Addressing shortfalls of laboratory HbA1c using a model that incorporates red cell lifespan.
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ABSTRACT:
SUBMITTER: Xu Y
PROVIDER: S-EPMC8437432 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundA recent kinetic model proposed a new individualized glycaemic marker, calculated HbA1c (cHbA1c), based on kinetic parameters and glucose levels that are specific to each person. The aims of the current work were to validate the accuracy of this glucose metric for clinical use and evaluate data requirements for the estimation of personal kinetic factors.MethodsWe retrieved HbA1c and glucose data from a group of 51 Japanese T1D patients under sensor-augmented pump (SAP) therapy. Two patient-specific kinetic parameters were identified by data sections, defined as continuous glucose data between two laboratory HbA1c measurements. The cHbA1c was prospectively validated employing subsequent HbA1c data that were not originally used to determine personal kinetic parameters.ResultsCompared to estimated HbA1c (eHbA1c) and glucose management indicator (GMI), cHbA1c showed clinically relevant accuracy improvement, with 20% or more within ±0.5% (±5.5 mmol/mol) of laboratory HbA1c. The mean absolute deviation of the cHbA1c calculation was 0.11% (1.2 mmol/mol), substantially less than for eHbA1c and GMI at 0.54% (5.9 mmol/mol) and 0.47% (5.1 mmol/mol), respectively.ConclusionOur study shows superior performance of cHbA1c compared with eHbA1c and GMI at reflecting laboratory HbA1c, making it a credible glucose metric for routine clinical use.
| S-EPMC8481730 | biostudies-literature
Project description:We introduce a new, minimally invasive laboratory technique called reticulocyte-based estimation of lifespan (REBEL) of erythrocytes in humans. Its major advantage over existing techniques is its applicability to patients with both changing and steady-state erythropoiesis status. The feasibility of REBEL was tested in five patients with hemodialysis-dependent end-stage renal disease. The RNA degradation half-life was first determined for each subject on day 1 by flow cytometry measurement of the decay rate of thiazole orange stain. Reticulocyte age distribution was then measured from residual RNA content weekly for 2 months to estimate the RBC production rate time course. Mean RBC lifespan per subject was estimated by fitting the integrated RBC production rate over time to the measured RBC count and optimizing the integration limits. The mean reticulocyte RNA half-life was 0.71 ± 0.11 days. The small coefficient of variation (15.6%) indicated that the degradation rate of RNA did not vary substantially between subjects. The mean RBC lifespan (TRBC = 76.6 ± 23.8 days) was comparable to the reported values for this patient population.
| S-EPMC4061324 | biostudies-literature
Project description:BackgroundDietary habits formed in early childhood can track into later life with important impacts on health. Food-based dietary guidelines (FBDGs) may have a role in improving population health but are lacking for young children.ObjectivesWe aimed to establish a protocol for addressing nutrient shortfalls in 1- to 5-y-old children (12-60 mo) using diet modeling in a population-based sample.MethodsSecondary analysis of 2010-2011 Irish National Pre-School Nutrition Survey data (n = 500) was conducted to identify typical food consumption patterns in 1- to 5-y-olds. Nutrient intakes were assessed against dietary reference values [European Food Safety Authority (EFSA) and Institute of Medicine (IOM)]. To address nutrient shortfalls using diet modeling, 4-d food patterns were developed to assess different milk-feeding scenarios (human milk, whole or low-fat cow milk, and fortified milks) within energy requirement ranges aligned with the WHO growth standards. FBDGs to address nutrient shortfalls were established based on 120 food patterns.ResultsCurrent mean dietary intakes for the majority of 1- to 5-y-olds failed to meet reference values (EFSA) for vitamin D (≤100%), vitamin E (≤88%), DHA (22:6n-3) + EPA (20:5n-3) (IOM; ≤82%), and fiber (≤63%), whereas free sugars intakes exceeded recommendations of <10% energy (E) for 48% of 1- to 3-y-olds and 75% of 4- to 5-y-olds. "Human milk + Cow milk" was the only milk-feeding scenario modeled that predicted sufficient DHA + EPA among 1- to 3-y-olds. Vitamin D shortfalls were not correctable in any milk-feeding scenario, even with supplementation (5 µg/d), apart from the "Follow-up Formula + Fortified drink" scenario in 1- to 3-y-olds (albeit free sugars intakes were estimated at 12%E compared with ≤5%E as provided by other scenarios). Iron and vitamin E shortfalls were most prevalent in scenarios for 1- to 3-y-olds at ≤25th growth percentile.ConclusionsUsing WHO growth standards and international reference values, this study provides a protocol for addressing nutrient shortfalls among 1- to 5-y-olds, which could be applied in country-specific population health.
| S-EPMC8755081 | biostudies-literature
Project description:ObjectiveA computational model that accounts for heterogeneous tissue properties was used to compare multiple independent current control (MICC), multi-stim set (MSS), and concurrent activation (co-activation) current steering technologies utilized in deep brain stimulation (DBS) on volume of tissue activated (VTA) and power consumption.MethodsA computational model was implemented in Sim4Life v4.0 with the multimodal image-based detailed anatomical (MIDA) model, which accounts for heterogeneous tissue properties. A segmented DBS lead placed in the subthalamic nucleus (STN). Three milliamperes of current (with a 90 μs pseudo-biphasic waveform) was distributed between two electrodes with various current splits. The laterality, directional accuracy, volume, and shape of the VTAs using MICC, MSS and co-activation, and their power consumption were computed and compared.ResultsMICC, MSS, and coactivation resulted in less laterality of steering than single-segment activation. Both MICC and MSS show directional inaccuracy (more pronounced with MSS) during radial current steering. Co-activation showed greater directional accuracy than MICC and MSS at centerline between the two activated electrodes. MSS VTA volume was smaller and more compact with less current spread outside the active electrode plane than MICC VTA. There was no consistent pattern of power drain between MSS and MICC, but electrode co-activation always used less power than either fractionating paradigm.ConclusionWhile current fractionalization technologies can achieve current steering between two segmented electrodes, this study shows that there are important limitations in accuracy and focus of tissue activation when tissue heterogeneity is accounted for.
| S-EPMC7318189 | biostudies-literature
Project description:Abnormalities of red blood cell (RBC) indices may affect glycated haemoglobin (HbA1c) levels. We assessed the influence of haemoglobin (Hb) and mean corpuscular volume (MCV) on the performance of HbA1c in detecting dysglycaemia among reproductive aged women planning to conceive. Women aged 18-45 years (n = 985) were classified as normal (12 ≤ Hb ≤ 16 g/dL and 80 ≤ MCV ≤ 100 fL) and abnormal (Hb < 12 g/dL and/or MCV < 80 fL). The Area Under the Receiver Operating Characteristic (AUROC) curve was used to determine the performance of HbA1c in detecting dysglycaemic status (prediabetes and diabetes). There were 771 (78.3%) women with normal RBC indices. The AUROCs for the normal and abnormal groups were 0.75 (95% confidence interval 0.69, 0.81) and 0.80 (0.70, 0.90), respectively, and were not statistically different from one another [difference 0.04 (- 0.16, 0.08)]. Further stratification by ethnicity showed no difference between the two groups among Chinese and Indian women. However, Malay women with normal RBC indices displayed lower AUROC compared to those with abnormal RBC indices (0.71 (0.55, 0.87) vs. 0.98 (0.93, 1.00), p = 0.002). The results suggest that the performance of HbA1c in detecting dysglycaemia was not influenced by abnormal RBC indices based on low Hb and/or low MCV. However, there may be ethnic variations among them.
| S-EPMC8531017 | biostudies-literature
Project description:A key goal of molecular/cell biology/biotechnology is to identify essential genes in virtually every physiological process to uncover basic mechanisms of cell function and to establish potential targets of drug therapy combating human disease. This article describes a semester-long, project-oriented molecular/cellular/biotechnology laboratory providing students, within a framework of bone cell biology, with a modern approach to gene discovery. Students are introduced to the topics of bone cells, bone synthesis, bone resorption, and osteoporosis. They then review the theory of microchip gene arrays, and study microchip array data generated during the differentiation of bone-resorbing osteoclasts in vitro. The class selects genes whose expression increases during osteoclastogenesis, and researches them in small groups using web-based bioinformatics tools. Students then go to a biotechnology company website to find and order small inhibitory RNAs (siRNAs) designed to "knockdown" expression of the gene of interest. Students then learn to transfect these siRNAs into osteoclasts, stimulate the cells to differentiate, assay osteoclast differentiation in vitro, and measure specific gene expression using real-time PCR and immunoblotting. Specific siRNA knockdown resulting in a decrease in osteoclastogenesis is indicative of a gene's physiological relevance. The results are analyzed statistically and presented to the class in groups. In the past 2 years, students identified several genes essential for optimal osteoclast differentiation, including Myo1d. The students hypothesize that the myo1d protein functions in osteoclasts to deliver important proteins to the cell surface via vesicular transport along microfilaments. Student response to the new course was overwhelmingly positive.
| S-EPMC4090094 | biostudies-literature
Project description:A quantitative systems pharmacology model for metastatic melanoma was developed for immuno-oncology with the goal of predicting efficacy of combination checkpoint therapy with pembrolizumab and ipilimumab. This literature-based model is developed at multiple scales: (i) tumor and immune cell interactions at a lesion level; (ii) multiple heterogeneous target lesions, nontarget lesion growth, and appearance of new metastatic lesion at a patient level; and (iii) interpatient differences at a population level. The model was calibrated to pembrolizumab and ipilimumab monotherapy in patients with melanoma from Robert et al., specifically, waterfall plot showing target lesion response and overall response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), which additionally considers nontarget lesion growth and appearance of new metastatic lesions. We then used the model to predict waterfall and RECIST version 1.1 for combination treatment reported in Long et al. A key insight from this work was that nontarget lesions growth and appearance of new metastatic lesion contributed significantly to disease progression, despite reduction in target lesions. Further, the lesion level simulations of combination therapy show substantial efficacy in warm lesions (intermediary immunogenicity) but limited advantage of combination in both cold and hot lesions (low and high immunogenicity). Because many patients with metastatic disease are expected to have a mixture of these lesions, disease progression in such patients may be driven by a subset of cold lesions that are unresponsive to checkpoint inhibitors. These patients may benefit more from the combinations which include therapies to target cold lesions than double checkpoint inhibitors.
| S-EPMC8302246 | biostudies-literature
Project description:As the population ages, risks for cognitive decline threaten independence and quality of life of older adults. Classically, psychological assessment tools that evaluate cognitive functioning are administered in face-to-face laboratory sessions, which are time- and resource-consuming. The present study set out to examine whether the eCOGTEL-an online adaptation of the Cognitive Telephone Screening Instrument (COGTEL; Kliegel et al. in J Psychol 141(2):147-170, 2007)-represents a reliable measure of cognitive performance in adulthood. Therefore, an age-stratified adult lifespan sample of 253 participants (aged 19-86 years) completed a face-to-face assessment in the laboratory and a self-administered online version, at their homes. A second, independent sample of 176 younger adults (aged 19-30 years) performed a test-retest assessment of the eCOGTEL. Results showed strong correlations between overall cognitive scores assessed online and in the laboratory, as well as a high test-retest reliability. Further, comparable data distributions between both assessment modes underline the feasibility of the eCOGTEL across the adult lifespan and particularly in older age. Our findings thereby indicate that the eCOGTEL can reliably measure cognitive performance across the lifespan at reduced costs, which may help detecting individuals at risk of developing age-related cognitive decline. Due to these strengths, the eCOGTEL represents a valuable contemporary approach for the resource-efficient online assessment of cognition, which may benefit a broad array of fundamental and applied research fields, such as clinical and organizational psychology.Supplementary informationThe online version contains supplementary material available at 10.1007/s10433-021-00667-x.
| S-EPMC8655327 | biostudies-literature
Project description:HbA1c is commonly used to monitor glycemic control. However, there is growing evidence that the relationship between HbA1c and mean blood glucose (MBG) is influenced by variation in red blood cell (RBC) lifespan in hematologically normal individuals. Correction of HbA1c for mean RBC age (MRBC ) requires a noninvasive, accurate, and affordable method to measure RBC survival. In this study, we evaluated whether a stable isotope approach would satisfy these requirements. RBC lifespan and MRBC were determined in a group of nine hematologically normal diabetic and nondiabetic subjects using oral (15) N-glycine to label heme in an age cohort of RBC. The MRBC was 58.7 ± 9.1 (2SD) days and RBC lifespan was 106 ± 21 (2SD) days. This degree of variation (±15-20%) is consistent with previous studies using other techniques. In a subset of seven subjects, MRBC determined with the biotin label technique were available from approximately five years prior, and strongly correlated with the stable isotope values (R(2) = 0.79). This study suggests that the MRBC is stable over time but varies substantially among individuals, and supports the importance of its variation in HbA1c interpretation. The characteristics of the stable isotope method support its suitability for studies to directly evaluate the impact of variation in MRBC on the interpretation of HbA1c.
| S-EPMC4276493 | biostudies-literature
Project description:Laboratory rats are commonly used in life science research as a model for human biology and disease, but the composition and development of their gut microbiota during life is poorly understood. We determined the fecal microbiota composition of healthy Sprague Dawley laboratory rats from 3 weeks to 2 y of age, kept under controlled environmental and dietary conditions. Additionally, we determined fecal short-chain fatty acid profiles, and we compared the rat fecal microbiota with that of mice and humans. Gut microbiota and to a lesser extent SCFAs profiles separated rats into 3 different clusters according to age: before weaning, first year of life (12- to 26-week-old animals) and second year of life (52- to 104-week-old). A core of 46 bacterial species was present in all rats but its members' relative abundance progressively decreased with age. This was accompanied by an increase of microbiota ?-diversity, likely due to the acquisition of environmental microorganisms during the lifespan. Contrastingly, the functional profile of the microbiota across animal species became more similar upon aging. Lastly, the microbiota of rats and mice were most similar to each other but at the same time the microbiota profile of rats was more similar to that of humans than was the microbiota profile of mice. These data offer an explanation as to why germ-free rats are more efficient recipients and retainers of human microbiota than mice. Furthermore, experimental design should take into account dynamic changes in the microbiota of model animals considering that their changing gut microbiota interacts with their physiology.
| S-EPMC5628645 | biostudies-literature