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Hemorrhagic transformation (HT) is a complication occurring in patients with acute ischemic stroke (AIS) either spontaneously or post-thrombolysis leading to significant morbidity and mortality. We assessed circulating matrix metalloproteinase-9 (MMP-9), Claudin-5, and soluble serum stimulation-2 (sST2) in HT and stroke severity in AIS based on their temporal distribution.We prospectively enrolled 111 AIS patients within 12 h from onset. Patient demographic, clinical, and imaging details were documented. Follow-up imaging was conducted 24-48 h after admission. Blood samples were taken at three time-points from stroke onset. HT was classified according to the European Co-operative Acute Stroke Study-III(ECASS-III). Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Multiple logistic regression and receiver operating characteristic curve were conducted to determine the discriminative capacity.Mean age was 62.3 ± 11.7 years and median baseline NIHSS was 12[IQR 8.0-18.0]. HT was detected in 30(27%) patients. Biomarker levels at 12 h were elevated with median MMP-9 concentration of 153.9 ng/mL[IQR 110.6-309 ng/mL] indicating a trend toward significant positive correlation with HT(P = 0.05). Claudin-5 levels at 12 h was elevated but was not statistically significant (43.1 pg/mL[IQR:26.7-72.6 pg/mL] vs 59.4 pg/mL[IQR:24.5-100.8 pg/mL];P = 0.4). Multiple logistic regression indicated Claudin-5 levels at 12 h (OR 9.46;95% CI:1.97-64.6;P = 0.010) and baseline low ASPECTS score(OR 20.3;95% CI:3.46-193; P = 0.003) independently predicted HT. MMP-9 at 12 h was significantly elevated in patients with moderate to severe strokes (P = 0.04).Claudin-5 and low ASPECTS independently predicted HT. MMP-9 was positively correlated with baseline stroke severity.

Background: Symptomatic intracranial atherosclerotic disease (sICAD) is associated with risk of recurrence of cerebral ischemic events in 4-19% of stroke patients annually. Previous studies indicate elevated high-sensitivity C-Reactive Protein (hs-CRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) to be associated with risk of recurrence. Objective: This prospective, observational study investigated serum levels of hs-CRP and the activity of Lp-PLA2 in patients with sICAD in predicting the risk of long-term stroke recurrence. Methods: We enrolled 48 patients with sICAD at 3 months from onset. The demographics, clinical, and imaging characteristics were recorded. Serum hs-CRP and Lp-PLA2 activity were assessed using automated high-sensitivity C-reactive protein assay and photometric technique, respectively. Patients were followed up at 6 months and 1 year and the presence of new vascular events was recorded. Results: The mean age of our study population was 59.5 ± 10.3 years and 91.7% were men. Four patients developed recurrent strokes during follow-up. The mean Hs-CRP was elevated in patients with events than in patients without events (5.9 ± 10.4 mg/L vs. 1.7 ± 2.4 mg/L, P=0.03). However, there was no significant association of mean Lp-PLA2 activity (118.3±42.9 nmol/min/ml vs. 111.9 ± 34.2 nmol/min/ml, P=0.73) with recurrence. Elevation of hs-CRP (3.02 ± 4.8 mg/L vs. 0.95 ± 0.57mg/L, P=0.02) and Lp-PLA2 activity (120.1±40.3 nmol/min/ml vs. 103.3 ± 23.9 nmol/min/ml, P=0.04) was correlated with high-grade stenosis in these patients. Conclusion: Our study suggests serum levels of hs-CRP may serve as a predictor of long-term stroke recurrence risk in sICAD and elevation of hs-CRP and Lp-PLA2 correlated with the severity of stenosis in symptomatic intracranial atherosclerotic disease.

High-density lipoprotein (HDL) is known to have atheroprotective properties which could become dysfunctional under certain disease conditions, particularly during the atherosclerotic progression. The present study sought to assess HDL functionality in acute ischemic stroke (AIS) patients in comparison with controls and the functional alteration among the ischemic stroke subtypes. The HDL functionality was evaluated in 71 statin-naïve, adult patients of South Indian descent, admitted with AIS and were compared with that of 25 age- and sex-matched healthy volunteers. Functional assay of HDL was based on its antioxidant ability to inhibit low-density lipoproteins (LDL) oxidation by air using a dichlorodihydrofluorescein-based fluorescent assay and expressed as HDL oxidant index (HOI). The HOI was higher in ischemic stroke patients as compared with controls (1.07±0.32 vs. 0.51±0.12; P1 in all stroke subtypes: 1.05±0.301 for Cardioembolic subtype, 1.15±0.41 for large vessel disease, and 1.01±0.25 for small vessel disease when compared with controls. However, no significant difference was noted in HOI values among the three stroke subtypes in the post hoc analysis. It was found that HDL in all ischemic stroke subtypes had less antioxidant capacity, indicating dysfunctional HDL. Functional alteration occurred in HDL of patients even in the presence of normal HDL-cholesterol levels suggesting that dysfunctionality in HDL is unrelated to cholesterol content.

Background: Hemorrhagic transformation (HT) is a complication that occurs spontaneously or after thrombolysis in acute ischemic stroke (AIS) and can increase morbidity and mortality. The association of biomarkers with the risk of HT has been variably reported. We conducted a systematic review of the literature and meta-analysis and sought to compare blood biomarkers associated with HT and its subtypes by evaluating its predictability and correlation with outcome in AIS. Methods: The study protocol was registered in the PROSPERO database (CRD42020201334) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Among 2,230 articles identified from Cochrane Library, PubMed, and Web of Science databases, 30 quality-appraised articles were found eligible. Meta-analysis was conducted for matrix metalloproteinase-9 (MMP-9), cellular fibronectin (c-Fn), ferritin, S100 calcium-binding protein B (S100B), and neutrophil-lymphocyte ratio (NLR). We also reviewed biomarkers for correlation with the functional outcome at 90 days from stroke onset (poor outcome modified Rankin scale >2). Results: The pooled diagnostic odds ratio (DORpooled) was the highest for baseline c-Fn levels (299.253 [95% CI, 20.508–4,366.709]), followed by MMP-9 (DORpooled, 29.571 [95% CI 17.750–49.267]) and ferritin (DORpooled, 24.032 [95% CI 2.557–225.871]). However, wide confidence intervals for ferritin and c-Fn suggested lesser reliability of the markers. Patients with MMP-9 levels ≥140 ng/mL were 29.5 times at higher risk of developing symptomatic HT after AIS (area under the curve = 0.881). S100B (DORpooled, 6.286 [95% CI, 1.861–21.230]) and NLR (DORpooled, 5.036 [95% CI, 2.898–8.749]) had lower diagnostic accuracies. Among the markers not included for meta-analysis, caveolin-1, thrombin-activated fibrinolysis inhibitor, plasminogen activator inhibitor-1, and soluble ST2 were highly sensitive. Elevated levels of MMP-9, ferritin, and NLR were found to be associated with poor functional outcomes and mortality. Conclusion: Of the 5 biomarkers, there was enough evidence that MMP-9 has higher diagnostic accuracy for predicting the risk of HT before thrombolysis. MMP-9, ferritin, and NLR also predicted poor short-term outcomes.

Introduction: Elevated serum apolipoprotein B and the apolipoprotein B/A1 ratio have been associated with ischemic stroke and intracranial atherosclerotic disease. We sought to assess the relationship between serum levels of apolipoprotein B, apolipoprotein A1, and the apolipoprotein B/A1 ratio with ischemic stroke subtypes and large artery atherosclerosis location. Materials and Methods: We evaluated serum apolipoprotein B and apolipoprotein A1 levels in consecutive, statin-naive, adult ischemic stroke patients admitted to an academic medical center in southern India. We evaluated for differences in the mean serum levels of apolipoprotein B, apolipoprotein A1, and the apolipoprotein B/A1 ratio between patients with ischemic stroke attributed to intracranial atherosclerotic disease, extracranial atherosclerotic disease, small vessel disease, and cardioembolism. In secondary analysis, we assessed for differences in these serum apolipoproteins between patients with moderate-severe intracranial atherosclerotic disease and extracranial atherosclerotic disease, irrespective of ischemic stroke subtype. Results: Among the 156 ischemic stroke patients enrolled in this study, there were no significant differences in serum levels of apolipoprotein B, apolipoprotein A1, and the apolipoprotein B/A1 ratio between patients with distinct ischemic stroke subtypes. No significant differences were found in serum levels of apolipoprotein B, A1 and the apolipoprotein B/A1 ratio between patients with moderate-severe intracranial atherosclerotic disease and moderate-severe extracranial atherosclerotic disease. Discussion: Serum levels of apolipoprotein B and A1 did not differ between ischemic stroke subtypes. Additional studies are needed to validate our findings and to better understand the relationship between serum apolipoproteins and stroke.

Introduction Impulse control disorders (ICD) are reported to occur at variable frequencies in different ethnic groups. Genetic vulnerability is suspected to underlie the individual risk for ICD. We investigated whether the allelic variants of dopamine (DRD3), glutamate (GRIN2B) and serotonin (HTR2A) receptors are linked to ICD in Indian Parkinson’s disease (PD) patients. Methods We conducted a prospective, case-control study which included PD patients (70 with ICD, 100 without ICD categorized after direct psychiatric interview of patient and caregiver) and 285 healthy controls. Single nucleotide polymorphism (SNP) variants of DRD3 p.S9G (rs6280), GRIN2B c.2664C>T (rs1806201) and HTR2A c.102T>C (rs6313) were genotyped. Results Multivariate regression analysis revealed that DRD3 p.Ser9Gly (rs6280) heterozygous variant CT (OR = 2.22, 95% CI: 1.03–4.86, p = 0.041), higher daily Levodopa equivalent doses (LED) of drugs (for 100 mg LED, OR = 1.14, 95% CI: 1.01–1.29, p = 0.041), current dopamine agonist but not Levodopa use (OR = 2.16, 95% CI: 1.03–4.55, p = 0.042) and age of onset of motor symptoms under 50 years (OR 2.09, 95% CI: 1.05–4.18, p = 0.035) were independently associated with ICD. Conclusion DRD3 p.Ser9Gly (rs6280) CT genotype is associated with ICD in Indian PD patients and this association is novel. Enhanced D3 receptor affinity due to gain-of-function conferred by the glycine residues could impair reward-risk assessment in the mesolimbic system and contribute to development of impulsive behaviour, in carriers of this genotype.

Biological MEMS devices are being developed for applications in collection, monitoring, diagnostics and drug delivery. The objective of this work is to develop a simulation tool for the design, analysis and optimization of these devices. Simulations of biological MEMS devices are challenging due to the non-Newtonian behavior of biological fluids, coupling of flow with electric fields in electrophoretic separations, transport of non-homogeneous cellular structures and mixing between Newtonian and non-Newtonian fluids. This paper presents Computational Fluid Dynamic (CFD) simulations of biological fluid flow, mixing, electro-kinetics and transport of particles in microfluidic systems. A commercial CFD code, CFD-ACE+, that solves the full Navier-Stokes equations using a finite-volume approach has been adapted to perform these simulations of biological MEMS devices. Model predictions are validated through comparisons with experimental data.