Skin Autofluorescence and Pentosidine Are Associated With Aortic Stiffening:The Maastricht Study

Arterial stiffening, as characterized by an increase in carotid-femoral pulse-wave velocity or pulse pressure, increases the risk of cardiovascular disease, especially among individuals with type 2 diabetes mellitus. Advanced glycation end products are hypothesized to play a role in the development of arterial stiffness. Therefore, we investigated the association between skin autofluorescence, an estimate of tissue advanced glycation end products, and plasma advanced glycation end products on the one hand and arterial stiffening on the other in 862 participants of The Maastricht Study (mean age of 60 years; 45% women) with normal glucose metabolism (n=469), impaired glucose metabolism (n=140), or type 2 diabetes (n=253). Associations were analyzed with linear regression analysis and adjusted for potential confounders. We found that higher skin autofluorescence as measured by the AGE Reader and plasma pentosidine were independently associated with higher carotid-femoral pulse-wave velocity (s 0.10; 95% confidence interval, 0.03-0.17 and 0.10; 0.04-0.16, respectively) and central pulse pressure (s 0.08; 95% confidence interval 0.01-0.15 and 0.07; 0.01-0.13, respectively). The associations between skin autofluorescence and pentosidine, and carotid-femoral pulse-wave velocity were more pronounced in individuals with type 2 diabetes mellitus (P-interaction</p

Vitreous advanced glycation endproducts and alpha-dicarbonyls in retinal detachment patients with type 2 diabetes mellitus and non-diabetic controls

Purpose Advanced glycation endproducts (AGEs) and their precursors alpha-dicarbonyls are implicated in the progression of diabetic retinopathy. The purpose of this study was to assess AGEs and a-dicarbonyls in the vitreous of patients with type 2 diabetes mellitus (T2DM) with early stages or absence of diabetic retinopathy. Methods We examined vitreous samples obtained during vitrectomy from 31 T2DM patients presenting themselves with rhegmatogenous retinal detachment and compared these to 62 nondiabetic rhegmatogenous retinal detachment patients, matched on age, estimated glomerular filtration rate, smoking, intra-ocular lens implantation, and proliferative vitreoretinopathy. AGEs (pentosidine, N-epsilon-(carboxymethyl) lysine, N-epsilon-(carboxyethyl) lysine, and 5-hydro-5methylimidazolone) and a-dicarbonyls (3-deoxyglucosone, methylglyoxal, and glyoxal) were measured by ultra performance liquid chromatography or high performance liquid chromatography. Skin autofluorescence was measured by the AGE Reader. Results Mean age was 64 +/- 7.6 years for T2DM patients and 63 +/- 8.1 years for controls. For T2DM patients, median diabetes duration was 2.2 (0.3-7.4) years. Non-proliferative diabetic retinopathy was present in 1 patient and classified as absent or background retinopathy in 30 patients. Vitreous levels of pentosidine (2.20 vs. 1.59 mu mol/mol lysine, p = 0.012) and 3-deoxyglucosone (809 vs. 615 nmol/L, p = 0.001) were significantly elevated in T2DM patients compared to controls. Other AGEs and a-dicarbonyls in the vitreous were not significantly different. There was a trend for increased skin autofluorescence in T2DM patients as compared to controls (p = 0.07). Conclusions Pentosidine and 3-deoxyglucosone concentrations were increased in the vitreous of rhegmatogenous retinal detachment patients with a relatively short duration of diabetes compared to non-diabetic rhegmatogenous retinal detachment patients

Vitreous advanced glycation endproducts and α-dicarbonyls in retinal detachment patients with type 2 diabetes mellitus and non-diabetic controls

Several advanced glycation endproducts (AGEs) and α-dicarbonyls were measured by ultra performance liquid chromatography or high performance liquid chromatography in retinal detachment patients with type 2 diabetes mellitus and non-diabetic controls. Patients were matched on age, estimated glomerular filtration rate, smoking, intra-ocular lens implantation, and proliferative vitreoretinopathy. Skin autofluorescence was measured by the AGE Reader

Comparing dual energy CT and subtraction CT on a phantom: which one provides the best contrast in iodine maps for sub-centimetre details?

Contains fulltext : 199006.pdf (publisher's version ) (Open Access

Surface Area of Detachment, Proliferative Vitreoretinopathy, and Pulse Pressure, but not AGEs, are Associated With Retinal Redetachment

PURPOSE. Advanced glycation endproducts (AGEs) have been suggested to play a role in retinal redetachment by promoting proliferative vitreoretinopathy (PVR). The purpose of this study was to investigate whether AGEs, in combination with other clinical characteristics, were able to identify patients at high risk for redetachment after vitrectomy for rhegmatogenous retinal detachment (RRD). METHODS. In this prospective cohort study, 410 RRD patients were included. Skin autofluorescence (SAF), as a reflection of tissue AGE accumulation, was measured by the AGE Reader. In a subgroup of 90 patients, the well characterised AGEs N-epsilon-(carboxymethyl)lysine (CML), N-epsilon-(carboxyethyl) lysine (CEL), 5-hydro-5-methylimidazolone (MG-H1), and pentosidine, and the alpha-dicarbonyls methylglyoxal, glyoxal, and 3-deoxyglucosone were measured in vitreous biopsies using ultra-or high-performance liquid chromatography. The main outcome was retinal redetachment within 3 months after surgery. RESULTS. Fifty-three patients developed a redetachment (aged 64 +/- 9.6, 64% male) and were compared with 352 patients without a redetachment (aged 61 +/- 9.4, 69% male); five patients were excluded for various reasons. Univariable analysis revealed that SAF, vitreous AGEs, and vitreous a-dicarbonyls were not significantly elevated in patients with a redetachment. Multivariable logistic regression analysis showed that surface area of detachment greater than 50% (odds ratio [OR] 2.74, confidence interval [CI] 1.45-5.17), PVR grade C (OR 4.57, CI 1.68-12.42), and pulse pressure (OR 1.37, CI 1.03-1.83 per SD) were independently associated with the occurrence of redetachment. CONCLUSIONS. Skin autofluorescence and vitreous AGEs are not suitable to identify patients at high risk for redetachment after vitrectomy surgery. Surface area of detachment greater than 50%, PVR grade C, and pulse pressure were associated with redetachment

Clinical characteristics of the study population.

<p>Clinical characteristics of the study population.</p

The impact of the implementation of physician assistants in inpatient care: A multicenter matched-controlled study.

Medical care for admitted patients in hospitals is increasingly reallocated to physician assistants (PAs). There is limited evidence about the consequences for the quality and safety of care. This study aimed to determine the effects of substitution of inpatient care from medical doctors (MDs) to PAs on patients' length of stay (LOS), quality and safety of care, and patient experiences with the provided care.In a multicenter matched-controlled study, the traditional model in which only MDs are employed for inpatient care (MD model) was compared with a mixed model in which besides MDs also PAs are employed (PA/MD model). Thirty-four wards were recruited across the Netherlands. Patients were followed from admission till one month after discharge. Primary outcome measure was patients' LOS. Secondary outcomes concerned eleven indicators for quality and safety of inpatient care and patients' experiences with the provided care.Data on 2,307 patients from 34 hospital wards was available. The involvement of PAs was not significantly associated with LOS (β 1.20, 95%CI 0.99-1.40, p = .062). None of the indicators for quality and safety of care were different between study arms. However, the involvement of PAs was associated with better experiences of patients (β 0.49, 95% CI 0.22-0.76, p = .001).This study did not find differences regarding LOS and quality of care between wards on which PAs, in collaboration with MDs, provided medical care for the admitted patients, and wards on which only MDs provided medical care. Employing PAs seems to be safe and seems to lead to better patient experiences.ClinicalTrials.gov Identifier: NCT01835444

Fragile site orthologs FHIT/FRA3B and Fhit/Fra14A2: Evolutionarily conserved but highly recombinogenic

Common fragile sites are regions that show elevated susceptibility to DNA damage, leading to alterations that can contribute to cancer development. FRA3B, located at chromosome region 3p14.2, is the most frequently expressed human common fragile site, and allelic losses at FRA3B have been observed in many types of cancer. The FHIT gene, encompassing the FRA3B region, is a tumor-suppressor gene. To identify the features of FHIT/FRA3B that might contribute to fragility, sequences of the human FHIT and the flanking PTPRG gene were compared with those of murine Fhit and Ptprg. Human and mouse orthologous genes, FHIT and Fhit, are more highly conserved through evolution than PTPRG/Ptprg and yet contain more sequence elements that are exquisitely sensitive to genomic rearrangements, such as high-flexibility regions and long interspersed nuclear element 1s, suggesting that common fragile sites serve a function. The conserved AT-rich high-flexibility regions are the most characteristic of common fragile sites

Patient experiences with care.

<p>Patient experiences with care.</p

Flow-chart of patients.

<p>Flow-chart of patients.</p