Transcriptome profiling reveals morphogenesis-related candidate genes and pathways in the chick embryonic small intestine.

1. A better understanding of intestinal development is essential for the intestinal health of poultry. Intestinal villification starts on embryo day E15 and is generally completed before hatching (E21). The development of lymphoid organs in the intestine starts during embryogenesis. However, transcriptional information on the processing of intestinal morphogenesis and immune development during chick embryogenesis is limited.2. In this work, RNA-sequencing was performed using 12 biological replicates to investigate Hy-Line brown chick embryonic small intestinal transcription at E15 and E21. Differentially expressed genes (DEGs) between E15 and E21 were identified. GO and KEGG enrichment analyses, based on the DEGs, were performed to identify key GO terms in the biological process category and key KEGG pathways. PPI networks were constructed based on the DEGs in the key pathways to screen hub genes. The embryonic small intestinal morphology and IgA distribution were observed by histological processing. The serum levels of IgA and lysozyme were measured by ELISA.3. A total of 76.38 Gb of high-quality RNA-sequencing data were generated and uploaded. A total of 2,676 DEGs, between E15 and E21, were identified. Structural development and villification of the small intestine at E15 tended to proceed via the expression of nervous system development-related genes. A combination of the histological and serological results with the transcriptome data indicated that the identified genes and pathways may be strong candidates for intestinal morphogenesis-regulation.4. The small intestine appears to have developed a relatively complete morphology and transport, metabolism, digestion and immunity functions by E21. This work provided a transcriptome profile of the chick embryonic small intestine and provided insights into the intestinal development and health of poultry.

Intravenous thrombolysis in wake-up stroke: real-world data from the Austrian Stroke Unit Registry.

BACKGROUND AND PURPOSE: Data on real-world experience with intravenous thrombolysis (IV tPA) in wake-up stroke (WUS) are limited. The aim of this study was to examine the efficacy and safety of IV tPA in patients with WUS included in the Austrian Stroke Unit Registry. METHODS: Data from a large nationwide stroke unit registry including initial stroke severity, vascular risk factors, comorbidities, treatment with IV tPA, symptomatic intracerebral haemorrhage (sICH) and functional outcome were extracted and analysed. Patients with WUS were compared with patients with known-onset stroke (KOS) regarding the frequency of IV tPA treatment, neurological improvement (National Institutes of Health Stroke Scale score ≥4), sICH and 3-month functional outcome by modified Rankin Scale score using standard statistical tests. RESULTS: A total of 107 895 stroke patients entered the analysis, including 12 534 with WUS and 91 899 with KOS. Altogether, 904 (7.2%) patients with WUS received IV tPA as compared with 16 694 (18.2%) patients with KOS. Patients with WUS who received IV tPA treatment had twofold higher initial National Institutes of Health Stroke Scale score (median 8 vs. median 4) as compared with patients with KOS. There was no statistical difference in functional outcome by modified Rankin Scale score 0-1 at 3 months between patients with WUS and patients with KOS treated with IV tPA (adjusted odds ratio, 1.08; 95% confidence interval, 0.9-1.31). Also, the rate of sICH did not differ (4.1% vs. 4%, P = 0.852). CONCLUSIONS: In this large non-randomized comparison, the safety and efficacy of IV tPA in patients with WUS in the real-world setting seems to be comparable to patients with KOS.

Familial hypercholesterolaemia in patients with ischaemic stroke or transient ischaemic attack.

BACKGROUND AND PURPOSE: Identification of patients with familial hypercholesterolaemia (FH) is a prerequisite for the appropriate management of their excess cardiovascular risk. It is currently unknown how many patients with acute ischaemic stroke or transient ischaemic attack (TIA) are affected by FH and whether systematic screening for FH is warranted in these patients. METHODS: The prevalence of a clinical diagnosis of FH was estimated in a large representative series of patients with acute ischaemic stroke or TIA (ABCD2 score ≥ 3) using the Dutch Lipid Clinic Network Algorithm (DLCNA; possible FH ≥3, probable/definite FH ≥6). RESULTS: Out of 1054 patients included in the present analysis, 14 had probable/definite FH (1.3%; 95% confidence interval 0.6-2.0) and 107 possible FH (10.2%; 8.4-12.0) corresponding to an overall prevalence of potential FH of 11.5%. Prevalences were even higher in patients with stroke/TIA manifestation before age 55 in men or 60 in women (3.1%, 0.6-5.6; and 13.1%, 8.3-17.9) and those with a prior history of cardiovascular disease (2.6%, 0.9-4.3; and 15.1%, 11.3-18.9). Of note, in two-thirds of our patients with probable/definite and possible FH, stroke or TIA was the initial clinical disease manifestation. CONCLUSIONS: The frequency of potential FH, based on clinical criteria, in patients with acute ischaemic stroke or TIA was 11.5% and that of probable/definite FH (1.3%) was similar to recently reported counts for patients with acute coronary syndrome (1.6%). FH screening using the DLCNA is feasible in clinical routine and should be considered as part of the usual diagnostic work-up.

Validation of EORTC QLQ-OES18 for Chinese patients with esophageal cancer.

The aim of this study is to evaluate the reliability, validity, and acceptability of the Chinese version of the EORTC QLQ-OES18 in patients with esophageal cancer. The questionnaire was translated according to the guideline of the EORTC. One hundred and forty-nine patients with esophageal cancer from Tianjin Medical University Cancer Institute and Hospital completed the Karnofsky performance scale (KPS) and the simplified Chinese EORTC QLQ-C30/OES18 scales during July 2013 to January 2014. The results were statistically analyzed by Cronbach's α coefficient, Spearman correlation test with multiple strengthen analysis, and Wilcoxon Rank Sum test. The internal consistency (Cronbach's α coefficient) of all four scales (dysphagia, eating, reflux, and pain) was 0.689-0.822, which were satisfactory or near satisfactory. The absolute values of correlation of each scale between EORTC QLQ-OES18 and EORTC QLQ-C30 were 0.002-0.750 while there was no significant difference between groups divided by KPS scores. We confirmed the Chinese version of EORTC QLQ-OES18 appears to be a reliable, valid, and acceptable instrument for measuring the health-related quality of life of patients with esophageal cancer in mainland China.

Endovascular stroke therapy in Austria: a nationwide 1-year experience.

BACKGROUND AND PURPOSE: Based on a tight network of stroke units (SUs) and interventional centres, endovascular treatment of acute major intracranial vessel occlusion has been widely implemented in Austria. Documentation of all patients in the nationwide SU registry has thereby become mandatory. METHODS: Demographic, clinical and interventional characteristics of patients who underwent endovascular treatment for acute ischaemic stroke in 11 Austrian interventional centres between 1 October 2013 and 30 September 2014 were analysed. RESULTS: In total, 301 patients (50.5% women; median age 70.5 years; median National Institutes of Health Stroke Scale score 17) were identified.193 patients (64.1%) additionally received intravenous thrombolysis. The most frequent vessel occlusion sites were the M1 segment of the middle cerebral artery (n = 161, 53.5%), the intracranial internal carotid artery (n = 60, 19.9%) and the basilar artery (n = 40, 13.3%). Stent retrievers were used in 235 patients (78.1%) and adequate reperfusion (modified Thrombolysis in Cerebral Infarction scores 2b and 3, median onset to reperfusion time 254 min) was achieved in 242 patients (81.4%). Symptomatic intracranial haemorrhage occurred in 7%. 43.8% of patients (n = 132) had good functional outcome (modified Rankin Scale score 0-2) and the mortality rate was 20.9% (n = 63) after 3 months. Compared to the anterior circulation, vertebrobasilar stroke patients had higher mortality. Patients with secondary hospital transportation had better outcomes after 3 months than in-house treated patients. CONCLUSION: Our results document nationwide favourable outcome and safety rates of endovascular stroke treatment comparable to recent randomized trials. The ability to provide such data and the need to further optimize such an approach also underscore the contribution of respective registries.

A randomized, placebo-controlled, double-blind study of sapropterin to treat ADHD symptoms and executive function impairment in children and adults with sapropterin-responsive phenylketonuria.

Symptoms of attention deficit-hyperactivity disorder (ADHD), particularly inattention, and impairments in executive functioning have been reported in early and continuously treated children, adolescents, and adults with phenylketonuria (PKU). In addition, higher blood phenylalanine (Phe) levels have been correlated with the presence of ADHD symptoms and executive functioning impairment. The placebo-controlled PKU ASCEND study evaluated the effects of sapropterin therapy on PKU-associated symptoms of ADHD and executive and global functioning in individuals who had a therapeutic blood Phe response to sapropterin therapy. The presence of ADHD inattentive symptoms and executive functioning deficits was confirmed in this large cohort of 206 children and adults with PKU, of whom 118 responded to sapropterin therapy. In the 38 individuals with sapropterin-responsive PKU and ADHD symptoms at baseline, sapropterin therapy resulted in a significant improvement in ADHD inattentive symptoms in the first 4 weeks of treatment, and improvements were maintained throughout the 26 weeks of treatment. Sapropterin was well-tolerated with a favorable safety profile. The improvements in ADHD inattentive symptoms and aspects of executive functioning in response to sapropterin therapy noted in a large cohort of individuals with PKU indicate that these symptoms are potentially reversible when blood Phe levels are reduced.

Daily insulin doses and injection frequencies of neutral protamine hagedorn (NPH) insulin, insulin detemir and insulin glargine in type 1 and type 2 diabetes: a multicenter analysis of 51 964 patients from the German/Austrian DPV-wiss database.

BACKGROUND: We performed a comparative analysis of the use of long-acting insulin (analogues) neutral protamine hagedorn (NPH), detemir (Det) and glargine (Gla), and quantified injection frequencies and daily insulin doses in patients with type 1 and 2 diabetes in daily practice. METHODS: A total number of 51 964 patients from 336 centres in Germany and Austria with type 1 and 2 diabetes with exclusive insulin therapy were retrospectively analysed. RESULTS: A total number of 42.1%/75.9% (type 1/type 2) of patients used NPH, 19.9%/6.7% Det and 38.0%/17.4% Gla, with similar glycaemic control and proportion of severe hypoglycaemia for NPH/Det/Gla in type 1 (Mean HbA(1c) 7.98%/7.98%/8.07%; mean proportion of severe hypoglycaemia 11.06%/11.93%/10.86%) and type 2 diabetes (Mean HbA(1c) 7.61%/7.78%/7.61%; mean proportion of severe hypoglycaemia 5.66%/4.48%/5.03%). In type 1 diabetes, the mean daily injection frequencies of NPH versus Det versus Gla were 1.9 vs 1.8 vs 1.1, and total daily insulin injections were 5.3 vs 5.6 vs 5.0. The adjusted mean daily basal insulin doses were 0.36, 0.39 and 0.31 IU/kg, mean daily total insulin dose was lowest for Gla (0.74 IU/kg), followed by NPH (0.76 IU/kg) and Det (0.81 IU/kg). In type 2 diabetes patients, mean daily injection frequencies were 1.6 for NPH, 1.4 for Det and 1.1 for Gla, total daily insulin injections were 4.0 vs 4.1 vs 3.6. The mean daily basal insulin dosages were 0.30 IU/kg (NPH), 0.33 IU/kg (Det) and 0.29 IU/kg (Gla), mean total insulin doses per day were 0.63 IU/kg (NPH), 0.77 IU/kg (Det) and 0.67 IU/kg (Gla). CONCLUSIONS: In a 'real-world' setting, the injection frequencies and doses of basal and total insulin per day are lowest with the use of insulin glargine compared with NPH-insulin or insulin detemir at similar glycaemic control and rates of severe hypoglycaemia.

Measuring teacher dispositions using the DAATS battery: a multifaceted Rasch analysis of rater effect.

The purpose of this study was to examine the extent to which raters' subjectivity impacts measures of teacher dispositions using the Dispositions Assessments Aligned with Teacher Standards (DAATS) battery. This is an important component of the collection of evidence of validity and reliability of inferences made using the scale. It also provides needed support for the use of subjective affective measures in teacher training and other professional preparation programs, since these measures are often feared to be unreliable because of rater effect. It demonstrates the advantages of using the Multi-Faceted Rasch Model as a better alternative to the typical methods used in preparation programs, such as Cohen's Kappa. DAATS instruments require subjective scoring using a six-point rating scale derived from the affective taxonomy as defined by Krathwohl, Bloom, and Masia (1956). Rater effect is a serious challenge and can worsen or drift over time. Errors in rater judgment can impact the accuracy of ratings, and these effects are common, but can be lessened through training of raters and monitoring of their efforts. This effort uses the multifaceted Rasch measurement models (MFRM) to detect and understand the nature of these effects.

A thiocarbamate inhibitor of endothelial lipase raises HDL cholesterol levels in mice.

By screening directed libraries of serine hydrolase inhibitors using the cell surface form of endothelial lipase (EL), we identified a series of carbamate-derived (EL) inhibitors. Compound 3 raised plasma HDL-C levels in the mouse, and a correlation was found between HDL-C and plasma compound levels. Spectroscopic and kinetic studies support a covalent mechanism of inhibition. Our findings represent the first report of EL inhibition as an effective means for increasing HDL-C in an in vivo model.

[Extended skin and soft tissue defects after vascular wounds: plastic surgical concepts]. / Ausgedehnte Gewebedefekte bei vaskulären Wunden--Möglichkeiten der plastischen Chirurgie.

INTRODUCTION: Skin and soft-tissue defects at the ischaemic lower extremity represent a challenging condition. Major amputations can be prevented by optimised surgical therapy. The aim of any intervention is the revascularisation and defect reconstruction of the extremity. METHODS: This article aims to provide a structured overview on up-to-date therapeutic strategies and differentiated indications for certain surgical flaps in combination with bypass surgery for the treatment of chronic "vascular" wounds. RESULTS: Optimised conservative wound therapy, skin grafts, pedicled or microsurgical free flaps in combination with vascular bypasses can be applied to salvage ischaemic extremities. These operations require an interdisciplinary cooperation between vascular surgeons and plastic surgeons. DISCUSSION: These procedures should accordingly only be performed in specialised high-volume centres with significant vascular surgical and microsurgical expertise.

Effects of Vitamin D, Omega-3 Fatty Acids and a Home Exercise Program on Prevention of Pre-Frailty in Older Adults: The DO-HEALTH Randomized Clinical Trial.

BACKGROUND: The benefits of supplemental vitamin D3, marine omega-3 fatty acids, and a simple home exercise program (SHEP) on frailty prevention in generally healthy community-dwelling older adults are unclear. OBJECTIVE: To test the effect of vitamin D3, omega-3s, and a SHEP, alone or in combination on incident pre-frailty and frailty in robust older adults over a follow-up of 36 months. METHODS: DO-HEALTH is a multi-center, double-blind, placebo-controlled, 2x2x2 factorial randomized clinical trial among generally healthy European adults aged 70 years or older, who had no major health events in the 5 years prior to enrollment, sufficient mobility and intact cognitive function. As a secondary outcome of the DO-HEALTH trial, among the subset of participants who were robust at baseline, we tested the individual and combined benefits of supplemental 2,000 IU/day of vitamin D3, 1 g/day of marine omega-3s, and a SHEP on the odds of being pre-frail and frail over 3 years of follow-up. RESULTS: At baseline, 1,137 out of 2,157 participants were robust (mean age 74.3 years, 56.5% women, mean gait speed 1.18 m/s). Over a median follow-up time of 2.9 years, 696 (61.2%) became pre-frail and 29 (2.6%) frail. Odds ratios for becoming pre-frail were not significantly lower for vitamin D3, or omega 3-s, or SHEP, individually, compared to control (placebo for the supplements and control exercise). However, the three treatments combined showed significantly decreased odds (OR 0.61 [95% CI 0.38-0.98; p=0.04) of becoming pre-frail compared to control. None of the individual treatments or their combination significantly reduced the odds of becoming frail. CONCLUSION: Robust, generally healthy and active older adults without major comorbidities, may benefit from a combination of high-dose, supplemental vitamin D3, marine omega-3s, and SHEP with regard to the risk of becoming pre-frail over 3 years.

Cryobiopsy increases the diagnostic yield of endobronchial biopsy: a multicentre trial.

Forceps, brushes or needles are currently the standard tools used during flexible bronchoscopy when diagnosing endobronchial malignancies. The new biopsy technique of cryobiopsy appears to provide better diagnostic samples. The aim of this study was to evaluate cryobiopsy over conventional endobronchial sampling. A total of 600 patients in eight centres with suspected endobronchial tumours were included in a prospective, randomised, single-blinded multicentre study. Patients were randomised to either sampling using forceps or the cryoprobe. After obtaining biopsy samples, a blinded histological evaluation was performed. According to the definitive clinical diagnosis, the diagnostic yield for malignancy was evaluated by a Chi-squared test. A total of 593 patients were randomised, of whom 563 had a final diagnosis of cancer. 281 patients were randomised to receive endobronchial biopsies using forceps and 282 had biopsies performed using a flexible cryoprobe. A definitive diagnosis was achieved in 85.1% of patients randomised to conventional forceps biopsy and 95.0% of patients who underwent cryobiopsy (p<0.001). Importantly, there was no difference in the incidence of significant bleeding. Endobronchial cryobiopsy is a safe technique with superior diagnostic yield in comparison with conventional forceps biopsy.

Multiple complications and frequent severe hypoglycaemia in 'elderly' and 'old' patients with Type 1 diabetes.

AIM: Elderly and old patients with Type 1 diabetes represent a growing population that requires thorough diabetes care. The increasing relevance of this subgroup, however, plays only a minor role in the literature. Here, we describe elderly patients with Type 1 diabetes on the basis of a large multi-centre database in order to point out special features of this population. METHOD: Data of 64609 patients with Type 1 diabetes treated by 350 qualified diabetes treatment centres were assessed and analysed by age group. RESULTS: Compared with the age group ≤ 60 years, patients aged >60 years (n=3610 61-80 years and n=377 >80 years old) were characterized by a longer diabetes duration (27.7 vs. 7.7 years), an almost double risk for severe hypoglycaemia (40.1 vs. 24.3/100 patient-years), a lower level of HbA(1c) [60 vs. 67 mmol/mol (7.6 vs. 8.3%)] and higher percentages of microalbuminuria (34.5 vs. 15.6%), diabetic retinopathy (45.2 vs. 8.3%), myocardial infarction (9.0 vs. 0.4%) or stroke (6.8 vs. 0.3%). Elderly patients used insulin pumps less frequently (12.2 vs. 23.8%), but more often used conventional premixed insulin treatment (10.8 vs. 3.8%). Differences between elderly and younger patient groups were significant, respectively. CONCLUSION: Diabetes care of elderly patients with Type 1 diabetes involves individualized treatment concepts. Increased hypoglycaemia risk and functional impairment attributable to diabetes-associated and/or age-related disorders must be taken into account.

High velocity vortex channeling in vicinal YBCO thin films.

We report on electrical transport measurements at high current densities on optimally doped YBa2Cu3O7-δ thin films grown on vicinal SrTiO3 substrates. Data were collected by using a pulsed-current technique in a four-probe arrangement, allowing to extend the current-voltage characteristics to high supercritical current densities (up to 24 MA cm-2) and high electric fields (more than 20 V/cm), in the superconducting state at temperatures between 30 and 80 K. The electric measurements were performed on tracks perpendicular to the vicinal step direction, such that the current crossed between ab planes, under magnetic field rotated in the plane defined by the crystallographic c axis and the current density. At magnetic field orientation parallel to the cuprate layers, evidence for the sliding motion along the ab planes (vortex channeling) was found. The signature of vortex channeling appeared to get enhanced with increasing electric field, due to the peculiar depinning features in the kinked vortex range. They give rise to a current-voltage characteristics steeper than in the more off-plane rectilinear vortex orientations, in the electric field range below approximately 1 V/cm. Roughly above this value, the high vortex channeling velocities (up to 8.6 km/s) could be ascribed to the flux flow, although the signature of ohmic transport appeared to be altered by unavoidable macroscopic self-heating and hot-electron-like effects.

Thrombolytic therapy for acute stroke in Austria: data from the Safe Implementation of Thrombolysis in Stroke (SITS) register.

BACKGROUND: We aimed at determining the safety and efficacy of IV alteplase in Austrian versus non-Austrian centres as documented in the Internet-based registers Safe Implementation of Thrombolysis for Stroke - MOnitoring STudy (SITS-MOST) and - International Stroke Thrombolysis Register (SITS-ISTR). METHODS: We analysed patient data entered in the registers SITS-MOST and SITS-ISTR in the period December 2002 to 15 November 2007. RESULTS: Compared to the non-Austrian cohort (n=15153), the Austrian cohort (n=896) was slightly older [median, interquartile range (IQR): 70, 60-77 years vs. 69, 60-76 years, P=0.05] and included more women (44.6% vs. 41.0%, P=0.03). Austrian patients had a significantly shorter stroke onset-to-treatment time (OTT; median, IQR: 135, 105-160 min vs. 145, 115-170 min, P<0.0005). Symptomatic intracerebral haemorrhages were observed in 1.6% of Austrian and 1.7% of non-Austrian patients (P=0.82). At 3 months, 50.8% of Austrian and 53.0% of non-Austrian patients were independent (P=0.23), but death was less frequent in Austrian patients (12.1% vs. 14.9%, P=0.03). Multivariate analyses adjusted for demographic and baseline characteristics confirmed lower mortality at 3 months in the Austrian cohort (odds ratio 0.81, 95% confidence intervals 0.71-0.92, P=0.001). Longer OTT was associated with increased mortality at 3 months, with a hazard ratio of 1.02 (95% CI 1.01-1.03; P=0.005) for each 10-min increase in OTT. CONCLUSIONS: The implementation of intravenous alteplase for acute stroke has been safe and efficacious in Austrian centres. OTT and mortality were significantly lower in Austrian patients compared to non-Austrian SITS centres.

Evaluation of the PC-1 K121Q and G2906C variants as independent risk factors for ischaemic stroke.

UNLABELLED: Overexpression of plasma cell membrane glycoprotein-1 (PC-1) inhibits insulin receptor tyrosine kinase activity and thus favours insulin resistance and atherosclerotic vascular disease. Recent findings indicate that the minor variant K121Q in the PC-1 gene confers an increased risk for early myocardial infarction independent of other established risk factors. We hypothesized that genetic variants in PC-1 may also influence the risk for cerebrovascular disease. AIM: Therefore, we assessed the association of the PC-1 K121Q variant in the coding region and a polymorphism (G2906C) in the 3' untranslated region of the PC-1 gene with the risk of stroke. PATIENTS: We analyzed 1014 patients with a history of ischaemic stroke from the Vienna stroke registry and 1001 control individuals without vascular disease. RESULTS, CONCLUSION: Genotype frequencies of both genetic variants were similar in patients and controls in the total study population. By multivariate analysis, no interactions were observed between the PC-1 genotype and established vascular risk factors. However, the PC-1 2906C allele was significantly more frequent in patients who suffered from stroke before the age of 40 years. In these patients the risk for ischaemic stroke was increased four-fold.