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.

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.

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.

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.

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.

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.

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.

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.

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.

Gender related differences in pain in spinal cord injured individuals.

STUDY DESIGN: Out of a population of 456 patients with spinal cord injuries (SCI), 130 having pain were selected after matching, based on gender, age, American Spinal Injury Association (ASIA) impairment grade and level of lesion. OBJECTIVE: To investigate whether gender differences with regard to pain perception and prevalence exist in a population of patients following spinal cord injury. SETTING: Spinalis SCI Unit (out-patient clinic), Stockholm, Sweden. METHOD: 130 patients suffering from pain were assessed over a 12-month period in a yearly health control. RESULTS: SCI women had a higher prevalence of nociceptive pain than men and their use of analgesics was greater. However, no differences between the sexes could be seen regarding pain and localization, onset, distribution, factors affecting pain, number of painful body regions, pain descriptors, ratings of pain intensities or in pain and life satisfaction. CONCLUSION: This study showed that SCI men and women describe their pain very similarly. However, SCI women had a higher prevalence of nociceptive pain than men and their use of opiates and non-steroid anti-inflammatory drugs (NSAIDs) was greater.

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.

Sensory stimulation (massage) reduces blood pressure in unanaesthetized rats.

The objective of this study was to investigate how sensory stimulation by massage-like stroking influences blood pressure and heart rate in conscious rats. Also, the influence of different locations and durations of the stimulation were assessed. For this purpose, the ventral side of the abdomen or the dorsal side of the back was manually stroked at a speed of approximately 20 cm/s, with a frequency of 0.67 Hz and at an estimated pressure of 100 mm H2O. During the treatment, the rats were held across the scapula and the neck region. Blood pressure and heart rate were measured with the cuff technique before treatment and repeatedly during the post-stimulatory period. Massage-like stroking for 5 min of the abdominal area produced a maximum decrease of approximately 20 mm Hg in blood pressure and 60 beats/min in heart rate. This reduction remained significant at 3 and 4 h after stimulation, respectively. Stimulation of the abdominal area for 2 min produced a less pronounced decrease in blood pressure as compared to the 5-min stroking. Stroking of the back resulted in a short-lasting blood pressure increase that gradually returned to the baseline level within the post-stimulatory observation time. Control animals that were handled in the same way as the experimental animals except for the stroking showed an increase of approximately 20 mm Hg in blood pressure and 60 beats/min for about 1 h after the cessation of the handling. The responses of the blood pressure and heart rate to both abdominal and back massage were significantly inhibited as compared to the control animals. These results suggest that massage-like stroking of the skin produces an inhibitory effect on the cardiovascular excitatory responses in rats. Especially, the results of the present study demonstrate that massage-like stroking of the abdomen reduces both blood pressure and heart rate below the pre-stimulus baseline levels.

[Gerontopsychiatric treatment in comparison between integrated management at a university and separated management at a district hospital. 1: Patient characteristics]. / Gerontopsychiatrische Behandlung im Vergleich zwischen integrierter Versorgung an einer Universität und separierter Versorgung an einem Landeskrankenhaus. Teil 1: Patientencharakteristik.

OBJECTIVE: We wanted to study differences between geriatric psychiatric patients and their management in an integrated (with other adult age groups) care in the University Psychiatric Hospital (PUK) compared to those in a separated (only according to age) care in the Psychiatric State Hospital (LKH), which together treat all psychiatric inpatients in Goettingen, Germany. METHOD: We performed standardized chart reviews of randomly selected groups of patients, who had been treated in the PUK (n = 151) and the LKH (n = 145) in the years 1991 and 1992. RESULTS: The LKH patients were significantly older (74.8 +/- 8.7 y versus 70.3 +/- 8.3 y), more often living alone and/or without children. 31.9% of them were living in a nursing home compared to 6.5% of the PUK patients. Psychic disorders had not shown up before old age in 55.7% of all cases. 50.4% of the patients were in a psychiatric hospital for the first time. The majority of the patients (65.6%) had not been investigated by a psychiatrist before admission. CONCLUSIONS: More socially handicapped patients were treated in the LKH. For most cases, the hospital treatment had been the first psychiatric treatment at all.

[Gerontopsychiatric treatment in comparison between integrated management at a university and separated management at a district hospital. 2: Diagnoses and treatment]. / Gerontopsychiatrische Behandlung im Vergleich zwischen integrierter Versorgung an einer Universität und separierter Versorgung an einem Landeskrankenhaus. Teil 2: Diagnosen und Behandlung.

OBJECTIVE: We wanted to study differences between geriatric psychiatric patients and their management in an integrated (with other adult age groups) care in the University Psychiatric Hospital (PUK) compared to those in a separated (only according to age) care in the Psychiatric State Hospital (LKH), which together treat all psychiatric inpatients in Goettingen, Germany. METHOD: We performed standardized chart reviews of randomly selected groups of patients, who had been treated in the PUK (n = 151) and the LKH (n = 145) in the years 1991 and 1992. RESULTS: Most patients of the LKH suffered from organic brain diseases/dementia (63.4%; PUK: 29.1%). In the PUK, depression was the most frequent diagnosis (57.6%; LKH: 21.1%). A part of about 25% of the patients showed neurological deficits. Specialised diagnostics were performed mostly in the PUK. Both institutions treated the wide majority of patients with CNS drugs. Antidementia drugs were given significantly more often in the LKH. About one third of the patients were released into changed living environments. CONCLUSIONS: Patients with further progressed dementias were treated mainly in the LKH. This has consequences for diagnostics, treatment duration and side effect rate.

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.

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.

Massage-like stroking of the abdomen lowers blood pressure in anesthetized rats: influence of oxytocin.

The aim of this study was to determine how massage-like stroking of the abdomen in rats influences arterial blood pressure. The participation of oxytocinergic mechanisms in this effect was also investigated. The ventral and/or lateral sides of the abdomen were stroked at a speed of 20 cm/s with a frequency of 0.017-0.67 Hz in pentobarbital anesthetized, artificially ventilated rats. Arterial blood pressure was recorded with a pressure transducer via a catheter in the carotid artery. Stroking of the ventral, or both ventral and lateral sides of the abdomen for 1 min with a frequency of 0.67 Hz caused a marked decrease in arterial blood pressure (approx. 50 mmHg). After cessation of the stimulation blood pressure returned to the control level within 1 min. The maximum decrease in blood pressure was achieved at frequencies of 0.083 Hz or more. Stroking only the lateral sides of the abdomen elicited a significantly smaller decrease in blood pressure (approx. 30 mmHg decrease) than stroking the ventral side. The decrease in blood pressure caused by stroking was not altered by s.c. administration of an oxytocin antagonist (1-deamino-2-D-Tyr-(Oet)-4-Thr-8-Orn-oxytocin, 1 mg/kg) directed against the uterine receptor. In contrast, the administration of 0.1 mg/kg of oxytocin diminished the effect, which was antagonized by a simultaneous injection of the oxytocin antagonist. These results indicate that the massage-like stroking of the abdomen decreases blood pressure in anesthetized rats. This effect does not involve intrinsic oxytocinergic transmission. However, since exogenously applied oxytocin was found to diminish the effect of stroking, oxytocin may exert an inhibitory modulatory effect on this reflex arc.