OBJECTIVE To assess the effect of prenatal exposure to maternal malnutrition on coronary heart disease in people born around the time of the Dutch famine, 1944–45. DESIGN Historical cohort study. ...SETTING Community study. PATIENTS Singletons born alive between November 1943 and February 1947 for whom detailed birth records were available. DESIGN The prevalence of coronary heart disease was compared between those exposed to famine in late gestation (n = 120), in mid-gestation (n = 108), or in early gestation (n = 68), and those born in the year before the famine or those conceived in the year after the famine (non-exposed subjects, n = 440). MAIN OUTCOME MEASURES Prevalence of coronary heart disease, defined as the presence of angina pectoris according to the Rose questionnaire, Q waves on the ECG, or a history of coronary revascularisation. RESULTS The prevalence of coronary heart disease was higher in those exposed in early gestation than in non-exposed people (8.8% v 3.2%; odds ratio adjusted for sex 3.0, 95% confidence interval (CI) 1.1 to 8.1). The prevalence was not increased in those exposed in mid gestation (0.9%) or late gestation (2.5%). People with coronary heart disease tended to have lower birth weights (3215 g v 3352 g, p = 0.13), and smaller head circumferences at birth (32.2 cmv 32.8 cm, p = 0.05), but the effect of exposure to famine in early gestation was independent of birth weight (adjusted odds ratio 3.2, 95% CI 1.2 to 8.8). CONCLUSIONS Although the numbers are very small, this is the first evidence suggesting that maternal malnutrition during early gestation contributes to the occurrence of coronary heart disease in the offspring.
Despite the fact that the cost-effectiveness of robot-assisted radical cystectomy (RARC) is not yet proven, and open radical (ORC) cystectomy is recommended as the standard of care in patients with ...high-risk non-muscle-invasive and muscle-invasive bladder cancer, the use of RARC is still increasing. The objective of the current ongoing comparative effectiveness trial therefore is to study the (cost-)effectiveness of RARC compared to ORC, both in terms of objective (complication rates, oncological outcomes) and patient-reported (health-related quality of life) outcome measures.
This study is designed as a non-randomized, multicentre comparative effectiveness trial. Centres with an annual caseload of > 20 radical cystectomies can include patients after informed consent has been given. Centres that perform RARC must have passed the (initial) learning curve of 40 cases. A total of 338 (2 × 169) patients will be enrolled from 23 participating centres (12 ORC, 10 RARC and 1 LRC). Follow-up visits will be scheduled at 1, 3, 6 and 12 months. During each follow-up visit, clinical data and health-related quality of life questionnaires will be administered. Costs will be studied using a monthly resource usage questionnaire. Impact on complications and quality of life will be calculated as the average difference between the groups with 95% confidence intervals, adjusted for potential baseline differences by means of propensity score matching.
This study aims to contribute to the development of evidence-based guidelines regarding the most cost-effective surgical technique for radical cystectomy.
Nederlands Trial Register/Dutch Trial Registry, trial identifying number: NTR5362. Registered on 14 August 2015. ( http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5362 ).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To determine whether type 1 diabetes preferentially affects the inner retinal layers by comparing the thickness of six retinal layers in type 1 diabetic patients who have no or minimal diabetic ...retinopathy (DR) with those of age- and sex-matched healthy controls.
Fifty-seven patients with type 1 diabetes with no (n = 32) or minimal (n = 25) DR underwent full ophthalmic examination, stereoscopic fundus photography, and optical coherence tomography (OCT). After automated segmentation of intraretinal layers of the OCT images, mean thickness was calculated for six layers of the retina in the fovea, the pericentral area, and the peripheral area of the central macula and were compared with those of an age- and sex-matched control group.
In patients with minimal DR, the mean ganglion cell/inner plexiform layer was 2.7 microm thinner (95% confidence interval CI, 2.1-4.3 microm) and the mean inner nuclear layer was 1.1 microm thinner (95% CI, 0.1-2.1 microm) in the pericentral area of the central macula compared to those of age-matched controls. In the peripheral area, the mean ganglion cell/inner plexiform layer remained significantly thinner. No other layers showed a significant difference.
Thinning of the total retina in type 1 diabetic patients with minimal retinopathy compared with healthy controls is attributed to a selective thinning of inner retinal layers and supports the concept that early DR includes a neurodegenerative component.
Aims/hypothesis
Glucose fluctuations may help predict diabetic complications. We evaluated the relation between glucose variability and oxidative stress in patients with type 1 diabetes.
Methods
...Continuous glucose monitors were inserted subcutaneously in 25 patients. During the measurement, patients collected two 24 h urine samples, while 24 healthy controls collected one 24 h urine sample for determination of 15(
S
)-8-
iso
-prostaglandin
using HPLC tandem mass spectrometry. Mean of the daily differences (MODD), mean amplitude of glycaemic excursions (MAGE) and continuous overlapping net glycaemic action calculated with
n
hour time-intervals (CONGA-
n
) were calculated as markers for glucose variability and correlation with
excretion was calculated.
Results
Median interquartile range (IQR) urinary
was higher in patients than healthy controls: 161 (140–217) pg/mg creatinine vs 118 (101–146) pg/mg creatinine (
p
= 0.001). Median (IQR) MODD was 3.7 (3.2–5.0) mmol/l, MAGE 7.6 (6.4–9.0) mmol/l and CONGA-1 2.3 (2.1–2.8) mmol/l. Univariate regression did not reveal an association for MODD (
r
2
= 0.01), MAGE (0.08) or CONGA-1 (0.07) with
excretion, nor was an association revealed when corrected for HbA
1c
, age, sex and smoking. Spearman correlation coefficients (
r
) between
excretion and MODD, MAGE and CONGA-1 were non-significant: −0.112, −0.381 and −0.177.
Conclusions/interpretation
We report that there is no relationship between glucose variability and urinary
. We also confirm that patients with type 1 diabetes have higher levels of urinary
than healthy controls, suggesting that in addition to glucose variability, other factors favouring oxidative stress may exist. We did not see a relation between high glucose variability and elevated levels of oxidative stress in patients with type 1 diabetes.
Aims/hypothesis People who were small at birth have an increased risk of type 2 diabetes in later life. People who were in utero during the Dutch famine had decreased glucose tolerance and raised ...insulin concentrations at age 50. We aimed to evaluate whether prenatal famine exposure leads to more rapid progression of impaired glucose/insulin homeostasis with increasing age. Methods We performed an OGTT in 702 men and women at age 50 and in 699 men and women at age 58, all born as term singletons immediately before, during or after the 1944-1945 Dutch famine. Results People who had been exposed to famine in utero had significantly higher 120-min glucose concentrations at age 58 compared with people who had not been exposed to famine (difference=0.4 mmol/l, 95% CI 0.1 to 0.7, adjusted for sex and BMI). Glucose tolerance deteriorated between the age of 50 and 58. The unadjusted 120-min glucose concentrations rose by 0.2 mmol/l (95% CI 0.0 to 0.4), while 120-min insulin concentrations had increased by 64 pmol/l (95% CI 48 to 82). There were no differences in the rates of glucose and insulin level increase between the famine-exposed group and the unexposed group (p=0.28 for the difference in increase in glucose concentrations and p=0.09 for insulin concentrations). Conclusions/interpretation Although we confirmed that undernutrition during gestation is linked to decreased glucose tolerance, the effect does not seem to become more pronounced at age 58 as compared with age 50.
Reduced growth in utero is associated with type 2 (non-insulin-dependent) diabetes and impaired glucose tolerance in adult life. There is no direct evidence in human beings that maternal nutrition ...during gestation affects insulin-glucose metabolism. We investigated glucose tolerance in people born around the time of famine in the Netherlands during 1944–45.
We included 702 people born between Nov 1, 1943, and Feb 28, 1947, in Amsterdam, for whom we had detailed prenatal and birth records. We compared glucose and insulin responses to a standard oral glucose load in participants exposed to famine at any stage during gestation (exposed participants) with those who were born in the year before or conceived in the year after the famine (non-exposed participants).
Glucose concentrations were increased 2 h after a standard glucose load among exposed participants (p=0·006), and were highest in men and women exposed during mid and late gestation. Mean 2 h glucose concentration among non-exposed participants was 5·8 mmol/L; concentrations were 0·5 mmol/L (95% CI 0·1–0·9) higher among participants exposed during late gestation, 0·4 mmol/L (0–0·8) higher among those exposed during mid gestation, and 0·1 mmol/L (-0·4 to 0·6) among those exposed during early gestation. Participants born as thin babies to mothers with low bodyweights had the highest concentrations and concentrations were especially high among people exposed to famine who became obese as adults. Prenatal exposure to famine was related to increased fasting proinsulin (p=0·05) and 2 h insulin concentrations (p=0·04), which suggests an association with insulin resistance.
Prenatal exposure to famine, especially during late gestation, is linked to decreased glucose tolerance in adults. Poor nutrition in utero may lead to permanent changes in insulin-glucose metabolism, even if the effect on fetal growth is small. This effect of famine on glucose tolerance is especially important in people who become obese.
The Extreme-ultraviolet, Imaging Telescope (EIT) will provide wide-field images of the corona and transition region on the solar disc and up to 1.5 R sub() above the solar limb. Its normal incidence ...multilayer-coated optics will select spectral emission lines from Fe IX (171 A), Fe XII (195 A), Fe XV (284 A), and He II (304 A) to provide sensitive temperature diagnostics in the range from 6 x 10 super(4) K to 3 x 10 super(6) K. The telescope has a 45 x 45 arcmin field of view and 2.6 arcsec pixels which will provide approximately 5-arcsec spatial resolution. The EIT will probe the coronal plasma on a global scale, as well as the underlying cooler and turbulent atmosphere, providing the basis for comparative analyses, with observations from both the ground and other SOHO instruments. This paper presents details of the EIT instrumentation, its performance and operating modes.
PURPOSE. To determine which retinal layers are most affected by diabetes and contribute to thinning of the inner retina and to investigate the relationship between retinal layer thickness (LT) and ...diabetes duration, diabetic retinopathy (DR) status, age, glycosylated hemoglobin (HbA1c), and the sex of the individual, in patients with type 1 diabetes who have no or minimal DR. METHODS. Mean LT was calculated for the individual retinal layers after automated segmentation of spectral domain-optical coherence tomography scans of patients with diabetes and compared with that in control subjects. Multiple linear regression analysis was used to determine the relationship between LT and HbA1c, age, sex, diabetes duration, and DR status. RESULTS. In patients with minimal DR, the mean ganglion cell layer (GCL) in the pericentral area was 5.1 mum thinner (95% confidence interval CI, 1.1-9.1 mum), and in the peripheral macula, the mean retinal nerve fiber layer (RNFL) was 3.7 mum thinner (95% CI, 1.3-6.1 mum) than in the control subjects. There was a significant linear correlation (R = 0.53, P < 0.01) between GCL thickness and diabetes duration in the pooled group of patients. Multiple linear regression analysis (R = 0.62, P < 0.01) showed that DR status was the most important explanatory variable. CONCLUSIONS. This study demonstrates GCL thinning in the pericentral area and corresponding loss of RNFL thickness in the peripheral macula in patients with type 1 diabetes and no or minimal DR compared with control subjects. These results support the concept that diabetes has an early neurodegenerative effect on the retina, which occurs even though the vascular component of DR is minimal.
The structural and magnetic properties of a cobalt nanorod array have been studied by means of magnetic field dependent small‐angle neutron scattering (SANS). Measurement of the unpolarized SANS ...cross section dΣ/dΩ of the saturated sample in the two scattering geometries where the applied magnetic field H is either perpendicular or parallel to the wavevector ki of the incoming neutron beam allows one to separate nuclear from magnetic SANS, without employing the usual sector‐averaging procedure. The analysis of the SANS data in the saturated state provides structural parameters (rod radius and centre‐to‐centre distance) that are in good agreement with results from electron microscopy. Between saturation and the coercive field, a strong field dependence of dΣ/dΩ is observed (in both geometries), which cannot be explained using the conventional expression of the magnetic SANS cross section of magnetic nanoparticles in a homogeneous nonmagnetic matrix. The origin of the strong field dependence of dΣ/dΩ is believed to be related to intradomain spin misalignment, due to magnetocrystalline and magnetoelastic anisotropies and magnetostatic stray fields.
Background
C3 glomerulopathy (C3G) is a rare kidney disorder characterized by predominant glomerular depositions of complement C3. C3G can be subdivided into dense deposit disease (DDD) and C3 ...glomerulonephritis (C3GN). This study describes the long-term follow-up with extensive complement analysis of 29 Dutch children with C3G.
Methods
Twenty-nine C3G patients (19 DDD, 10 C3GN) diagnosed between 1992 and 2014 were included. Clinical and laboratory findings were collected at presentation and during follow-up. Specialized assays were used to detect rare variants in complement genes and measure complement-directed autoantibodies and biomarkers in blood.
Results
DDD patients presented with lower estimated glomerular filtration rate (eGFR). C3 nephritic factors (C3NeFs) were detected in 20 patients and remained detectable over time despite immunosuppressive treatment. At presentation, low serum C3 levels were detected in 84% of all patients. During follow-up, in about 50% of patients, all of them C3NeF-positive, C3 levels remained low. Linear mixed model analysis showed that C3GN patients had higher soluble C5b-9 (sC5b-9) and lower properdin levels compared to DDD patients. With a median follow-up of 52 months, an overall benign outcome was observed with only six patients with eGFR below 90 ml/min/1.73 m
2
at last follow-up.
Conclusions
We extensively described clinical and laboratory findings including complement features of an exclusively pediatric C3G cohort. Outcome was relatively benign, persistent low C3 correlated with C3NeF presence, and C3GN was associated with higher sC5b-9 and lower properdin levels. Prospective studies are needed to further elucidate the pathogenic mechanisms underlying C3G and guide personalized medicine with complement therapeutics.
Graphical abstract
PDF
