Clinical Course of Suspected Diagnosis of Pulmonary Tumor Thrombotic Microangiopathy: A 10-Year Experience of Rapid Progressive Right Ventricular Failure Syndrome in Advanced Cancer Patients.

BACKGROUND AND OBJECTIVES: Several cases involving severe right ventricular (RV) failure in advanced cancer patients have been found to be pulmonary tumor thrombotic microangiopathies (PTTMs). This study aimed to discover the nature of rapid RV failure syndrome with a suspected diagnosis of PTTM for better diagnosis, treatment, and prognosis prediction in clinical practice. METHODS: From 2011 to 2021, all patients with clinically suspected PTTM were derived from the one tertiary cancer hospital with more than 2000 in-hospital bed. RESULTS: A total of 28 cases of clinically suspected PTTM with one biopsy confirmed case were included. The most common cancer types were breast (9/28, 32%) and the most common tissue type was adenocarcinoma (22/26, 85%). The time interval from dyspnea New York Heart Association (NYHA) Grade 2, 3, 4 to death, thrombocytopenia to death, desaturation to death, admission to death, RV failure to death, cardiogenic shock to death were 33.5 days, 14.5 days, 7.4 days, 6.4 days, 6.1 days, 6.0 days, 3.8 days and 1.2 days, respectively. The NYHA Grade 4 to death time was 7 days longer in those who received chemotherapy (7.1 days vs. 13.8 days, p value=0.030). However, anticoagulation, vasopressors or intensive care could not change clinical course. CONCLUSIONS: Rapid RV failure syndrome with a suspected diagnosis of PTTM showed a rapid progressive course from symptom onset to death. Although chemotherapy was effective, increased life survival was negligible, and treatments other than chemotherapy did not help to improve the patient's prognosis.

Electrochemical Sensors for Sustainable Precision Agriculture-A Review.

Greenhouse gases released by agriculture account for 19% of global greenhouse gas emission. Moreover, the abuse of pesticides and fertilizers is a fundamental cause of soil and water pollution. Finding sustainable countermeasures for these problems requires completely new approaches and the integration of knowledge. Precision agriculture (PA) is a technology that reduces environmental pollution with minimal input (e.g., fertilizer, herbicides, and pesticides) and maximize the production of high-quality crops by monitoring the conditions and environment of farmland and crops. However, the lack of data-a key technology for realizing PA-remains a major obstacle to the large-scale adoption of PA. Herein, we discuss important research issues, such as data managements and analysis for accurate decision-making, and specific data acquisition strategies. Moreover, we systematically review and discuss electrochemical sensors, including sensors that monitor the plant, soil, and environmental conditions that directly affect plant growth.

Structural and anionic effects of microcrystalline Zn-CPs on 4-nitrophenol sensing performances.

Coordination polymers (CPs: [ZnL3] n (X)2n , L = trans-1,4-bis(imidazolyl)-2-butene; X- = BF4 -, ClO4 -, NO3 -) allow for detection of the 4-nitrophenol (4-NP) oxidation process by enhanced electrochemical signals. Electrochemical measurement is a highly sensitive method providing much evidence of chemical reactions on an electrode surface. In the present study, we designed and synthesized, with reference to X-ray diffraction data and by spectroscopic analyses, new 3D coordination structures containing imidazolyl donors and zinc(ii). The presence of microcrystals [ZnL3] n (BF4)2n on the working electrode enhanced the redox signals. Therefore, we propose a simple catalytic process that can explain these results and clarify the influence of anions that constitute CP materials used to improve electrochemical detection applications. The CP materials were characterized by nuclear magnetic resonance (NMR), infrared spectroscopy (IR), thermogravimetric (TG) analyses, single crystal X-ray diffraction (SC-XRD), and electrochemical analyses.

Structure and antiviral activity of a pectic polysaccharide from the root of Sanguisorba officinalis against enterovirus 71 in vitro/vivo.

The increasing prevalence and pandemic risk of viral diseases warrant the development of safe and effective treatments. In this study, we aimed to elucidate the structure and anti-enterovirus 71 (EV71) effects of polysaccharides isolated from the roots of Sanguisorba officinalis (SO), traditionally used for infectious diseases. The purified polysaccharide (S-a3) was a homogenous macromolecule (260.4 kDa) with a concave and porous surface. Linkage and NMR analyses confirmed that S-a3 is a polysaccharide interlinked with homogalacturonan, rhamnogalacturonan-I, 1,4-α-glucan, and arabinogalactan. S-a3 significantly inhibited cell death and viral gene expression in EV71-infected Vero cells, and alleviated EV71-induced body weight loss, death, and paralysis in the hSCARB2-transgenic mouse model. The effective dose of S-a3 was non-toxic to cells and mice. The antiviral mechanism of S-a3 was associated with the disruption of EV71 attachment to host cells. Our findings demonstrate that polysaccharides from SO can be a safe and effective treatment for EV71 infection.

Guided-mode waves structure of electric and magnetic dipole resonances in a metamaterial slab.

The electric dipole (ED) and magnetic dipole (MD) resonances in a slab of dielectric nanostructures induced by oblique light incidence were analyzed in terms of guided-mode wave theory for transverse electric (TE) and transverse magnetic (TM) polarization. Owing to the symmetry breaking in TE and TM polarizations at oblique incidences of light, the resonance modes produced different features, which were analyzed with comprehensive studies of energy fluxes associated with the resonance modes. The MD resonances are excited by the guided-mode wave with an energy flux in the opposite direction in the incident plane for TM polarization and excited by two guided-mode waves with energy fluxes orthogonal to the incident plane for TE polarized light. Meanwhile, the ED resonances are excited by the guided-mode waves with energy fluxes in both directions, incident plane, and out of the incident plane for both TE and TM polarizations. The proposed analyses provide clear explanations of the stability or vanishing of resonance modes, with variations in the inter-distance between nanostructures near the Rayleigh anomaly condition, which were verified by the experimental measurements performed with 2D arrays of Si nanostructures for various incident angles with TE and TM polarizations.

Comparative Cerebroprotective Potential of d- and l-Carnosine Following Ischemic Stroke in Mice.

l-carnosine is an attractive therapeutic agent for acute ischemic stroke based on its robust preclinical cerebroprotective properties and wide therapeutic time window. However, large doses are needed for efficacy because carnosine is rapidly degraded in serum by carnosinases. The need for large doses could be particularly problematic when translating to human studies, as humans have much higher levels of serum carnosinases. We hypothesized that d-carnosine, which is not a substrate for carnosinases, may have a better pharmacological profile and may be more efficacious at lower doses than l-carnosine. To test our hypothesis, we explored the comparative pharmacokinetics and neuroprotective properties of d- and L-carnosine in acute ischaemic stroke in mice. We initially investigated the pharmacokinetics of d- and L-carnosine in serum and brain after intravenous (IV) injection in mice. We then investigated the comparative efficacy of d- and l-carnosine in a mouse model of transient focal cerebral ischemia followed by in vitro testing against excitotoxicity and free radical generation using primary neuronal cultures. The pharmacokinetics of d- and l-carnosine were similar in serum and brain after IV injection in mice. Both d- and l-carnosine exhibited similar efficacy against mouse focal cerebral ischemia. In vitro studies in neurons showed protection against excitotoxicity and the accumulation of free radicals. d- and l-carnosine exhibit similar pharmacokinetics and have similar efficacy against experimental stroke in mice. Since humans have far higher levels of carnosinases, d-carnosine may have more favorable pharmacokinetics in future human studies.

LRP-1 functionalized polymersomes enhance the efficacy of carnosine in experimental stroke.

Stroke is one of the commonest causes of death with limited treatment options. L-Carnosine has shown great promise as a neuroprotective agent in experimental stroke, but translation to the clinic is impeded by the large doses needed. We developed and evaluated the therapeutic potential of a novel delivery vehicle which encapsulated carnosine in lipoprotein receptor related protein-1 (LRP-1)-targeted functionalized polymersomes in experimental ischemic stroke. We found that following ischemic stroke, polymersomes encapsulating carnosine exhibited remarkable neuroprotective effects with a dose of carnosine 3 orders of magnitude lower than free carnosine. The LRP-1-targeted functionalization was essential for delivery of carnosine to the brain, as non-targeted carnosine polymersomes did not exhibit neuroprotection. Using Cy3 fluorescence in vivo imaging, we showed that unlike non-targeted carnosine polymersomes, LRP-1-targeted carriers accumulated in brain in a time dependent manner. Our findings suggest that these novel carriers have the ability to deliver neuroprotective cargo effectively to the brain.

Detection of Nitric Oxide from Living Cells Using Polymeric Zinc Organic Framework-Derived Zinc Oxide Composite with Conducting Polymer.

Sensitive and selective detection of nitric oxide (NO) in the human body is crucial since it has the vital roles in the physiological and pathological processes. This study reports a new type of electrochemical NO biosensor based on zinc-dithiooxamide framework derived porous ZnO nanoparticles and polyterthiophene-rGO composite. By taking advantage of the synergetic effect between ZnO and poly(TTBA-rGO) (TTBA = 3'-(p-benzoic acid)-2,2':5',2″-terthiophene, rGO = reduced graphene oxide) nanocomposite layer, the poly(TTBA-rGO)/ZnO sensor probe displays excellent electrocatalytic activity and explores to detect NO released from normal and cancer cell lines. The ZnO is immobilized on a composite layer of poly(TTBA-rGO). The highly porous ZnO offers a high electrolyte accessible surface area and high ion-electron transport rates that efficiently catalyze the NO reduction reaction. Amperometry with the modified electrode displays highly sensitive response and wide dynamic range of 0.019-76 × 10-6 m with the detection limit of 7.7 ± 0.43 × 10-9 m. The sensor probe is demonstrated to detect NO released from living cells by drug stimulation. The proposed sensor provides a powerful platform for the low detection limit that is feasible for real-time analysis of NO in a biological system.

Disposable all-solid-state pH and glucose sensors based on conductive polymer covered hierarchical AuZn oxide.

Poly(terthiophene benzoic acid) (pTBA) layered-AuZn alloy oxide (AuZnOx) deposited on the screen printed carbon electrode (pTBA/AuZnOx/SPCE) was prepared to create a disposable all-solid-state pH sensor at first. Further, FAD-glucose oxidase (GOx) was immobilized onto the pTBA/AuZnOx/SPCE to fabricate a glucose sensor. The characterizations of the sensor probe reveal that AuZnOx forms a homogeneous hierarchical structure, and that the polymerized pTBA layer on the alloy oxide surface captures GOx covalently. The benzoic acid group of pTBA coated on the probe layer synergetically improved the pH response of the alloy oxide and provide chemical binding sites to enzyme, which resulted in a Nernstian behavior (59.2 ± 0.5 mV/pH) in the pH range of 2-13. The experimental parameters affecting the glucose analysis were studied in terms of pH, temperature, humidity, and interferences. The sensor exhibited a fast response time <1s and a dynamic range between 30 and 500 mg/dL glucose with a detection limit of 17.23 ± 0.32 mg/dL. The reliabilities of the disposable pH and glucose sensors were examined for biological samples.

Autophagy sustains the survival of human pancreatic cancer PANC-1 cells under extreme nutrient deprivation conditions.

Pancreatic ductal adenocarcinomas are an extremely aggressive and devastating type of cancer with high mortality. Given the dense stroma and poor vascularization, accessibility to nutrients is limited in the tumor microenvironment. Here, we aimed to elucidate the role of autophagy in promoting the survival of human pancreatic cancer PANC-1 cells exposed to nutrient-deprived media (NDM) lacking glucose, amino acids, and serum. NDM inhibited Akt activity and phosphorylation of p70 S6K, and induced AMPK activation and mitochondrial depolarization. NDM also time-dependently increased LC3-II accumulation, number of GFP-LC3 puncta, and colocalization between GFP-LC3 and lysosomes. These results suggested that autophagy was progressively activated through Akt- and AMPK-mTOR pathway in nutrient-deficient PANC-1 cells. Autophagy inhibitors (chloroquine and wortmannin) or silencing of Atg5 augmented PANC-1 cell death in NDM. In cells exposed to NDM, chloroquine and wortmannin induced apoptosis and Z-VAD-fmk inhibited cytotoxicity of these inhibitors. These data demonstrate that autophagy is anti-apoptotic and sustains the survival of PANC-1 cells following extreme nutrient deprivation. Autophagy modulation may be a viable therapeutic option for cancer cells located in the core of solid tumors with a nutrient-deficient microenvironment.

Electron-transfer mediator for a NAD-glucose dehydrogenase-based glucose sensor.

A new electron-transfer mediator, 5-[2,5-di (thiophen-2-yl)-1H-pyrrol-1-yl]-1,10-phenanthroline iron(III) chloride (FePhenTPy) oriented to the nicotinamide adenine dinucleotide-dependent-glucose dehydrogenase (NAD-GDH) system was synthesized through a Paal-Knorr condensation reaction. The structure of the mediator was confirmed by Fourier-transform infrared spectroscopy, proton and carbon nucler magnetic resonance spectroscopy, and mass spectroscopy, and its electron-transfer characteristic for a glucose sensor was investigated using voltammetry and impedance spectroscopy. A disposable amperometric glucose sensor with NAD-GDH was constructed with FePhenTPy as an electron-transfer mediator on a screen printed carbon electrode (SPCE) and its performance was evaluated, where the addition of reduces graphene oxide (RGO) to the mediator showed the enhanced sensor performance. The experimental parameters to affect the analytical performance and the stability of the proposed glucose sensor were optimized, and the sensor exhibited a dynamic range between 30 mg/dL and 600 mg/dL with the detection limit of 12.02 ± 0.6 mg/dL. In the real sample experiments, the interference effects by acetaminophen, ascorbic acid, dopamine, uric acid, caffeine, and other monosaccharides (fructose, lactose, mannose, and xylose) were completely avoided through coating the sensor surface with the Nafion film containing lead(IV) acetate. The reliability of proposed glucose sensor was evaluated by the determination of glucose in artificial blood and human whole blood samples.

Relationship between Alcohol Consumption and Metabolic Syndrome according to Facial Flushing in Korean Males.

BACKGROUND: The aim of the present study is to evaluate the risk of metabolic syndrome (MS) according to alcohol consumption for those subjects showing facial flushing, as well as the absence of facial flushing. METHODS: One thousand two hundred and one males were recruited in the health promotion center of a university hospital. Evaluation of alcohol consumption and facial flushing was assessed via questionnaires and interviews. The criteria for MS were defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria with a modified waist circumference cutoff value (men ≥ 90 cm) for Korean subjects. Subjects were divided into three groups according to the amount of alcohol they consume: nondrinkers, moderate drinkers (≤14 standard drinks per week), and heavy drinkers (>14 standard drinks per week). They were also separated into two groups according to facial flushing: non-flushers (no occurrence) and flushers (steady occurrence). Factors related to MS were assessed by logistic regression analysis. RESULTS: In non-flushing moderate drinkers, the risk of MS did not significantly increase compared to non-drinkers. However in flushing moderate drinkers, there was significant increase (odds ratio [OR], 1.81; confidence interval [CI], 1.08 to 3.06) compared to non-drinkers. In non-flushing and flushing heavy drinkers, significant increase (OR, 2.23; CI, 1.23 to 4.04; OR, 2.90; CI, 1.25 to 6.73, respectively) was evident compared to non-drinkers. CONCLUSION: Non-flushing moderate drinkers did not show an increased risk of metabolic syndrome compared to the non-drinkers, but flushing moderate drinkers showed an increased risk of metabolic syndrome compared to non-drinkers.

Non-invasive assessment of hepatic steatosis: prospective comparison of the accuracy of imaging examinations.

BACKGROUND & AIMS: Despite increasing use of various imaging examinations for non-invasive assessment of hepatic steatosis (HS), their relative accuracy is unknown. The objective of this study is to prospectively compare the accuracy of computed tomography (CT), dual gradient echo magnetic resonance imaging (DGE-MRI), proton magnetic resonance spectroscopy ((1)H-MRS), and ultrasonography (US) for the diagnosis and quantitative estimation of HS. METHODS: A total of 161 consecutive potential living liver donors underwent US (performed by two independent radiologists, US1 and US2), CT, DGE-MRI, (1)H-MRS, and liver biopsy on the same day. Using the histologic degree of HS as the reference standard, we compared the diagnostic performance of US1, US2, CT, DGE-MRI, and (1)H-MRS for diagnosing HS >or= 5% and HS >or= 30% and compared the accuracy of CT, DGE-MRI, and (1)H-MRS in the quantitative estimation of HS. RESULTS: DGE-MRI and (1)H-MRS significantly outperformed CT and US for the diagnosis of HS5%. DGE-MRI showed a tendency of higher accuracy than the other examinations for diagnosing HS >or= 30%. The cross-validated sensitivity and specificity of DGE-MRI at the optimal cut-off were 76.7% and 87.1%, respectively, for diagnosing HS >or= 5% and 90.9% and 94%, respectively, for diagnosing HS >or= 30%. The cross-validated Bland-Altman 95% limits of agreement between the estimated degree of HS on imaging examinations and the histologic degree of HS, were the narrowest with DGE-MRI, yielding -12.7% to 12.7%. CONCLUSIONS: Among CT, DGE-MRI, (1)H-MRS, and US, DGE-MRI is the most accurate method for the diagnosis and quantitative estimation of HS. Therefore, DGE-MRI may be the preferred imaging examination for the non-invasive assessment of HS.

Volume rendering with color coding of tagged stool during endoluminal fly-through CT colonography: effect on reading efficiency.

Institutional review board approval and informed consent were obtained. This study was conducted to evaluate a newly developed technique for discriminative color coding of tagged stool during three-dimensional (3D) endoluminal fly-through computed tomographic (CT) colonography and to determine its effect on reading efficiency. Thirty patients, including three dropouts, were prepared with moderate cathartic preparation (20 mg bisacodyl, three doses of 200 mL of 5% wt/vol barium sulfate). Images were reviewed by two independent readers with and without color coding. Reader preference, interpretation time, and diagnostic performance were evaluated. Both reviewers preferred color coding. With color coding, interpretation time was shortened by 3 minutes (reader 1, P = .002) and 2.5 minutes (reader 2, P = .009); sensitivity for 6-mm-diameter or larger lesions remained constant at 96% (24 of 25; 95% confidence interval: 78.9%, <100%; P = >.99). This technique facilitates primary 3D interpretation of images obtained with moderate cathartic preparation.