Field-portable optofluidic plasmonic biosensor for wide-field and label-free monitoring of molecular interactions

We demonstrate a field-portable optofluidic plasmonic sensing device, weighing 40 g and 7.5 cm in height, which merges plasmonic microarrays with dual-wavelength lensfree on-chip imaging for real-time monitoring of protein binding kinetics

Lensfree optofluidic plasmonic sensor for real-time and label-free monitoring of molecular binding events over a wide field-of-view

We demonstrate a high-throughput biosensing device that utilizes microfluidics based plasmonic microarrays incorporated with dual-color on-chip imaging toward real-time and label-free monitoring of biomolecular interactions over a wide field-of-view of >20 mm^2. Weighing 40 grams with 8.8 cm in height, this biosensor utilizes an opto-electronic imager chip to record the diffraction patterns of plasmonic nanoapertures embedded within microfluidic channels, enabling real-time analyte exchange. This plasmonic chip is simultaneously illuminated by two different light-emitting-diodes that are spectrally located at the right and left sides of the plasmonic resonance mode, yielding two different diffraction patterns for each nanoaperture array. Refractive index changes of the medium surrounding the near-field of the nanostructures, e.g., due to molecular binding events, induce a frequency shift in the plasmonic modes of the nanoaperture array, causing a signal enhancement in one of the diffraction patterns while suppressing the other. Based on ratiometric analysis of these diffraction images acquired at the detector-array, we demonstrate the proof-of-concept of this biosensor by monitoring in real-time biomolecular interactions of protein A/G with immunoglobulin G (IgG) antibody. For high-throughput on-chip fabrication of these biosensors, we also introduce a deep ultra-violet lithography technique to simultaneously pattern thousands of plasmonic arrays in a cost-effective manner

Relationship between maternal blood ceruloplasmin level, catalase and myeloperoxidase activity and neural tube defects

Objectives: The exact pathogenesis of neural tube defects (NTDs) is poorly understood. We aimed at evaluating maternal anti-oxidant capacity (ceruloplasmin level, myeloperoxidase and catalase activity) in pregnancies complicated by NTDs. Material and methods: Fifty-four mothers with NTD-affected pregnancies and 61 healthy mothers, matched for gestational age, were recruited. Maternal venous blood samples were obtained after detailed fetal ultrasound examination to measure myeloperoxidase, catalase activity and ceruloplasmin levels. The clinical characteristics of all participants were collected. Results: Maternal blood catalase activity was significantly lower in the study group (117.1 ± 64.8 kU/L) as compared to controls (152.2 ± 110.6 kU/L) (p = 0.044). Maternal blood ceruloplasmin levels were also significantly lower in the study group (180.5 ± 37.7 U/L) as compared to controls (197.9 ± 35.9 U/L) (p = 0.012). Myeloperoxidase activity was similar in both groups (112.6 ± 22.2 U/L vs. 113.6 ± 38.1 U/L) (p = 0.869). Conclusions: In the present study, maternal blood ceruloplasmin level and catalase activity were found to be lower in NTD-affected pregnancies as compared to healthy controls. Thus, it seems safe to conclude that impaired antioxidant capacity may play a role in the development of NTDs during pregnancy, in addition to the genetic, environmental and metabolic factors

Effect of angiotensin converting enzyme inhibitors on periprocedural myocardial infarction in patients with metabolic syndrome

Background: Metabolic syndrome (MetS) has been reported as a risk factor for cardiovascular events. The aim of the present study is to investigate the association between chronic angiotensin-converting enzyme inhibitors (ACE-I) therapy and the rate of periprocedural myocardial infarction (PMI) after elective coronary stenting among patients with MetS. Methods: The inclusion criteria were MetS and plan for elective percutaneous coronary intervention. To assess the effect of ACE-I treatment on the incidence of PMI, measurements of cardiac biomarkers (CK-MB mass and troponin I) were performed at baseline and 24 h after the procedure. Results: A total of 459 patients fulfilling the inclusion criteria were recruited to chronic ACE-I treatment and ACE-I naive groups in a 2/1 ratio. Baseline troponin I and CK-MB levels were similar in both treatment groups, whereas they were significantly lower in ACE-I group 24 h after the procedure. Univariate analysis identified body mass index (BMI), LDL cholesterol, nitrate and ACE-I use as significant factors for the development of PMI. Multivariate regression model revealed that body mass index increased and use of nitrate and ACE-I decreased the probability of PMI independent from confounding factors (OR 1.14, 95% CI 1.05–1.23, p = 0.002 for BMI; OR 0.26, 95% CI 0.14–0.48, p = 0.01 for nitrate use, OR 0.51, 95% CI 0.27–0.93, p = 0.03 for ACE-I use). Conclusions: This prospective observational cohort trial demonstrated that chronic ACE-I therapy was an independent predictor for reduced PMI among patients with MetS who underwent elective coronary intervention

Elevated Red Blood Cell Distribution Width May Be a Novel Independent Predictor of Poor Functional Outcome in Patients Treated with Mechanical Thrombectomy

Purpose Red blood cell distribution width (RDW) evaluates the variation (size heterogeneity) in red blood cells. Elevated RDW has been identified as a predictor of poor functional outcomes for acute ischemic stroke. The association between elevated RDW level and poor functional outcome in stroke patients undergoing mechanical thrombectomy has not been reported before. This study aims to investigate this relationship. Materials and Methods This was a multicenter retrospective study involving the prospectively and consecutively collected data of 205 adult stroke patients who underwent mechanical thrombectomy for anterior circulation large vessel occlusion (middle cerebral artery M1, anterior cerebral artery A1, tandem ICA-MCA, carotid T) between July 2017 and December 2019. RDW cut off levels were accepted as >16%. The effect of elevated RDW on poor functional outcome (modified Rankin scale 3–6) was investigated using bivariate and multivariate regression analysis. Results Elevated RDW was significantly associated with poor functional outcome in bivariate and multivariate analysis (odds ratio [OR] for RDW >16%, 2.078; 95% confidence interval [95% CI], 1.083–3.966; P=0.027 and OR for RDW >16%, 2.873; 95% CI, 1.342–6.151; P=0.007; respectively). Conclusion These findings suggest that elevated RDW may be an independent predictor of poor functional outcomes in ischemic stroke patients undergoing mechanical thrombectomy

Loss of heme oxygenase 2 causes reduced expression of genes in cardiac muscle development and contractility and leads to cardiomyopathy in mice

Obstructive sleep apnea (OSA) is a common breathing disorder that affects a significant portion of the adult population. In addition to causing excessive daytime sleepiness and neurocognitive effects, OSA is an independent risk factor for cardiovascular disease; however, the underlying mechanisms are not completely understood. Using exposure to intermittent hypoxia (IH) to mimic OSA, we have recently reported that mice exposed to IH exhibit endothelial cell (EC) activation, which is an early process preceding the development of cardiovascular disease. Although widely used, IH models have several limitations such as the severity of hypoxia, which does not occur in most patients with OSA. Recent studies reported that mice with deletion of hemeoxygenase 2 (Hmox2-/-), which plays a key role in oxygen sensing in the carotid body, exhibit spontaneous apneas during sleep and elevated levels of catecholamines. Here, using RNA-sequencing we investigated the transcriptomic changes in aortic ECs and heart tissue to understand the changes that occur in Hmox2-/- mice. In addition, we evaluated cardiac structure, function, and electrical properties by using echocardiogram and electrocardiogram in these mice. We found that Hmox2-/- mice exhibited aortic EC activation. Transcriptomic analysis in aortic ECs showed differentially expressed genes enriched in blood coagulation, cell adhesion, cellular respiration and cardiac muscle development and contraction. Similarly, transcriptomic analysis in heart tissue showed a differentially expressed gene set enriched in mitochondrial translation, oxidative phosphorylation and cardiac muscle development. Analysis of transcriptomic data from aortic ECs and heart tissue showed loss of Hmox2 gene might have common cellular network footprints on aortic endothelial cells and heart tissue. Echocardiographic evaluation showed that Hmox2-/- mice develop progressive dilated cardiomyopathy and conduction abnormalities compared to Hmox2+/+ mice. In conclusion, we found that Hmox2-/- mice, which spontaneously develop apneas exhibit EC activation and transcriptomic and functional changes consistent with heart failure

Handheld high-throughput plasmonic biosensor using computational on-chip imaging

We demonstrate a handheld on-chip biosensing technology that employs plasmonic microarrays coupled with a lens-free computational imaging system towards multiplexed and high-throughput screening of biomolecular interactions for point-of-care applications and resource-limited settings. This lightweight and field-portable biosensing device, weighing 60 g and 7.5 cm tall, utilizes a compact optoelectronic sensor array to record the diffraction patterns of plasmonic nanostructures under uniform illumination by a single-light emitting diode tuned to the plasmonic mode of the nanoapertures. Employing a sensitive plasmonic array design that is combined with lens-free computational imaging, we demonstrate label-free and quantitative detection of biomolecules with a protein layer thickness down to 3 nm. Integrating large-scale plasmonic microarrays, our on-chip imaging platform enables simultaneous detection of protein mono- and bilayers on the same platform over a wide range of biomolecule concentrations. In this handheld device, we also employ an iterative phase retrieval-based image reconstruction method, which offers the ability to digitally image a highly multiplexed array of sensors on the same plasmonic chip, making this approach especially suitable for high-throughput diagnostic applications in field settings

Maternal serum ischemia-modified albumin as an oxidative stress biomarker in preterm pre-labor rupture of membranes

Objectives: To evaluate the maternal serum ischemia-modified albumin (IMA) concentration as an oxidative stress biomarker in pregnancies complicated by preterm pre-labor rupture of membranes (PPROM) without maternal clinical infection and compare these results with healthy pregnancies. Material and methods: The present cohort study included 40 pregnancies complicated by PPROM and 49 similar gestational age healthy pregnancies in the third trimester of gestation. Maternal venous blood specimens were obtained at the day of first diagnosis. Maternal serum IMA level was assayed with an Albumin Cobalt Binding test. The subjects were followed up until delivery and perinatal outcomes were recorded. Results: The maternal serum IMA concentrations were significantly higher in the study group (0.56 ± 0.05 absorbance units) as compared to controls (0.54 ± 0.03 absorbance units) (p = 0.020). The maternal serum IMA concentrations were not significantly correlated with the initial maternal white blood cell count (r: 0.118, p = 0.269) and C-reactive protein levels (r: 0.066, p = 0.541). The maternal serum IMA concentrations were negatively correlated with gestational age at delivery (r: –0.248, p = 0.019), birthweight (r: –0.247, p = 0.020) and Apgar scores (r: –0.200, p = 0.049; r: –0.245, p = 0.020). The threshold value of maternal serum IMA concentration above 0.55 absorbance units indicated the pregnancy complicated by PPROM by 57.5% sensitivity and 57.1% specificity (Area under curve 0.613, confidence interval 0.50–0.73). Conclusions: The current study supported for the first time that there is an association between increased maternal serum IMA levels and the development of PPROM in the third trimester of gestation without maternal clinical infection. Elevated maternal serum IMA levels may alert the obstetrician about poor ongoing perinatal outcomes in the early phase of PPROM before increased maternal C-reactive protein and white blood cell count

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration