bluuebunny/crossref_metadata_2025 huggingface dataset:
Pattern of and Risk Factors for Brain Microbleeds in Neurodegenerative Dementia
Authors: Olazarán Javier , Ramos Ana , Boyano Inmaculada , Alfayate Eva , Valentí Meritxell , Rábano Alberto , Álvarez-Linera Juan
Published: January 2014

Objective:

A cross-sectional study was conducted to describe the prevalence, locations, and risk factors for brain microbleeds (BMBs) in neurodegenerative dementia.

Methods:

The database of the Alzheimer Center Reina Sofía Foundation was searched, BMBs were described, and the potential associations of BMBs were investigated using univariate statistics.

Results:

A total of 148 patients (age 81.6 [standard deviation 6.7], 79.1% female) were studied. Prevalence of BMBs was 44.6%. A group of patients with unusually high (ie, ≥4) number of BMBs were identified, which displayed higher number of vascular risk factors and vascular diseases. Brain microbleeds were also associated with ischemic lesions in the basal ganglia ( r = .39), clinical diagnosis of Alzheimer’s disease (AD) and cerebrovascular disease ( r = .33), cortical infarction ( r = .20), and antiaggregant or anticoagulant treatment duration ( r = .20).

Conclusions:

Brain microbleeds are associated with vascular burden and AD diagnosis in old patients with neurodegenerative dementia. More research is warranted regarding the mechanisms and potential clinical implications of these results.
Neuropsychiatric Symptoms in Patients With Alzheimer’s Disease
Authors: García-Alberca José María , Lara José Pablo , Garrido Victoria , Gris Esther , González-Herero Vanessa , Lara Almudena
Published: January 2014

This study was conducted to obtain data regarding the association of caregiver burden (CB) and neuropsychiatric symptoms (NPSs) in patients with Alzheimer’s disease. We conducted a series of multiple linear regressions to determine the relationship between CB and NPSs and whether the caregiver coping strategies mediated this relationship. The NPSs were assessed using the Neuropsychiatric Inventory, and caregivers were evaluated with the Caregiver Burden Interview and the Inventory and the Coping Strategies Inventory. Results show that patients with more frequent and severe NPS were more likely to be cared for by more burdened caregivers, and this was partially mediated by caregiver coping strategies. More disengagement (β = .330, P < .001) and less engagement coping (β = −.347, P < .001) were predictors for NPS after adjusting for patient and caregiver characteristics. These results may be useful with a view to designing treatment interventions that aim to modify the use of caregiver coping strategies and to reduce NPSs.
Gastritis May Boost Odds of Dementia
Authors: Momtaz Yadollah Abolfathi , Hamid Tengku Aizan , Ibrahim Rahimah
Published: January 2014

Introduction:

Given the high prevalence of dementia and its devastating consequences, identifying risk factors for dementia is a public health priority. The present study aims to assess whether gastritis increases the odds of dementia.

Methodology:

The data for this study, consisting of 2926 community-dwelling older adults, were obtained from the National survey entitled “Mental Health and Quality of Life of Older Malaysians.” Dementia was diagnosed using the Geriatric Mental State-Automated Geriatric Examination for Computer-Assisted Taxonomy.

Results:

Prevalence of dementia was considerably higher among older adults with gastritis (29.5%) compared to those without gastritis (13.2%). After adjusting for age, gender, marital status, educational attainment, hypertension, stroke, and diabetes, gastritis was significantly associated with more than twice odds of dementia (adjusted odds ratio = 2.42, P < .001, 95% confidence interval = 1.68-3.49).

Conclusions:

The findings from this population-based observational study showing evidence that gastritis may increase the risk of dementia provide avenue for further inquiries into dementia.
Predictors of Restenosis After Carotid Endarterectomy
Authors: Chan R. C. , Chan Y. C. , Cheung G. C. , Cheng S. W.
Published: January 2014

Introduction:

Carotid endarterectomy (CEA) is a well-established surgical technique in stroke prophylaxis. Long-term follow-up data on restenosis or recurrent neurological symptoms in Oriental patients are unclear.

Methods:

Patients’ notes from 1994 to 2011 were retrospectively reviewed and analyzed. A total of 301 cases of CEA were identified.

Results:

A lower restenosis rate was associated with the use of patch and never smokers in both univariate and multivariate analysis. Use of patch and never smokers were also found to be significantly associated with longer restenosis-free survival. Use of patch and postoperative use of statin were associated with better overall survival in both univariate and multivariate analysis.

Conclusion:

Use of patch and lack of smoking history are associated with less restenosis and longer restenosis-free survival. Use of patch and use of postoperative statin improves overall survival. Although restenosis after CEA is relatively common, reintervention was rarely necessary.
Evaluation of Readmission Rates for Carotid Endarterectomy Versus Carotid Artery Stenting in the US Medicare Population
Authors: Galiñanes Edgar Luis , Dombroviskiy Viktor Y. , Hupp Colleen S. , Kruse Robin L. , Vogel Todd R.
Published: January 2014

Objective:

We evaluated rates and identified predictors of readmission in the Medicare population after carotid endarterectomy (CEA) compared to carotid artery stenting (CAS).

Methods:

MedPAR data (2005-2009) were used to select patients who underwent CEA or CAS (utilizing International Classification of Diseases, Ninth Revision, Clinical Modification codes). Readmission was evaluated using chi-square and multivariable logistic regression.

Results:

A total of 235 247 carotid interventions were performed (211 118 CEA and 24 129 CAS). Readmission rates (%) for patients undergoing CEA and CAS, respectively, were 8.84 and 11.11 (30 days; P < .0001); 13.31 and 17.98 (60 days; P < .0001); and 16.86 and 22.68 (90 days; P < .0001). Patients aged >80 (odds ratio [OR] = 1.25; 95% confidence interval [CI] = 1.20-1.30) and patients with renal failure (OR = 1.6 95%; CI = 1.56-1.73), congestive heart failure (OR = 1.6; 95%CI = 1.57-1.73), diabetes (OR = 1.4; 95% CI 1.27-1.52), and CAS (OR = 1.2; 95%CI = 1.15-1.25) were more likely to be readmitted.

Conclusions:

Interventions for carotid artery disease had high overall readmission rates. After adjustment for comorbidities, utilization of less invasive techniques (CAS) did not result in lower readmission rates. Further evaluation is needed to determine strategies to reduce hospital readmission rates after carotid interventions.
Clinical Evaluation of an Internal Adjustable Retractor in Laparoscopic Cholecystectomy
Authors: Dhumane Parag , Dallemagne Bernard , Barry Brian , Perretta Silvana , Leroy Joel , Mutter Didier , Marescaux Jacques
Published: January 2014

Introduction. Reducing the number of abdominal incisions in laparoscopic cholecystectomy introduces ergonomic challenges while establishing the critical view during dissection of the triangle of Calot (TC). This study investigates the use of a novel internal retracting device in performing cholecystectomy with a reduced number of ports. Methods. A 3-port laparoscopic cholecystectomy was attempted by 4 surgeons unfamiliar with the novel device. Exposure of the TC was obtained using the internal retractor, which comprises 2 clips, linked by an adjustable thread. One clip is fixed on the gallbladder and the other is fixed to the peritoneum. The endpoint was to evaluate the efficacy and reliability of the device in establishing the critical view of safety. Results. Thirteen patients with a mean body mass index of 25.29 kg/m2 (standard deviation = 6.24; range = 17.6-36.7 kg/m2) were included in the study. The critical view was obtained in 10 of 13 patients. Application of the device was completed in a median time of 2.25 minutes without injury of the gallbladder or bile leak. Failure occurred in 3 patients, related to wrong manipulation of the device (2 patients), and correct placement of the device but inadequate exposure (1 patient). A conventional 4-port technique was used in these patients. Operators rated their experience with the device as an “easy-to-operate” device with a good safety profile and without any interference with the operative process. Conclusions. Throughout the minimization process specific to minimal access surgery, internal retractors will certainly allow for a reduction in the number of trocars used in laparoscopic procedures.
Study of microfluidic cell chip for the toxicity test of artemisinin on Hep-G2 cells
Authors: Wang Yao , Xu Yi , Zhou Zhen , Li Whenjuan , Dong Chunyan , Liu He , Zhao Lianguo
Published: January 2014

A novel microfluidic chip composed of a 6 × 6 array of cell culture microchambers was designed and fabricated in this article. The microchip analytical system combined with the designed microchip, measuring device and environmental control unit was established for cell culture and parallel drug cytotoxicity assay. Human hepatoma cell Hep-G2 and artemisinin were taken as the objective samples in the experiments. Hep-G2 cells were successfully cultured in the microchip for over 72 h. Moreover, the viability percentage of the Hep-G2 cells was higher than 90% with staining of trypan blue. The Hep-G2 cells were exposed to the artemisinin solutions at different concentrations (0, 10, 25, 50, 100 and 150 µmol L−1) for 12, 24 and 48 h. The viability of the Hep-G2 cells in chambers was measured by observing cellular morphology and detecting fluorescence intensity. Results showed that artemisinin could inhibit the viability of Hep-G2 cells, which depended on the dose of artemisinin and action time. The microchip analytical system could not only solve the shortcomings of conventional in vitro cell culture, such as labor intensive, reagent consuming and time consuming, but also improve great potential for the study of cell biology in the directions of miniaturization, automation, high efficiency and high sensitivity.
Satisfying the needs of Japanese cancer patients: A comparative study of detailed and standard informed consent documents
Authors: Sato Keiko , Watanabe Toru , Katsumata Noriyuki , Sato Tosiya , Ohashi Yasuo
Published: January 2014

Background

Simplified informed consent forms have been successful in improving patient satisfaction and decreasing patient anxiety. However, unsolved problems remain about whether these documents improve comprehension and satisfaction of patients with standard literacy skills.

Purposes

To investigate whether a detailed consent form explaining the key elements of informed consent, in comparison to a standard consent form, would increase the comprehension and satisfaction of adult cancer patients.

Methods

Patients who were eligible for the National Surgical Adjuvant Study of Breast Cancer (protocol 01(N-SAS/BC-01)) were randomly selected to receive one of the following four versions: detailed document with graphics, detailed document without graphics, standard document with graphics, and standard document without graphics. The forms were written in plain language from the patients’ point of view. A total of 85 patients were administered questionnaires via interview to assess levels of comprehension, satisfaction, and anxiety.

Results

Patients demonstrated a strong understanding of information regarding treatment and research. Patient comprehension did not differ significantly between the detailed document arms and the standard document arms. Patient satisfaction level increased according to the amount of information presented in the consent form; most patients preferred the detailed document with graphics. Anxiety and accrual rates in the parent study were not affected by informed consent procedures.

Limitations

Findings were limited to adults who had standard literacy skills and may not be generalizable to a population with lower literacy.

Conclusion

Informed consent can be a significant experience for a population with standard literacy skills, as long as the document is easily comprehensible. Such information should be provided in a format that corresponds with patient needs, education levels, and preferences.
A disturbed interaction with accessory cells upon opportunistic infection with Pseudomonas aeruginosa contributes to an impaired IFN-γ production of NK cells in the lung during sepsis-induced immunosuppression
Authors: Pastille Eva , Pohlmann Stephanie , Wirsdörfer Florian , Reib Anna , Flohé Stefanie B
Published: January 2014

Impaired resistance to Pseudomonas aeruginosa-induced pneumonia after cecal ligation and puncture (CLP), a mouse model for human polymicrobial sepsis, is associated with decreased IFN-γ, but increased IL-10, levels in the lung. We investigated the so far unknown mechanisms underlying this reduced IFN-γ synthesis in CLP mice. CD11b+ NK cells, but not T or NKT cells in the lung were impaired in IFN-γ synthesis upon challenge with Pseudomonas in vitro and in vivo after CLP. The inhibition of NK cells was independent of IL-10. IFN-γ synthesis of NK cells was only partly restored by addition of recombinant IL-12. Accessory cells including dendritic cells and alveolar macrophages were required for maximal IFN-γ secretion. But accessory cells of CLP mice suppressed the IFN-γ secretion from naive lung leukocytes. In turn, naive accessory cells were unable to restore the IFN-γ production from lung leukocytes of CLP mice. Thus, a disturbed interaction of accessory cells and NK cells is involved in the impaired IFN-γ release in response to Pseudomonas in the lung of CLP mice. Considering the importance of IFN-γ in the immune defense against bacteria the dysfunction of accessory cells and NK cells might contribute to the enhanced susceptibility to Pseudomonas after CLP.
Advancing Emotion Theory with Multivariate Pattern Classification
Authors: Kragel Philip A. , LaBar Kevin S.
Published: January 2014

Characterizing how activity in the central and autonomic nervous systems corresponds to distinct emotional states is one of the central goals of affective neuroscience. Despite the ease with which individuals label their own experiences, identifying specific autonomic and neural markers of emotions remains a challenge. Here we explore how multivariate pattern classification approaches offer an advantageous framework for identifying emotion-specific biomarkers and for testing predictions of theoretical models of emotion. Based on initial studies using multivariate pattern classification, we suggest that central and autonomic nervous system activity can be reliably decoded into distinct emotional states. Finally, we consider future directions in applying pattern classification to understand the nature of emotion in the nervous system.
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.
Analysis of the Role of Electronic Blood Glucose Trending Software in Improving Health Outcomes in a Primary Care Setting
Authors: Holland Renee
Published: January 2014

With the increasing prevalence of diabetes reaching 7% of the total U.S. population1 the need for additional tools and resources to help physicians treating diabetes in a primary care setting is needed and often times lacking. In this issue of Journal of Diabetes Science and Technology (DST), Janssen et at.4 evaluate the role of Ascensia® WinGLUCOFACTS® Professional Blood Glucose Management Software in improving blood glucose control, diabetes related behaviors, and patient knowledge and attitudes in a primary care setting versus the traditional handwritten blood glucose (BG) logs. Results from their analysis include a clinically significant reduction in A1C from baseline in comparison to the 9 and 12 month checks (−0.64 at 9 months, and −0.41 at 12 months).
Engineering Approaches to Energy Balance and Obesity: Opportunities for Novel Collaborations and Research
Authors: Ershow Abby G. , Ortega Alfonso , Baldwin J. Timothy , Hill James O.
Published: January 2014

Energy balance disorders account for a large public health burden. The obesity epidemic in particular is one of the most rapidly evolving public health problems of our day. At present, two-thirds of American adults and one-sixth of American children and adolescents are considered either overweight or obese. Public health concern about obesity is high because of the increased risk and increased mortality of cardiovascular disease, Type 2 diabetes, many forms of cancer, gallbladder disease, and osteoarthritis. These risks increase with the severity of the obesity. Excess adipose tissue, representing fat storage, ultimately derives from an imbalance between energy intake and energy expenditure. Conversely, undesirable and inadvertent loss of body weight and muscle mass, as seen in aging and cachectic states of chronic diseases such as heart failure and cancer, have serious clinical and functional consequences without satisfactory clinical or behavioral solutions. Innovative engineering technologies could help to address unresolved problems in energy balance, intake, and expenditure. Novel sensors, devices, imaging technologies, nanotechnologies, biomaterials, technologies to detect biochemical markers of energy balance, mathematical modeling, systems biology, and other approaches could be developed, evaluated, and leveraged through multidisciplinary collaborations. Engineers, physical scientists, and mathematicians can work with scientists from other relevant disciplines who possess expertise in obesity and nutrition. Furthermore, the possibility of re-engineering the “built environment” to encourage higher levels of physical activity has been suggested as another promising and important approach to which engineers can contribute (see http://www.obesityresearch.nih.gov ). Ultimately, systematic application of the “Engineering Approach” can help in developing the needed technologies and tools to facilitate research and eventually support therapeutic advances and behavioral change. This article summarizes important public health concerns related to disordered energy balance and describes research priorities identified at a recent National Science Foundation-National Institutes of Health workshop. Research funding opportunities are described as posted on the NIH Guide to Grants and Contracts (see http://www.nih.gov/grants/guide ).
Approaches for Improving Glucose Monitor Measurements for Self-Monitoring of Blood Glucose: From Measurement Harmonization to External Quality Assessment Programs
Authors: Vesper Hubert W. , Myers Gary L.
Published: January 2014

Self-monitoring of blood glucose (SMBG) is an important component in diabetes management, helping patients to achieve and maintain normal blood glucose levels. The benefit of SMBG depends on the quality of the measurement performed. Therefore, it is important to know the factors affecting the measurements and to assure that the quality of SMBG measurements is at the highest achievable level possible. To accomplish this, all aspects of the measurement procedure need to be taken into consideration. Sources of variability can be related to the monitor itself, its calibration and use, including blood collection. Improving the variability caused by each source requires specifically designed and targeted efforts. Variability related to the monitor can be assessed in studies that minimize other sources of variability. Variability related to monitor calibration can be assessed and minimized through harmonization or standardization programs, while variability related to the use of the monitors can be addressed through patient-oriented assessment and training. The latter may follow procedures similar to external quality assessment (EQA) programs used in clinical laboratory medicine. However, to obtain an optimal impact on patient care, such programs need to have a wide reach and the social and cultural competency to work efficiently with all patients. The EQA approach or approaches that would provide the most benefit to the patient remain to be determined.
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.
How to Design a Biosensor
Authors: Ward W. Kenneth
Published: January 2014

Amperometric sensors for continuous glucose monitoring could prevent acute and chronic complications of diabetes, but research is needed to improve accuracy and stability. In designing sensors, interference from non-glucose analytes can be minimized by use of filtration membranes or electron transfer mediators that allow polarization at low potentials. If oxygen is required for the enzymatic reaction with glucose, then the outer permselective membrane must have substantial oxygen permeability. For this reason, during development of permselective membranes, permeability studies (such as performed by Tipnis and colleagues in this issue) can be used to measure transport of glucose and oxygen and optimize membrane structure. Tipnis and colleagues present a novel biosensor based with separate layers for glucose-oxygen permselectivity, enzymatic conversion, and avoidance of interference. They also address sensor stability, in part by comparing sensor function during ascending vs descending glucose levels. By measuring the difference, they were able to minimize this aspect of instability (hysterisis), which assisted them in selecting a promising permselective membrane based on iron and humic acid.
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.
Prospects and Challenges for Islet Regeneration as a Treatment for Diabetes: A Review of Islet Neogenesis Associated Protein
Authors: Fleming Alexander , Rosenberg Lawrence
Published: January 2014

Diabetes mellitus results from inadequate insulin action, which can be viewed as a consequence of the limited ability to restore β cells after they are lost as the result of metabolic exhaustion, autoimmune destruction, or surgical insult. Arguably, a uniformly effective therapeutic pathway to address all forms of diabetes would be to reverse the restrictions on β-cell and islet regeneration. The development from progenitor cells of islets with normal endocrine function does occur in adult humans; it is referred to as islet neogenesis. The induction of islet neogenesis is an important, if not essential, therapeutic approach for curing type 1 diabetes mellitus (T1DM) and could be valuable in the treatment of type 2 diabetes mellitus (T2DM) as well. Islet neogenesis associated protein (INGAP) is the first therapeutic candidate to be identified as the result of a purposeful search for an endogenous molecule with islet neogenic activity. It was found that partial obstruction of the pancreatic duct in hamsters induced islet neogenesis; under this condition, a neogenesis-promoting activity was identified and partially purified from a soluble tissue fraction. A 168-kDa protein product of the cloned gene was found to be responsible for the neogenesis activity. This molecule named INGAP contains an active core sequence of amino acids called INGAP peptide. Results from in vitro, animal, and human studies suggest that INGAP and INGAP peptide are neogenic in at least several vertebrate species, including humans. INGAP has since been found to be a member of the family of Reg proteins, which are found across and in multiple versions within species and are closely associated with embryonic and regenerative processes. Clinical results suggest that INGAP peptide can be a suitable neogenesis therapy, but optimization of the therapy and more data are required to fully access this potential. Understanding of the signaling pathways of INGAP and other related Reg proteins is a promising means of advancing therapeutic development for people with T1DM and T2DM. The quest for the fundamental restorative approach to lost insulin secretion is an enticing target for drug development.
Microformats: Three Proposed Standards for Solving the Need for Standard Data Presentation
Authors: Farrell Bernard
Published: January 2014

The continuous glucose monitor market is just starting to develop. Current trends in the availability of diabetes information tools highlight the need for standard data presentation for continuous glucose monitors. These trends and their implications are discussed. This article proposes a set of standards for blood glucose data presentation. If device manufacturers adopt these standards, they will ensure that their continuous glucose monitors meet both the short-term and the long-term needs of users. This should increase the demand for these monitors and enable future device developments that appeal to a wider range of users.
Electrical Stimulation as Treatment for Obesity and Diabetes
Authors: Greenway Frank , Zheng Jolene
Published: January 2014

The prevalence of obesity is growing, is driving an increase in the prevalence of diabetes, and is creating a major public health crisis in the United States. Lifestyle and behavior therapy rarely give durable weight loss. There are few medications approved for the treatment of obesity. Those that exist are limited in efficacy and using them in combination does not result in greater weight loss. Surgical treatments for obesity are effective and give durable weight loss, but are accompanied by measurable morbidity and mortality. Several pacing approaches are being tried and are an outgrowth of pacing for gastroparesis. The Transcend® pacemaker blocks vagal efferents and delays gastric emptying, giving a 40% loss of excess body weight, if certain screening procedures are employed. The Tantulus™ pacemaker is still in development but increases antral muscular contractions and delays gastric emptying by stimulation during the absolute refractory period. Weight loss has been 30% of excess body weight, and glycohemoglobin decreased 1.6% in a trial of obese type 2 diabetes. Stimulation to the subdiaphragmatic sympathetics, vagal nerve stimulation with or without unilateral vagotomy, and intestinal pacing are other approaches that are still being evaluated preclinically. Clearly a safe, effective, and durable treatment for obesity is desperately needed. Electrical pacing of the gastrointestinal tract is promising therapeutically, and because pacemakers work through different mechanisms, combining pacemaker treatments may be possible. Rapid progress is being made in the field of electrical stimulation as a treatment for obesity and even greater progress can be expected in the foreseeable future.
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.
Lab-on-a-Chip Technology for Continuous Glucose Monitoring
Authors: Gravesen Peter , Poulsen Kristian Raaby , Dirac Holger
Published: January 2014

The demand for continuous glucose monitoring systems is greater than ever. The microelectromechanical systems (MEMS) approach has the advantage of being relatively easy to upscale to a commercial level; the preferred MEMS technique would be to run several detectors at once and, through the improved statistics, get a both more accurate and more reliable device than is currently available. Lab-on-a-chip technology may be seen as a further development of MEMS technology for analytical sensors. Lab-on-a-chip systems may be used to obtain improvements on several important characteristics of a sensor system: remove or decrease cross-sensitivity, improve sensor stability, improve accuracy, and/or improve response time compared to similar laboratory-equipment methods.
Replacements for Trans Fats—Will There Be an Oil Shortage?
Authors: Klonoff David C.
Published: January 2014

Manufacturers use the process of hydrogenation to create trans fats in order to increase the shelf life of baked and fried foods. Ingestion of trans fats is associated with an increased risk of cardiovascular disease. A groundswell of public sentiment is causing regulatory bodies to ban the use of trans fats in foods. Alternatives to trans fats are needed now in order to preserve the freshness and provide an appealing texture of many packaged foods. As trans fats become phased out, there are eight types of approaches currently being developed to substitute for these fats as ingredients for baked and fried foods: (1) modified hydrogenation, (2) genetically modified seeds, (3) interesterification, (4) fractionation and blending, (5) butter and animal fat, (6) natural saturated oils, (7) natural unsaturated oils, and (8) fat substitutes. These alternatives to trans fats will require close scrutiny to ascertain whether they will also turn out to be linked with cardiovascular disease.
Is There a Future for DNA-Based Molecular Devices in Diabetes Management?
Authors: Taylor Steven , Stojanovic Milan N.
Published: January 2014

We provide a thought experiment in advanced molecular engineering leading to the construction of a molecular robot acting as a DNA-based closed-loop device for the management of diabetes mellitus. The key components of this robot are nucleic acid enzymes regulated allosterically by glucose. In the presence of glucose above a threshold level the robot moves, releasing insulin from a lawn covered with insulin, but stops in its tracks whenever glucose decreases to a level below threshold; thus, the robot could provide an insulin release response to spikes in glucose concentration in real time.
New Technologies for Diabetes Presented at International Congresses in 2006
Authors: Donicova Viera
Published: January 2014

Diabetes is a medical specialty that is currently experiencing the rapid development of new technologies that can be applied to clinical management. At three international Diabetes Congresses held in 2006 (the annual meeting of European Association of Diabetes in Copenhagen, the World Congress of the International Diabetes Federation in Cape Town, and the Diabetes and Technology meeting in Atlanta), several new technologies and devices were demonstrated that are applicable to diabetes care. Out of various technological innovations, this article highlights three new interesting areas, which may represent the principal direction of future developments in science that may help improve the quality of life for the person with diabetes.
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.