Acute ischemic stroke cases were classified as PCiS or ACiS based on lesion location on diffusion-weighted MRI. Exclusion criteria were lesions in both vascular territories or uncertain territory; supratentorial PCiS with ipsilateral fetal posterior cerebral artery; and cases with atrial fibrillation. We generated migraine PRS for three migraine phenotypes (any migraine; migraine without aura; migraine with aura) using publicly available GWAS data and compared mean PRSs separately for PCiS and ACiS vs. non-stroke control subjects, and between each stroke phenotype. RESULTS: Our primary analyses included 464 PCiS and 1079 ACiS patients with genetic European ancestry. Compared to non-stroke control subjects (n=15396), PRSs of any migraine were associated with increased risk of PCiS (p=0.01-0.03) and decreased risk of ACiS (p=0.010-0.039). Migraine without aura PRSs were significantly associated with PCiS (p=0.008-0.028), but not with ACiS. When comparing PCiS vs. ACiS directly, migraine PRSs were higher in PCiS vs. ACiS for any migraine (p=0.001-0.010) and migraine without aura (p=0.032-0.048). Migraine with aura PRS did not show a differential association in our analyses. CONCLUSIONS: Our results suggest a stronger genetic overlap between unspecified migraine and migraine without aura with PCiS compared to ACiS. Possible shared mechanisms include dysregulation of cerebral vessel endothelial function.

Value of treatment by comprehensive stroke services for the reduction of critical gaps in acute stroke care in Europe.

Stroke is the second leading cause of death and dependency in Europe and costs the European Union more than €30bn, yet significant gaps in the patient pathway remain and the cost-effectiveness of comprehensive stroke care to meet these needs is unknown. The European Brain Council Value of Treatment Initiative combined patient representatives, stroke experts, neurological societies and literature review to identify unmet needs in the patient pathway according to Rotterdam methodology. The cost-effectiveness of comprehensive stroke services was determined by a Markov model, using UK cost data as an exemplar and efficacy data for prevention of death and dependency from published systematic reviews and trials, expressing effectiveness as quality-adjusted life-years (QALYs). Model outcomes included total costs, total QALYs, incremental costs, incremental QALYs and the incremental cost-effectiveness ratio (ICER). Key unmet needs in the stroke patient pathway included inadequate treatment of atrial fibrillation (AF), access to neurorehabilitation and implementation of comprehensive stroke services. In the Markov model, full implementation of comprehensive stroke services was associated with a 9.8% absolute reduction in risk of death of dependency, at an intervention cost of £9566 versus £6640 for standard care, and long-term care costs of £35 169 per 5.1251 QALYS vs. £32 347.40 per 4.5853 QALYs, resulting in an ICER of £5227.89. Results were robust in one-way and probabilistic sensitivity analyses. Implementation of comprehensive stroke services is a cost-effective approach to meet unmet needs in the stroke patient pathway, to improve acute stroke care and support better treatment of AF and access to neurorehabilitation.

Polypharmacy, functional outcome and treatment effect of intravenous alteplase for acute ischaemic stroke.

BACKGROUND AND PURPOSE: Polypharmacy is an important challenge in clinical practice. Our aim was to determine the effect of polypharmacy on functional outcome and treatment effect of alteplase in acute ischaemic stroke. METHODS: This was a post hoc analysis of the randomized, placebo-controlled WAKE-UP trial of magnetic resonance imaging guided intravenous alteplase in unknown onset stroke. Polypharmacy was defined as an intake of five or more medications at baseline. Comorbidities were assessed by the Charlson Comorbidity Index (CCI). The primary efficacy variable was favourable outcome defined by a score of 0-1 on the modified Rankin Scale at 90 days. Logistic regression analysis was used to test for an association of polypharmacy with functional outcome, and for interaction of polypharmacy and the effect of thrombolysis. RESULTS: Polypharmacy was present in 133/503 (26%) patients. Patients with polypharmacy were older (mean age 70 vs. 64 years; p < 0.0001) and had a higher score on the National Institutes of Health Stroke Scale at baseline (median 7 vs. 5; p = 0.0007). A comorbidity load defined by a CCI score ≥ 2 was more frequent in patients with polypharmacy (48% vs. 8%; p < 0.001). Polypharmacy was associated with lower odds of favourable outcome (adjusted odds ratio 0.50, 95% confidence interval 0.30-0.85; p = 0.0099), whilst the CCI score was not. Treatment with alteplase was associated with higher odds of favourable outcome in both groups, with no heterogeneity of treatment effect (test for interaction of treatment and polypharmacy, p = 0.29). CONCLUSION: In stroke patients, polypharmacy is associated with worse functional outcome after intravenous thrombolysis independent of comorbidities. However, polypharmacy does not interact with the beneficial effect of alteplase.

Correction to: Features of intracranial hemorrhage in cerebral venous thrombosis.

The original version of this article unfortunately contained mistakes. The correct information is given below.

Features of intracranial hemorrhage in cerebral venous thrombosis.

BACKGROUND: Cerebral venous thrombosis (CVT) is associated with intracranial hemorrhage. AIM: To identify clinical and imaging features of CVT-associated intracranial hemorrhage. We hypothesized that higher clot burden would be associated with a higher risk of intracranial hemorrhage. METHODS: We performed a retrospective analysis of an international, multicenter cohort of patients with confirmed cerebral venous thrombosis who underwent computed tomography within 2 weeks of symptom onset. Clinical and imaging features were compared between patients with and without intracranial hemorrhage. Clot burden was assessed by counting the number of thrombosed venous sinuses and veins on confirmatory imaging. RESULTS: We enrolled 260 patients from 10 institutions in Europe and Mexico. The mean age was 42 years and 74% were female. Intracranial hemorrhage was found in 102 (39%). Among them parenchymal hemorrhage occurred in 64 (63%), in addition, small juxta-cortical hemorrhage was found in 30 (29%), subarachnoid hemorrhage in 24 (24%) and subdural hemorrhage in 11 (11%). Multiple concomitant types of hemorrhage occurred in 23 (23%). Older age and superior sagittal thrombosis involvement were associated with presence of hemorrhage. The number of thrombosed venous sinuses was not associated with intracranial hemorrhage (median number IQRInterquartile ratio] of sinuses/veins involved with hemorrhage 2 (1-3) vs. 2 (1-3) without hemorrhage, p = 0.4). CONCLUSION: The high rate of intracranial hemorrhage in cerebral venous thrombosis is not explained by widespread involvement of the venous sinuses. Superior sagittal sinus involvement is associated with higher bleeding risk.

Detailed phenotyping of posterior vs. anterior circulation ischemic stroke: a multi-center MRI study.

OBJECTIVE: Posterior circulation ischemic stroke (PCiS) constitutes 20-30% of ischemic stroke cases. Detailed information about differences between PCiS and anterior circulation ischemic stroke (ACiS) remains scarce. Such information might guide clinical decision making and prevention strategies. We studied risk factors and ischemic stroke subtypes in PCiS vs. ACiS and lesion location on magnetic resonance imaging (MRI) in PCiS. METHODS: Out of 3,301 MRIs from 12 sites in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN), we included 2,381 cases with acute DWI lesions. The definition of ACiS or PCiS was based on lesion location. We compared the groups using Chi-squared and logistic regression. RESULTS: PCiS occurred in 718 (30%) patients and ACiS in 1663 (70%). Diabetes and male sex were more common in PCiS vs. ACiS (diabetes 27% vs. 23%, p < 0.05; male sex 68% vs. 58%, p < 0.001). Both were independently associated with PCiS (diabetes, OR = 1.29; 95% CI 1.04-1.61; male sex, OR = 1.46; 95% CI 1.21-1.78). ACiS more commonly had large artery atherosclerosis (25% vs. 20%, p < 0.01) and cardioembolic mechanisms (17% vs. 11%, p < 0.001) compared to PCiS. Small artery occlusion was more common in PCiS vs. ACiS (20% vs. 14%, p < 0.001). Small artery occlusion accounted for 47% of solitary brainstem infarctions. CONCLUSION: Ischemic stroke subtypes differ between the two phenotypes. Diabetes and male sex have a stronger association with PCiS than ACiS. Definitive MRI-based PCiS diagnosis aids etiological investigation and contributes additional insights into specific risk factors and mechanisms of injury in PCiS.

Prognostic significance of pulsatile tinnitus in cervical artery dissection.

BACKGROUND AND PURPOSE: Our aim was to investigate whether pulsatile tinnitus (PT) in cervical artery dissection (CeAD) has prognostic significance. METHODS: All CeAD patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) study with documentation of PT were analysed. The presence of PT was systematically assessed using a standardized questionnaire. Stroke severity at admission was defined according to the National Institutes of Health Stroke Scale (NIHSS). Excellent outcome after 3 months was defined as a modified Rankin Scale of 0-1. RESULTS: Sixty-three of 778 patients (8.1%) reported PT. PT+ patients presented less often with ischaemic stroke (41.3% vs. 63.9%, P < 0.001), more often with dissection in the internal carotid artery (85.7% vs. 64.2%, P = 0.001), less often with vessel occlusion (19.0% vs. 34.1%, P = 0.017) and more often with excellent outcome at 3 months (92.1% vs. 75.4%, P = 0.002). Logistic regression analysis identified PT as an independent predictor of excellent outcome after 3 months [odds ratio (OR) 3.96, 95% confidence interval (CI) 1.22-12.87] adjusted to significant outcome predictors NIHSS on admission (OR 0.82, 95% CI 0.79-0.86), Horner syndrome (OR 1.95, 95% CI 1.16-3.29) and vessel occlusion (OR 0.62, 95% CI 0.40-0.94) and to non-significant predictors age, sex, pain and location of CeAD. CONCLUSION: The presence of PT in CeAD is associated with a benign clinical course and predicts a favourable outcome.

Frequency and predictors of acute ischaemic lesions on brain magnetic resonance imaging in young patients with a clinical diagnosis of transient ischaemic attack.

BACKGROUND AND PURPOSE: Acute lesions in patients with transient ischaemic attack (TIA) are important as they are associated with increased risk for recurrence. Characteristics associated with acute lesions in young TIA patients were therefore investigated. METHODS: The sifap1 study prospectively recruited a multinational European cohort (n = 5023) of patients aged 18-55 years with acute cerebrovascular event. The detection of acute ischaemic lesions was based on diffusion-weighted imaging (DWI). The frequency of DWI lesions was assessed in 829 TIA patients who met the criteria of symptom duration <24 h and their association with demographic, clinical and imaging variables was analysed. RESULTS: The median age was 46 years (interquartile range 40-51 years); 45% of the patients were female. In 121 patients (15%) ≥1 acute DWI lesion was detected. In 92 patients, DWI lesions were found in the anterior circulation, mostly located in cortical-subcortical areas (n = 63). Factors associated with DWI lesions in multiple regression analysis were left hemispheric presenting symptoms [odds ratio (OR) 1.92, 95% confidence interval (CI) 1.27-2.91], dysarthria (OR 2.17, 95% CI 1.38-3.43) and old brain infarctions on MRI (territories of the middle and posterior cerebral artery: OR 2.43, 95% CI 1.42-4.15; OR 2.41, 95% CI 1.02-5.69, respectively). CONCLUSIONS: In young patients with a clinical TIA 15% demonstrated acute DWI lesions on brain MRI, with an event pattern highly suggestive of an embolic origin. Except for the association with previous infarctions there was no clear clinical predictor for acute ischaemic lesions, which indicates the need to obtain MRI in young individuals with TIA.

Challenges and misconceptions in the aetiology and management of atrial fibrillation-related strokes.

Strokes, whether ischaemic or haemorrhagic, are the most feared complications of atrial fibrillation (AF) and its treatment. Vitamin K antagonists have been the mainstay of stroke prevention. Recently, direct oral anticoagulants have been introduced. The advantages and disadvantages of these treatment strategies have been extensively discussed. In this narrative review, we discuss dilemmas faced by primary care clinicians in the context of stroke and transient ischaemic attack (TIA) in patients with AF. We discuss the classification of stroke, the different types of stroke seen with AF, the prognosis of AF-related strokes, the early management after AF-related stroke or TIA and the therapeutic options after anticoagulant-associated intracerebral haemorrhage. Most importantly, we aim to dispel common misconceptions on the part of non-stroke specialists that can lead to suboptimal stroke prevention and management.

Anemia in young patients with ischaemic stroke.

BACKGROUND AND PURPOSE: To investigate the association of anemia on admission with ischaemic stroke (IS), stroke severity and early functional outcome in patients with cervical artery dissection (CeAD) or with IS of other causes (non-CeAD-IS patients). METHODS: The study sample comprised all patients from the Cervical Artery Dissection and Ischaemic Stroke Patients (CADISP) study without pre-existing disability and with documentation of stroke severity and hemoglobin (Hb) concentration on admission. Anemia was classified as mild (Hb < 12 g/dl in women and Hb < 13 g/dl in men) or moderate to severe (Hb < 10 g/dl in women and Hb < 11 g/dl in men). Stroke severity on admission was assessed with the National Institutes of Health Stroke Scale (NIHSS). Outcome after 3 months was assessed with the modified Rankin Scale (mRS-3mo). Unfavorable outcome was defined as mRS-3mo ≥ 3. RESULTS: Amongst 1206 study patients (691 CeAD and 515 non-CeAD), 87 (7.2%) had anemia, which was moderate to severe in 18 (1.5%) patients. Anemia was associated with female sex in both study samples, but no further associations with risk factors or comorbidities were observed. In CeAD patients, anemia was associated with occurrence of stroke (P = 0.042). In both study samples, anemic patients had more severe strokes (CeAD, P = 0.023; non-CeAD, P = 0.005). Functional outcome was not associated with anemia in general, but moderate to severe anemia was significantly associated with unfavorable outcome (P = 0.004). CONCLUSION: Anemia on admission was associated with stroke in CeAD patients and with more severe strokes in both study samples. Moderate to severe anemia may predict unfavorable outcome.

Stroke in first-degree relatives of patients with cervical artery dissection.

BACKGROUND AND PURPOSE: Patients with ischaemic stroke (IS) caused by a spontaneous cervical artery dissection (CeAD) worry about an increased risk for stroke in their families. The occurrence of stroke in relatives of patients with CeAD and in those with ischaemic stroke attributable to other (non-CeAD) causes were compared. METHODS: The frequency of stroke in first-degree relatives (family history of stroke, FHS) was studied in IS patients (CeAD patients and age- and sex-matched non-CeAD patients) from the Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) database. FHS ≤ 50 and FHS > 50 were defined as having relatives who suffered stroke at the age of ≤50 or >50 years. FHS ≤ 50 and FHS > 50 were studied in CeAD and non-CeAD IS patients and related to age, sex, number of siblings, hypertension, hypercholesterolemia, smoking and body mass index (BMI). RESULTS: In all, 1225 patients were analyzed. FHS ≤ 50 was less frequent in CeAD patients (15/598 = 2.5%) than in non-CeAD IS patients (38/627 = 6.1%) (P = 0.003; odds ratio 0.40, 95% confidence interval 0.22-0.73), also after adjustment for age, sex and number of siblings (P = 0.005; odds ratio 0.42, 95% confidence interval 0.23-0.77). The frequency of FHS > 50 was similar in both study groups. Vascular risk factors did not differ between patients with positive or negative FHS ≤ 50. However, patients with FHS > 50 were more likely to have hypertension and higher BMI. CONCLUSION: Relatives of CeAD patients had fewer strokes at a young age than relatives of non-CeAD IS stroke patients.

Elevated peripheral leukocyte counts in acute cervical artery dissection.

BACKGROUND AND PURPOSE: It has been suggested that inflammation may play a role in the development of cervical artery dissection (CeAD), but evidence remains scarce. METHODS: A total of 172 patients were included with acute (< 24 h) CeAD and 348 patients with acute ischaemic stroke (IS) of other (non-CeAD) causes from the Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) study, and 223 age- and sex-matched healthy control subjects. White blood cell (WBC) counts collected at admission were compared across the three groups. RESULTS: Compared with healthy control subjects, CeAD patients and non-CeAD stroke patients had higher WBC counts (P < 0.001). Patients with CeAD had higher WBC counts and were more likely to have WBC > 10 000/µl than non-CeAD stroke patients (38.4% vs. 23.0%, P < 0.001) and healthy controls (38.4% vs. 8.5%, P < 0.001). WBC counts were higher in CeAD (9.4 ± 3.3) than in IS of other causes (large artery atherosclerosis, 8.7 ± 2.3; cardioembolism, 8.2 ± 2.8; small vessel disease, 8.4 ± 2.4; undetermined cause, 8.8 ± 3.1; P = 0.022). After adjustment for age, sex, stroke severity and vascular risk factors in a multiple regression model, elevated WBC count remained associated with CeAD, as compared with non-CeAD stroke patients [odds ratio (OR) = 2.56; 95% CI 1.60-4.11; P < 0.001) and healthy controls (OR = 6.27; 95% CI 3.39-11.61; P < 0.001). CONCLUSIONS: Acute CeAD was associated with particularly high WBC counts. Leukocytosis may reflect a pre-existing inflammatory state, supporting the link between inflammation and CeAD.

Etiology of first-ever ischaemic stroke in European young adults: the 15 cities young stroke study.

BACKGROUND AND PURPOSE: Risk factors for IS in young adults differ between genders and evolve with age, but data on the age- and gender-specific differences by stroke etiology are scare. These features were compared based on individual patient data from 15 European stroke centers. METHODS: Stroke etiology was reported in detail for 3331 patients aged 15-49 years with first-ever IS according to Trial of Org in Acute Stroke Treatment (TOAST) criteria: large-artery atherosclerosis (LAA), cardioembolism (CE), small-vessel occlusion (SVO), other determined etiology, or undetermined etiology. CE was categorized into low- and high-risk sources. Other determined group was divided into dissection and other non-dissection causes. Comparisons were done using logistic regression, adjusting for age, gender, and center heterogeneity. RESULTS: Etiology remained undetermined in 39.6%. Other determined etiology was found in 21.6%, CE in 17.3%, SVO in 12.2%, and LAA in 9.3%. Other determined etiology was more common in females and younger patients, with cervical artery dissection being the single most common etiology (12.8%). CE was more common in younger patients. Within CE, the most frequent high-risk sources were atrial fibrillation/flutter (15.1%) and cardiomyopathy (11.5%). LAA, high-risk sources of CE, and SVO were more common in males. LAA and SVO showed an increasing frequency with age. No significant etiologic distribution differences were found amongst southern, central, or northern Europe. CONCLUSIONS: The etiology of IS in young adults has clear gender-specific patterns that change with age. A notable portion of these patients remains without an evident stroke mechanism according to TOAST criteria.

[Rivaroxaban: Xarelto--recommendations for pharmacists]. / Le Rivaroxaban (Xarelto): guide de la pratique officinale.

Rivaroxaban is one of the new oral anticoagulants (NOACs). It has many potential advantages in comparison with Vitamin K Antagonists (VKA). It has a predictable anticoagulant effect and does not theoretically require biological monitoring. It is also characterized by less food and drug interactions. However, due to major risks associated with over- and under-dosage, its optimal use in patients should be carefully followed by health care professionals. The aim of this article is to provide recommendations for pharmacists on the practical use of Xarelto in its different approved indications. This document is adapted from the practical user guide of rivaroxaban which was developed by an independent group of Belgian experts in the field of thrombosis and haemostasis.

CT density measurement and H:H ratio are useful in diagnosing acute cerebral venous sinus thrombosis.

BACKGROUND AND PURPOSE: Brain CT is widely used to exclude or confirm acute cerebral venous sinus thrombosis. The purpose of this study was to assess the value of attenuation measurement and the H:H ratio on unenhanced brain CT scans in the diagnosis of acute cerebral venous sinus thrombosis. MATERIALS AND METHODS: This retrospective study evaluated 20 patients with acute cerebral venous sinus thrombosis and 20 age- and sex-matched control participants without thrombosis. Three experienced observers independently evaluated the unenhanced brain CT scan for the presence of cerebral venous sinus thrombosis and measured the attenuation in the dural sinuses. Interreader differences were examined, as well as densities and H:H ratio between patients with acute cerebral venous sinus thrombosis and control participants. RESULTS: A significant difference in the average sinus attenuation was found between patients with acute cerebral venous sinus thrombosis (73.9 ± 9.2 HU) and the control group (52.8 ± 6.7 HU; P < .0001). A similar difference was found for the H:H ratio (1.91 ± 0.32 vs 1.33 ± 0.12 in patients with and without cerebral venous sinus thrombosis, respectively; P < .0001). Optimal thresholds of 62 HU and 1.52 lead to accuracies of 95% for average sinus attenuation and 97.5% for the H:H ratio, respectively. CONCLUSIONS: Hyperattenuation and the H:H ratio in the dural sinuses on unenhanced brain CT scans have a high accuracy in the detection of acute cerebral venous sinus thrombosis.

Migraine in cervical artery dissection and ischemic stroke patients.

OBJECTIVE: Several small to medium-sized studies indicated a link between cervical artery dissection (CeAD) and migraine. Migrainous CeAD patients were suggested to have different clinical characteristics compared to nonmigraine CeAD patients. We tested these hypotheses in the large Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) population. METHODS: A total of 968 CeAD patients and 653 patients with an ischemic stroke of a cause other than CeAD (non-CeAD IS) were recruited. CeAD patients with stroke (CeAD(stroke), n = 635) were compared with non-CeAD IS patients regarding migraine, clinical characteristics, and outcome. CeAD patients with and without migraine were compared in terms of clinical characteristics and outcome. RESULTS: Migraine was more common among CeAD(stroke) patients compared to non-CeAD IS patients (35.7 vs 27.4%, p = 0.003). The difference was mainly due to migraine without aura (20.2 vs 11.2%, p < 0.001). There were no differences in prevalence of strokes, arterial distribution, or other clinical or prognostic features between migrainous and nonmigrainous CeAD patients. CONCLUSION: Migraine without aura is more common among CeAD(stroke) patients compared to non-CeAD IS patients. The mechanisms and possible causative link remain to be proved. Although CeAD is often complicated by stroke, our data do not support increased risk of stroke in migrainous CeAD patients.