Calprotectin is a noninvasive biomarker that can distinguish inflammatory bowel disease from irritable bowel syndrome. We investigated four automated fecal calprotectin methods on five different ...platforms for their preanalytical process, analytical performance, and clinicopathologic correlation.
Four calprotectin methods (Bühlmann, EliA CN, EliA CN2, and DiaSorin) were performed on five platforms (Cobas 8000 E502, Phadia Immunocap 100 and 250, and Liaison and Liaison XL) in two hospital laboratories.
Overall variation for the different extraction devices was less than 19% when feces were of normal consistency. Freeze-thawing of samples resulted in comparable results compared with fresh samples. The different methods had a good analytic correlation (R = 0.83-0.95). Their clinicopathologic correlation was comparable, but the Bühlmann method showed significantly higher calprotectin values in every patient category.
The automated calprotectin methods showed a good performance and comparable clinicopathologic correlation. Due to lack of standardization, the numerical values differ for the various methods.
The INT/WFC Photometric H... Survey of the Northern Galactic Plane (IPHAS) is a 1800 deg... imaging survey covering Galactic latitudes |b| < 5... and longitudes ... = 30...-215... in the r, i, and Hα ...filters using the Wide Field Camera (WFC) on the 2.5-m Isaac Newton Telescope (INT) in La Palma. We present the first quality-controlled and globally calibrated source catalogue derived from the survey, providing single-epoch photometry for 219 million unique sources across 92 per cent of the footprint. The observations were carried out between 2003 and 2012 at a median seeing of 1.1 arcsec (sampled at 0.33 arcsec pixel...) and to a mean 5... depth of 21.2 (r), 20.0 (i), and 20.3 (Hα) in the Vega magnitude system. We explain the data reduction and quality control procedures, describe and test the global re-calibration, and detail the construction of the new catalogue. We show that the new calibration is accurate to 0.03 mag (root mean square) and recommend a series of quality criteria to select accurate data from the catalogue. Finally, we demonstrate the ability of the catalogue's unique (r - Hα,...r - i) diagram to (i) characterize stellar populations and extinction regimes towards different Galactic sightlines and (ii) select and quantify Hα emission-line objects. IPHAS is the first survey to offer comprehensive CCD photometry of point sources across the Galactic plane at visible wavelengths, providing the much-needed counterpart to recent infrared surveys. (ProQuest: ... denotes formulae/symbols omitted.)
Non‐Hodgkin orbital lymphoma (NHOL) and idiopathic orbital inflammation (IOI) are common orbital conditions with largely unknown pathophysiology that can be difficult to diagnose. In this study we ...aim to identify serum miRNAs associated with NHOL and IOI. We performed OpenArray® miRNA profiling in 33 patients and controls. Differentially expressed miRNAs were technically validated across technology platforms and replicated in an additional cohort of 32 patients and controls. We identified and independently validated a serum miRNA profile of NHOL that was remarkably similar to IOI and characterized by an increased expression of a cluster of eight miRNAs. Pathway enrichment analysis indicated that the miRNA‐cluster is associated with immune‐mediated pathways, which we supported by demonstrating the elevated expression of this cluster in serum of patients with other inflammatory conditions. The cluster contained miR‐148a, a key driver of B‐cell tolerance, and miR‐365 that correlated with serum IgG and IgM concentrations. In addition, miR‐29a and miR‐223 were associated with blood lymphocyte and neutrophil populations, respectively. NHOL and IOI are characterized by an abnormal serum miRNA‐cluster associated with immune pathway activation and linked to B cell and neutrophil dysfunction.
MicroRNA profiling in non‐Hodgkin orbital lymphoma and idiopathic orbital inflammation identified and independently replicated the increased expression of a pan‐inflammatory cluster of microRNAs accompanied by B cell and neutrophil dysfunction.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The objective of this study was to demonstrate the 3-year outcome of the covered endovascular reconstruction of the aortic bifurcation (CERAB) technique for the treatment of extensive aortoiliac ...occlusive disease (AIOD).
Between February 2009 and July 2016, all patients treated with the CERAB technique for AIOD were identified in the local databases of two centers and analyzed. Demographics and lesion characteristics were scored. Follow-up consisted of clinical assessment, duplex ultrasound, and ankle-brachial indices. Patency rates and clinically driven target lesion revascularization were calculated by Kaplan-Meier analysis.
Of 130 patients (69 male and 61 female) treated, 68% were diagnosed with intermittent claudication and 32% suffered from critical limb ischemia. The majority (89%) were TransAtlantic Inter-Society Consensus II D lesions, and the remaining were B and C lesions (both 5%). Median follow-up was 24 months (range, 0-67 months). The technical success rate was 97%, and 67% of cases were performed completely percutaneously. The ankle-brachial index improved significantly from 0.65 ± 0.22 preoperatively to 0.88 ± 0.15 after the procedure. The 30-day minor and major complication rate was 33% and 7%. The median hospital stay was 2 days (range, 1-76 days). At 1 year and 3 years of follow-up, 94% and 96% of the patients clinically improved at least one Rutherford category (2% and 0% unchanged, 4% and 4% worsened). Limb salvage rate was 98% at 1 year and 97% at 3 years of follow-up. Primary, primary assisted, and secondary patency was 86%, 91%, and 97% at 1 year; 84%, 89%, and 97% at 2 years; and 82%, 87%, and 97% at 3 years. Freedom from clinically driven target lesion revascularization was 87% at 1-year follow-up and 86% at both 2-year and 3-year follow-up.
The CERAB technique is a safe and feasible technique for the treatment of extensive AIOD with good 3-year results regarding patency and clinical improvement.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary
Background Incidence rates of both obesity and gastro‐oesophageal reflux disease (GERD) are increasing, particularly in the Western world. It has been suggested that GERD symptoms may be ...improved by weight reduction.
Aim To review the literature on the effect of various weight reducing modalities on manifestations of GERD in obese patients.
Methods A literature search was performed using PubMed, EMBASE and the Cochrane Library, combining the words obesity and gastro‐oesophageal reflux with bariatric surgery, diet, lifestyle intervention and weight loss.
Results With regard to diet/lifestyle intervention (conservative), four of seven studies reported an improvement of GERD. For Roux‐en‐Y gastric bypass, a positive effect on GERD was found in all studies, although this was mainly evaluated by questionnaires. In contrast, for vertical banded gastroplasty, no change or even an increase of GERD was noted, whereas the results for laparoscopic adjustable gastric banding were conflicting.
Conclusions Dietary and lifestyle intervention may improve GERD in obese patients; however, the most favourable effect is likely to be found after bariatric surgery, especially after Roux‐en‐Y gastric bypass. Future studies need to elucidate for which GERD patients laparoscopic adjustable gastric banding might have a beneficial effect and how they can be identified preoperatively.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Background and purpose: α4 and β2 nicotinic acetylcholine (ACh) receptor subunits expressed heterologously in Xenopus oocytes assemble into a mixed population of (α4)2(β2)3 and (α4)3(β2)2 receptors. ...In order to express these receptors separately in heterologous systems, we have engineered pentameric concatenated (α4)2(β2)3 and (α4)3(β2)2 receptors.
Experimental approach: α4 and β2 subunits were concatenated by synthetic linkers into pentameric constructs to produce either (α4)2(β2)3 or (α4)3(β2)2 receptors. Using two‐electrode voltage‐clamp techniques, we examined the ability of the concatenated constructs to produce functional expression in Xenopus oocytes. Functional constructs were further characterized in respect to agonists, competitive antagonists, Ca2+ permeability, sensitivity to modulation by Zn2+ and sensitivity to up‐regulation by chaperone protein 14‐3‐3.
Key results: We found that pentameric concatamers with a subunit arrangement of β2_α4_β2_α4_β2 or β2_α4_β2_α4_α4 were stable and functional in Xenopus oocytes. By comparison, when α4 and β2 were concatenated with a subunit order of β2_β2_α4_β2_α4 or β2_α4_α4_β2_α4, functional expression in Xenopus oocytes was very low, even though the proteins were synthesized and stable. Both β2_α4_β2_α4_β2 and β2_α4_β2_α4_α4 concatamers recapitulated the ACh concentration response curve, the sensitivity to Zn2+ modulation, Ca2+ permeability and the sensitivity to up‐regulation by chaperone protein 14‐3‐3 of the corresponding non‐linked (α4)2(β2)3 and (α4)3(β2)2 receptors respectively. Using these concatamers, we found that most α4β2‐preferring compounds studied, including A85380, 5I‐A85380, cytisine, epibatidine, TC2559 and dihydro‐β‐erythroidine, demonstrate stoichiometry‐specific potencies and efficacies.
Conclusions and implications: We concluded that the α4β2 nicotinic ACh receptors produced with β2_α4_β2_α4_β2 or β2_α4_β2_α4_α4 pentameric constructs are valid models of non‐linked (α4)2(β2)3 and (α4)3(β2)2 receptors respectively.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Microvascular function is an important component in the physiology of muscle. One of the major parameters, blood perfusion, can be measured noninvasively and quantitatively by arterial spin labeling ...(ASL) MRI. Most studies using ASL in muscle have only reported data from a single slice, thereby assuming that muscle perfusion is homogeneous within muscle, whereas recent literature has reported proximodistal differences in oxidative capacity and perfusion. Here, we acquired pulsed ASL data in 12 healthy volunteers after dorsiflexion exercise in two slices separated distally by 7 cm. We combined this with a Look‐Locker scheme to acquire images at multiple postlabeling delays (PLDs) and with a multiecho readout to measure T2*. This enabled the simultaneous evaluation of quantitative muscle blood flow (MBF), arterial transit time (ATT), and T2* relaxation time in the tibialis anterior muscle during recovery. Using repeated measures analyses of variance we tested the effect of time, slice location, and their interaction on MBF, ATT, and T2*. Our results showed a significant difference as a function of time postexercise for all three parameters (MBF: F = 34.0, p < .0001; T2*: F = 73.7, p < .0001; ATT: F = 13.6, p < .001) and no average differences between slices over the total time postexercise were observed. The interaction effect between time postexercise and slice location was significant for MBF and T2* (F = 5.5, p = 0.02, F = 6.1, p = 0.02, respectively), but not for ATT (F = 2.2, p = .16). The proximal slice showed a higher MBF and a lower ATT than the distal slice during the first 2 min of recovery, and T2* showed a delayed response in the distal slice. These results imply a higher perfusion and faster microvascular response to exercise in the proximal slice, in line with previous literature. Moreover, the differences in ATT indicate that it is difficult to correctly determine perfusion based on a single PLD as is commonly performed in the muscle literature.
We used quantitative arterial spin labeling to assess microvascular response to exercise at two locations of the tibialis anterior (TA) muscle. We found initial increased muscle blood flow (MBF) and slower microvascular response to exercise proximally in the TA, indicating regional differences. Arterial transit time (ATT) was decreased after exercise and different between slices. This indicates that commonly used single postlabeling delay measurements have a risk of underestimating perfusion or finding perfusion differences influenced by changes in ATT.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The ability to visualize neurons inside living brain tissue is a fundamental requirement in neuroscience and neurosurgery. Especially the development of a noninvasive probe of brain morphology with ...micrometer-scale resolution is highly desirable, as it would provide a noninvasive approach to optical biopsies in diagnostic medicine. Two-photon laser-scanning microscopy (2PLSM) is a powerful tool in this regard, and has become the standard for minimally invasive high-resolution imaging of living biological samples. However, while 2PLSM-based optical methods provide sufficient resolution, they have been hampered by the requirement for fluorescent dyes to provide image contrast. Here we demonstrate high-contrast imaging of live brain tissue at cellular resolution, without the need for fluorescent probes, using optical third-harmonic generation (THG). We exploit the specific geometry and lipid content of brain tissue at the cellular level to achieve partial phase matching of THG, providing an alternative contrast mechanism to fluorescence. We find that THG brain imaging allows rapid, noninvasive labelfree imaging of neurons, white-matter structures, and blood vessels simultaneously. Furthermore, we exploit THG-based imaging to guide micropipettes towards designated neurons inside live tissue. This work is a major step towards label-free microscopic live brain imaging, and opens up possibilities for the development of laser-guided microsurgery techniques in the living brain.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Elevated plasma homocysteine has been linked to reduced mobility and muscle functioning in the elderly. The relation of methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism with these ...associations has not yet been studied. This study aimed to investigate (1) the association of plasma homocysteine and the MTHFR 677C-->T polymorphism with muscle mass, handgrip strength, physical performance and postural sway; (2) the interaction between plasma homocysteine and the MTHFR 677C-->T polymorphism.
Baseline data from the B-PROOF study (n=2919, mean age=74.1±6.5) were used. Muscle mass was measured using dual X-ray absorptiometry, handgrip strength with a handheld dynamometer, and physical performance with walking-, chair stand- and balance tests. Postural sway was assessed on a force platform. The data were analyzed using regression analyses with plasma homocysteine levels in quartiles.
There was a significant inverse association between plasma homocysteine and handgrip strength (quartile 4: regression coefficient B=-1.14, 95% confidence interval (CI)=-1.96; -0.32) and physical performance score (quartile 3: B=-0.53, 95% CI=-0.95; -0.10 and quartile 4: -0.94; 95% CI=-1.40; -0.48) in women only, independent of serum vitamin B12 and folic acid. No association was observed between the MTHFR 677C-->T polymorphism and the outcomes. High plasma homocysteine in the 677CC and 677CT genotypes, but not in the 677TT genotype, was associated with lower physical performance.
Elevated plasma homocysteine concentrations are associated with reduced physical performance and muscle strength in older women. There is an urgent need for randomized controlled trials to examine whether lowering homocysteine levels might delay physical decline.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Despite intensive surveillance, a high rate of interval malignancies is still seen in women at increased breast cancer risk. Therefore, novel screening modalities aiming at early detection remain ...needed. The intraductal approach offers the possibility to directly sample fluid containing cells, DNA and proteins from the mammary ductal system where, in the majority of cases, breast cancer originates. Fluid from the breast can non-invasively be obtained by oxytocin-assisted vacuum aspiration, called nipple fluid aspiration (NFA). The goal of this feasibility study was to evaluate the potential of repeated NFA, which is a critical and essential step to evaluate its possible value as a breast cancer screening method.
In this multicenter, prospective study, we annually collected nipple fluid for up to 5 consecutive years from women at increased breast cancer risk, and performed a questionnaire-based survey regarding discomfort of the aspiration. Endpoints of the current interim analyses were the feasibility and results of 994 NFA procedures in 451 women with total follow-up of 560 person years of observation.
In this large group of women at increased risk of breast cancer, repetitive NFA appeared to be feasible and safe. In 66.4% of aspirated breasts, nipple fluid was successfully obtained. Independent predictive factors for successful NFA were premenopausal status, spontaneous nipple discharge, smaller breast size, bilateral oophorectomy and previous use of hormone replacement therapy or anti-hormonal treatment. The procedure was well tolerated with low discomfort. Drop-out rate was 20%, which was mainly due to repeated unsuccessful aspiration attempts. Only 1.6% of women prematurely declined further participation because of side effects.
Repeated NFA in women at increased breast cancer risk is feasible and safe. Therefore, NFA is a promising method to non-invasively obtain a valuable source of potential breast cancer specific biomarkers.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK