The E23K variant of Kir6.2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes

The E23K polymorphism of the pancreatic beta-cell ATP-sensitive K(+) (K(ATP)) channel subunit Kir6.2 (KCNJ11) is associated with type 2 diabetes in whites, and a recent in vitro study of the E23K variant suggests that the association to diabetes might be explained by a slight inhibition of serum insulin release. In a study comprising 519 unrelated glucose-tolerant subjects, we addressed the question as to whether the E23K variant was related to reduced serum insulin release during an oral glucose tolerance test (OGTT). Furthermore, the polymorphism was examined in a case-control study comprising 803 type 2 diabetic patients and 862 glucose-tolerant control subjects. The E23K variant was associated with significant reductions in the insulinogenic index (P = 0.022) and serum insulin levels under the response curve during an OGTT (0-120 min) (P = 0.014) as well as with an increase in BMI (P = 0.013). In the present study, the association of the E23K polymorphism with type 2 diabetes was not significant (P = 0.26). However, the K23K genotype significantly associated with type 2 diabetes in a meta-analysis of white case and control subjects (n = 2,824, odds ratio [OR] 1.49, P = 0.00022). In conclusion, the widespread E23K polymorphism may have a diabetogenic effect by impairing glucose-induced insulin release and increasing BMI.     

Circulating Lipoproteins in Subjects with Morbid Obesity Undergoing Bariatric Surgery with Gastric Bypass or Sleeve Gastrectomy

The efficacy of various bariatric procedures on the mitigation of the obese dyslipidemia remains debated, and the impact of these measures on lipoprotein(a) (Lp(a)) levels is unknown. In this study we aimed to compare the two most commonly used procedures: gastric bypass (RYGB) and sleeve gastrectomy (SG). Adult patients with morbid obesity were assigned to receive either RYGB or SG. The levels of non-HDL cholesterol, LDL/HDL-ratio and Lp(a) at examinations conducted 6 and 12 months postoperatively were determined and compared to preoperative levels to estimate the efficacy of the two surgical methods. All results 6 and 12 months after surgery were used in the comparisons with the preoperative results. A linear mixed regression model for repeated analyses was used. The Lp(a) and the non-HDL cholesterol levels were considerably reduced in the RYGB group, in contrast to the minor changes in the SG group. In addition, the LDL/HDL ratio was significantly more reduced in the RYGB group when compared to the SG group. Conclusively, RYGB was found to be more efficient than SG for the mitigation of obese dyslipidemia, including preoperative high Lp(a)-levels. This might have important individual and societal implications, especially regarding the potential to reduce the risk of cardiovascular disease and the related societal costs.     

cDC1-derived IL-27 regulates small intestinal CD4+ T cell homeostasis in mice

The small intestinal lamina propria contains large numbers of IFNγ-producing T helper (Th1) cells that play important roles in intestinal homeostasis and host defense, but the mechanisms underlying their development remain poorly understood. Here, we demonstrate that Th1 cells accumulate in the SI-LP after weaning and are maintained there long term. While both Th17 and Th1 cell accumulation in the SI-LP was microbiota dependent, Th1 cell accumulation uniquely required IL-27 and MHCII expression by cDC1. This reflected a requirement for IL-27 signaling in the priming of Th1 cells rather than for their maintenance once in the mucosa. cDC1-derived IL-27 was essential for maintaining the Th1–Th17 balance within the SI-LP, and in its absence, remaining Th1 cells expressed enhanced levels of Th17 signature genes. In conclusion, we identify cDC1-derived IL-27 as a key regulator of SI-LP Th1–Th17 cell homeostasis.     

Modelling and implementing electronic health records in Denmark

The Danish Health IT strategy [Danish Ministry of Interior and Health, National Strategy for IT in the Health Sector 2003-2007, Copenhagen, 2003 (in Danish). http://www.im.dk/publikationer/itstrategi/itstrategi.pdf. notes that integration between electronic health records (EHR) systems has a high priority. A prerequisite for real integration and semantic interoperability is agreement of the data content and the information models. The National Board of Health is working on a common model for EHR, and its adoption is now being promoted through pilot projects. At the same time, several development and implementation projects are taking place at a regional level. These EHRs are built on information models from different vendors and are based on different integration platforms. The Danish EHR observatory, which has been monitoring the development of EHRs in Denmark since 1998, has analysed the challenges of using different information models and integration platforms. This paper also maps the development in Denmark to the new paradigms in modelling techniques and integration technology.     

The xylosyltransferase I gene polymorphism c.343G>T (p.A125S) is a risk factor for diabetic nephropathy in type 1 diabetes

OBJECTIVE: Xylosyltransferase I (XT-I) is the chain-initiating enzyme in the biosynthesis of proteoglycans in basement membranes. It catalyzes the transfer of xylose to selected serine residues in the core protein. The XYLT-II gene codes for a protein highly homologous to XT-I. Proteoglycans are important components of basement membranes and are responsible for their permeability properties. Type 1 diabetic patients have an altered proteoglycan metabolism, which results in microvascular complications. Thus, genetic variations in the xylosyltransferase genes might be implicated in the initiation and progression of these complications. RESEARCH DESIGN AND METHODS: Genotyping of four genetic variations in the genes XYLT-I and XYLT-II was performed in 912 type 1 diabetic patients (453 with and 459 without diabetic nephropathy) using restriction fragment-length polymorphism. RESULTS: The distribution of the c.343G>T polymorphism in XYLT-I is significantly different between patients with and without diabetic nephropathy (P = 0.03). T-alleles were more frequent in patients with diabetic nephropathy (odds ratio 2.47 [95% CI 1.04-5.83]). The allelic frequencies of the other investigated XYLT-I and XYLT-II variations (XYLT-I: c.1989T>C in exon 9; XYLT-II: IVS6-9T>C and IVS6-14_IVS6-13insG in intron 5; and c.2402C>G: p.T801R in exon 11) were not different between patients with and without diabetic nephropathy. CONCLUSIONS: The XYLT-I c.343G>T polymorphism contributes to the genetic susceptibility to development of diabetic nephropathy in type 1 diabetic patients.     

In vitro strain measurement in the porcine antrum using ultrasound doppler strain rate imaging

Strain rate imaging (SRI) enables study of deformation in soft tissues. The aim of this study was to evaluate the accuracy of SRI in measuring strain in the porcine antral wall in vitro. An experimental set-up enabled controlled distension of a porcine stomach in a saline reservoir. Radial strain obtained by SRI was compared with radial strain calculated from B-mode ultrasonography. Circumferential strain obtained by SRI was compared with circumferential strain calculated from sonomicrometry. The agreement between radial strain values measured by SRI and B-mode, along and across several ultrasound (US) beams, using US frequency 6.7 MHz and strain length (SL) = 1.9 mm was = -1.0 +/- 12.1% and 0.5 +/- 13.4%, respectively (mean difference +/- 2SD%) and it was better than with SL 1.2 mm. Compared with sonomicrometry, SRI-determined circumferential strain using 6.7 MHz and SL = 1.9 mm was less accurate, whether averaging along or across several US beams (-9.2 +/- 46.7% and 13.8 +/- 51.2%, respectively). In conclusion, SRI gave accurate measurement of radial strain of the antral wall, but seemed to be less accurate for measurement of circumferential strain for this in vitro set-up.     

Follow-up at age 10 years in ELBW children — Functional outcome,brain morphology and results from motor assessments in infancy

Background

Extremely-low-birth-weight (ELBW) children without severe brain injury or CP are at high risk of developing deficits within cognition, attention, behavior and motor function. Assessing the quality of an infant's spontaneous motor-repertoire included in Prechtl's General-Movement-Assessment (GMA) has been shown to relate to later motor and cognitive functioning in preterm children without CP.

Aims

To investigate functional outcome and cerebral MRI morphometry at 10 years in ELBW children without CP compared to healthy controls and to examine any relationship with the quality of infant-motor-repertoire included in the GMA.

Study design

A cohort-study-design.

Subjects

31 ELBW children (mean birth-weight: 773 g, SD 146, mean gestational age 26.1 weeks, SD 1.8) and 33 term-born, age-matched controls.

Outcome measures

GMA was performed in ELBW children at 3 months corrected age. At 10 years the children underwent comprehensive motor, cognitive, behavioral assessments and cerebral MRI.

Results

The non-CP ELBW children had similar full-IQ but poorer working memory, poorer motor skills, and more attentional and behavioral problems compared to controls. On cerebral MRI reduced volumes of globus pallidus, cerebellar white matter and posterior corpus callosum were found. Cortical surface-area was reduced in temporal, parietal and anterior-medial-frontal areas. Poorer test-results and reduced brain volumes were mainly found in ELBW children with fidgety movements combined with abnormal motor-repertoire in infancy.

Conclusion

Non-CP ELBW children have poorer functional outcomes, reduced brain volumes and cortical surface-area compared with term-born controls at 10 years. ELBW children with abnormal infant motor-repertoire seem to be at increased risk of later functional deficits and brain pathology.     

Surveillance of respiratory diseases among construction and trade workers at Department of Energy nuclear sites

BACKGROUND: Medical screening programs were begun in 1996 and 1997 at three Department of Energy (DOE) nuclear weapons facilities (Hanford Nuclear Reservation, Oak Ridge, and the Savannah River Site) to evaluate whether current and former construction workers are at significant risk for occupational illnesses. The focus of this report is pneumoconiosis associated with exposures to asbestos and silica among workers enrolled in the screening programs through September 30, 2001. METHODS: Workers provided a detailed work and exposure history and underwent a respiratory examination, which included a respiratory history and symptom questionnaire, a posterior-anterior (P-A) chest radiograph, and spirometry. Both stratified and multivariate logistic regression analyses were used to explore the risk of disease by duration of DOE employment and frequency of exposure, while controlling for potential confounders such as age, race, sex, and other work in the construction and building trades. RESULTS: Of the 2602 workers, 25.2% showed one or more chest X-ray changes by ILO criteria and 42.7% demonstrated one or more pulmonary function defects. The overall prevalence of parenchymal changes by ILO criteria (profusion 1/0 or greater) was 5.4%. In the logistic regression models, the odds ratio for parenchymal disease was 2.6 (95% confidence interval (CI) = 1.0-6.6) for workers employed 6 to 20 years at Hanford or Savannah River and increased to 3.6 (95% CI = 1.1-11.6) for workers employed more than 35 years, with additional incremental risks for workers reporting routine exposures to asbestos or silica. CONCLUSIONS: Continued surveillance of workers is important given their increased risk of disease progression and their risk for asbestos related malignancies. Smoking cessation programs should also be high priority and continued abstinence for former smokers reinforced. Although the observed respiratory disease patterns are largely reflective of past exposures, these findings suggest that DOE needs to continue to review industrial hygiene control programs for work tasks involving maintenance, repair, renovation, and demolition.