Core Outcome Set for IgE-mediated food allergy clinical trials and observational studies of interventions: International Delphi consensus study 'COMFA'.

BACKGROUND: IgE-mediated food allergy (FA) is a global health concern with substantial individual and societal implications. While diverse intervention strategies have been researched, inconsistencies in reported outcomes limit evaluations of FA treatments. To streamline evaluations and promote consistent reporting, the Core Outcome Measures for Food Allergy (COMFA) initiative aimed to establish a Core Outcome Set (COS) for FA clinical trials and observational studies of interventions. METHODS: The project involved a review of published clinical trials, trial protocols and qualitative literature. Outcomes found as a result of review were categorized and classified, informing a two-round online-modified Delphi process followed by hybrid consensus meeting to finalize the COS. RESULTS: The literature review, taxonomy mapping and iterative discussions with diverse COMFA group yielded an initial list of 39 outcomes. The iterative online and in-person meetings reduced the list to 13 outcomes for voting in the formal Delphi process. One more outcome was added based on participant suggestions after the first Delphi round. A total of 778 participants from 52 countries participated, with 442 participating in both Delphi rounds. No outcome met a priori criteria for inclusion, and one was excluded as a result of the Delphi. Thirteen outcomes were brought to the hybrid consensus meeting as a result of Delphi and two outcomes, 'allergic symptoms' and 'quality of life' achieved consensus for inclusion as 'core' outcomes. CONCLUSION: In addition to the mandatory reporting of adverse events for FA clinical trials or observational studies of interventions, allergic symptoms and quality of life should be measured as core outcomes. Future work by COMFA will define how best to measure these core outcomes.

Myocardial Blood Flow Determination From Contrast-Free Magnetic Resonance Imaging Quantification of Coronary Sinus Flow.

BACKGROUND: Determination of myocardial blood flow (MBF) with MRI is usually performed with dynamic contrast enhanced imaging (MBFDCE ). MBF can also be determined from coronary sinus blood flow (MBFCS ), which has the advantage of being a noncontrast technique. However, comparative studies of MBFDCE and MBFCS in large cohorts are lacking. PURPOSE: To compare MBFCS and MBFDCE in a large cohort. STUDY TYPE: Prospective, sequence-comparison study. POPULATION: 147 patients with type 2 diabetes mellitus (age: 56+/-12 years; 106 male; diabetes duration: 12.9+/-8.1 years), and 25 age-matched controls. FIELD STRENGTH/SEQUENCES: 1.5 Tesla scanner. Saturation recovery sequence for MBFDCE vs. phase-contrast gradient-echo pulse sequence (free-breathing) for MBFCS . ASSESSMENT: MBFDCE and MBFCS were determined at rest and during coronary dilatation achieved by administration of adenosine at 140 µg/kg/min. Myocardial perfusion reserve (MPR) was calculated as the stress/rest ratio of MBF values. Coronary sinus flow was determined twice in the same imaging session for repeatability assessment. STATISTICAL TESTS: Agreement between MBFDCE and MBFCS was assessed with Bland and Altman's technique. Repeatability was determined from single-rater random intraclass and repeatability coefficients. RESULTS: Rest and stress flows, including both MBFDCE and MBFCS values, ranged from 33 to 146 mL/min/100 g and 92 to 501 mL/min/100 g, respectively. Intraclass and repeatability coefficients for MBFCS were 0.95 (CI 0.90; 0.95) and 5 mL/min/100 g. In Bland-Altman analysis, mean bias at rest was -1.1 mL/min/100 g (CI -3.1; 0.9) with limits of agreement of -27 and 24.8 mL/min/100 g. Mean bias at stress was 6.3 mL/min/100 g (CI -1.1; 14.1) with limits of agreement of -86.9 and 99.9. Mean bias of MPR was 0.11 (CI: -0.02; 0.23) with limits of agreement of -1.43 and 1.64. CONCLUSION: MBF may be determined from coronary sinus blood flow, with acceptable bias, but relatively large limits of agreement, against the reference of MBFDCE . LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Near-infrared spectroscopy to measure brain oxygenation: A comparison of measurements on the skin, skull and dura mater.

BACKGROUND: The reliability of near-infrared spectroscopy (NIRS) for measuring cerebral oxygenation (ScO2 ) is controversial due to the possible contamination from extracranial tissues. We compared ScO2 measured with the NIRS optode on the forehead, the skull and the dura mater in anaesthetised patients undergoing craniotomy. We hypothesised that ScO2 measured directly on the skull and the dura mater would differ from ScO2 measured on the skin. METHODS: This prospective observational study included 17 adult patients scheduled for elective craniotomy. After induction of general anaesthesia, ScO2 was measured on the forehead skin, as well as on the skull and on the dura mater in the surgical field. The primary comparison was the difference in ScO2 measured on the dura mater and on ScO2 measured on the skin; secondary comparisons were the differences in ScO2 on the skull and ScO2 on the skin and the dura mater, respectively. Data were described with median (5%-95% range) and analysed with the Wilcoxon signed-rank test. RESULTS: ScO2 values on the dura mater were obtained in 11 patients, and median ScO2 (48%, 29%-95%) did not differ significantly from ScO2 on the skin (73%, 49%-92%; p = .052), median difference -25% (-35.6% to -1.2%). ScO2 on the skull (N = 16) was lower than that on the skin (63% [43%-79%] vs. 75% [61%-94%]; p = .0002), median difference -10% (-20.8 to -3.0). CONCLUSION: In adults undergoing craniotomy, NIRS-based ScO2 measured on the dura mater did not reach statistically significantly lower values than ScO2 measured on the skin, whereas values on the skull were lower than on the skin, indicating a contribution from scalp tissue to the signal.

The independent association of myocardial extracellular volume and myocardial blood flow with cardiac diastolic function in patients with type 2 diabetes: a prospective cross-sectional cohort study.

BACKGROUND: Diffuse myocardial fibrosis and microvascular dysfunction are suggested to underlie cardiac dysfunction in patients with type 2 diabetes, but studies investigating their relative impact are lacking. We aimed to study imaging biomarkers of these and hypothesized that fibrosis and microvascular dysfunction would affect different phases of left ventricular (LV) diastole. METHODS: In this cross-sectional study myocardial blood flow (MBF) at rest and adenosine-stress and perfusion reserve (MPR), as well as extracellular volume fraction (ECV), were determined with cardiovascular magnetic resonance (CMR) imaging in 205 patients with type 2 diabetes and 25 controls. Diastolic parameters included echocardiography-determined lateral e' and average E/e', and CMR-determined (rest and chronotropic-stress) LV early peak filling rate (ePFR), LV peak diastolic strain rate (PDSR), and left atrial (LA) volume changes. RESULTS: In multivariable analysis adjusted for possible confounders including each other (ECV for blood flow and vice versa), a 10% increase of ECV was independently associated with ePFR/EDV (rest: ß = - 4.0%, stress: ß = - 7.9%), LAmax /BSA (rest: ß = 4.8%, stress: ß = 5.8%), and circumferential (ß = - 4.1%) and radial PDSR (ß = 0.07%/sec). A 10% stress MBF increase was associated with lateral e' (ß = 1.4%) and average E/e' (ß = - 1.4%) and a 10% MPR increase to lateral e' (ß = 2.7%), and average E/e' (ß = - 2.8%). For all the above, p < 0.05. No associations were found with longitudinal PDSR or left atrial total emptying fraction. CONCLUSION: In patients with type 2 diabetes, imaging biomarkers of microvascular dysfunction and diffuse fibrosis impacts diastolic dysfunction independently of each other. Microvascular dysfunction primarily affects early left ventricular relaxation. Diffuse fibrosis primarily affects diastasis. Trial registration https://www. CLINICALTRIALS: gov . Unique identifier: NCT02684331. Date of registration: February 18, 2016.

Impact of hyperoxia and phenylephrine on cerebral oxygenation: An experimental clinical study.

BACKGROUND: Oxygen supply to the brain is of special importance during intracranial surgery because it may be compromised by intracranial pathology. A high arterial blood pressure (mean arterial pressure above 80 mmHg) and a high arterial oxygen tension (PaO2 above 12 kPa) is therefore often targeted in these patients, when for example intracranial pressure is increased or when a mass effect on brain tissue from a tumour is present, and it is pursued by administering vasopressors such as phenylephrine and by increasing inspiratory oxygen fraction (FiO2 ). However, whether these interventions increase cerebral oxygenation remains uncertain. We aimed to investigate the effect of hyperoxia and phenylephrine on brain tissue oxygen tension (PbtO2 ) in patients undergoing craniotomy. METHODS: In this experimental study, we included 17 adult patients scheduled for elective craniotomy. After securing a stable baseline of the oxygen probe, PbtO2 was measured in white matter peripherally in the surgical field during general anaesthesia. Primary comparisons were PbtO2 before versus after an increase in FiO2 from 0.30 to 0.80 as well as before versus after a bolus dose of phenylephrine (0.1-0.2 mg depending on patient haemodynamics). Data were analysed with the Wilcoxon signed rank test. RESULTS: We obtained complete data sets in 11 patients undergoing the FiO2 increase and six patients receiving the phenylephrine bolus. PbtO2 was 22 (median; 5%-95% range, 4.6-54) mmHg during 30% oxygen, 68 (8.4-99) mmHg during 80% oxygen (p = .004 compared to 30% oxygen), 21 (4.5-81) mmHg before phenylephrine, and 19 (4.2-56) mmHg after phenylephrine (p = .56 compared to before phenylephrine). CONCLUSION: In patients undergoing craniotomy under general anaesthesia, brain tissue oxygen tension increased with a high inspiratory oxygen fraction but remained unchanged after a bolus dose of phenylephrine.

Effects of feeding level, milking frequency, and single injection of cabergoline on blood metabolites, hormones, and minerals around dry-off in dairy cows.

This study aimed to investigate the effect of the different dry-off strategies based on reducing feeding level (normal vs. reduced energy density), reducing milking frequency (twice vs. once daily), and administration of a dopamine agonist after last milking (i.e. saline vs. cabergoline injection) on blood metabolites, hormones, and minerals around dry-off. In this experiment, 119 Holstein dairy cows were used in a 2 × 2 × 2 factorial arrangement. In the last week before dry-off, cows were allocated to 1 of the 4 possible dry-off strategies based on feeding level and milking frequency. Within 3 h after last milking, cows were injected with either saline or a D2 dopamine agonist (cabergoline; Velactis, Ceva Santé Animale, Libourne, France; labeled for use only with abrupt dry-off, e.g., no preceding reduction in feeding level or milking frequency before last milking). After dry-off, all cows were fed the same dry cow diet and data collection continued for a week. Blood samples were collected from the coccygeal vein on d -9, -6, -5, -2, 1, 2, 5, and 7 relative to dry-off. Additionally, blood was sampled at 0, 3, and 6 h relative to injection of either cabergoline or saline, equivalent to d 0.125, 0.250, and 0.375 relative to last milking (dry-off). The reduced feeding level before dry-off caused reduced glucose and insulin concentrations as well as increased free fatty acid concentrations, particularly when reduced feeding level was combined with milking the cows 2× daily. The intramuscular injection of cabergoline caused the expected reduction in circulating prolactin concentrations. In addition, dopamine-agonist cabergoline induced an atypical simultaneous pattern of plasma metabolites (i.e., increased glucose and free fatty acid concentrations), hormones (i.e., reduced insulin and increased cortisol concentrations), and minerals (i.e., reduced calcium concentration), indicating that normal metabolic and mineral homeostatic regulations were hindered after the injection of ergot alkaloid cabergoline. In conclusion, reducing milking frequency seems the best management strategy to reduce milk production at dry-off among those tested in this study.

Phylogenomic analyses of mud dragons (Kinorhyncha).

Mud dragons (Kinorhyncha) are microscopic invertebrates, inhabiting marine sediments across the globe from intertidal to hadal depths. They are segmented, moulting animals like arthropods, but grouping with the unsegmented priapulans and loriciferans within Ecdysozoa. There are more than 300 species of kinorhynchs described within 31 genera and 11 families, however, their evolutionary relationships have so far only been investigated using morphology and a few molecular markers. Here we aim to resolve the relationships and classification of major clades within Kinorhyncha using transcriptomic data. In addition, we wish to revisit the position of three indistinctly segmented, aberrant genera in order to reconstruct the evolution of distinct segmentation within the group. We conducted a phylogenomic analysis of Kinorhyncha including 21 kinorhynch transcriptomes (of which 18 are new) representing 15 genera, and seven outgroups including priapulan, loriciferan, nematode and nematomorph transcriptomes. Results show a congruent and robust tree that supports the division of Kinorhyncha into two major clades: Cyclorhagida and Allomalorhagida. Cyclorhagida is composed of three subclades: Xenosomata, Kentrorhagata comb. nov. (including the aberrant Zelinkaderes) and Echinorhagata. Allomalorhagida is composed of two subclades: Pycnophyidae and Anomoirhaga nom. nov. Anomoirhaga nom. nov. accommodates the aberrant genera Cateria (previously nested within Cyclorhagida) and Franciscideres together with five additional genera. The distant and derived positions of the aberrant Zelinkaderes, Cateria and Franciscideres species suggest that their less distinct trunk segmentation evolved convergently, and that segmentation evolved among kinorhynch stem groups.

Variability and specificity of bone cutting mark properties in cases involving stabbing with knives.

Sharp force traumas are frequently encountered in stabbing crime victims. During an examination, the properties of cutting marks in bones are compared with the properties of suspect tools, particularly knives. Therefore, the variation and specificity of knife and cutting mark properties must be known. This article provides the variability and specificity of a set of knife blade and cutting mark properties. Plain and serrated knives are used to create experimental cutting marks in porcine ribs, knife properties are derived from surface acquisitions of the blades and mark properties from Micro-CT data. We consider two conditions, automated stabbing using a motorized stage and manual stabbing. In addition, we study the influence of maceration on marks. For knives, the blade edge angle, blade thickness, and bevel height, and for cutting marks, the shape, the wall angle, the width, and the bevel height are determined and compared. The results show that the relationship between corresponding properties of blades and marks depends on the knife type. For plain knives, the width and wall angle of the marks are dependent on the mark depth and are significantly smaller than the blade properties edge angle and width. For serrated knives, this is not the case. The mark shape only provides slight support for a knife type for marks deeper than the blade bevel height. In conclusion, mark properties are only specific for a particular knife brand and model if the blade properties differ significantly and assuming a specific knife type.

Temperature change in children undergoing magnetic resonance imaging-An observational cohort study.

AIM: An increasing number of children undergo magnetic resonance imaging requiring anesthesia or sedation to ensure their immobility; however, magnetic resonance imaging may increase body temperature whereas sedation or anesthesia may decrease it. We investigated changes in body temperature in children who underwent sedation or anesthesia for magnetic resonance imaging. METHODS: Children aged 12 weeks-12 years undergoing anesthesia and magnetic resonance imaging were included in this prospective observational study. Tympanic body temperature was measured before and after magnetic resonance imaging, and the difference between measurements was calculated. Associations between the temperature difference and patient- or procedure-related factors were evaluated with linear and logistic regression analysis. RESULTS: A total of 74 children were included, of whom 5 (7%) had a temperature increase ≥0.5°C. Mean temperature difference was -0.24°C (SD 0.48) for the entire group and -0.28°C for the youngest children (0-2 years). The temperature difference correlated positively with the duration of imaging (unadjusted coefficient 0.26, 95% confidence interval (CI), (0.01; 0.52)). CONCLUSION: In this study of sedated or anesthetized children undergoing magnetic resonance imaging, clinically relevant increases in body temperature above 0.5°C were only found in a few patients. However, longer imaging duration tended to be associated with increased body temperature.

Revisiting kinorhynch segmentation: variation of segmental patterns in the nervous system of three aberrant species.

BACKGROUND: Kinorhynch segmentation differs from the patterns found in Chordata, Arthropoda and Annelida which have coeloms and circulatory systems. Due to these differences and their obsolete status as 'Aschelminthes', the microscopic kinorhynchs are often not acknowledged as segmented bilaterians. Yet, morphological studies have shown a conserved segmental arrangement of ectodermal and mesodermal organ systems with spatial correspondence along the anterior-posterior axis. However, a few aberrant kinorhynch lineages present a worm-like body plan with thin cuticle and less distinct segmentation, and thus their study may aid to shed new light on the evolution of segmental patterns within Kinorhyncha. RESULTS: Here we found the nervous system in the aberrant Cateria styx and Franciscideres kalenesos to be clearly segmental, and similar to those of non-aberrant kinorhynchs; hereby not mirroring their otherwise aberrant and posteriorly shifted myoanatomy. In Zelinkaderes yong, however, the segmental arrangement of the nervous system is also shifted posteriorly and misaligned with respect to the cuticular segmentation. CONCLUSIONS: The morphological disparity together with the distant phylogenetic positions of F. kalenesos, C. styx and Z. yong support a convergent origin of aberrant appearances and segmental mismatches within Kinorhyncha.

Geographical sampling bias on the assessment of endemism areas for marine meiobenthic fauna.

Species distribution patterns are constrained by historical and ecological processes in space and time, but very often the species range sizes are geographical sampling biases resulting from unequal sampling effort. One of the most common definitions of endemism is based on the "congruence of distributional areas" criterion, when two or more species have the same distributional limits. By acknowledging that available data of marine meiobenthic species are prone to geographical sampling bias and that can affect the accuracy of the biogeographical signals, the present study combines analyses of inventory incompleteness and recognition of spatial congruence of Gastrotricha, Kinorhyncha, meiobenthic Annelida and Tardigrada in order to better understand the large-scale distribution of these organisms in coastal and shelf areas of the world. We used the marine bioregionalization framework for geographical operative units to quantify the inventory incompleteness effect (by modelling spatial predictions of species richness) and to recognize areas of endemism. Our models showed that the difference between observed and expected species richness in the Southern Hemisphere is much higher than in the Northern Hemisphere. Parsimony Analysis of Endemicity delimited 20 areas of endemism, most found in the Northern Hemisphere. Distribution patterns of meiobenthic species are shown to respond to events of geographical barriers and abiotic features, and their distribution is far from homogeneous throughout the world. Also, our data show that ecoregions with distinct biotas have at least some cohesion over evolutionary time. However, we found that inventory incompleteness may significantly affect the explanatory power of areas of endemism delimitation in both hemispheres. Yet, whereas future increases in sampling efforts are likely to change the spatial congruence ranges in the Southern Hemisphere, patterns for the Northern Hemisphere may prove to be relatively more resilient.

Metabolic improvement with short-term, glucagon-like peptide-1 receptor agonist treatment does not improve cardiac diastolic dysfunction in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial.

AIM: To investigate if short-term treatment with liraglutide, a glucagon-like peptide-1 receptor agonist, improves left ventricular diastolic function. MATERIALS AND METHODS: An investigator-initiated, double-blind, randomized, placebo-controlled trial on the effect of 18 weeks of treatment with liraglutide on diastolic function was assessed in patients with type 2 diabetes with signs of diastolic dysfunction (echo-Doppler determined E/e' ≥ 9 and/or lateral e' ≤ 10 cm/s). Primary outcomes were improved left ventricle filling (the early peak filling rate [ePFR]) and left atrium ease of emptying (the passive emptying fraction [LAPEF ]), assessed by cardiac magnetic resonance imaging at rest and during chronotropic stress. Secondary outcomes included left ventricular and left atrial volumes and systolic function, measures of aortic stiffness and echocardiographic diastolic variables. RESULTS: Forty patients were randomized to liraglutide subcutaneously 1.8 mg/day (n = 20) or placebo (n = 20). Liraglutide reduced HbA1c (-0.47%, 95% CI [-0.88% to -0.06%] [-5.1, 95% CI {-9.7 to -0.62} mmol/mol]) and weight (-2.9, 95% CI [-4.6 to -1.2] kg); both P < .03. Liraglutide did not change ePFR at rest (-24 ± 60 vs. -6 ± 46 mL/s), during stress (2 ± 58 vs. -2 ± 38 mL/s), or the changes from rest to stress (12.9 ± 72.5 vs. 4.7 ± 104.0; all P > .05). LAPEF decreased with liraglutide during stress (-3.1% [-9.0%, 1.1%] vs. 1.0% [-2.9%, 6.1%]; P = .049), but no changes were evident at rest (-4.3% [-7.9%, 1.9%] vs. -0.6% [-3.1%, 2.2%]; P = .19), or for the changes from rest to stress (-1.7 ± 8.4 vs. 0.8 ± 8.2; P = .4). Secondary outcomes were unchanged by liraglutide. CONCLUSIONS: Short-term treatment with liraglutide did not improve left ventricular diastolic function, suggesting the cardioprotective effect is not exerted through the improvement in diastolic dysfunction.

Effects of feeding level, milking frequency, and single injection of cabergoline on feed intake, milk yield, milk leakage, and clinical udder characteristics during dry-off in dairy cows.

Abrupt and gradual dry-off strategies by reducing feeding level (normal vs. reduced energy density), reducing milking frequency (twice vs. once daily), and administration of a dopamine agonist after last milking (i.m. saline vs. cabergoline injection) were investigated (2 × 2 × 2 factorial arrangement) for their effects on feed intake, milk yield, energy balance, milk leakage, and clinical udder characteristics in 119 Holstein cows. In the last week before dry-off, cows were assigned to 1 of 4 combinations of feeding level and milking frequency. Within 3 h after last milking, cows were injected with either saline or a dopamine agonist (cabergoline; Velactis, Ceva Santé Animale; labeled for use only with abrupt dry-off, i.e., no preceding reduction in feeding level or milking frequency before last milking). After dry-off, all cows were fed the same diet for dry cows, and data collection continued for a week. Dry matter intake (DMI) was recorded in automated feed bins and milk yield in an automatic milking system where additional concentrate was fed. Clinical udder characteristics and milk leakage were scored 10 times during the week before and the week after dry-off. Before dry-off, total DMI decreased with reduced feeding level compared with normal feeding level, but did not differ between milking frequencies. The combined effect of reduced DMI and diet energy concentration resulted in a 47% lower net energy intake with reduced feeding level compared with normal feeding level during the week before dry-off. Milk yield was approximately 30% lower during the week before dry-off when either feeding level or milking frequency was reduced compared with no change in feeding level or milking frequency, whereas milk yield was 45% lower when both feeding level and milking frequency were reduced. The net energy balance during the week before dry-off was negative with reduced feeding level and more negative when combined with twice-daily milking. After dry-off, udder engorgement was reduced in the 3 gradual dry-off treatments compared with abrupt dry-off. Cabergoline injection after last milking resulted in least udder engorgement and signs of milk leakage for 48 h, but also resulted in abrupt reduction of DMI lasting approximately 24 h irrespective of treatment before dry-off. In conclusion, gradual cessation of lactation by reducing milking frequency to once daily without reducing the feeding level decreased milk yield before dry-off in high-yielding dairy cows and reduced udder engorgement after dry-off without inducing negative energy balance during the period of dry-off. In contrast, reduced feeding level induced negative energy balance, which may compromise welfare due to metabolic stress and hunger. No clear differences in risk of milk leakage after dry-off were observed between abrupt and gradual dry-off management strategies. Use of cabergoline led to fewer signs of milk leakage and reduced udder engorgement during the first days after dry-off, which may positively affect welfare at dry-off. However, the mechanism behind and the welfare consequences of the concomitant abrupt decrease in DMI lasting approximately 24 h needs further investigation to complete our understanding of dopamine agonist use for dry-off.

Distinct non-ischemic myocardial late gadolinium enhancement lesions in patients with type 2 diabetes.

BACKGROUND: Cardiovascular magnetic resonance imaging (CMR) have described localised non-ischemic late gadolinium enhancement (LGE) lesions of prognostic importance in various non-ischemic cardiomyopathies. Ischemic LGE lesions are prevalent in diabetes (DM), but non-ischemic LGE lesions have not previously been described or systematically studied in DM. METHODS: 296 patients with type 2 DM (T2DM) and 25 sex-matched control subjects underwent echocardiography and CMR including adenosine-stress perfusion, T1-mapping and LGE. RESULTS: 264 patients and all control subjects completed the CMR protocol. 78.4% of patients with T2DM had no LGE lesions; 11.0% had ischemic LGE lesions only; 9.5% had non-ischemic LGE lesions only; and 1.1% had both one ischemic and one non-ischemic lesion. The non-ischemic LGE lesions were situated mid-myocardial in the basal lateral or the basal inferolateral part of the left ventricle and the affected segments showed normal to high wall thickness and normal contraction. Patients with non-ischemic LGE lesions in comparison with patients without LGE lesions had increased myocardial mass (150 ± 34 vs. 133 ± 33 g, P = 0.02), average E/e'(9.9 IQR8.7-12.6 vs. 8.8 IQR7.4-10.7, P = 0.04), left atrial maximal volume (102 IQR84.6-115.2 vs. 91 IQR75.2-100.0 mL, P = 0.049), NT-proBNP (8.9 IQR5.9-19.7 vs. 5.9 IQR5.9-10.1 µmol/L, P = 0.02) and high-sensitive troponin (15.6 IQR13.0-26.1 vs. 13.0 IQR13.0-14.6 ng/L, P = 0.007) and a higher prevalence of retinopathy (48 vs. 25%, P = 0.009) and autonomic neuropathy (52 vs. 30.5%, P = 0.005). CONCLUSION: A specific LGE pattern with lesions in the basal lateral or the basal inferolateral part of the left ventricle was found in patients with type 2 diabetes. Trial registration https://www.clinicaltrials.gov . Unique identifier: NCT02684331.

Fibroblast growth factor-23 is associated with imaging markers of diabetic cardiomyopathy and anti-diabetic therapeutics.

BACKGROUND: The biomarker fibroblast growth factor-23 (FGF-23) has been associated with increased cardiovascular morbidity and mortality in both patients with and without type 2 diabetes. The aim of this study was to evaluate the relationship between FGF-23 and cardiac structure, function and perfusion in patients with type 2 diabetes and normal or mildly impaired kidney function. Furthermore, to investigate the association between FGF-23, anti-diabetes therapy and the classic complications and risk factors associated with type 2 diabetes. METHODS: In this cross-sectional study, 246 patients with type 2 diabetes underwent echocardiography and advanced cardiac magnetic resonance imaging to assess left ventricular (LV) structure and function. In addition, myocardial blood flow (MBF) during rest and pharmacological stress (adenosine 140 µg/kg/min) were evaluated in 183 of the patients. Patients with eGFR < 60 ml/min/1.73 m2 were excluded. RESULTS: Median (Q1-Q3) FGF-23 was 74 (58-91) ng/L. Patients with FGF-23 above the median had lower MBF during stress (2.3 ± 0.9 vs. 2.7 ± 0.9 ml/min/g, P = 0.001) and lower overall myocardial perfusion reserve (MPR) (2.7 ± 0.8 vs. 3.3 ± 1.1, P < 0.001). LV mass (143 ± 40 vs. 138 ± 36 g, P = 0.04) and E/e* (8.5 ± 3.2 vs. 7.6 ± 2.7, P = 0.04) were higher in patients with FGF-23 above the median. In a linear model adjusted for age, sex, eGFR and hypertension, increasing FGF-23 was associated with decreased MPR (P < 0.01, R2 = 0.11) and increased E/e* (P < 0.01, R2 = 0.07). FGF-23 was lower in patients receiving glucagon like peptide-1 (GLP-1) analogues (71 (57-86) vs. 80 (60-98) ng/L, P = 0.01) than in those who did not receive GLP-1 analogues. CONCLUSIONS: In patients with type 2 diabetes and normal or mildly impaired kidney function, increased levels of FGF-23 are associated with impaired cardiac diastolic function and decreased MPR, caused by a decrease in maximal MBF during stress. Use of GLP-1 analogues is associated with decreased levels of FGF-23. Clinical trial registration https://www.clinicaltrials.gov . Unique identifier: NCT02684331. Date of registration: February 18, 2016.

Changes in long-chain fatty acid composition of milk fat globule membrane and expression of mammary lipogenic genes in dairy cows fed sunflower seeds and rumen-protected choline.

The aim of this experiment was to investigate the effect of dietary supplementation of crushed high oleic sunflower seeds (HOS) and rumen-protected choline (RPC) on the fatty acid (FA) profile of phospholipids and sphingomyelin and mammary transcription of genes that are important for milk fat synthesis and de novo synthesis of sphingolipids. Twenty-four cows were divided into four groups that either received an unsupplemented diet (Control), the Control diet supplemented with 50 g RPC per day, a diet supplemented with HOS at 10% of dry matter, or RPC and HOS in combination (RPC + HOS). RPC supplementation had no effect on the FA composition of milk or sphingomyelin. Cows receiving RPC and RPC + HOS had increased incorporation of C22:5 (n-3) into phospholipids. Milk FA proportion of C18:0 and C18:1 isomers was increased in cows receiving HOS (HOS and RPC + HOS). Sphingomyelin proportion of C22:0 was increased in cows receiving HOS and RPC + HOS, at the expense of C23:0. HOS supplementation further increased the proportion of unsaturated fatty acids (UFA) in milk phospholipids. HOS supplementation increased mammary transcription of UDP-glucose ceramide glycosyltransferase (UGCG), sterol response element-binding protein cleavage-activating protein (SCAP) and peroxisome proliferation-activated receptor Gamma subunit C 1b (PPARGC1b), and reduced transcription of insulin induced gene 1 (INSIG1) and fatty acid-binding protein 3 (FABP3). Dietary supplementation of RPC increased mammary transcription of fatty acid desaturase 1 (FADS1) and longevity assurance gene 2 (LASS2), and reduced transcription of sphingomyelin synthase (SGMS). The results show that the FA profile of milk phospholipids is sensitive to dietary lipid supplementation and, to a minor degree, RPC supplementation. Furthermore, transcription of genes that are important for milk fat synthesis and sphingolipids synthesis is affected by dietary supplementation of RPC and HOS.

A preliminary validation of a Norwegian version of the Tinnitus Sample Case History Questionnaire.

At present there is no validated tinnitus questionnaire available in Norway. The aim of the present study was to psychometrically evaluate and report on a Norwegian translation of the Tinnitus Sample Case History Questionnaire (TSCHQ). Furthermore, the results were compared to those of a recent Swedish validation of TSCHQ. More than two hundred (N = 218) participants with tinnitus participated in the study, of which 78% completed the Norwegian TSCHQ on two occasions so that test-retest reliability could be evaluated. Results show that the Norwegian TSCHQ has acceptable test-retest reliability with the exception of 10 items, which is slightly better than the recent Swedish validation of TSCHQ. At the item level, there were both similarities and differences between the Norwegian and Swedish validation studies. It is concluded that the Norwegian TSCHQ is an appropriate measure of patients' history and experience of tinnitus, and while we recommend further validation of the Norwegian TSCHQ, we encourage Norwegian researchers and clinicians to use the Norwegian translation of TSCHQ.

Revisiting metazoan phylogeny with genomic sampling of all phyla.

Proper biological interpretation of a phylogeny can sometimes hinge on the placement of key taxa-or fail when such key taxa are not sampled. In this light, we here present the first attempt to investigate (though not conclusively resolve) animal relationships using genome-scale data from all phyla. Results from the site-heterogeneous CAT + GTR model recapitulate many established major clades, and strongly confirm some recent discoveries, such as a monophyletic Lophophorata, and a sister group relationship between Gnathifera and Chaetognatha, raising continued questions on the nature of the spiralian ancestor. We also explore matrix construction with an eye towards testing specific relationships; this approach uniquely recovers support for Panarthropoda, and shows that Lophotrochozoa (a subclade of Spiralia) can be constructed in strongly conflicting ways using different taxon- and/or orthologue sets. Dayhoff-6 recoding sacrifices information, but can also reveal surprising outcomes, e.g. full support for a clade of Lophophorata and Entoprocta + Cycliophora, a clade of Placozoa + Cnidaria, and raising support for Ctenophora as sister group to the remaining Metazoa, in a manner dependent on the gene and/or taxon sampling of the matrix in question. Future work should test the hypothesis that the few remaining uncertainties in animal phylogeny might reflect violations of the various stationarity assumptions used in contemporary inference methods.

Serum perfluoroalkyl substances (PFAS) and risk of asthma and various allergies in adolescents. The Tromsø study Fit Futures in Northern Norway.

BACKGROUND: Exposure to environmental pollutants may contribute to the development of asthma and other allergies. The aim of this study was to investigate possible associations between asthma and other allergies with exposure to perfluoroalkyl substances (PFASs) in adolescents from the Arctic region of Norway. METHODS: The Tromsø study Fit Futures 1 (TFF1) and 3-year follow-up Fit Futures 2 study (TFF2) included 675 adolescents that completed a questionnaire about health conditions and underwent a clinical examination with blood tests and fractional nitric oxide (FeNO) measurement. Serum concentrations of 18 PFASs were measured by UHPLC-MS/MS method. RESULTS: Total PFASs (ΣPFAS) serum concentration over 4th quartile was positively associated with asthma in the TFF1 (OR 3.35 (95% CI 1.54-7.29), p = 0.002). Total perfluorooctane sulfonate (ΣPFOS), linear PFOS (linPFOS), linear perfluorohexane sulfonate (linPFHxS) concentrations over 4th quartiles were associated with 2 times higher odds of asthma in the TFF1. The positive associations between ΣPFAS, ΣPFOS, linPFOS and asthma remained statistically significant in the TFF2. ΣPFAS and linPFHxS concentrations over 3rd tertiles were associated with positive marker of eosinophilic airways inflammation FeNO> 25 ppb. Concentrations of ΣPFOS and linPFOS over 3rd quartiles were positively associated with self-reported nickel allergy (OR 2.25 (95% CI 1.17-4.35) p = 0.016 and OR 2.53 (95% CI 1.30-4.90) p = 0.006, respectively). Allergic rhinitis, self-reported pollen allergy, food allergy and atopic eczema were not associated with PFASs concentrations. CONCLUSIONS: This study of Norwegian adolescents showed a positive association between several PFASs and asthma, as well as between PFOS and nickel allergy.

Molecular palaeontology illuminates the evolution of ecdysozoan vision.

Colour vision is known to have arisen only twice-once in Vertebrata and once within the Ecdysozoa, in Arthropoda. However, the evolutionary history of ecdysozoan vision is unclear. At the molecular level, visual pigments, composed of a chromophore and a protein belonging to the opsin family, have different spectral sensitivities and these mediate colour vision. At the morphological level, ecdysozoan vision is conveyed by eyes of variable levels of complexity; from the simple ocelli observed in the velvet worms (phylum Onychophora) to the marvellously complex eyes of insects, spiders, and crustaceans. Here, we explore the evolution of ecdysozoan vision at both the molecular and morphological level; combining analysis of a large-scale opsin dataset that includes previously unknown ecdysozoan opsins with morphological analyses of key Cambrian fossils with preserved eye structures. We found that while several non-arthropod ecdysozoan lineages have multiple opsins, arthropod multi-opsin vision evolved through a series of gene duplications that were fixed in a period of 35-71 million years (Ma) along the stem arthropod lineage. Our integrative study of the fossil and molecular record of vision indicates that fossils with more complex eyes were likely to have possessed a larger complement of opsin genes.