An oxygen-insensitive and minimally invasive polymeric microneedle sensor for continuous and wide-range transdermal glucose monitoring.

Despite significant advances in diabetes management, particularly with the introduction of the most recent continuous glucose monitoring devices (CGMDs) that can monitor glucose actively in the transdermal interstitial fluid (ISF) in vivo, CGMDs still have significant disadvantages in terms of accuracy, low interference effect, precision, and stability. This is mostly because they detect hydrogen peroxide at higher potentials and require an oxygen-rich environment. First in its class, we developed an oxygen-insensitive polymeric glucose microneedle (MN) that was functionalized using a new electron-transfer mediator, 3-(3'-phenylimino)-3H-phenothiazinesulfonic acid-based enzyme cocktail for the NAD-GDH system. The inclusion of reduced graphene oxide aided in the absorption of the cocktail via the π-π interaction and enhanced the conductivity and sensor performance. The MN exhibited a dynamic linear range (1-30 mM) with a low detection limit of 26 µM, high sensitivity (18.05 µAmM-1 cm-2), stability (up to 7 days), high selectivity (due to a low oxidation potential of 0.15 V), and a fast response time (∼3 s). In vivo, deployment of the MN in a rabbit model demonstrated that the ISF glucose concentrations measured with the MN for up to 24 h correlate very well with the blood glucose concentrations measured with a commercial glucometer.

Keystroke Dynamics based Hybrid Nanogenerators for Biometric Authentication and Identification using Artificial Intelligence.

Cyberattack is one of the severe threats in the digital world as it encompasses everything related to personal information, health, finances, intellectual properties, and even national security. Password-based authentication is the most practiced authentication system, however, is vulnerable to several attacks such as dictionary attack, shoulder surfing attack, and guessing attack. Here, a new keystroke dynamics-based hybrid nanogenerator for biometric authentication and identification integrated with artificial intelligence (AI) is reported. Keystroke dynamics offer behavioral and contextual information that can distinguish and authorize the individuals based on their typing rhythms. The hybrid electromagnetic-triboelectric nanogenerators/sensors efficiently convert the keystroke mechanical energy into electrical signals, which are fed into an artificial neural network based AI system. The self-powered hybrid sensors-based biometric authentication system integrated with a neural network achieves an accuracy of 99% and offers a promising hybrid security layer against password vulnerability.

Comparison of electroretinographic measurements between tabletop and handheld stimulators in healthy subjects.

PURPOSE: To compare full-field electroretinography (ffERG) parameters obtained from handheld and tabletop electroretinography (ERG) devices in normal subjects. METHODS: Twenty volunteers underwent ffERG using a tabletop and handheld stimulator. The responses obtained from the right eyes were compared. The coefficient of variation and intraclass correlation coefficient (ICC) were derived to assess inter- and intra-individual reliability. RESULTS: The b-wave in the rod response, a- and b-waves in the maximal combined response, a-wave in the cone response, and the 30-Hz flicker response showed significantly greater amplitudes when recorded with the tabletop stimulator than with the handheld stimulator. The implicit time of response (ITR) in the 30-Hz flicker response was longer when recorded with the handheld stimulator than when recorded with the tabletop stimulator. With regard to amplitude, the ICC indicated moderate-to-high reliability in the measurement of the b-wave in the rod response, and a- and b-waves in the maximal combined response. With regard to ITR, measurement of the b-wave in the rod response and a-wave in the maximal combined response showed moderate-to-high reliability. CONCLUSION: Despite the significantly lower ERG amplitude measurements recorded by the handheld stimulator, there were no significant differences in variability between the two stimulators.

Usefulness of Heart Rate Control in Atrial Fibrillation Patients With Obstructive Sleep Apnea.

In patients without atrial fibrillation and flutter (AF), obstructive sleep apnea (OSA) is associated with cyclic and often marked changes in heart rate (HR). We aimed to assess whether presence of OSA impacts optimal HR control in patients in AF. We retrospectively correlated diurnal HR patterns (recorded by 24-hour Holter monitoring) in patients with AF who independently also underwent diagnostic polysomnography. Exclusion criteria were paced rhythm or inadequate recordings from polysomnography and Holter monitoring. The relationship between the presence and severity of OSA and the mean, minimum, maximum HR, as well as pauses (>2 seconds) and their diurnal variation were studied. Of the 494 studied patients (age 69 ± 10 years; 26% women) mild-moderate OSA (apnea hypoxia index ≥5 and <20) was present in 171 (34%) and severe OSA (apnea hypoxia index ≥20) in 254 (51%). Mean 24-hour HR in patients with severe OSA and mild-moderate OSA was similar to those without OSA (78 vs 80 vs 79 beats per minute; p = 0.39), and there was no significant difference observed in minimum and maximum HR of these groups. However, the frequency of short pauses was greater in OSA patients (p = 0.009), with a prominent nocturnal distribution. In conclusion, OSA was not associated with increased HR in patients with AF suggesting that adequate HR control was similarly achievable in patients with and without OSA. The increased frequency of nocturnal pauses in OSA patients may function as a clinical hallmark, and the timing of pauses (during sleep vs wakefulness) should be noted before making therapeutic decisions regarding HR control.

Wearable, robust, non-enzymatic continuous glucose monitoring system and its in vivo investigation.

Electroplating of nanoporous Pt (nPt) induces an extremely strong tensile stress, which results in the exfoliation of nPt on flexible polymer substrate despite plasma treatment to improve adhesion. Here, we overcame this challenge by modifying flexible stainless-steel, and developed wearable, robust, flexible, and non-enzymatic continuous glucose monitoring system. The flexible stainless-steel was highly effective in improving the adhesion between the metal layer and substrate. The developed wireless system included electrochemical analysis circuits, a microcontroller unit, and a wireless communication module. Finally, we evaluated the continuous glucose monitoring system through two animal testing, by implanting into subcutaneous tissue and measuring interstitial fluid (ISF) glucose values at 5-15-min intervals. Comparison of the measured ISF glucose with blood glucose determined by the Clarke error grid analysis showed that 82.76% of the measured glucose was within zone A. Furthermore, the wearable glucose sensor exhibited bio-compatible to implant through various bio-compatibility tests.

Serum Testosterone Levels Are Negatively Correlated with International Prostate Symptom Score and Transitional Prostate Volume.

OBJECTIVES: To investigate the correlation of serum total testosterone levels with International Prostate Symptom Score and prostate volume in aging men. METHODS: A cross-sectional study was conducted in 50 men who had participated in a medical examination. Prostate specific antigen levels, International Prostate Symptom Score, total/transitional prostate volume, body mass index, maximal flow rate, and serum total testosterone levels were evaluated. The correlation between serum total testosterone levels and additional parameters was statistically analyzed. RESULTS: The median age and total testosterone levels were 60.4 years (interquartile range: 55.0-68.0 years) and 4.3 ng/mL (interquartile range: 3.6-5.1 ng/mL), respectively. Total testosterone levels showed a significant negative correlation with body mass index, transitional prostate volume, International Prostate Symptom Score (including voiding/storage sub scores). On multivariate linear regression models, the total testosterone level was associated with body mass index and total International Prostate Symptom Score. CONCLUSIONS: As total testosterone levels decrease, both International Prostate Symptom Score and transitional prostate volume increase significantly. These findings provide evidence of the presence of more severe lower urinary tract symptoms and larger transitional prostate volume in aging men.

A wearable electrochemical glucose sensor based on simple and low-cost fabrication supported micro-patterned reduced graphene oxide nanocomposite electrode on flexible substrate.

In this study, a reduced graphene oxide (rGO)-based nanostructured composite working electrode of high quality was successfully microfabricated and micro-patterned on a flexible polyimide substrate using simple low-cost fabrication processes. Gold and platinum alloy nanoparticles were electrochemically deposited onto the microfabricated rGO surface and chitosan-glucose oxidase composites were integrated onto the modified surface of the working electrode to develop a human sweat-based wearable glucose sensor application. The fabricated biosensor exhibited excellent amperometric response to glucose at a detection range of 0-2.4 mM (covers the glucose range in sweat), with a sensitivity of 48 µA/mMcm2, a short response time (20 s), and high linearity (0.99). The detection limit for glucose was calculated as 5 µm. The human sweat/mixing glucose samples initially used for testing indicated acceptable detection performance and stability for low glucose concentrations. These results confirm that the proposed nanostructured composite flexible working electrode and fabrication process are highly promising for application as human sweat-based electrochemical glucose sensors.

The effects of a heating pad on anxiety, pain, and distress during urodynamic study in the female patients with stress urinary incontinence.

AIMS: Although generally well tolerated, a urodynamic study is an unpleasant and stressful procedure for some patients. This study evaluated the effects of a heating pad on anxiety, pain, and distress during urodynamic studies in female patients with stress urinary incontinence. METHODS: A total of 74 female patients with stress urinary incontinence who underwent a urodynamic study between May 2015 and October 2015 were randomized to either the experimental group using a heating pad (n = 37) or control group (n = 37). In the experimental group, a heating pad was applied on the patient's sacrum during the urodynamic study. All patients completed the State-Trait Anxiety Inventory (20-80) before and after the procedure and assessed their degree of pain and distress after the procedure by the visual analog scale (0-10). Systolic and diastolic blood pressure and pulse rate were also checked before and after the procedure. RESULTS: Demographic characteristics, mean age, procedure duration, pre and post-procedural systolic, and diastolic blood pressures, and pulse rate were statistically similar between the experimental and control groups. The mean State-Trait Anxiety Inventory was significantly lower in the experimental group than in the control group (30.9 ± 7.5 vs 42.5 ± 10.1, P < 0.001). The experimental group showed significantly lower pain and distress scores (Visual Analog Scale, 2.7 ± 1.5, 3.0 ± 1.5) compared with the control group (4.0 ± 1.6, 4.7 ± 2.0, both P < 0.001). CONCLUSIONS: Using a heating pad for female patients with stress urinary incontinence during a urodynamic study is a simple, economical, and effective therapy that enhances patient comfort and decreases anxiety, pain, and distress.

Trimetallic Pd@Au@Pt nanocomposites platform on -COOH terminated reduced graphene oxide for highly sensitive CEA and PSA biomarkers detection.

In this paper, a trimetallic Pd@Au@Pt nanocomposites platform on -COOH terminated reduced graphene oxide (COOH-rGO) was newly developed for sensing carcinoembryonic antigen (CEA) and prostate specific antigen (PSA) biomarkers. Trimetallic electro-catalytic surfaces were prepared by the electrodeposition of noble metals (Pd@Au@Pt) nanoparticles on COOH- rGO. After EDC/NHS treatment, the anti-CEA and anti-PSA were immobilized separately on two different platforms. Under optimized conditions, the platforms were analyzed by cyclic voltammetry and differential pulse voltammetry (DPV). The platform shows good electro catalytic activity, high sensitivity, and acceptable stability for sensing CEA and PSA biomarkers. For CEA, we obtained sensitivity of 0.099 ± 0.007µAng-1ml, wide linear range from 12pgml-1 to 85ngml-1 and a limit of detection (LOD) of 8pgml-1, while for PSA sensitivity is 0.267 ± 0.02µAng -1 ml, wide linear range from 3pgml-1 to 60ngml-1 and LOD of 2pgml-1. The validation of the platform was observed through standard addition method. Thus, the sensing platform could be used for the point of care detection of CEA and PSA.

Circulating TNF receptors predict cardiovascular disease in patients with chronic kidney disease.

Cardiovascular disease (CVD) is the main public health problem in patients with chronic kidney disease (CKD); however, there is no established biomarker for predicting CVD morbidity and mortality in CKD. The aim of this study was to evaluate the role of circulating tumor necrosis factor receptors (cTNFRs) in predicting CVD risk in CKD patients.We prospectively recruited 984 patients with CKD from 11 centers between 2006 and 2012. The levels of cTNFR1 and cTNFR2 were determined by performing an enzyme-linked immunosorbent assay. During the mean follow-up period of 4 years, 36 patients experienced a CVD event. The median serum concentrations of cTNFR1 and cTNFR2 were 2703.4 (225.6-13,057.7) and 5661.0 (634.9-30,599.6) pg/mL, respectively, and the cTNFR1 level was closely correlated with the cTNFR2 level (r = 0.86, P < .0001). The urinary protein-to-creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) were significantly correlated with the cTNFR2 level (r = 0.21 for UPCR, r = -0.67 for eGFR; P < .001 for all). Similar correlations were observed for serum cTNFR1 (r = 0.21 for UPCR, r = -0.75 for eGFR; P < .001 for all). In the Cox proportional hazard analyses, cTNFR1 (hazard ratio [HR] 2.506, 95% confidence interval [CI] 1.186-5.295, P = .016) and cTNFR2 (HR 4.156, 95% CI 1.913-9.030, P < .001) predicted CVD risk even after adjustment for clinical covariates, such as UPCR, eGFR, and high-sensitivity C-reactive protein. cTNFR1 and 2 are associated with CVD and other risk factors in CKD, independently of eGFR and UPCR. Furthermore, cTNFRs could be relevant predictors of CVD in CKD patients.

Fabrication of sensitive enzymatic biosensor based on multi-layered reduced graphene oxide added PtAu nanoparticles-modified hybrid electrode.

A highly sensitive amperometric glucose sensor was developed by immobilization of glucose oxidase (GOx) onto multi-layer reduced graphene oxide (MRGO) sheets decorated with platinum and gold flower-like nanoparticles (PtAuNPs) modified Au substrate electrode. The fabricated MRGO/PtAuNPs modified hybrid electrode demonstrated high electrocatalytic activities toward oxidation of H2O2, to which it had a wide linear response that ranged from 0.5 to 8 mM (R2 = 0.997), and high sensitivity of 506.25 µA/mMcm2. Furthermore, glucose oxidase-chitosan composite and cationic polydiallyldimethylammonium chloride (PDDA) were assembled by a casting method on the surface of MRGO/PtAuNPs modified electrode. This as-fabricated hybrid biosensor electrode exhibited high electrocatalytic activity for the detection of glucose in PBS. It demonstrated good analytical properties in terms of a low detection limit of 1 µM (signal-to-noise ratio of 3), short response time (3 s), high sensitivity (17.85 µA/mMcm2), and a wide linear range (0.01-8 mM) for glucose sensing. These results reveal that the newly developed sensing electrode offers great promise for new type enzymatic biosensor applications.

Editor's Choice-Clinical impact of delirium and antipsychotic therapy: 10-Year experience from a referral coronary care unit.

BACKGROUND: Little is known about safety of antipsychotic therapy for delirium in the coronary care unit (CCU). Our aim was to examine the effect of delirium and antipsychotic therapy among CCU patients. METHODS AND RESULTS: Pre-study Confusion Assessment Method-Intensive Care Unit (CAM-ICU) criteria were implemented in screening consecutive patients admitted to a referral CCU from 2004-2013. Death status was prospectively ascertained. Of 11,079 study patients, the incidence of delirium was 8.3% ( n=925). Delirium was associated with an increased risk of in-hospital mortality (adjusted odds ratio (OR) 1.49; 95% confidence interval (CI), 1.08-2.08; p=0.02) and one-year mortality among patients who survived from CCU admission (adjusted hazard ratio (HR) 1.46; 95% CI, 1.12-1.87; p=0.005). A total of 792 doses of haloperidol (5 mg/day; interquartile range (IQR) 3-10) or quetiapine (25 mg/day; IQR 13-50) were given to 244 patients with delirium. The clinical characteristics of patients with delirium who did and did not receive antipsychotic therapy were not different (baseline corrected QT (QTc) interval 457±58 ms vs 459±60 ms, respectively; p=0.65). In comparison to baseline, mean QTc intervals after the first and third doses of the antipsychotics were not significantly prolonged in haloperidol (448±56, 458±57 and 450±50 ms, respectively) or quetiapine groups (470±66, 467±68 and 462±46 ms, respectively) ( p>0.05 for all). Additionally, in-hospital mortality (adjusted OR 0.67; 95% CI, 0.42-1.04; p=0.07), ventricular arrhythmia (adjusted OR 0.87; 95% CI, 0.17-3.62; p=0.85) and one-year mortality among the hospital survivors (adjusted HR 0.86; 95% CI 0.62-1.17; p=0.34) were not different in patients with delirium irrespective of whether or not they received antipsychotics. CONCLUSION: In patients admitted to the CCU, delirium was associated with an increase in both in-hospital and one-year mortality. Low doses of haloperidol and quetiapine appeared to be safe, without an increase in risk of sudden cardiac death, in-hospital mortality, or one-year mortality in carefully monitored patients.

Plain to point network reduced graphene oxide-activated carbon composites decorated with platinum nanoparticles for urine glucose detection.

In this study, a hydrothermal technique was applied to synthesize glucose-treated reduced graphene oxide-activated carbon (GRGO/AC) composites. Platinum nanoparticles (PtNP) were electrochemically deposited on the modified GRGO/AC surface, and chitosan-glucose oxidase (Chit-GOx) composites and nafion were integrated onto the modified surface of the working electrode to prepare a highly sensitive glucose sensor. The fabricated biosensor exhibited a good amperometric response to glucose in the detection range from 0.002 mM to 10 mM, with a sensitivity of 61.06 µA/mMcm(2), a short response time (4 s) and a low detection limit of 2 µM (signal to noise ratio is 3). The glucose sensor exhibited a negligible response to interference and good stability. In addition, the glucose levels in human urine were tested in order to conduct a practical assessment of the proposed sensor, and the results indicate that the sensor had superior urine glucose recognition. These results thus demonstrate that the noble nano-structured electrode with a high surface area and electrocatalytic activity offers great promise for use in urine glucose sensing applications.

Interaction effect of serum 25-hydroxyvitamin D levels and CYP1A1, CYP1B1 polymorphisms on blood pressure in an elderly population.

OBJECTIVE: Hypertension and vitamin D deficiency are prevalent worldwide, especially in the elderly. Considering the possibility of gene-environment contributions to disease development, we evaluated the influence of certain cytochrome P450 polymorphisms and vitamin D levels on blood pressure (BP). METHODS: We measured serum 25-hydroxyvitamin D levels [25(OH)D] and BP in 535 individuals over 60 years old and identified single-nucleotide polymorphisms (SNPs) of CYP1A1 and CYP1B1 in lymphocyte DNA. Repeated measure analyses were used to determine the statistical association. RESULTS: The relationship between 25(OH)D and SBP or DBP was inversely significant, and influence of several CYP1A1 and CYP1B1 SNPs on BP was found across different genotypes. Estimated effect of 25(OH)D levels on BP in the group with higher risky genotype scores of selected SNPs (rs4646421, rs2551188, and rs1056836) was greater (ß = -2.841, P = 0.004 for SBP; ß = -2.035, P = 0.001 for DBP) than the group with lower genotype score (ß = -0.878, P = 0.347 for SBP; ß = 0.037, P = 0.947 for DBP), and synergistic interaction between vitamin D levels and genotype variations was observed (P-interaction = 0.081 for SBP and 0.008 for DBP). When stratified by the hypertension medication status, interaction effect was found only in individuals taking medication (P-interaction = 0.004 for SBP and 0.001 for DBP). CONCLUSION: Genetic variations in CYP1A1 and CYP1B1 and the serum levels of 25(OH)D showed synergistic effect on BP, especially in individuals currently in treatment for hypertension.

Nuclear clusterin is associated with neuronal apoptosis in the developing rat brain upon ethanol exposure.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is often accompanied by reduced brain volumes, reflecting brain cell death induced by ethanol, but the molecular mechanisms were less elucidated. This study was set up to investigate whether clusterin (Clu) was involved in neuronal cell death in developing rats. METHODS: Seven-day-old rats were subcutaneously injected with 20% ethanol in normal saline at 3 g/kg twice. The upregulation of Clu and cell death was detected by immunohistochemistry, immunofluorescence microscopy, and/or Western blotting. Protein-protein interaction was detected by immunoprecipitation and immunoblotting. To identify the isoform interacting with Bcl-XL, HT22 mouse hippocampal cells were transfected with nuclear Clu(nClu)- or secretory Clu-expressing vector, and confocal microscopy was performed. Clu transcripts were knocked down in primary cortical cells using siRNA. RESULTS: We found that Clu increased in the cerebral cortex following acute ethanol treatment. The Clu upregulation was related to increased cell death, which was assessed by activated caspase-3 and TUNEL staining. The upregulated Clu was a nuclear isoform that was nuclear translocated upon ethanol exposure and interacted with Bcl-XL, mediating apoptosis. CONCLUSIONS: This study shows that nClu plays a pro-apoptotic role in ethanol-induced cell death in the developing brain, providing new insights for development of FASD.

Prevalence of chronic obstructive pulmonary disease in Korea: the fourth Korean National Health and Nutrition Examination Survey, 2008.

BACKGROUND AND OBJECTIVE: Because the mortality and social burden associated with COPD is increasing, repeated surveys of the prevalence of COPD have been used to assess risk factors, detect potential patients, and establish early diagnoses and management protocols. We report the prevalence of spirometrically detected COPD in Korea in 2008, using data from the fourth Korean National Health and Nutrition Survey. METHODS: Using nationwide stratified random sampling, based on the Korean Statistical Office census, 6840 subjects aged ≥19years underwent spirometry, which was performed by four trained technicians, during 2008. The place of residence, levels of education and income and smoking status, as well as other results from a COPD survey questionnaire were also assessed. RESULTS: Airflow obstruction (FEV(1) /FVC<0.7) was detected in 8.8% of subjects aged ≥19years (11.6% of men and 5.9% of women) and COPD was detected in 13.4% of subjects aged ≥40years (19.4% of men and 7.9% of women). Of the 6840 subjects, 27.3% were current smokers and 17.2% were former smokers, and the prevalence of COPD was higher in current and former smokers than in never smokers. Approximately 94% of patients with COPD had mild-to-moderate disease, without apparent symptoms; only 2.4% had been diagnosed by a physician and only 2.1% of patients had been treated. The independent risk factors for COPD were smoking, advanced age and male gender. CONCLUSIONS: Although the prevalence of COPD in Korea is high, the disease is underdiagnosed and most COPD patients are under-treated.