Use of CoZmonitor in youth with type 1 diabetes.

Background: The purpose of this study was to evaluate the effectiveness of directly integrating self-monitoring blood glucose (BG) information with insulin pump therapy on overall glycemic control.

Methods: In this randomized trial, 34 youth with type 1 diabetes using insulin pump therapy were trained on the use of the Deltec Cozmo Insulin Pump. Seventeen were randomized to use the CoZmonitor Blood Glucose Module, a device that attaches to the back of the pump using FreeStyle technology to perform BG tests which read directly on the pump screen.

Novel bioreactors for the culture and expansion of aggregative neural stem cells.

Neural stem cells have been cultured as three-dimensional aggregates in a number of different types of bioreactors. The design and configuration of the bioreactor are shown to be crucial factors for the successful propagation of the cells. A novel bioreactor with liquid re-circulation and a working volume of 200 ml has been designed, tested and shown to be able to produce a higher cell vitality compared to those produced in multi-well plates, shake flasks and stirred flasks.

Improved glycemic control after long-term insulin pump use in pediatric patients with type 1 diabetes.

Background: There are currently few data available on the long-term use of continuous subcutaneous insulin infusion (CSII) (insulin pump) therapy in children.

Methods: Charts from 291 youth with type 1 diabetes (T1D) who were treated with CSII therapy for at least 1 year were reviewed. Data analysis included hemoglobin A(1c)(HbA(1c)) values, body mass index (BMI) values, and the occurrence of severe hypoglycemia (SH) or diabetic ketoacidosis (DKA) events.

Omega-3 polyunsaturated fatty acid intake and islet autoimmunity in children at increased risk for type 1 diabetes.

Context: Cod liver oil supplements in infancy have been associated with a decreased risk of type 1 diabetes mellitus in a retrospective study.

Objective: To examine whether intakes of omega-3 and omega-6 fatty acids are associated with the development of islet autoimmunity (IA) in children.

Design, Setting, And Participants: A longitudinal, observational study, the Diabetes Autoimmunity Study in the Young (DAISY), conducted in Denver, Colorado, between January 1994 and November 2006, of 1770 children at increased risk for type 1 diabetes, defined as either possession of a high diabetes risk HLA genotype or having a sibling or parent with type 1 diabetes.

A study of the influence of yeast cell debris on protein and alpha-glucosidase adsorption at various zones within the expanded bed using in-bed sampling.

Expanded bed adsorption chromatography is used to capture products directly from unclarified feedstocks, thus combining solid-liquid separation, product concentration and preliminary purification into a single step. However, when non-specific ion-exchangers are used as the adsorbent in the expanded bed, there is the possibility that electrostatic interactions of cells or cell debris with the adsorbent may interfere with the adsorption of soluble products. These interactions depend on the particle size of the cell debris and its surface charge, which in turn depend on the extent of disruption used to release the intracellular products.

Separation and enrichment of neural stem cells using segregation in an expanded bed.

An expanded bed system has been developed for a novel application in which the separation and enrichment of neural stem cells from a sample containing a mixture of stem and progenitor cells is achieved based on the difference in the sizes of the aggregates of these types of cells. Inert Sephadex beads and flocculated yeast cells were used as experimental controls and references. The characteristics of the separation of neural stem cell aggregates based on size are similar to those achieved with flocculated yeast where cell-to-cell aggregation controls the pattern of size separation different from those of inert Sephadex beads.

Increasing the accuracy of oral glucose tolerance testing and extending its application to individuals with normal glucose tolerance for the prediction of type 1 diabetes: the Diabetes Prevention Trial-Type 1.

Objective: We assessed the extent to which both standard and alternative indexes from 2-h oral glucose tolerance testing predict type 1 diabetes and whether oral glucose tolerance tests (OGTTs) predict type 1 diabetes in individuals with normal glucose tolerance.

Research Design And Methods: The prediction of type 1 diabetes from baseline OGTTs was studied in 704 Diabetes Prevention Trial-Type 1 participants (islet-cell autoantibody [ICA]-positive relatives of type 1 diabetic patients). The maximum follow-up was 7.

Pre-type 1 diabetes dysmetabolism: maximal sensitivity achieved with both oral and intravenous glucose tolerance testing.

Objective: To determine the relationship of intravenous (IVGTT) and oral (OGTT) glucose tolerance tests abnormalities to diabetes development in a high-risk pre-diabetic cohort and to identify an optimal testing strategy for detecting preclinical diabetes.

Study Design: Diabetes Prevention Trial-Type 1 Diabetes (DPT-1) randomized subjects to oral (n = 372) and parenteral (n = 339) insulin prevention trials. Subjects were followed with IVGTTs and OGTTs.

Prevention strategies for type 1 diabetes.

Type 1 diabetes (T1D) is a common chronic disease of childhood. Patients with T1D are at significant risk for developing serious health complications. Understanding of the genetics, environmental factors, and natural history of diabetes has lead to greater understanding of the etiology and epidemiology of T1D.

Bedside monitoring of blood beta-hydroxybutyrate levels in the management of diabetic ketoacidosis in children.

Introduction: Diabetic ketoacidosis (DKA) affects many children with type 1 diabetes. Insulin treatment of DKA is traditionally guided by changes in the blood glucose levels and blood gases, whereas beta-hydroxybutyrate (beta-OHB)--the main ketoacid causing acidosis--is rarely measured. The purpose of this study was to evaluate if bedside monitoring of blood beta-OHB levels can simplify management of DKA through elimination of superfluous laboratory monitoring.

Production of enzymatically active ketosteroid isomerase following insoluble expression in Escherichia coli.

Enzymatically active Delta(5)-3-ketosteroid isomerase (KSI) protein with a C-terminus his(6)-tag was produced following insoluble expression using Escherichia coli. A simple, integrated process was used to extract and purify the target protein. Chemical extraction was shown to be as effective as homogenization at releasing the inclusion body proteins from the bacterial cells, with complete release taking less than 20 min.

Intensified process for the purification of an enzyme from inclusion bodies using integrated expanded bed adsorption and refolding.

This work describes the integration of expanded bed adsorption (EBA) and adsorptive protein refolding operations in an intensified process used to recover purified and biologically active proteins from inclusion bodies expressed in E. coli. Delta(5)-3-Ketosteroid isomerase with a C-terminal hexahistidine tag was expressed as inclusion bodies in the cytoplasm of E.

Adsorptive refolding of histidine-tagged glutathione S-transferase using metal affinity chromatography.

Column-based protein refolding strategies are often advantageous due to their ease of integration with purification operations, improved refolding yields, and the high concentrations at which the refolded protein can be recovered. His6-tagged glutathione S-transferase (GST-(His6)) was refolded while it was adsorbed in a metal affinity chromatography column. The redox environment could be controlled during the refolding reaction by the addition of reduced and oxidized glutathione without reducing the immobilized nickel metal ions.

Mixing rapid-acting insulin analogues with insulin glargine in children with type 1 diabetes mellitus.

Objective: To determine whether mixing insulin glargine (IG) with a rapid-acting insulin (RAI) analogue in the same syringe had any deleterious effects on glycemic control in children with type 1 diabetes mellitus.

Study Design: Data from 55 children mixing the IG with a RAI analogue was collected for 6 months before and 6 months after the insulin mixing began. Data from a control group of 55 children not mixing the insulins was collected at similar intervals.

The use of insulin pumps with meal bolus alarms in children with type 1 diabetes to improve glycemic control.

Objective: The aim of this study was to determine whether the use of meal bolus alarms would result in fewer missed meal boluses per week in youth with type 1 diabetes using continuous subcutaneous insulin infusion (CSII) therapy.

Research Design And Methods: This was a randomized trial of 48 youth using CSII, who were in suboptimal glycemic control with HbA(1c) (A1C) values > or =8.0%.

Refolding strategies for ketosteroid isomerase following insoluble expression in Escherichia coli.

Dilution and column-based protein refolding techniques are compared for refolding Delta 5-3-ketosteroid isomerase (KSI) with a C-terminus his6-tag. Column refolding was performed by removing the denaturant while the protein was adsorbed in an immobilized metal affinity chromatography column. Both dilution refolding and a single-step column-based refolding strategy were optimized to maximize the recovery of KSI enzyme activity, and achieved refolding yields of 87% and 70% respectively.

Patterns of metabolic progression to type 1 diabetes in the Diabetes Prevention Trial-Type 1.

Objective: There is little information regarding the pattern of metabolic deterioration before the onset of type 1 diabetes. The goal of this study was to utilize data from the Diabetes Prevention Trial-Type 1 (DPT-1) to obtain a picture of the metabolic progression to type 1 diabetes over a period of approximately 2.5 years before its diagnosis.

A critical assessment of the impact of mixing on dilution refolding.

Refolding often presents a bottleneck in the generation of recombinant protein expressed as inclusion bodies. Few studies have looked at the effect of physical factors on the yield from refolding steps. Refold reactors typically operate in fed-batch mode with a slow injection rate.

Accuracy of newer-generation home blood glucose meters in a Diabetes Research in Children Network (DirecNet) inpatient exercise study.

Background: The objective of this study was to assess how the accuracy of the FreeStyle Flash (Abbott Diabetes Care, Alameda, CA) meter compares with that of the One Touch Ultra (Lifescan, Milpitas, CA) home glucose meter (HGM).

Research Design And Methods: Fifty children with type 1 diabetes (T1D), 10-17 years old, were admitted for two separate 24-h periods to assess the effect of exercise on subsequent nocturnal hypoglycemia. Resulting data were used in a preplanned analysis of the accuracy of the Ultra and FreeStyle HGMs.

Impact of exercise on overnight glycemic control in children with type 1 diabetes mellitus.

Objective: To examine the effect of exercise on overnight hypoglycemia in children with type 1 diabetes mellitus (T1DM).

Study Design: At 5 clinical sites, 50 subjects with T1DM (age 11 to 17 years) were studied in a clinical research center on 2 separate days. One day included an afternoon exercise session on a treadmill.

Upgrading of anaerobic digestion by incorporating two different hydrolysis processes.

The purpose of this study was to increase the efficiency of anaerobic digestion of waste activated sludge (WAS). Either thermochemical or biological hydrolysis was used as a pretreatment and the effects of both were investigated and compared. Two different three-stage digestion systems showed improved performance, although thermochemical hydrolysis showed better results than biological hydrolysis in a bench-scale operation.

Removal of poly-histidine fusion tags from recombinant proteins purified by expanded bed adsorption.

Enzymatic methods have been used to cleave the C- or N-terminus polyhistidine tags from histidine tagged proteins following expanded bed purification using immobilized metal affinity chromatography (IMAC). This study assesses the use of Factor Xa and a genetically engineered exopeptidase dipeptidyl aminopeptidase-1 (DAPase-1) for the removal of C-terminus and N-terminus polyhistidine tags, respectively. Model proteins consisting of maltose binding protein (MBP) having a C- or N-terminal polyhistidine tag were used.

A randomized multicenter trial comparing the GlucoWatch Biographer with standard glucose monitoring in children with type 1 diabetes.

Objective: This study assesses whether use of the GlucoWatch G2 Biographer (GW2B) in addition to standard glucose monitoring lowers HbA(1c) and reduces hypoglycemia compared with standard glucose monitoring alone.

Research Design And Methods: In all, 200 subjects aged 7 to <18 years with type 1 diabetes were randomly assigned at five centers to standard glucose monitoring (usual care) or standard glucose monitoring plus GW2B use for 6 months. Study outcomes included HbA(1c) values obtained at 6 months and occurrence of severe hypoglycemia.