Determinants of trabecular bone score and prevalent vertebral fractures in women with fragility fractures: a cross-sectional sub-study of NoFRACT.

Determinants of trabecular bone score (TBS) and vertebral fractures assessed semiquantitatively (SQ1-SQ3) were studied in 496 women with fragility fractures. TBS was associated with age, parental hip fracture, alcohol intake and BMD, not SQ1-SQ3 fractures. SQ1-SQ3 fractures were associated with age, prior fractures, and lumbar spine BMD, but not TBS. INTRODUCTION: Trabecular bone score (TBS) and vertebral fractures assessed by semiquantitative method (SQ1-SQ3) seem to reflect different aspects of bone strength. We therefore sought to explore the determinants of and the associations between TBS and SQ1-SQ3 fractures. METHODS: This cross-sectional sub-study of the Norwegian Capture the Fracture Initiative included 496 women aged ≥ 50 years with fragility fractures. All responded to a questionnaire about risk factors for fracture, had bone mineral density (BMD) of femoral neck and/or lumbar spine assessed, TBS calculated, and 423 had SQ1-SQ3 fracture assessed. RESULTS: Mean (SD) age was 65.6 years (8.6), mean TBS 1.27 (0.10), and 33.3% exhibited SQ1-SQ3 fractures. In multiple variable analysis, higher age (ßper SD = - 0.26, 95% CI: - 0.36,- 0.15), parental hip fracture (ß = - 0.29, 95% CI: - 0.54,- 0.05), and daily alcohol intake (ß = - 0.43, 95% CI - 0.79, - 0.08) were associated with lower TBS. Higher BMD of femoral neck (ßper SD = 0.34, 95% CI 0.25-0.43) and lumbar spine (ßper SD = 0.40, 95% CI 0.31-0.48) were associated with higher TBS. In multivariable logistic regression analyses, age (ORper SD = 1.94, 95% CI 1.51-2.46) and prior fragility fractures (OR = 1.71, 95% CI 1.09-2.71) were positively associated with SQ1-SQ3 fractures, while lumbar spine BMD (ORper SD = 0.75 95% CI 0.60-0.95) was negatively associated with SQ1-SQ3 fractures. No association between TBS and SQ1-SQ3 fractures was found. CONCLUSION: Since TBS and SQ1-SQ3 fractures were not associated, they may act as independent risk factors, justifying the use of both in post-fracture risk assessment.

Chromosomal microarray in fetuses with increased nuchal translucency.

OBJECTIVE: To assess the clinical value of using high-resolution chromosomal microarray (CMA) for the examination of genomic imbalances in prenatal uncultured chorionic villus samples from fetuses with increased nuchal translucency (NT) and a normal quantitative fluorescent polymerase chain reaction (QF-PCR) result, in a clinical setting in which more than 95% of pregnant women receive first-trimester combined screening. METHODS: From January 2013 to July 2014, we included 132 chorionic villus samples from consecutive ongoing pregnancies, with fetal NT ≥ 3.5 mm at 11-13 weeks' gestation, from obstetric units (publicly funded healthcare) in Central and North Denmark Regions. DNA was extracted directly from the samples and examined with QF-PCR (n = 132) and 180 kb oligonucleotide array-based comparative genomic hybridization (n = 94). RESULTS: In 38 cases, aneuploidies for chromosomes 18, 21 or X, or triploidy, were detected by QF-PCR. Among the 94 cases with a normal QF-PCR result, we detected pathogenic copy number variants (CNVs) by CMA in 12 fetuses (12.8% (95% CI, 7.5-21.0%)). In an additional three (3.2%) cases, CNVs with uncertain clinical significance were detected. CONCLUSION: CMA is a valuable diagnostic technique in pregnancies with isolated fetal NT ≥ 3.5 mm.

Silicide-induced multi-wall carbon nanotube growth on silicon nanowires.

A novel multi-walled carbon nanotube (MWNT) growth process is reported based on carbon incorporation in a nickel catalyst layer deposited via plasma-enhanced atomic layer deposition (PEALD) on silicon nanowires and silicon wafer substrates. As-deposited PEALD Ni films containing relatively high amounts of carbon (>18 at.%) were observed to promote the growth of MWNTs upon post-deposition rapid thermal annealing. For these films the carbon originated from the ALD precursor ligand and MWNT growth occurred in the absence of a vapor-phase carbon feedstock. MWNT growth relied on the formation of nickel silicide at the PEALD Ni/Si interface which increased the local carbon concentration in the Ni film sufficiently to promote carbon saturation/precipitation at Ni catalyst grains and nucleate MWNT growth. Similar MWNT growth from annealed PEALD Ni films was not observed on SiO(2)-coated Si wafer substrates, consistent with the role of silicidation in the observed Ni-catalyzed MWNT growth on Si. This MWNT growth mode requires neither the catalytic decomposition of a gaseous hydrocarbon source nor the high-temperature pyrolysis of metallocene materials and purposely avoids a catalyst diffusion barrier at the Si substrate, commonly used in MWNT growth processes on Si.

Esterification and modification of [1-14C] n-3 and n-6 polyunsaturated fatty acids in pikeperch (Sander lucioperca) larvae reared under linoleic or α-linolenic acid-based diets and variable environmental salinities.

To elucidate the in vivo endogenous ability of pikeperch (Sander lucioperca) larvae to deacylate and reacylate phospholipids and to elongate and desaturate PUFAs, 20 days post hatch (DPH) fish were incubated with either [1-14C]20:4n-6 bound to PC and PE, or with free [1-14C]-labelled fatty acids (18:2n-6, 18:3n-3, 20:4n-6, 20:5n-3 and 22:6n-3). The modulation capacity of both low LC-PUFAs but high 18C PUFAs precursors dietary supply and increasing salinity on larval fatty acid metabolic pathways was also investigated. [1-14C]DHA was incorporated into larval tissues to a lower extent than [1-14C]ARA or [1-14C] EPA. [1-14C]ARA was significantly less abundant in larval tissues when provided bound to PE than when esterified into PC, indicating that PC is a better phospholipid source to provide LC-PUFA to pikeperch larvae. Radioactivity was mainly recovered into phospholipids, especially that of the three LC-PUFAs ARA, EPA and DHA. All substrates were primarily incorporated into PC except [1-14C]ARA which significantly did into PI. Both [1-14C]EPA and [1-14C]DHA showed a similar esterification pattern into lipid classes: PC > PE > PI > TAG, with [1-14C]DHA presenting the highest esterification into PE of all radiolabelled compounds (26.3% vs 3.6-14.2%). Although higher rearing salinities tended to increase ∆6 desaturase activity, no radioactivity from [1-14C]18:2n-6 or [1-14C]18:3n-3 was detected in ARA or EPA, proving a deficiency of Δ5 activity and the inability of pikeperch to biosynthesize DHA. This work provides novel information on the lipid metabolism of pikeperch at early development necessary for the design of live prey enrichment protocols and dietary formulations adapted to larval metabolic capabilities.

The role of transcription factors cyclic-AMP responsive element modulator (CREM) and inducible cyclic-AMP early repressor (ICER) in epileptogenesis.

Alterations in the brain that contribute to the development of epilepsy, also called epileptogenesis, are not well understood, which makes it difficult to develop strategies for preventing epilepsy. Here we have studied the role of the CRE binding transcription factors, cyclic-AMP responsive element modulator (CREM) and inducible cyclic-AMP early repressor (ICER), in the development of epilepsy following pilocarpine induced status epilepticus (SE) in mice. Following SE, ICER mRNA and protein are increased in neurons. The increase in ICER, however, is not necessary for neuronal injury following SE as pilocarpine treatment induces equivalent neuronal injury in pyramidal neurons of wild type and CREM/ICER null mice. Following SE, the CREM/ICER null mice develop a more severe epileptic phenotype experiencing approximately threefold more frequent spontaneous seizures. Together these data suggest that the increase in ICER mRNA following SE may have a role in suppressing the severity of epilepsy.

Ratings of pain and activity limitation on the visual analogue scale and global impression of change in multimodal rehabilitation of back pain - analyses at group and individual level.

PURPOSE: To evaluate changes in pain intensity and activity limitation, at group and individual levels, and their associations with the global impression of change after multimodal rehabilitation in patients with back pain. METHOD: Patients with long-term back pain (n = 282) participated in a 4-week programme with a follow-up after 6 months. Visual analogue scales (VAS) were used to rate pain intensity and activity limitation. Global impression of change (GIC) was rated on a 7-category scale. The sign test, the Svensson method and the Spearman rank correlation were used for analyses. RESULTS: Significantly lower ratings in pain and activity limitation at follow-up were found at group level. However, a large individual variability was found by the Svensson method. The correlations between GIC and changes in pain and activity limitation were rs = 0.49 and rs = 0.50, respectively. A rated GIC of at least "much better" on group level showed changes of ≥20 mm on the VAS. CONCLUSIONS: At group level, lower VAS ratings were found in patients with back pain. However, a large individual variability in pain and activity limitation was also found resulting in low to moderate associations between GIC and the change in VAS ratings. The large individual variability might be due to the impreciseness in the ratings on the VAS. We have presented a critical discussion of statistical methods in connection with the VAS. Implications for Rehabilitation The use of VAS as a rating instrument may be questioned, especially for perceived pain intensity which is a too complex experience to be rated on a line without any visible categories. Single ratings of pain intensity should preferably be complemented with the ratings of activity limitation in patients with long-term back pain. Global impression of change is a suggested inclusive rating after rehabilitation. The improvement desired by the patient should preferably be determined before rehabilitation.

Mechanism of protein tyrosine phosphatase 1B-mediated inhibition of leptin signalling.

Upon leptin binding, the leptin receptor is activated, leading to stimulation of the JAK/STAT signal transduction cascade. The transient character of the tyrosine phosphorylation of JAK2 and STAT3 suggests the involvement of protein tyrosine phosphatases (PTPs) as negative regulators of this signalling pathway. Specifically, recent evidence has suggested that PTP1B might be a key regulator of leptin signalling, based on the resistance to diet-induced obesity and increased leptin signalling observed in PTP1B-deficient mice. The present study was undertaken to investigate the mechanism by which PTP1B mediates the cessation of the leptin signal transduction. Leptin-induced activation of a STAT3 responsive reporter was dose-dependently inhibited by co-transfection with PTP1B. No inhibition was observed when a catalytically inactive mutant of PTP1B was used or when other PTPs were co-transfected. PTP1B was able to dephosphorylate activated JAK2 and STAT3 in vitro, whereas either no or a minimal effect was observed with cluster of differentiation 45 (CD45), PTPalpha and leukocyte antigen-related (LAR). By utilisation of a selective PTP1B inhibitor, the leptin-induced STAT3 activation was enhanced in cells. In conclusion, these results suggested that the negative regulatory role of PTP1B on leptin signalling is mediated through a direct and selective dephosphorylation of the two signalling molecules, JAK2 and STAT3.

Stroking of the abdomen causes decreased locomotor activity in conscious male rats.

The specific aim of the present study was to determine if stroking in conscious rats can influence spontaneous locomotor behavior in an open-field arena. For this purpose, conscious rats were held across the scapula and the ventral side of the abdomen was stroked at a pressure of 100-150 mm H2O and at a speed of approximately 20 cm/s. The stimulation frequency was approximately 40 strokes/min and the duration 2, 5, and 10 min. Animals held for 10 min served as controls. There was a significant decrease in rearing and locomotion and a significant increase in peripheral activity in the open-field arena after the treatment. Maximal effects were obtained after 5 min of stroking. These effects were consistent with a stroking-induced sedative effect similar to that seen in this open-field arena model following neuroleptics or large doses of oxytocin.

Myocardial and microvascular injury following coronary surgery and its attenuation by mode of reperfusion.

In 14 patients undergoing coronary surgery, repeated atrial biopsies were obtained before and at the end of ischemia, and at 20 and 60 min of reperfusion. In half of the patients reperfusion was initiated with an abrupt rise in blood temperature and pressure, in the other half with a gradual rise. The biopsies were prepared for transmission electron microscopy and analyzed by stereological technique. In all biopsies, myocytic injury, as revealed by mitochondrial changes and intracellular edema, occurred following ischemia (P = 0.0003 and 0.007, respectively). The intracellular edema regressed following 20 min of reperfusion (P = 0.008). The myocytic mitochondrial changes persisted during reperfusion towards the end of the observation period (P = 0.0001). Interstitial edema increased following ischemia (P = 0.007) and persisted following 60 min of reperfusion (P = 0.009). The capillary part was significantly reduced after 20 min of reperfusion (P = 0.003), probably reflecting interstitial edema. Most changes were reversible in nature, although foci of irreversible changes were shown. In patients with a gradual start of reperfusion there was a significant regression of interstitial edema (P = 0.005) at 60 min reperfusion compared to the patients with an abrupt start, where the same changes seemed to persist or even increase. The study demonstrates that "reperfusion injury" occurs in human myocardium. It can be discerned from "ischemic" injury, and it may be reduced by a gentle mode of reperfusion.

Reliability and responsiveness of three different pain assessments.

The visual analogue scale (VAS) and ordered categorical scales, i.e. numeric rating scales (NRS), are commonly used in the assessment of pain. However, these scales are bounded by fixed endpoints and thus the range of measurement is limited. The disparity in repeated assessments of perceived pain intensity with the VAS, NRS, and electrical stimulation applied as a matching stimulus was studied in 69 patients (48 women and 21 men, 19-72 years) with chronic nociceptive or neurogenic pain. Responsiveness with transcutaneous electrical nerve stimulation (TENS) using the same measurement procedures was evaluated in the same patients. Comparison of results from the three pain assessments showed that the painmatcher is at least as reliable and responsive as VAS and NRS. None of the three measurements showed evidence for systematic disagreement and had only significant random individual disagreement. They also showed evidence for responsiveness.

Acro-osteolysis (Hajdu-Cheney) syndrome: report of a case with abnormal tooth structure.

The acro-osteolysis (Hajdu-Cheney) syndrome is a rare disorder of bone metabolism characterized by progressive dissolution of a number of bones. Although previous reports have detailed several dental abnormalities associated with this syndrome, this is the first report describing structural changes in the dentin and cementum of teeth.

[Periorbital and orbital cellulitis in children]. / Periorbital og orbital cellulitis hos børn.

During a six-year period 28 febrile children with acute periorbital swelling were identified. Median age was 1.8 years (range, two weeks-nine years). When possible, the children were classified as having preseptal cellulitis (infectious focus in the subcutaneous tissue in front of the orbital septum) or postseptal cellulitis (focus in the paranasal sinuses). In six children a diagnosis of preseptal subcutaneous cellulitis was based upon the clinical presentation and positive culture results. Five children were additionally classified as having preseptal cellulitis due to severe conjunctivitis. Fifteen children were classified as having postseptal cellulitis due to infection in the paranasal sinuses (ethmoiditis). In seven of the latter cases the diagnosis was based upon the results of CT/MR-scans or operation. Two children could not be classified. All children were given antibiotic treatment and four had an operation. There were no recurrences or sequelae. In our study a presumed diagnosis could be made in retrospect in most cases, but at the time of presentation the clinical picture was often confusing. We found a CT- or MR-scan to be most helpful, especially in identifying the children requiring surgical treatment.

Prognostic significance of circulating intact and cleaved forms of urokinase plasminogen activator receptor in inoperable chemotherapy treated cholangiocarcinoma patients.

BACKGROUND: High levels of intact and cleaved forms of the urokinase-type plasminogen activator receptor (uPAR) in both tissue and blood are associated with poor survival in several cancer diseases. The prognostic significance of uPAR in cholangiocarcinoma is unknown. The aims of this study were to determine if pre-treatment serum levels of uPAR forms and a decrease in levels during chemotherapy are predictive of survival in patients with inoperable cholangiocarcinoma. DESIGN AND METHODS: Patients with inoperable cholangiocarcinoma were consecutively included in the training set (n=108). A test set included patients from a different hospital using similar treatment guidelines (n=60). Serum levels of the different uPAR forms were determined using time-resolved fluorescence immunoassays (TR-FIA). The Cox proportional hazards model was used for the uni- and multivariate survival analyses. RESULTS: Baseline level of uPAR(I-III)+uPAR(II-III) was an independent predictor of survival (HR=2.08, 95% CI:1.46-2.97, p<0.0001). Applying the linear predictor from the training set to the test set, it was validated that uPAR(I-III)+uPAR(II-III) predicted overall survival (p=0.049). A high level of uPAR(I-III)+uPAR(II-III) after 2cycles of chemotherapy was associated with poor survival (HR=1.79, 95% CI:1.08-2.97, p=0.023, n=57). This predictor, however, was not significant in the test set (p=0.21, 26 events in 27 patients). CONCLUSION: The baseline level of uPAR(I-III)+uPAR(II-III) is a predictor of survival in inoperable cholangiocarcinoma patients.

Effects of organic plant oils and role of oxidation on nutrient utilization in juvenile rainbow trout (Oncorhynchus mykiss).

Producing organic fish diets requires that the use of both fishmeal and fish oil (FO) be minimized and replaced by sustainable, organic sources. The purpose of the present study was to replace FO with organic oils and evaluate the effects on feed intake, feed conversion ratio (FCR), daily specific growth rate (SGR) and nutrient digestibility in diets in which fishmeal protein was partly substituted by organic plant protein concentrates. It is prohibited to add antioxidants to organic oils, and therefore the effects of force-oxidizing the oils (including FO) on feed intake and nutrient digestibility was furthermore examined. Four organic oils with either a relatively high or low content of polyunsaturated fatty acids were considered: linseed oil, rapeseed oil, sunflower oil and grapeseed oil. Substituting FO with organic oils did not affect feed intake (P > 0.05), FCR or SGR (P > 0.05) despite very different dietary fatty acid profiles. All organic plant oils had a positive effect on apparent lipid digestibility compared with the FO diet (P < 0.05), whereas there were no effects on the apparent digestibility of other macronutrients when compared with the FO diet (P > 0.05). Organic vegetable oils did not undergo auto-oxidation as opposed to the FO, and the FO diet consequently had a significantly negative effect on the apparent lipid digestibility. Feed intake was not affected by oxidation of any oils. In conclusion, the study demonstrated that it is possible to fully substitute FO with plant-based organic oils without negatively affecting nutrient digestibility and growth performance. Furthermore, plant-based organic oils are less likely to oxidize than FOs, prolonging the shelf life of such organic diets.

Egr3 stimulation of GABRA4 promoter activity as a mechanism for seizure-induced up-regulation of GABA(A) receptor alpha4 subunit expression.

GABA is the major inhibitory transmitter at CNS synapses. Changes in subunit composition of the pentameric GABA(A) receptor, including increased levels of alpha4 subunit in dentate granule cells and associated functional alterations such as increased zinc blockade of GABA currents, are hypothesized to be critical components of epileptogenesis. Here, we report that the minimal promoter of the human alpha4 subunit gene (GABRA4p), when used to drive reporter gene expression from adeno-associated viral vectors, controls condition-specific up-regulation in response to status epilepticus, defining a transcriptional mechanism for seizure-induced changes in levels of alpha4 subunit containing GABA(A) receptors. Transfection studies in primary hippocampal neurons show that inducible early growth response factor 3 (Egr3) up-regulates GABRA4p activity as well as the levels of endogenous alpha4 subunits. Given that Egr3 knockout mice display approximately 50% less GABRA4 mRNAs in the hippocampus and that increases in alpha4 and Egr3 mRNAs in response to pilocarpine-induced status epilepticus are accompanied by increased binding of Egr3 to GABRA4 in dentate granule cells, our findings support a role for Egr3 as a major regulator of GABRA4 in developing neurons and in epilepsy.

Cardiopulmonary resuscitation by lay people.

The survival-rate in 75 of 631 patients with cardiac arrest in whom resuscitation was started outside hospital by lay people was 36%. Only 8% survived when attempts at resuscitation were delayed until the arrival of an ambulance team which included an anaesthetist and a specially trained nurse. These data show the importance of anoxia-time (time from cessation of circulation to initiation of resuscitation) to the chances of survival after resuscitation) to the chances of survival after resuscitation, and support the idea that lay people should be taught and encourage to perform cardiopulmonary resuscitation.