Left Ventricular Diastolic Dysfunction Is Associated with Poor Functional Outcomes after Endovascular Thrombectomy.

INTRODUCTION: With the advent of endovascular thrombectomy (ET), patients with acute ischaemic strokes (AIS) with large vessel occlusion (LVO) have seen vast improvements in treatment outcomes. Left ventricular diastolic dysfunction (LVDD) has been shown to herald poorer prognosis in conditions such as myocardial infarction. However, whether LVDD is related to functional recovery and outcomes in ischaemic stroke remains unclear. We studied LVDD for possible relation with clinical outcomes in patients with LVO AIS who underwent ET. METHODS: We studied a retrospective cohort of 261 LVO AIS patients who had undergone ET at a single comprehensive stroke centre and correlated LVDD to short-term mortality (in-hospital death) as well as good functional recovery defined as modified Rankin Scale of 0-2 at 3 months. RESULTS: The study population had a mean age of 65-years-old and were predominantly male (54.8%). All of the patients underwent ET with 206 (78.9%) achieving successful reperfusion. Despite this, 25 (9.6%) patients demised during the hospital admission and 149 (57.1%) did not have good function recovery at 3 months. LVDD was present in 82 (31.4%) patients and this finding indicated poorer outcomes in terms of functional recovery at 3 months (OR 2.18, 95% CI 1.04-4.54, p = 0.038) but was not associated with increased in-hospital mortality (OR 2.18, 95% CI 0.60-7.99, p = 0.240) after adjusting for various confounders. CONCLUSION: In addition to conventional echocardiographic indices such as left ventricular ejection fraction, LVDD may portend poorer outcomes after ET, and this relationship should be investigated further.

Low HALP (Hemoglobin, Albumin, Lymphocyte, and Platelet) Score Increases the Risk of Post-Stroke Cognitive Impairment: A Multicenter Cohort Study.

Objective: The HALP (hemoglobin, albumin, lymphocyte, and platelet) score is a novel indicator that measures systemic inflammation and nutritional status that has not been correlated with the risk of post-stroke cognitive impairment in patients with acute ischemic stroke or transient ischemic attack (TIA). Methods: Study participants were recruited from 40 stroke centers in China. The HALP score was derived using a weighted sum of hemoglobin, albumin, lymphocytes and platelets, and study participants were categorized into 4 groups of equal sizes based on quartiles cutoffs of the HALP score. The Montreal Cognitive Assessment (MoCA)-Beijing Cognitive Assessment Scale (MoCA-Beijing) was performed at 2 weeks and 12 months following stroke onset. Post-stroke cognitive impairment was considered in patients with MoCA-Beijing≤22. Multiple logistic regression methods were employed to evaluate the relationship between the HALP score and the subsequent risk of developing post-stroke cognitive impairment. Results: The study population comprised 1022 patients (mean age 61.6±11.0 years, 73% men). The proportion of individuals with MoCA-Beijing≤22 at 2 weeks was 49.2% and 32.4% at one year. Patients in the lowest quartile of HALP score (<36.56) were observed to harbor the highest risk of post-stroke cognitive impairment at 12 months post-stroke/TIA compared to those in the highest quartile (odds ratio=1.59, 95% CI=1.07-2.37, p=0.022), and lower domain scores for executive function, naming, and attention. There were no statistically significant differences between patients in the different quartiles of HALP score and HALP score at 2 weeks post-stroke/TIA. Conclusion: The HALP score is a simple score that could stratify the risk of post-stroke cognitive impairment in stroke/TIA patients to facilitate early diagnosis and interventions.

Repurposing povidone-iodine to reduce the risk of SARS-CoV-2 infection and transmission: a narrative review.

BACKGROUND: Accumulating data suggest antiviral effects of povidone-iodine against the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. This narrative review aims to examine the antiviral mechanisms of povidone-iodine, efficacy of povidone-iodine against the SARS-CoV-2 virus, and safety of povidone-iodine to human epithelial cells and thyroid function. METHODS: We searched the electronic databases PubMed, Embase, Cochrane Library, ClinicalTrials.gov and World Health Organization's International Clinical Trials Registry Platform for articles containing the keywords "povidone-iodine", "SARS-CoV-2" and "COVID-19" from database inception till 3 June 2021. RESULTS: Despite in vitro data supporting the anti-SARS-CoV-2 effects of povidone-iodine, findings from clinical studies revealed differences in treatment response depending on study settings (healthy vs. hospitalized individuals), treatment target (nasal vs. oral vs. pharynx), method of administration (oral rinse vs. gargle vs. throat spray) and choice of samples used to measure study endpoints (nasopharyngeal vs. saliva). One large-scale clinical trial demonstrated reduction in the incidence of SARS-CoV-2 infection among participants who administered povidone-iodine 3 times daily during an active outbreak. Povidone-iodine is also used to disinfect the oro-pharyngeal space prior to dental or otolaryngology procedures. Although existing data suggest minimal impact of povidone-iodine on thyroid function, high-quality safety data are presently lacking. CONCLUSIONS: Povidone-iodine application to the oropharyngeal space could complement existing non-pharmacological interventions to reduce SARS-CoV-2 infection especially in high exposure settings.Key messagesAccumulating data suggest antiviral effects of povidone-iodine against the SARS-CoV-2 virus.Findings from clinical studies reveal differences in treatment response depending on study settings, treatment target, method of administration and choice of samples used to measure study endpoints. One large-scale clinical trial observed reduction in the incidence of SARS-CoV-2 infection among participants who administered povidone-iodine 3 times daily during an active outbreak.Povidone-iodine application to the oropharyngeal space could complement existing non-pharmacological interventions to reduce SARS-CoV-2 infection especially in high exposure settings.

Effect of Sex on Outcomes of Mechanical Thrombectomy in Basilar Artery Occlusion: A Multicentre Cohort Study.

INTRODUCTION: Identifying differences in outcome of basilar artery occlusion (BAO) between males and females may be useful in aiding clinical management. Recent studies have demonstrated widespread underrepresentation of women in acute stroke clinical trials. This international multicentre study aimed to determine sex differences in outcome after mechanical thrombectomy (MT) for patients with acute BAO. METHODS: We performed a retrospective analysis of consecutive patients with BAO who had undergone MT in seven stroke centres across five countries (Singapore, Taiwan, United Kingdom, Sweden, and Germany), between 2015 and 2020. Primary outcome was a favourable functional outcome measured by a modified Ranking Scale (mRS) of 0-3 at 90 days. Secondary outcomes were mRS 0-3 upon discharge, mortality, symptomatic intracranial haemorrhage (sICH) and subarachnoid haemorrhage (SAH). RESULTS: Among the 322 patients who underwent MT, 206 (64.0%) patients were male and 116 (36.0%) were female. Females were older than males (mean ± SD 70.9 ± 14.3 years vs. 65.6 ± 133.6 years; p = 0.001) and had higher rates of atrial fibrillation (38.9% vs. 24.2%; p = 0.012). Time from groin puncture to reperfusion was shorter in females than males (mean ± SD 57.2 ± 37.2 min vs. 71.1 ± 50.9 min; p = 0.021). Despite these differences, primary and secondary outcome measures were similar in females and males, with comparable rates of favourable 90-day mRS scores (mean ± SD 46 ± 39.7 vs. 71 ± 34.5; OR = 1.20; 95% confidence interval [CI] = 0.59-2.43; p = 0.611), favourable discharge mRS scores (mean ± SD 39 ± 31.6 vs. 43 ± 25.9; OR = 1.38; 95% CI = 0.69-2.78; p = 0.368) and in-hospital mortality (mean ± SD 30 ± 25.9 vs. 47 ± 22.8; OR = 1.15; 95% CI = 0.55-2.43; p = 0.710. Rates of complications such as sICH (mean ± SD 5 ± 4.3 vs. 9 ± 4.4; OR = 0.46; 95% CI = 0.08-2.66; p = 0.385) and SAH (mean ± SD 4 ± 3.4 vs. 5 ± 2.4; OR = 0.29; 95% CI = 0.03-3.09; p = 0.303) comparably low in both groups. CONCLUSION: Females achieved comparable functional outcomes compared with males after undergoing MT for BAO acute ischemic stroke.

Effect of frailty on outcomes of endovascular treatment for acute ischaemic stroke in older patients.

BACKGROUND: frailty has been shown to be a better predictor of clinical outcomes than age alone across many diseases. Few studies have examined the relationship between frailty, stroke and stroke interventions such as endovascular thrombectomy (EVT). OBJECTIVE: we aimed to investigate the impact of frailty measured by clinical frailty scale (CFS) on clinical outcomes after EVT for acute ischemic stroke (AIS) in older patients ≥70 years. METHODS: in this retrospective cohort study, we included all consecutive AIS patients age ≥ 70 years receiving EVT at a single comprehensive stroke centre. Patients with CFS of 1-3 were defined as not frail, and CFS > 3 was defined as frail. The primary outcome was modified Rankin Score (mRS) at 90 days. The secondary outcomes included duration of hospitalisation, in-hospital mortality, carer requirement, successful reperfusion, symptomatic intracranial haemorrhage and haemorrhagic transformation. RESULTS: a total of 198 patients were included. The mean age was 78.1 years and 52.0% were female. Frail patients were older, more likely to be female, had more co-morbidities. CFS was significantly associated with poor functional outcome after adjustment for age, NIHSS and time to intervention (adjusted odds ratio [aOR] 1.54, 95% confidence interval [CI] 1.04-2.28, P = 0.032). There was trend towards higher mortality rate in frail patients (frail: 18.3%; non-frail: 9.6%; P = 0.080). There were no significant differences in other secondary outcomes except increased carer requirement post discharge in frail patients (frail: 91.6%; non-frail: 72.8%; P = 0.002). CONCLUSIONS: frailty was associated with poorer functional outcome at 90 days post-EVT in patients ≥ 70 years.

Mitigating SARS-CoV-2 Transmission in Hospitals: A Systematic Literature Review.

Objectives: Hospital outbreaks of SARS-CoV-2 infection are dreaded but preventable catastrophes. We review the literature to examine the pattern of SARS-CoV-2 transmission in hospitals and identify potential vulnerabilities to mitigate the risk of infection. Methods: Three electronic databases (PubMed, Embase and Scopus) were searched from inception to July 27, 2021 for publications reporting SARS-CoV-2 outbreaks in hospital. Relevant articles and grey literature reports were hand-searched. Results: Twenty-seven articles that described 35 SARS-CoV-2 outbreaks were included. Despite epidemiological investigations, the primary case could not be identified in 37% of outbreaks. Healthcare workers accounted for 40% of primary cases (doctors 17%, followed by ancillary staff 11%). Mortality among infected patients was approximately 15%. By contrast, none of the infected HCWs died. Several concerning patterns were identified, including infections involving ancillary staff and healthcare worker infections from the community and household contacts. Conclusion: Continuous efforts to train-retrain and enforce correct personal protective equipment use and regular routine screening tests (especially among ancillary staff) are necessary to stem future hospital outbreaks of SARS-CoV-2.

Bridging Thrombolysis versus Direct Mechanical Thrombectomy in Stroke Due to Basilar Artery Occlusion.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is an effective treatment for patients with basilar artery occlusion (BAO) acute ischemic stroke. It remains unclear whether bridging intravenous thrombolysis (IVT) prior to MT confers any benefit. This study compared the outcomes of acute BAO patients who were treated with direct MT versus combined IVT plus MT. METHODS: This multicenter retrospective cohort study included patients who were treated for acute BAO from eight comprehensive stroke centers between January 2015 and December 2019. Patients received direct MT or combined bridging IVT plus MT. Primary outcome was favorable functional outcome defined as modified Rankin Scale 0-3 measured at 90 days. Secondary outcome measures included mortality and symptomatic intracranial hemorrhage (sICH). RESULTS: Among 322 patients, 127 (39.4%) patients underwent bridging IVT followed by MT and 195 (60.6%) underwent direct MT. The mean±standard deviation age was 67.5±14.1 years, 64.0% were male and median National Institutes of Health Stroke Scale was 16 (interquartile range, 8 to 25). At 90-day, the rate of favorable functional outcome was similar between the bridging IVT and direct MT groups (39.4% vs. 34.4%, P=0.361). On multivariable analyses, bridging IVT was not as Comorbidisociated with favorable functional outcome, mortality or sICH. In subgroup analyses, patients with underlying atherosclerosis treated with bridging IVT compared to direct MT had a higher rate of favorable functional outcome at 90 days (37.2% vs. 15.5%, P=0.013). CONCLUSIONS: Functional outcomes were similar in BAO patients treated with bridging IVT versus direct MT. In the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT may potentially confer benefit and this warrants further investigation.

Blood biomarkers to detect new-onset atrial fibrillation and cardioembolism in ischemic stroke patients.

BACKGROUND: Accumulating data suggest blood biomarkers could inform stroke etiology. OBJECTIVE: The purpose of this study was to investigate the performance of multiple blood biomarkers in elucidating stroke etiology with a focus on new-onset atrial fibrillation (AF) and cardioembolism. METHODS: Between January and December 2017, information on clinical and laboratory parameters and stroke characteristics was prospectively collected from ischemic stroke patients recruited from the National University Hospital, Singapore. Multiple blood biomarkers (N-terminal pro-brain natriuretic peptide [NT-proBNP], d-dimer, S100ß, neuron-specific enolase, vitamin D, cortisol, interleukin-6, insulin, uric acid, and albumin) were measured in plasma. These variables were compared with stroke etiology and the risk of new-onset AF and cardioembolism using multivariable regression methods. RESULTS: Of the 515 ischemic stroke patients (mean age 61 years; 71% men), 44 (8.5%) were diagnosed with new-onset AF, and 75 (14.5%) had cardioembolism. The combination of 2 laboratory parameters (total cholesterol ≤169 mg/dL; triglycerides ≤44.5 mg/dL) and 3 biomarkers (NT-proBNP ≥294 pg/mL; S100ß ≥64 pg/mL; cortisol ≥471 nmol/l) identified patients with new-onset AF (negative predictive value [NPV] 90%; positive predictive value [PPV] 73%; area under curve [AUC] 85%). The combination of 2 laboratory parameters (total cholesterol ≤169 mg/dL; triglycerides ≤44.5 mg/dL) and 2 biomarkers (NT-proBNP ≥507 pg/mL; S100ß ≥65 pg/mL) identified those with cardioembolism (NPV 86%; PPV 78%; AUC 87%). Adding clinical predictors did not improve the performance of these models. CONCLUSION: Blood biomarkers could identify patients with increased likelihood of cardioembolism and direct the search for occult AF.

Characterization and Functional Assessment of Endothelial Progenitor Cells in Ischemic Stroke Patients.

Endothelial dysfunction has been implicated in atherosclerosis, ischemic heart disease, and stroke. Endothelial progenitor cells (EPCs), found in the bone marrow and peripheral blood as rare cell population, demonstrated a high proliferation and differentiation capacity. Understanding how such diseases influence the quantity and functionality of EPCs is essential for the development of novel therapies. This study aims to investigate the factors that affect the quantity and functionality of circulating EPCs in stroke patients and healthy controls. Blood samples were collected once from healthy donors (n = 30) and up to 3 times (within 7 days (baseline), 3 and 12 months post-stroke) from stroke patients (n = 207). EPC subpopulations were isolated with flow cytometry for characterization. The Matrigel tubular formation assay was performed as a measure of functionality. An increased amount of circulating EPCs was observed in stroke patients over 45 years when compared to age-matched healthy individuals. EPCs showed a rising trend in stroke patients over the 12-month post-stroke period, reaching statistical significance at 12 months post-stroke. Isolated CD34+KDR+ cells from stroke patients showed impairment in tubular formation capability when compared to cells from healthy donors. The quantity and vasculogenic function of circulating EPCs in peripheral blood have been effectively evaluated in stroke patients and healthy control donors in this study. Age and stroke are found to be 2 influencing factors on the angiogenic capacity. It is suggested that the increase in EPC number is triggered by the recovery response following ischemic stroke. Graphical abstract.

Blood-Based Biomarkers Are Associated with Different Ischemic Stroke Mechanisms and Enable Rapid Classification between Cardioembolic and Atherosclerosis Etiologies.

Stroke is a top leading cause of death, which occurs due to interference in the blood flow of the brain. Ischemic stroke (blockage) accounts for most cases (87%) and is further subtyped into cardioembolic, atherosclerosis, lacunar, other causes, and cryptogenic strokes. The main value of subtyping ischemic stroke patients is for a better therapeutic decision-making process. The current classification methods are complex and time-consuming (hours to days). Specific blood-based biomarker measurements have promising potential to improve ischemic stroke mechanism classification. Over the past decades, the hypothesis that different blood-based biomarkers are associated with different ischemic stroke mechanisms is increasingly investigated. This review presents the recent studies that investigated blood-based biomarker characteristics differentiation between ischemic stroke mechanisms. Different blood-based biomarkers are specifically discussed (b-type natriuretic peptide, d-dimer, c-reactive protein, tumor necrosis factor-α, interleukin-6, interleukin-1ß, neutrophil-lymphocyte ratio, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein and apolipoprotein A), as well as the different cut-off values that may be useful in specific classifications for cardioembolic and atherosclerosis etiologies. Lastly, the structure of a point-of-care biosensor device is presented, as a measuring tool on-site. The information presented in this review will hopefully contribute to the major efforts to improve the care for stroke patients.

B-Type Natriuretic Peptide as a Significant Brain Biomarker for Stroke Triaging Using a Bedside Point-of-Care Monitoring Biosensor.

Stroke is a widespread condition that causes 7 million deaths globally. Survivors suffer from a range of disabilities that affect their everyday life. It is a complex condition and there is a need to monitor the different signals that are associated with it. Stroke patients need to be rapidly diagnosed in the emergency department in order to allow the admission of the time-limited treatment of tissue plasminogen activator (tPA). Stroke diagnostics show the use of sophisticated technologies; however, they still contain limitations. The hidden information and technological advancements behind the utilization of biomarkers for stroke triaging are significant. Stroke biomarkers can revolutionize the way stroke patients are diagnosed, monitored, and how they recover. Different biomarkers indicate different cascades and exhibit unique expression patterns which are connected to certain pathologies in the human body. Over the past decades, B-type natriuretic peptide (BNP) and its derivative N-terminal fragment (NT-proBNP) have been increasingly investigated and highlighted as significant cardiovascular biomarkers. This work reviews the recent studies that have reported on the usefulness of BNP and NT-proBNP for stroke triaging. Their classification association is also presented, with increased mortality in stroke, correlation with cardioembolic stroke, and an indication of a second stroke recurrence. Moreover, recent scientific efforts conducted for the technological advancement of a bedside point-of-care (POC) device for BNP and NT-proBNP measurements are discussed. The conclusions presented in this review may hopefully assist in the major efforts that are currently being conducted in order to improve the care of stroke patients.

Impact of the COVID-19 pandemic on hyperacute stroke treatment: experience from a comprehensive stroke centre in Singapore.

The Coronavirus disease 2019 (COVID-19) pandemic is rapidly evolving and affecting healthcare systems across the world. Singapore has escalated its alert level to Disease Outbreak Response System Condition (DORSCON) Orange, signifying severe disease with community spread. We aimed to study the overall volume of AIS cases and the delivery of hyperacute stroke services during DORSCON Orange. This was a single-centre, observational cohort study performed at a comprehensive stroke centre responsible for AIS cases in the western region of Singapore, as well as providing care for COVID-19 patients. All AIS patients reviewed as an acute stroke activation in the Emergency Department (ED) from November 2019 to April 2020 were included. System processes timings, treatment and clinical outcome variables were collected. We studied 350 AIS activation patients admitted through the ED, 206 (58.9%) pre- and 144 during DORSCON Orange. Across the study period, number of stroke activations showed significant decline (p = 0.004, 95% CI 6.513 to - 2.287), as the number of COVID-19 cases increased exponentially, whilst proportion of activations receiving acute recanalization therapy remained stable (p = 0.519, 95% CI - 1.605 to 2.702). Amongst AIS patients that received acute recanalization therapy, early neurological outcomes in terms of change in median NIHSS at 24 h (-4 versus -4, p = 0.685) were largely similar between the pre- and during DORSCON orange periods. The number of stroke activations decreased while the proportion receiving acute recanalization therapy remained stable in the current COVID-19 pandemic in Singapore.

Left Atrial Volume Index Predicts New-Onset Atrial Fibrillation and Stroke Recurrence in Patients with Embolic Stroke of Undetermined Source.

INTRODUCTION: It is unclear which surrogate of atrial cardiopathy best predicts the risk of developing a recurrent ischemic stroke in embolic stroke of undetermined source (ESUS). Left atrial diameter (LAD) and LAD index (LADi) are often used as markers of left atrial enlargement in current ESUS research, but left atrial volume index (LAVi) has been found to be a better predictor of cardiovascular outcomes in other patient populations. OBJECTIVE: We aim to compare the performance of LAVi, LAD, and LADi in predicting the development of new-onset atrial fibrillation (AF) and stroke recurrence in ESUS. METHODS: Between October 2014 and October 2017, consecutive patients diagnosed with ESUS were followed for new-onset AF, ischemic stroke recurrence, and a composite outcome of occult AF and stroke recurrence. LAVi and LADi were measured by transthoracic echocardiogram; "high" LAVi was defined as ≥35 mL/m2 in accordance with American Society of Echocardiography guidelines. RESULTS: 185 ischemic stroke patients with ESUS were recruited and followed for a median duration of 2.1 years. Increased LAVi was associated with new-onset AF detection (aOR 1.08; 95% CI 1.03-1.14; p = 0.003) and stroke recurrence (aOR 1.05; 95% CI 1.01-1.10; p = 0.026). Patients with "high" LAVi had a higher likelihood of developing a composite of AF detection and stroke recurrence (HR 3.45; 95% CI 1.55-7.67; p = 0.002). No significant association was observed between LADi and either occult AF or stroke recurrence. CONCLUSIONS: LAVi is associated with new-onset AF and stroke recurrence in ESUS patients and may be a better surrogate of atrial cardiopathy.

Functionalized silicon dioxide self-referenced plasmonic chip as point-of-care biosensor for stroke biomarkers NT-proBNP and S100ß.

Surface plasmon resonance (SPR) biosensors are often used in the detection of solid, liquid or gaseous samples in diagnostics, pharmaceutics and military defense. Plasmon waveguide resonance (PWR) mode is obtained when a dielectric waveguide layer is added to the metal film. In this study, a self-referenced PWR (SRPWR) silicon dioxide (SiO2) chip was examined. The self-referenced measurement is important to compensate for temperature fluctuations, other instabilities and allows RI signal measurement without an additional reference sample, thus minimising the sample volume needed. The chip was fabricated with a multi-layer of metals and dielectrics, consisting of a 420 nm SiO2 layer, a 40 nm Ag layer and another 480 nm SiO2 layer. This chip was shown to give one internal plasmon excited on the bottom interface SiO2/Ag, which is used as self-reference in the detection. The top layer acts as a waveguide layer and can be designed to give modes with ultrahigh penetration depth. A direct assay was developed, where the recognition molecule (specific antibody) was immobilized onto the SiO2 plasmonic chip surface, via a covalent coupling protocol based on 3-aminopropyltriethoxysilane (APTES) and glutaraldehyde. The SRPWR biosensor was developed for the sensing of two chosen stroke biomarkers: NT-proBNP and S100ß, which are sensitive and specific for stroke diagnostics. For both biomarkers, a linear decreasing pattern in the RI signal was recognized with the increasing biomarkers concentrations. Biomarkers detection was conducted in deionized water and validation was done in spiked porcine plasma. The SiO2 based plasmonic chip demonstrates a limit-of-detection of less than 1 ng/mL that is clinically relevant for both stroke biomarkers.

Heredity of type 2 diabetes confers increased susceptibility to oxidative stress and inflammation.

INTRODUCTION AND OBJECTIVE: Heredity of type 2 diabetes mellitus (T2DM) is associated with greater risk for developing T2DM. Thus, individuals who have a first-degree relative with T2DM (FDRT) provide a natural model to study factors of susceptibility towards development of T2DM, which are poorly understood. Emerging key players in T2DM pathophysiology such as adverse oxidative stress and inflammatory responses could be among possible mechanisms that predispose FDRTs to develop T2DM. Here, we aimed to examine the role of oxidative stress and inflammatory responses as mediators of this excess risk by studying dynamic postprandial responses in FDRTs. RESEARCH DESIGN AND METHODS: In this open-label case-control study, we recruited normoglycemic men with (n=9) or without (n=9) a family history of T2DM. We assessed plasma glucose, insulin, lipid profile, cytokines and F2-isoprostanes, expression levels of oxidative and inflammatory genes/proteins in circulating mononuclear cells (MNC), myotubes and adipocytes at baseline (fasting state), and after consumption of a carbohydrate-rich liquid meal or insulin stimulation. RESULTS: Postprandial glucose and insulin responses were not different between groups. Expression of oxidant transcription factor NRF2 protein (p<0.05 for myotubes) and gene (pgroup=0.002, ptime×group=0.016), along with its target genes TXNRD1 (pgroup=0.004, ptime×group=0.007), GPX3 (pgroup=0.011, ptime×group=0.019) and SOD-1 (pgroup=0.046 and ptime×group=0.191) was upregulated in FDRT-derived MNC after meal ingestion or insulin stimulation. Synergistically, expression of target genes of inflammatory transcription factor nuclear factor kappa B such as tumor necrosis factor alpha (pgroup=0.001, ptime×group=0.007) was greater in FDRT-derived MNC than in non-FDRT-derived MNC after meal ingestion or insulin stimulation. CONCLUSIONS: Our findings shed light on how heredity of T2DM confers increased susceptibility to oxidative stress and inflammation. This could provide early insights into the underlying mechanisms and future risk of FDRTs for developing T2DM and its associated complications.

Early and Sustained Increases in Leukotriene B4 Levels Are Associated with Poor Clinical Outcome in Ischemic Stroke Patients.

Leukotriene B4 (LTB4) has been implicated in ischemic stroke pathology. We examined the prognostic significance of LTB4 levels in patients with acute middle cerebral artery (MCA) infarction and their mechanisms in rat stroke models. In ischemic stroke patients with middle cerebral artery infarction, plasma LTB4 levels were found to increase rapidly, roughly doubling within 24 h when compared to initial post-stroke levels. Further analyses indicate that poor functional recovery is associated with early and more sustained increase in LTB4 rather than the peak levels. Results from studies using a rat embolic stroke model showed increased 5-lipoxygenase (5-LOX) expression in the ipsilateral infarcted cortex compared with sham control or respective contralateral regions at 24 h post-stroke with a concomitant increase in LTB4 levels. In addition, neutrophil influx was also observed in the infarcted cortex. Double immunostaining indicated that neutrophils express 5-LOX and leukotriene A4 hydrolase (LTA4H), highlighting the pivotal contributions of neutrophils as a source of LTB4. Importantly, rise in plasma LTB4 levels corresponded with an increase in LTB4 amount in the infarcted cortex, thereby supporting the use of plasma as a surrogate for brain LTB4 levels. Pre-stroke LTB4 loading increased brain infarct volume in tMCAO rats. Conversely, administration of the 5-LOX-activating protein (FLAP) inhibitor BAY-X1005 or B-leukotriene receptor (BLTR) antagonist LY255283 decreased the infarct volume by a similar extent. To conclude, targeted interruption of the LTB4 pathway might be a viable treatment strategy for acute ischemic stroke.

Point-of-Care Surface Plasmon Resonance Biosensor for Stroke Biomarkers NT-proBNP and S100ß Using a Functionalized Gold Chip with Specific Antibody.

Surface-plasmon-resonance (SPR) is a quantum-electromagnetic phenomenon arising from the interaction of light with free electrons at a metal-dielectric interface. At a specific angle/wavelength of light, the photon's energy is transferred to excite the oscillation of the free electrons on the surface. A change in the refractive-index (RI) may occur, which is influenced by the analyte concentration in the medium in close contact with the metal surface. SPR has been widely used for the detection of gaseous, liquid, or solid samples. In this study, a functionalized specific SPR chip was designed and used in a novel point-of-care SPR module (PhotonicSys SPR H5) for the detection of the stroke biomarkers NT-proBNP and S100ß. These biomarkers have proven to be good for stroke diagnosis, with sensitivity and specificity of >85%. Specific detection was done by binding a biomolecular-recognizing antibody onto the Au SPR-chip. Detection was tested in water and plasma samples. NT-proBNP and S100ß were detected in a range of concentrations for stroke, from 0.1 ng/mL to 10 ng/mL. The RI of the blank plasma samples was 1.362412, and the lowest concentration tested for both biomarkers showed a prominent shift in the RI signal (0.25 ng/mL NT-proBNP (1.364215) and S100ß (1.364024)). The sensor demonstrated a clinically relevant limit-of-detection of less than ng/mL.