Optimal cut-off criteria for duplex ultrasound for the diagnosis of restenosis in stented carotid arteries: Review and protocol for a diagnostic study

Background  

Carotid angioplasty with stenting is a relatively new, increasingly used, less-invasive treatment for the treatment of symptomatic carotid artery stenosis. It is being evaluated in ongoing and nearly finished randomized trials. An important factor in the evaluation of stents is the occurrence of in-stent restenosis. An un-stented carotid artery is likely to have a more elastic vessel wall than a stented one, even if stenosis is present. Therefore, duplex ultrasound cut-off criteria for the degrees of an in-stent stenosis, based on blood velocity parameters, are probably different from the established cut-offs used for un-stented arteries. Routine criteria can not be applied to stented arteries but new criteria need to be established for this particular purpose.     

Current MUAC Cut-Offs to Screen for Acute Malnutrition Need to Be Adapted to Gender and Age: The Example of Cambodia

Background

Early identification of children <5 yrs with acute malnutrition is a priority. Acute malnutrition is defined by the World Health Organization as a mid-upper-arm circumference (MUAC) <12.5 cm or a weight-for-height Z-score (WHZ) <-2. MUAC is a simple and low-cost indicator to screen for acute malnutrition in communities, but MUAC cut-offs currently recommended by WHO do not identify the majority of children with weight-for-height Z-score (<-2 (moderate malnourished) or r<-3 (severe malnourished). Also, no cut-offs for MUAC are established for children >5 yrs. Therefore, this study aimed at defining gender and age-specific cut-offs to improve sensitivity of MUAC as an indicator of acute malnutrition.

Methods

To establish new age and gender-specific MUAC cut-offs, pooled data was obtained for 14,173 children from 5 surveys in Cambodia (2011–2013). Sensitivity, false positive rates, and areas under receiver-operator characteristic curves (AUC) were calculated using wasting for children <5yrs and thinness for children ≥5yrs as gold standards. Among the highest values of AUC, the cut-off with the highest sensitivity and a false positive rate ≤33% was selected as the optimal cut-off.

Results

Optimal cut-off values increased with age. Boys had higher cut-offs than girls, except in the 8–10.9 yrs age range. In children <2yrs, the cut-off was lower for stunted children compared to non stunted children. Sensitivity of MUAC to identify WHZ<-2 and <-3 z-scores increased from 24.3% and 8.1% to >80% with the new cut-offs in comparison with the current WHO cut-offs.

Conclusion

Gender and age specific MUAC cut-offs drastically increased sensitivity to identify children with WHZ-score <-2 z-scores. International reference of MUAC cut-offs by age group and gender should be established to screen for acute malnutrition at the community level.     

Appropriate Body Mass Index Cut-Offs to Determine Thinness,Overweight and Obesity in South Asian Children in The Netherlands

Background

Asian populations have an increased risk of developing cardiometabolic disorders at a lower body mass index (BMI) than other ethnic groups. Therefore, lower adult BMI cut-offs to determine overweight and obesity are recommended to assess the associated health risks for Asian (23 and 27.5 kg/m² respectively) and Asian Indian (23, 25 kg/m²) populations. The objective of this study was to develop BMI cut-offs for thinness, overweight, and obesity for South Asian children in the Netherlands, and to compare the BMI cut-offs and distribution with an Asian Indian reference, the WHO Child Growth Reference, and universal BMI cut-offs.

Methods

A reference cohort of 546 Surinamese South Asian boys and 521 girls, born between 1974–1976 (during the pre-obesity era) with 3408 and 3267 BMI measurements respectively, was retrospectively analysed. BMI-for-age charts were created with the LMS method. BMI centile curves passing through the cut-off points of 15 (thinness), 23 (overweight), 25 and 27.5 kg/m² (obesity) at 18y were drawn as cut-off levels.

Results

The BMI of Surinamese South Asian children had a similar distribution to the Asian Indian reference, apart from a lower mean and less variation. The BMI distribution differed considerably from the WHO reference and universal BMI criteria. The calculated BMI cut-offs corresponding to a BMI of 15, 23, 25, and 27.5 kg/m² at 18y were at the 7.1, 81.1, 89.8, and 95.5 percentile respectively in boys, and at the 2.7, 79.5, 89.2, and 95.2 percentile in girls.

Conclusions

This is the first study proposing BMI cut-offs for South Asian children based on measurements from a prosperous population unaffected by the obesity epidemic. We recommend the use of these cut-offs in South Asian children in the Netherlands as these better reflect the health risks associated with thinness, overweight and obesity, and therefore may prevent the development of cardiometabolic disorders.     

Reanalyze unassigned reads in Sanger based metagenomic data using conserved gene adjacency

Background  

Investigation of metagenomes provides greater insight into uncultured microbial communities. The improvement in sequencing technology, which yields a large amount of sequence data, has led to major breakthroughs in the field. However, at present, taxonomic binning tools for metagenomes discard 30-40% of Sanger sequencing data due to the stringency of BLAST cut-offs. In an attempt to provide a comprehensive overview of metagenomic data, we re-analyzed the discarded metagenomes by using less stringent cut-offs. Additionally, we introduced a new criterion, namely, the evolutionary conservation of adjacency between neighboring genes. To evaluate the feasibility of our approach, we re-analyzed discarded contigs and singletons from several environments with different levels of complexity. We also compared the consistency between our taxonomic binning and those reported in the original studies.     

High Discrepancy in Abdominal Obesity Prevalence According to Different Waist Circumference Cut-Offs and Measurement Methods in Children: Need for Age-Risk-Weighted Standardized Cut-Offs?

Background

Waist circumference (WC) is a good proxy measure of central adiposity. Due to the multiplicity of existing WC cut-offs and different measurement methods, the decision to use one rather than another WC chart may lead to different prevalence estimates of abdominal obesity in the same population. Aim of our study was to assess how much the prevalence of abdominal obesity varies in Italian schoolchildren using the different available WC cut-offs.

Methods

We measured WC at just above the uppermost lateral border of the right ilium in 1062 Italian schoolchildren aged 7–14 years, 499 living in Northern Italy and 563 in Southern Italy. Abdominal obesity was defined as WC ≥90^th percentile for gender and age according to nine WC charts.

Results

We found an extremely high variability in the prevalence of abdominal obesity detected in our study-populations according to the different WC charts, ranging in the overall group from 9.1% to 61.4%. In Northern Italy children it varied from 2.4% to 35.7%, and in Southern ones from 15.1% to 84.2%.

Conclusions

On the basis of the chosen WC cut-offs the prevalence of abdominal obesity varies widely, because percentile-charts are strongly influenced by the population status in a particular moment. A further rate of variability may lay on the site of WC measurement and on the statistical method used to calculate WC cut-offs. Risk-weighted WC cut-offs measured in a standardized anatomic site and calculated by the appropriate method are needed to simply identify by WC measurement those children at high risk of cardio-metabolic complications to whom specific and prompt health interventions should be addressed.     

In silico evaluation of a control system and algorithm for automated insulin infusion in the ICU setting

Background  

It is known that tight control of glucose in the Intensive Care Unit reduces morbidity and mortality not only in diabetic patients but also in those non-diabetics who become transiently hyperglycemic. Taking advantage of a recently marketed subcutaneous glucose sensor we designed an Automatic Insulin Infusion System (AIIS) for inpatient treatment, and tested its stability under simulated clinical conditions.     

Diabetes and Pre-Diabetes among Persons Aged 35 to 60 Years in Eastern Uganda: Prevalence and Associated Factors

Background

Our aim was to estimate the prevalence of abnormal glucose regulation (AGR) (i.e. diabetes and pre-diabetes) and its associated factors among people aged 35-60 years so as to clarify the relevance of targeted screening in rural Africa.

Methods

A population-based survey of 1,497 people (786 women and 711 men) aged 35-60 years was conducted in a predominantly rural Demographic Surveillance Site in eastern Uganda. Participants responded to a lifestyle questionnaire, following which their Body Mass Index (BMI) and Blood Pressure (BP) were measured. Fasting plasma glucose (FPG) was measured from capillary blood using On-Call® Plus (Acon) rapid glucose meters, following overnight fasting. AGR was defined as FPG ≥6.1mmol L^-1 (World Health Organization (WHO) criteria or ≥5.6mmol L^-1 (American Diabetes Association (ADA) criteria. Diabetes was defined as FPG >6.9mmol L^-1, or being on diabetes treatment.

Results

The mean age of participants was 45 years for men and 44 for women. Prevalence of diabetes was 7.4% (95%CI 6.1-8.8), while prevalence of pre-diabetes was 8.6% (95%CI 7.3-10.2) using WHO criteria and 20.2% (95%CI 17.5-22.9) with ADA criteria. Using WHO cut-offs, the prevalence of AGR was 2 times higher among obese persons compared with normal BMI persons (Adjusted Prevalence Rate Ratio (APRR) 1.9, 95%CI 1.3-2.8). Occupation as a mechanic, achieving the WHO recommended physical activity threshold, and higher dietary diversity were associated with lower likelihood of AGR (APRR 0.6, 95%CI 0.4-0.9; APRR 0.6, 95%CI 0.4-0.8; APRR 0.5, 95%CI 0.3-0.9 respectively). The direct medical cost of detecting one person with AGR was two US dollars with ADA and three point seven dollars with WHO cut-offs.

Conclusions

There is a high prevalence of AGR among people aged 35-60 years in this setting. Screening for high risk persons and targeted health education to address obesity, insufficient physical activity and non-diverse diets are necessary.     

Dimensional analysis of MINMOD leads to definition of the disposition index of glucose regulation and improved simulation algorithm

Background  

Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) together with its mathematical model, the minimal model (MINMOD), have become important clinical tools to evaluate the metabolic control of glucose in humans. Dimensional analysis of the model is up to now not available.     

A1C as a diagnostic criteria for diabetes in low- and middle-income settings: evidence from Peru

Objectives

To determine the prevalence of type 2 diabetes mellitus, in three groups of Peruvian adults, using fasting glucose and glycosylated hemoglobin (A1C).

Methodology/Principal Findings

This study included adults from the PERU MIGRANT Study who had fasted ≥8 h. Fasting glucose ≥126 mg/dL and A1C≥6.5% were used, separately, to define diabetes. Subjects with a current diagnosis of diabetes were excluded. 964 of 988 subjects were included in this analysis. Overall, 0.9% (95%CI 0.3–1.5) and 3.5% (95%CI 2.4–4.7) had diabetes using fasting glucose and A1C criteria, respectively. Compared to those classified as having diabetes using fasting glucose, newly classified subjects with diabetes using A1C (n = 25), were older, poorer, thinner and more likely to come from rural areas. Of these, 40% (10/25) had impaired fasting glucose (IFG).

Conclusions

This study shows that the use of A1C as diagnostic criteria for type 2 diabetes mellitus identifies people of different characteristics than fasting glucose. In the PERU MIGRANT population using A1C to define diabetes tripled the prevalence; the increase was more marked among poorer and rural populations. More than half the newly diagnosed people with diabetes using A1C had normal fasting glucose.     

Butyrate ingestion improves hepatic glycogen storage in the re-fed rat

Background  

Butyrate naturally produced by intestinal fiber fermentation is the main nutrient for colonocytes, but the metabolic effect of the fraction reaching the liver is not totally known. After glycogen hepatic depletion in the 48-hour fasting rat, we monitored the effect of (butyrate 1.90 mg + glucose 14.0 mg)/g body weight versus isocaloric (glucose 18.2 mg/g) or isoglucidic (glucose 14.0 mg/g) control force-feeding on in vivo changes in hepatic glycogen and ATP contents evaluated ex vivo by NMR in the isolated and perfused liver.     

A mathematical model of brain glucose homeostasis

Background  

The physiological fact that a stable level of brain glucose is more important than that of blood glucose suggests that the ultimate goal of the glucose-insulin-glucagon (GIG) regulatory system may be homeostasis of glucose concentration in the brain rather than in the circulation.     

Assessment of single-dose benzodiazepines on insulin secretion,insulin sensitivity and glucose effectiveness in healthy volunteers: a double-blind,placebo-controlled,randomized cross-over trial [ISRCTN08745124]

Background  

The present study aimed at investigating in healthy volunteers the effects of diazepam and clonazepam on beta-cell function, insulin sensitivity and glucose effectiveness based on the frequently sampled intravenous (0.5 gkg^-1) glucose tolerance test with minimal-model analysis.     

Glycolysis and the regulation of glucose transport in <Emphasis Type="Italic">Lactococcus lactis</Emphasis> spp. <Emphasis Type="Italic">lactis</Emphasis> in batch and fed-batch culture

Background  

Despite the fact that many reports deal with glycolysis in Lactococcus lactis, there is not much information on the regulation of uptake of glucose itself. The aim of the present work was to investigate the effect of the glucose level on its specific uptake rate.     

Improved hit criteria for DNA local alignment

Background  

The hit criterion is a key component of heuristic local alignment algorithms. It specifies a class of patterns assumed to witness a potential similarity, and this choice is decisive for the selectivity and sensitivity of the whole method.     

<Emphasis Type="Italic">Bacillus subtilis</Emphasis> GlcK activity requires cysteines within a motif that discriminates microbial glucokinases into two lineages

Background  

Bacillus subtilis glucokinase (GlcK) (GenBank NP_390365) is an ATP-dependent kinase that phosphorylates glucose to glucose 6-phosphate. The GlcK protein has very low sequence identity (13.7%) to the Escherichia coli glucokinase (Glk) (GenBank P46880) and some other glucokinases (EC 2.7.1.2), yet glucose is merely its substrate. Our lab has previously isolated and characterized the glcK gene.     

Low cortisol levels in blood from dairy cows with ketosis: a field study

Background  

An elevated plasma glucose concentration has been considered to be a potential risk factor in the pathogenesis of left-displaced abomasums (DA). Therefore the present study was performed to investigate if spontaneous disease (parturient paresis, metritis, ketosis etc) in dairy cows results in elevated concentrations of glucose and cortisol in blood as cortisol is the major regulator of glucose in ruminants.     

An intracellular motif of GLUT4 regulates fusion of GLUT4-containing vesicles

Background  

Insulin stimulates glucose uptake by adipocytes through increasing translocation of the glucose transporter GLUT4 from an intracellular compartment to the plasma membrane. Fusion of GLUT4-containing vesicles at the cell surface is thought to involve phospholipase D activity, generating the signalling lipid phosphatidic acid, although the mechanism of action is not yet clear.     

Metabolites produced by probiotic Lactobacilli rapidly increase glucose uptake by Caco-2 cells

Background  

Although probiotic bacteria and their metabolites alter enterocyte gene expression, rapid, non-genomic responses have not been examined. The present study measured accumulation of tracer (2 μM) glucose by Caco-2 cells after exposure for 10 min or less to a chemically defined medium (CDM) with different monosaccharides before and after anaerobic culture of probiotic Lactobacilli.     

A novel hydroxyfuroic acid compound as an insulin receptor activator - structure and activity relationship of a prenylindole moiety to insulin receptor activation

Background  

Diabetes Mellitus is a chronic disease and many patients of which require frequent subcutaneous insulin injection to maintain proper blood glucose levels. Due to the inconvenience of insulin administration, an orally active insulin replacement has long been a prime target for many pharmaceutical companies. Demethylasterriquinone (DMAQ) B1, extracted from tropical fungus, Pseudomassaria sp., has been reported to be an orally effective agent at lowering circulating glucose levels in diabetic (db/db) mice; however, the cytotoxicity associated with the quinone moiety has not been addressed thus far.     

Optimization of treatment with interferon beta in multiple sclerosis. Usefulness of automatic system application criteria

Background  

A software based tool has been developed (Optem) to allow automatize the recommendations of the Canadian Multiple Sclerosis Working Group for optimizing MS treatment in order to avoid subjective interpretation.