bluuebunny/crossref_metadata_2025_split huggingface dataset:
Controlling Acute Inflammation with Fast Releasing Dexamethasone-PLGA Microsphere/PVA Hydrogel Composites for Implantable Devices
Authors: Bhardwaj Upkar , Sura Radhakrishna , Papadimitrakopoulos Fotios , Burgess Diane J. 
Published: January 2014

Background: Continuous release of dexamethasone from PLGA microsphere/PVA hydrogel composites has been shown to suppress the inflammatory tissue reaction in response to subcutaneously implanted foreign material for a period of one month. The scope of the present work is to investigate whether suppressing the initial acute inflammatory phase with fast releasing dexamethasone-PLGA microsphere/PVA composites (that release the drug over a period of one week) would prevent the development of a foreign body reaction in response to implantation in the subcutaneous tissue using a rat model. Methods: Dexamethasone loaded PLGA microspheres were prepared using the solvent evaporation method. In vitro release from microspheres was analyzed using USP apparatus 4 in phosphate buffered saline (PBS) at 37°C. Composites were fabricated in 18G needles by freeze-thaw cycling the PVA/microsphere dispersion. The composites were implanted in the subcutaneous tissue of anesthetized rats. The pharmacodynamic effect was evaluated by histological examination of the tissue surrounding the composites at pre-determined time points. Results: In vitro release studies showed that most of the drug entrapped in the microspheres was released within one week. At days 3 and 8, these fast releasing dexamethasone containing composites suppressed the acute phase of inflammation but did not prevent the development of an inflammatory reaction after dexamethasone was completely released from the composites. By day 30, chronic inflammation and fibrosis were observed in the tissue surrounding the drug-containing composites. On days 3 and 8, the number of inflammatory cells in the vicinity of the dexamethasone containing composites was similar to that in normal tissue. However, the number of inflammatory cells was higher in drug-containing composites as compared to drug-free composites by day 30. This was due to the inflammation being in a more advanced stage in drug-free composites where a granulomatous reaction had already developed. Conclusion: Fast release of dexamethasone from PLGA/PVA composites did not provide long-term protection against the foreign body reaction in response to implantation. It would appear that a sustained delivery of anti-inflammatory agents such as dexamethasone is necessary to suppress inflammation throughout the implant life-time.
Immobilization Techniques to Avoid Enzyme Loss from Oxidase-Based Biosensors: A One-Year Study
Authors: House Jody L. , Anderson Ellen M. , Ward W. Kenneth 
Published: January 2014

Background: Continuous amperometric sensors that measure glucose or lactate require a stable sensitivity, and glutaraldehyde crosslinking has been used widely to avoid enzyme loss. Nonetheless, little data is published on the effectiveness of enzyme immobilization with glutaraldehyde. Methods: A combination of electrochemical testing and spectrophotometric assays was used to study the relationship between enzyme shedding and the fabrication procedure. In addition, we studied the relationship between the glutaraldehyde concentration and sensor performance over a period of one year. Results: The enzyme immobilization process by glutaraldehyde crosslinking to glucose oxidase appears to require at least 24-hours at room temperature to reach completion. In addition, excess free glucose oxidase can be removed by soaking sensors in purified water for 20 minutes. Even with the addition of these steps, however, it appears that there is some free glucose oxidase entrapped within the enzyme layer which contributes to a decline in sensitivity over time. Although it reduces the ultimate sensitivity (probably via a change in the enzyme's natural conformation), glutaraldehyde concentration in the enzyme layer can be increased in order to minimize this instability. Conclusions: After exposure of oxidase enzymes to glutaraldehyde, effective crosslinking requires a rinse step and a 24-hour incubation step. In order to minimize the loss of sensor sensitivity over time, the glutaraldehyde concentration can be increased
SPCE Based Glucose Sensor Employing Novel Thermostable Glucose Dehydrogenase, FADGDH: Blood Glucose Measurement with 150nL Sample in One Second
Authors: Yamaoka Hideaki , Sode Koji 
Published: January 2014

Background: Self-monitoring of blood glucose (SMBG) is an important component of the modern therapy for diabetes mellitus. Thanks to the current progress in electronics and sensor fabrication technology, both the time and the blood sample volume required for the measurement have decreased drastically. However, devices that work with an even smaller sample volume and a shorter measurement time are in demand. Methods: A disposable glucose sensor that works with an ultra-small sample volume was developed employing the novel thermostable glucose-dehydrogenase (FADGDH) complex composed of a catalytic subunit, an electron transfer subunit (cytochrome c), and a small subunit. The electrode is a screen-printed carbon electrode (SPCE), and hexaammineruthenium (III) chloride (Ru complex) is utilized as the electron mediator. A disposable enzyme sensor was constructed by depositing the FADGDH complex and Ru complex onto the SPCE, and the sensor performance was evaluated. Results: Whole-blood glucose can be measured within 1 sec using this enzyme sensor and a 150-nL whole-blood sample, with high precision (>0.99br>) and high reproducibility (CV<0.45%br>) within the glucose concentration range of 0–533 mg/dL. The sensor reading was stable for more than 60 days even at 70°C. Conclusions: The simplicity of the construction and the high precision of this FADGDH-based glucose biosensor makes it an alternative to previously reported commercially available glucose sensors. Especially the sample volume of 150 nL and the 1-sec measurement time are the highest specifications in the world for currently available glucose sensors designed for the SMBG.
A Prospective Evaluation of Insulin Dosing Recommendations in Patients with Type 1 Diabetes at near Normal Glucose Control: Basal Dosing
Authors: King Allen B. , Armstrong Dana U. 
Published: January 2014

Background: Current basal insulin dosing recommendations are based on retrospective studies of Type 1 patients with diabetes in whom the glucose control was not intensely established. Using continuous glucose monitoring (CGM) we prospectively studied these recommendations in patients treated with continuous subcutaneous insulin infusion. Methods: With CGM 30 subjects were titrated with daily insulin adjustments to achieve a basal glucose targets of <5% of values <70 mg/dl and <20%, >170mg/dl. The basal rate during meal time was studied by a sequential daily single meal omission until the glucose goals were achieved. Results: Glucose targets were achieved in all subjects. The observed ratios of total basal dose (TBD) to total daily dose and TBD to weight, in kilograms, were 0.384 and 0.185, respectively. Previously reported formulas for estimating the TBD resulted in significantly higher values than we observed. The difference between the maximum to the minimum hourly basal insulin infusion rate was more than 100% and the peak rate was reached by 0200 hours in 73% of subjects. During the post study observation period in which there was no further study intervention and in those subjects with baseline A1C >6.9%, the A1C decreased 0.45 % (p = 0.0110) in a mean of 12.8 weeks. Conclusions: Current literature overestimates TBD dose and underestimates the degree and the time of onset of the dawn phenomenon. Maintaining near normal glycemia in the ambulatory setting may be achieved in selected Type 1 patients for at least two weeks and maybe longer.
Adaptive Closed-Loop Control Provides Blood-Glucose Regulation Using Dual Subcutaneous Insulin and Glucagon Infusion in Diabetic Swine
Authors: El-Khatib Firas H. , Jiang John , Damiano Edward R. 
Published: January 2014

Background: In order to stave off deleterious complications of the disease, the ultimate task for people with diabetes is to maintain their blood glucose in euglycemic range. Despite technological advancements, conventional open-loop therapy often results in prolonged hyperglycemia and episodic hypoglycemia, in addition to necessitating carbohydrate counting, frequent glucose monitoring, and drug administration. The logical conclusion in the evolution of exogenous insulin therapy is to develop an automated closed-loop control system. Methods: Eleven closed-loop control experiments were conducted in four anesthetized diabetic pigs, with carbohydrate loads simulated by intravenous glucose administration through ear-vein catheters. Type 1 diabetes-like pathology was induced using intravenous administration of cytotoxin streptozotocin. The augmented model-predictive control algorithm accounts for the accumulation of subcutaneous insulin, which is critical in avoiding excessive insulin dosing. Results: Control results consistently showed successful blood-glucose regulation to euglycemic range within 80–120 minutes after intravenous glucose loads, with no incidence of hypoglycemia. This is consistent with a negative oral glucose tolerance test for diabetes and is the optimal postprandial regulation that can be achieved with subcutaneous insulin administration. Results also demonstrated the potency of subcutaneous glucagon in staving off episodic hypoglycemia and revealed efficacy of the control algorithm in coping with a twofold variation in subject weights, while simultaneously overlooking erratic blood-glucose fluctuations. Conclusions: Using an automated adaptive glucose-control system, we show successful blood-glucose regulation in vivo and establish, definitively, the plausibility and practicality of closed-loop blood-glucose control using subcutaneous insulin and glucagon infusion in type 1 diabetes. The control system strikes an intricate balance between tight blood-glucose control and optimal drug consumption, while simultaneously maintaining emphasis on simplicity and reliability.
Layer-by-Layer Assembled Semipermeable Membrane for Amperometric Glucose Sensors
Authors: Tipnis Ritesh , Vaddiraju SanthiSagar , Jain Faquir , Burgess Diane J. , Papadimitrakopoulos Fotios 
Published: January 2014

Background: The performance of implantable glucose sensors is closely related to the behavior of the outer membrane. Such membranes govern the diffusion characteristics of glucose and, correspondingly, the sensitivity of the sensors. This manuscript discusses the selection of various membrane materials and their effect on the device response. Methods: Sensors were fabricated utilizing a 50-μm platinum wire followed by immobilization of the glucose oxidase (GOx) enzyme. Sequential adsorption of various ionic species via a layer-by-layer process created devices coated with bilayers of humic acids/ferric cations (HAs/Fe3+), humic acids/poly(diallyldimethylammonium chloride) (HAs/PDDA), and poly(styrene sulfonate)/poly(diallyldimethylammonium chloride) (PSS/PDDA). The in vitro amperometric response of the sensors was determined at 0.7 V vs an Ag/AgCl reference electrode in phosphate-buffered saline (37°C) for various glucose concentrations. The diffusion coefficients of glucose and hydrogen peroxide (H2O2) through these membranes were calculated and analyzed. Results: Outer membranes based on the sequential deposition of bilayers of HAs/Fe3+, HAs/PDDA, and PSS/PDDA were grown successfully on immobilized layers of GOx. The amperometric response and reversibility upon changing the in vitro concentration of glucose were investigated. Conclusions: Through alteration of the number of bilayers of the outer membrane, it was possible to modulate the diffusion of glucose toward the sensor as a result of its flux-limiting characteristics. Semipermeable membranes based on five HAs/Fe3+ bilayers exhibited a superior behavior with a minimum hysterisis response to glucose cycling and a lesser current saturation at hyperglycemic glucose concentrations because of a more balanced inward diffusion of glucose and outward diffusion of H2O2.
Recommending Blood Glucose Monitors, a Pharmacy Perspective
Authors: Carter Alan 
Published: January 2014

Introduction: Selection of what blood glucose monitoring system to utilize has become an issue for physicians, diabetes educators, pharmacists, and patients. The field of competing makes and models of blood glucose monitoring systems has become crowded, with manufacturers touting improvements in accuracy, ease of use/alternate site options, stored results capacity, software evaluation tools, and/or price point. Methods: Personal interviews of 12 pharmacists from community and academic practice settings about monitor preference, as well as results from a national survey of pharmacist recommendations, were compared to actual wholesale sales data to estimate the impact of such recommendations on final monitor selection by the patient. Results: Accu-Chek® monitors were recommended 34.65% of the time and represented 28.58% of sales, with a success rate of 82.48% of being the monitor selected. OneTouch® monitors had 27.72% of recommendations but represented 31.43% of sales, indicating possible patient brand loyalty or formulary preference for that product. FreeStyle® monitors came in third for pharmacist recommendations and were selected by the patient 61.68% of the time when recommended. The category of “other monitor” choices was selected 60.89% of the time by patients given those suggestions. Included in the “other monitor” category was the new disposable monitor marketed as the Sidekick®. Based on sales data provided, the Sidekick® made up 2.87% of “other monitor” category sales, representing 68% of the “other monitor” segment. Conclusions: While patients frequently follow pharmacist monitoring system suggestions, the ultimate deciding factor is most often the final out-of-pocket cost to the patient. As a result, cost of supplies often becomes the most important determining factor in final monitor selection at the patient level. If the patient cannot afford to perform the recommended daily testing intervals, all other determining factors and suggestions become moot.
Modeling of Calibration Effectiveness and Blood-to-Interstitial Glucose Dynamics as Potential Confounders of the Accuracy of Continuous Glucose Sensors during Hyperinsulinemic Clamp
Authors: King Christopher , Anderson Stacey M. , Breton Marc , Clarke William L. , Kovatchev Boris P. 
Published: January 2014

Background: Models of the dynamics of interstitial fluid-based continuous glucose sensors imply a variable sensor deviation from reference blood glucose (BG), depending on both sensor calibration procedure and BG dynamics. These effects could have a significant effect on the cross-interpretation of nonidentical accuracy studies. Methods: Hyperinsulinemic euglycemic and hypoglycemic clamps were performed on 39 subjects with type 1 diabetes wearing the Medtronic Continuous Glucose Monitoring System®. Sensor calibration and interstitial glucose (IG) dynamics were modeled and analyzed as potential confounders of sensor deviation from reference BG. Results: The mean absolute deviation (MAD) of sensor data was 20.9 mg/dl during euglycemia and 24.5 mg/dl during descent into and recovery from hypoglycemia. Computer-generated recalibration reduced MAD to 10.6 and 14.6 mg/dl, respectively. Modeling of IG dynamics reduced the MAD further to 10.0 and 10.4 mg/dl (using idiosyncratic parameters) or to 10.6 and 11.5 mg/dl (using model parameters common for all subjects), respectively. Conclusions: The sensor MAD from reference is strongly influenced by the choice of calibration points. Thus, cross-experiment comparisons of sensor accuracy are likely to be heavily dependent on the employed calibration procedures. Demanding calibration points substantially differing in value was found to improve calibration effectiveness. Simulation using existing IG models and population parameters reduced the bias resulting from BG—IG dynamics.
Selectivity Assessment of Noninvasive Glucose Measurements Based on Analysis of Multivariate Calibration Vectors
Authors: Arnold Mark A. , Liu Lingzhi , Olesberg Jonathon T. 
Published: January 2014

Background: Selectivity is paramount for the successful implementation of noninvasive spectroscopic sensing for the painless measurement of blood glucose concentrations in people with diabetes. Selectivity issues are explored for different multivariate calibration models based on noninvasive near-infrared spectra collected from an animal model. Methods: Noninvasive near-infrared spectra are collected through a fiber-optic interface attached to a thin fold of skin on the back of an anesthetized laboratory rat while glucose levels are varied in a controlled manner. Results and Discussion: Partial least-squares (PLS) calibration models are generated from noninvasive spectra collected during a single, 2-hour blood glucose transient. Calibration vectors are compared for optimized PLS calibration models created with correct and incorrect assignments of glucose concentrations to each noninvasive spectrum. Although both PLS models appear functional and seem capable of predicting glucose concentrations accurately during this transient, only the model generated from correct glucose assignments gives a credible calibration vector. When correct glucose assignments are used, the PLS calibration vector matches the corresponding net analyte signal calibration vector. No similarity in these calibration vectors is evident when incorrect glucose assignments are used. Conclusions: Glucose-specific spectral information is present within noninvasive near-infrared spectra collected from a rat model using a transmission geometry. Apparently functional, yet incorrect, calibration models can be generated, and the propensity to create such false PLS calibration models calls into question the validity of past reports. An analysis of calibration vectors can provide valuable insight into the chemical basis of selectivity for multivariate calibration models of complex systems.
Continuous Noninvasive Glucose Monitoring Technology Based on “Occlusion Spectroscopy”
Authors: Amir Orna , Weinstein Daphna , Zilberman Silviu , Less Malka , Perl-Treves Daniele , Primack Harel , Weinstein Aharon , Gabis Efi , Fikhte Boris , Karasik Avraham 
Published: January 2014

Background: A truly noninvasive glucose-sensing device could revolutionalize diabetes treatment by leading to improved compliance with recommended glucose levels, thus reducing the long-term complications and cost of diabetes. Herein, we present the technology and evaluate the efficacy of a truly noninvasive device for continuous blood glucose monitoring, the NBM (OrSense Ltd.). Methods: In vitro analysis was used to validate the technology and algorithms. A clinical study was performed to quantify the in vivo performance of the NBM device. A total of 23 patients with type 1 (n = 12) and type 2 (n = 11) diabetes were enrolled in the clinical study and participated in 111 sessions. Accuracy was assessed by comparing NBM data with paired self-monitoring of blood glucose meter readings. Results: In vitro experiments showed a strong correlation between calculated and actual glucose concentrations. The clinical trial produced a total of 1690 paired glucose values (NBM vs reference). In the paired data set, the reference glucose range was 40–496 mg/dl. No systematic bias was found at any of the glucose levels examined (70, 100, 150, and 200 mg/dl). The mean relative absolute difference was 17.2%, and a Clarke error grid analysis showed that 95.5% of the measurements fall within the clinically acceptable A&B regions (zone A, 69.7%; and zone B, 25.7%). Conclusions: This study indicates the potential use of OrSense's NBM device as a noninvasive sensor for continuous blood glucose evaluation. The device was safe and well tolerated.
Prediction Capability of Optical Coherence Tomography for Blood Glucose Concentration Monitoring
Authors: Kuranov Roman V. , Sapozhnikova Veronika V. , Prough Donald S. , Cicenaite Inga , Esenaliev Rinat O. 
Published: January 2014

Background: Optical coherence tomography (OCT) has been shown to be a promising optical approach to noninvasive monitoring of blood glucose concentration because of its capability of probing optical properties at different depths in tissue with high resolution. This article investigates the capability of OCT to predict changes in blood glucose concentration. Methods: We varied blood glucose concentration in the physiological range in three sets of experiments. In the first set, we investigated large variations of blood glucose concentration (=400 mg/dl) and used 2100 OCT A scans for signal averaging. In the second set, we varied blood glucose concentration by approximately 200 mg/dl and used 8400 A scans for signal averaging. In the third set, we improved OCT blood glucose monitoring by increasing and controlling skin temperature under the OCT probe. In this set of experiments we increased the glucose concentration by approximately 300 mg/dl and used 4200 A scans for averaging. Results: The predicted glucose concentrations in the first two sets were lower than actual glucose concentration by 10–20% (the mean shift), while the heating and temperature control in the third set of experiments reduced the mean shift down to 1.5%. Therefore, the mean shift was reduced substantially by tissue heating and temperature control. However, it did not depend on the number of A scans to be averaged. In contrast, the uncertainty in OCT prediction of glucose concentration (the standard deviation) did not depend on heating and temperature control, but was reduced substantially from 56 to 24 mg/dl by increasing the number of A scans from 2100 to 8400, respectively. Conclusion: These results suggest that the accuracy of OCT-based glucose monitoring is approaching that of standard invasive and minimally invasive techniques.
Accuracy of Digital Images for Assessing Diabetic Retinopathy
Authors: Kim Hyungjin Myra , Lowery Julie C. , Kurtz Ronald 
Published: January 2014

Background: To determine the accuracy of diabetic retinopathy status assessments with and without pupil dilation using digital fundus photographs acquired by a clinic staff person and interpreted remotely by ophthalmologists. Method: Using early treatment diabetic retinopathy study (EDTRS) grading criteria, diabetic retinopathy status assessments were made by an experienced (nonphysician) retinal grader (NPG) based on seven standard field 35-mm stereoscopic slides acquired by an experienced ophthalmic photographer. These assessments were compared with those of the same eyes made by two ophthalmologists and the NPG using digital photographs acquired by a clinic staff person using a high-resolution (800 × 600) digital color camera system. Results: Based on 35-mm slides, 38% of 244 diabetic patients had ETDRS >35 in at least one eye and 5% had vision-threatening diabetic retinopathy (ETDRS >53 or macular edema). The proportion of ungradable images was significantly greater for nonmydriatic than mydriatic assessments (30% versus 10% ungradable as determined by the NPG). For ETDRS level >35, specificity ranged from moderate to high (0.70 to 0.96) for the three graders, while sensitivity was poor to moderate (0.38 to 0.71), and the area under the receiver-operating characteristic curves was less than satisfactory (0.67 to 0.71). Conclusions: The low sensitivity of the digital assessments indicates a significant proportion of patients in need of referral would not have been referred. These findings suggest that implementation of a simplified screening system using nonphotographer clinic staff acquiring nonmydriatic images, with interpretation by an ophthalmologist, should take place with an understanding of potential limitations.