Glucose tolerance and insulin resistance/sensitivity associate with retinal layer characteristics: the LIFE-Adult-Study.

AIMS/HYPOTHESIS: As the prevalence of insulin resistance and glucose intolerance is increasing throughout the world, diabetes-induced eye diseases are a global health burden. We aim to identify distinct optical bands which are closely related to insulin and glucose metabolism, using non-invasive, high-resolution spectral domain optical coherence tomography (SD-OCT) in a large, population-based dataset. METHODS: The LIFE-Adult-Study randomly selected 10,000 participants from the population registry of Leipzig, Germany. Cross-sectional, standardised phenotyping included the assessment of various metabolic risk markers and ocular imaging, such as SD-OCT-derived thicknesses of ten optical bands of the retina. Global and Early Treatment Diabetic Retinopathy Study (ETDRS) subfield-specific optical retinal layer thicknesses were investigated in 7384 healthy eyes of 7384 participants from the LIFE-Adult-Study stratified by normal glucose tolerance, prediabetes (impaired fasting glucose and/or impaired glucose tolerance and/or HbA1c 5.7-6.4% [39-47 mmol/mol]) and diabetes. The association of optical retinal band characteristics with different indices of glucose tolerance (e.g. fasting glucose, area under the glucose curve), insulin resistance (e.g. HOMA2-IR, triglyceride glucose index), or insulin sensitivity (e.g. estimated glucose disposal rate [eGDR], Stumvoll metabolic clearance rate) was determined using multivariable linear regression analyses for the individual markers adjusted for age, sex and refraction. Various sensitivity analyses were performed to validate the observed findings. RESULTS: In the study cohort, nine out of ten optical bands of the retina showed significant sex- and glucose tolerance-dependent differences in band thicknesses. Multivariable linear regression analyses revealed a significant, independent, and inverse association between markers of glucose intolerance and insulin resistance (e.g. HOMA2-IR) with the thickness of the optical bands representing the anatomical retinal outer nuclear layer (ONL, standardised ß=-0.096; p<0.001 for HOMA2-IR) and myoid zone (MZ; ß=-0.096; p<0.001 for HOMA2-IR) of the photoreceptors. Conversely, markers of insulin sensitivity (e.g. eGDR) positively and independently associated with ONL (ß=0.090; p<0.001 for eGDR) and MZ (ß=0.133; p<0.001 for eGDR) band thicknesses. These global associations were confirmed in ETDRS subfield-specific analyses. Sensitivity analyses further validated our findings when physical activity, neuroanatomical cell/tissue types and ETDRS subfield categories were investigated after stratifying the cohort by glucose homeostasis. CONCLUSIONS/INTERPRETATION: An impaired glucose homeostasis associates with a thinning of the optical bands of retinal ONL and photoreceptor MZ. Changes in ONL and MZ thicknesses might predict early metabolic retinal alterations in diabetes.

NanoSQUID Magnetometry on Individual As-grown and Annealed Co Nanowires at Variable Temperature.

Performing magnetization studies on individual nanoparticles is a highly demanding task, especially when measurements need to be carried out under large sweeping magnetic fields or variable temperature. Yet, characterization under varying ambient conditions is paramount in order to fully understand the magnetic behavior of these objects, e.g., the formation of nonuniform states or the mechanisms leading to magnetization reversal and thermal stability. This, in turn, is necessary for the integration of magnetic nanoparticles and nanowires into useful devices, e.g., spin-valves, racetrack memories, or magnetic tip probes. Here, we show that nanosuperconducting quantum interference devices based on high critical temperature superconductors are particularly well suited for this task. We have successfully characterized a number of individual Co nanowires grown through focused electron beam induced deposition and subsequently annealed at different temperatures. Magnetization measurements performed under sweeping magnetic fields (up to ∼100 mT) and variable temperature (1.4-80 K) underscore the intrinsic structural and chemical differences between these nanowires. These point to significant changes in the crystalline structure and the resulting effective magnetic anisotropy of the nanowires, and to the nucleation and subsequent vanishing of antiferromagnetic species within the nanowires annealed at different temperatures.

Mycoplasma pneumoniae-Induced Mucocutaneous Rash: A New Syndrome Distinct from Erythema Multiforme? Report of a New Case and Review of the Literature. / Exantema mucocutáneo inducido por Mycoplasma pneumoniae: ¿un nuevo síndrome separado del eritema multiforme? Un nuevo caso y revisión de la literatura.

Respiratory tract infection due to Mycoplasma pneumoniae can provoke cutaneous and mucosal rashes, which have been classified within the spectrum of erythema multiforme or Stevens-Johnson syndrome. This classification is of therapeutic and prognostic importance and has generated intense debate in the literature. A recent systematic review of 202 cases of mucocutaneous rashes associated with M. pneumoniae infection concluded that these rashes might constitute a distinct entity, for which the term Mycoplasma-induced rash and mucositis was proposed. We describe a patient with acute M pneumoniae respiratory tract infection who presented mucosal and cutaneous lesions that were difficult to classify as erythema multiforme or Stevens-Johnson syndrome; the lesions were compatible with the proposed new disease.

Bile duct tumors.

Bile duct tumors are benign or malignant lesions which may be associated to risk factors or potentially malignant lesions. They constitute an heterogenous entities group with a different biological behavior and prognosis according to location and growth pattern. We revise the role of the radiologist in order to detect, characterize and stage these tumors, specially the importance of their classification when deciding an appropriate management and treatment.

Evaluation of a portable retinal imaging device: towards a comparative quantitative analysis for morphological measurements of retinal blood vessels.

This study investigated the possibility of using low-cost, handheld, retinal imaging devices for the automatic extraction of quantifiable measures of retinal blood vessels. Initially, the available handheld devices were compared using a Zeiss model eye incorporating a USAF resolution test chart to assess their optical properties. The only suitable camera of the five evaluated was the Horus DEC 200. This device was then subjected to a detailed evaluation in which images in human eyes taken from the handheld camera were compared in a quantitative analysis with those of the same eye from a Canon CR-DGi retinal desktop camera. We found that the Horus DEC 200 exhibited shortcomings in capturing images of human eyes by comparison with the Canon. More images were rejected as being unevaluable or suffering failures in automatic segmentation than with the Canon, and even after exclusion of affected images, the Horus yielded lower measurements of vessel density than the Canon. A number of issues affecting handheld cameras in general and some features of the Horus in particular have been identified that might contribute to the observed differences in performance. Some potential mitigations are discussed which might yield improvements in performance, thus potentially facilitating use of handheld retinal imaging devices for quantitative retinal microvascular measurements.

Lanthanoid single-ion magnets based on polyoxometalates with a 5-fold symmetry: the series [LnP5W30O110]12- (Ln3+ = Tb, Dy, Ho, Er, Tm, and Yb).

A robust, stable and processable family of mononuclear lanthanoid complexes based on polyoxometalates (POMs) that exhibit single-molecule magnetic behavior is described here. Preyssler polyanions of general formula [LnP(5)W(30)O(110)](12-) (Ln(3+) = Tb, Dy, Ho, Er, Tm, and Yb) have been characterized with static and dynamic magnetic measurements and heat capacity experiments. For the Dy and Ho derivatives, slow relaxation of the magnetization has been found. A simple interpretation of these properties is achieved by using crystal field theory.

Three-dimensional reconstruction of blood vessels extracted from retinal fundus images.

We present a 3D reconstruction of retinal blood vessel trees using two views of fundus images. The problem is addressed by using well known computer vision techniques which consider: 1) The recovery of camera-eyeball model parameters by an auto-calibration method. The camera parameters are found via the solution of simplified Kruppa equations, based on correspondences found by a LMedS optimisation correlation between pairs of eight different views. 2) The extraction of blood vessels and skeletons from two fundus images. 3) The matching of corresponding points of the two skeleton trees. The trees are previously labelled during the analysis of 2D binary images. Finally, 4) the lineal triangulation of matched correspondence points and the surface modelling via generalised cylinders using diameter measurements extracted from the 2D binary images. The method is nearly automatic and it is tested with 2 sets of 10 fundus retinal images, each one taken from different subjects. Results of 3D vein and artery trees reconstructions are shown.

Gd-based single-ion magnets with tunable magnetic anisotropy: molecular design of spin qubits.

We report ac susceptibility and continuous wave and pulsed EPR experiments performed on GdW10 and GdW30 polyoxometalate clusters, in which a Gd3+ ion is coordinated to different polyoxometalate moieties. Despite the isotropic character of gadolinium as a free ion, these molecules show slow magnetic relaxation at very low temperatures, characteristic of single molecule magnets. For T≲200 mK, the spin-lattice relaxation becomes dominated by pure quantum tunneling events, with rates that agree quantitatively with those predicted by the Prokof'ev and Stamp model [Phys. Rev. Lett. 80, 5794 (1998)]. The sign of the magnetic anisotropy, the energy level splittings, and the tunneling rates strongly depend on the molecular structure. We argue that GdW30 molecules are also promising spin qubits with a coherence figure of merit Q(M)≳50.

Strong paramagnetism of gold nanoparticles deposited on a Sulfolobus acidocaldarius S layer.

Magnetic properties of Au nanoparticles deposited on an archaeal S layer are reported. X-ray magnetic circular dichroism and superconducting quantum interference device magnetometries demonstrate that the particles are strongly paramagnetic, without any indication of magnetic blocking down to 16 mK. The average magnetic moment per particle is M(part)=2.36(7) µ(B). This contribution originates at the particle's Au 5d band, in which an increased number of holes with respect to the bulk value is observed. The magnetic moment per Au atom is 25 times larger than any measured in other Au nanoparticles or any other configurations up to date.

Molecular prototypes for spin-based CNOT and SWAP quantum gates.

We show that a chemically engineered structural asymmetry in [Tb2] molecular clusters renders the two weakly coupled Tb3+ spin qubits magnetically inequivalent. The magnetic energy level spectrum of these molecules meets then all conditions needed to realize a universal CNOT quantum gate. A proposal to realize a SWAP gate within the same molecule is also discussed. Electronic paramagnetic resonance experiments confirm that CNOT and SWAP transitions are not forbidden.

Usefulness of intestinal ultrasound in inflammatory bowel disease. / Utilidad de la ecografía intestinal en la enfermedad inflamatoria intestinal.

Imaging techniques play a fundamental role in the initial diagnosis and follow-up of inflammatory bowel disease. Intestinal ultrasound has high sensitivity and specificity in patients with suspected Crohn's disease and in the detection of inflammatory activity. This technique enables the early diagnosis of intra-abdominal complications such as stenosis, fistulas, and abscesses. It has also proven useful in monitoring the response to treatment and in detecting postsurgical recurrence. Technical improvements in ultrasound scanners, technological advances such as ultrasound contrast agents and elastography, and above all increased experience have increased the role of ultrasound in the evaluation of the gastrointestinal tract. The features that make ultrasound especially attractive include its wide availability, its noninvasiveness and lack of ionizing radiation, its low cost, and its good reproducibility, which is important because it is easy to repeat the study and the study is well tolerated during follow-up. This review summarizes the role of intestinal ultrasound in the detection and follow-up of inflammatory bowel disease.

Size-dependent properties of magnetoferritin.

We report a detailed experimental study of maghemite nanoparticles, with sizes ranging from 1.6 to 6 nm, synthesized inside a biological mould of apoferritin. The structural characterization of the inorganic cores, using TEM and x-ray diffraction, reveals a low degree of crystalline order, possibly arising from the nucleation and growth of multiple domains inside each molecule. We have also investigated the molecular structure by means of atomic force microscopy in liquid. We find that the synthesis of nanoparticles inside apoferritin leads to a small, but measurable, decrease in the external diameter of the protein, probably associated with conformational changes. The magnetic response of the maghemite cores has been studied by a combination of techniques, including ac susceptibility, dc magnetization and Mössbauer spectroscopy. From the equilibrium magnetic response, we have determined the distribution of magnetic moments per molecule. The results show highly reduced magnetic moments. This effect cannot be ascribed solely to the canting of spins located at the particle surface but, instead, it suggests that magnetoferritin cores have a highly disordered magnetic structure in which the contributions of different domains compensate each other. Finally, we have also determined, for each sample, the distribution of the activation energies required for the magnetization reversal and, from this, the size-dependent magnetic anisotropy constant K. We find that K is enormously enhanced with respect to the maghemite bulk value and that it increases with decreasing size. The Mössbauer spectra suggest that low-symmetry atomic sites, probably located at the particle surface and at the interfaces between different crystalline domains, are the likely source of the enhanced magnetic anisotropy.

Bowel ultrasound: examination techniques and normal and pathologic patterns. / Ecografía intestinal: técnicas de examen, patrones normales y patológicos.

Ultrasound is being increasingly used to study the digestive tract because it has certain advantages over other techniques such as endoscopy, CT enterography, and MR enterography. Ultrasound can be used to evaluate the bowel wall and the elements that surround it without the need for contrast agents; its ability to evaluate the elasticity and peristalsis of these structures is increasing interest in its use. This article describes the techniques and modalities of bowel ultrasound, as well as the normal features of the bowel wall and contiguous structures. It uses a practical approach to review the main pathological findings and their interpretation, and the different patterns of presentation, which will help orient the diagnosis.

Magnetic vortex nucleation and annihilation in bi-stable ultra-small ferromagnetic particles.

Vortex-mediated magnetization reversal in individual ultra-small (∼100 nm) ferromagnetic particles at low temperatures is studied by nanoSQUID magnetometry. At zero applied bias field, the flux-closure magnetic state (vortex) and the quasi uniform configuration are bi-stable. This stems from the extremely small size of the nanoparticles that lies very close to the limit of single-domain formation. The analysis of the temperature-dependent (from 0.3 to 70 K) hysteresis of the magnetization allows us to infer the nature of the ground state magnetization configuration. The latter corresponds to a vortex state as also confirmed by electron holography experiments. Based on the simultaneous analysis of the vortex nucleation and annihilation data, we estimate the magnitude of the energy barriers separating the quasi single-domain and the vortex state and their field dependence. For this purpose, we use a modified power-law scaling of the energy barriers as a function of the applied bias field. These studies are essential to test the thermal and temporal stability of flux-closure states stabilized in ultra-small ferromagnets.

Comparison of the retinal microvasculature in European and African-Caribbean people with diabetes.

Diabetes aggravates the impact of elevated BP (blood pressure) on the microcirculation, and people of African ancestry with diabetes are more susceptible to microvascular damage than Europeans. In the present study, we investigated possible differences in the retinal microcirculation in people of European and African-Caribbean ethnicity with diabetes that might account for this. A total of 51 subjects with Type 2 diabetes (age 40-65 years; 25 male; 29 African-Caribbean) were studied. Clinic and 24 h ambulatory BP, and fasting glucose, insulin and lipids were measured. Digital retinal images were analysed using custom-written semi-automatic software to determine: LDR (length/diameter ratio) and AVR (arteriolar/venular diameter ratio), branching angles, vessel tortuosity and NT (number of terminal vessel branches). Arterioles were narrower in European people with diabetes than in African-Caribbean people with diabetes [mean (S.D.) arteriolar diameter, 76 (7) compared with 82 (11) microm respectively (P=0.03); arteriolar LDR, 28.1 (8.5) compared with 23.7 (7.0) respectively (P=0.046); and AVR, 0.66 (0.21) compared with 0.90 (0.36) respectively (P=0.028)]. Ethnic differences in arteriolar LDR, arteriolar diameter and AVR were not explained by differences in BP, but were attenuated by adjustment for the duration of diabetes. There was no significant relationship between BP and arteriolar narrowing in the group as a whole, although the relationship between arteriolar LDR and systolic BP was stronger in Europeans than African-Caribbeans [beta=0.08 (0.07) compared with beta=0.03 (0.06); P=0.03]. In conclusion, in the presence of diabetes, a relationship between BP and retinal arteriolar diameter was not evident and implies impaired small artery remodelling in the presence of diabetes. African-Caribbean people with diabetes have wider retinal arterioles and this could contribute to enhanced microvascular damage in this ethnic group.

Conjugated linoleic acid and betaine affect lipolysis in pig adipose tissue explants.

Consumers' demand of leaner meat products is a challenge. Although betaine and conjugated linoleic acid (CLA) have the potential to decrease porcine adipose tissue, their mode of action is poorly understood. The aim of the study was to determine the lipolytic effect of betaine and CLA in the adipose tissue of Iberian pigs. Adipose tissue explants from five pigs (38 kg BW) were prepared from dorsal subcutaneous adipose tissue samples and cultivated for 2 h (acute experiments) or 72 h (chronic experiments). Treatments included 100 µM linoleic acid (control), 100 µM trans-10, cis-12 CLA, 100 µM linoleic acid + 1 mM betaine and 100 µM trans-10, cis-12 CLA + 1 mM betaine (CLABET). To examine the ability of betaine or CLA to inhibit insulin's suppression of isoproterenol-stimulated lipolysis, test medium was amended with 1 µM isoproterenol ±10 nM insulin. Media glycerol was measured at the end of the incubations. Acute lipolysis (2 h) was increased by CLA and CLABET (85% to 121%; P < 0.05) under basal conditions. When lipolysis was stimulated with isoproterenol (1090%), acute exposure to betaine tended to increase (13%; P = 0.071), while CLA and CLABET increased (14% to 18%; P < 0.05) isoproterenol-stimulated lipolysis compared with control. When insulin was added to isoproterenol-stimulated explants, lipolytic rate was decreased by 50% (P < 0.001). However, supplementation of betaine to the insulin + isoproterenol-containing medium tended to increase (P = 0.07), while CLABET increased (45%; P < 0.05) lipolysis, partly counteracting insulin inhibition. When culture was extended for 72 h, CLA decreased lipolysis under basal conditions (18%; P < 0.05) with no effect of betaine and CLABET (P > 0.10). When lipolysis was stimulated by isoproterenol (125% increase in rate compared with basal), CLA and CLABET decreased glycerol release (27%; P < 0.001) compared with control (isoproterenol alone). When insulin was added to isoproterenol-stimulated explants, isoproterenol stimulation of lipolysis was completely blunted and neither betaine nor CLA altered the inhibitory effect of insulin on lipolysis. Isoproterenol, and especially isoproterenol + insulin, stimulated leptin secretion compared with basal conditions (68% and 464%, respectively; P < 0.001), with no effect of CLA or betaine (P > 0.10). CLA decreased leptin release (25%; P < 0.001) when insulin was present in the media, partially inhibiting insulin stimulation of leptin release. In conclusion, betaine and CLA produced a biphasic response regarding lipolysis so that glycerol release was increased in acute conditions, while CLA decreased glycerol release and betaine had no effect in chronic conditions. Furthermore, CLA and CLABET indirectly increased lipolysis by reducing insulin-mediated inhibition of lipolysis during acute conditions.

Automatic optic disc detection in colour fundus images by means of multispectral analysis and information content.

The optic disc (OD) in retinal fundus images is widely used as a reference in computer-based systems for the measurement of the severity of retinal disease. A number of algorithms have been published in the past 5 years to locate and measure the OD in digital fundus images. Our proposed algorithm, automatically: (i) uses the three channels (RGB) of the digital colour image to locate the region of interest (ROI) where the OD lies, (ii) measures the Shannon information content per channel in the ROI, to decide which channel is most appropriate for searching for the OD centre using the circular Hough transform. A series of evaluations were undertaken to test our hypothesis that using the three channels gives a better performance than a single channel. Three different databases were used for evaluation purposes with a total of 2,371 colour images giving a misdetection error of 3% in the localisation of the centre of the OD. We find that the area determined by our algorithm which assumes that the OD is circular, is similar to that found by other algorithms that detected the shape of the OD. Five metrics were measured for comparison with other recent studies. Combining the two databases where expert delineation of the OD is available (1,240 images), the average results for our multispectral algorithm are: TPR = 0.879, FPR = 0.003, Accuracy = 0.994, Overlap = 80.6% and Dice index = 0.878.

Effect of antihypertensive treatment on retinal microvascular changes in hypertension.

OBJECTIVE: Hypertension causes arteriolar narrowing and rarefaction in the retinal circulation, but the extent to which these changes are reversible by antihypertensive treatment is not well studied. We compared the effect of antihypertensive treatment with a calcium-channel-blocker-based regimen and an angiotensin-converting-enzyme-inhibitor-based regimen on the retinal microvasculature. METHODS: Twenty-five patients (17 men, age range 24-71 years) with untreated hypertension were randomized to treatment with an amlodipine-based (n = 12) or lisinopril-based (n = 13) regimen in a double-blind, prospective parallel limb trial for 52 weeks. Measurements of blood pressure and the retinal microvasculature were made at baseline and at the end of the study. RESULTS: Both the amlodipine-based and lisinopril-based treatments reduced blood pressure to similar extents. Blood pressure reduction was associated with a reduction in arteriolar narrowing, a widening of arteriolar branch angle and an increase in arteriolar density. There were no significant differences between the two treatment regimens. CONCLUSION: Antihypertensive treatment is associated with improvement in arteriolar narrowing and rarefaction. Improved microvascular structure may contribute to the beneficial effects of antihypertensive treatment in hypertension.