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"text": "\n156456\nMechanical characterization of human brain tissue.\n\nBudday, S\n\nSommer, G\n\nBirkl, C\n\nLangkammer, C\n\nHaybaeck, J\n\nKohnert, J\n\nBauer, M\n\nPaulsen, F\n\nSteinmann, P\n\nKuhl, E\n\nHolzapfel, GA\n\nBeiträge in Fachzeitschriften\nISI:000393247000027\n27989920.0\n10.1016/j.actbio.2016.10.036\nNone\nMechanics are increasingly recognized to play an important role in modulating brain form and function. Computational simulations are a powerful tool to predict the mechanical behavior of the human brain in health and disease. The success of these simulations depends critically on the underlying constitutive model and on the reliable identification of its material parameters. Thus, there is an urgent need to thoroughly characterize the mechanical behavior of brain tissue and to identify mathematical models that capture the tissue response under arbitrary loading conditions. However, most constitutive models have only been calibrated for a single loading mode. Here, we perform a sequence of multiple loading modes on the same human brain specimen - simple shear in two orthogonal directions, compression, and tension - and characterize the loading-mode specific regional and directional behavior. We complement these three individual tests by combined multiaxial compression/tension-shear tests and discuss effects of conditioning and hysteresis. To explore to which extent the macrostructural response is a result of the underlying microstructural architecture, we supplement our biomechanical tests with diffusion tensor imaging and histology. We show that the heterogeneous microstructure leads to a regional but not directional dependence of the mechanical properties. Our experiments confirm that human brain tissue is nonlinear and viscoelastic, with a pronounced compression-tension asymmetry. Using our measurements, we compare the performance of five common constitutive models, neo-Hookean, Mooney-Rivlin, Demiray, Gent, and Ogden, and show that only the isotropic modified one-term Ogden model is capable of representing the hyperelastic behavior under combined shear, compression, and tension loadings: with a shear modulus of 0.4-1.4kPa and a negative nonlinearity parameter it captures the compression-tension asymmetry and the increase in shear stress under superimposed compression but not tension. Our results demonstrate that material parameters identified for a single loading mode fail to predict the response under arbitrary loading conditions. Our systematic characterization of human brain tissue will lead to more accurate computational simulations, which will allow us to determine criteria for injury, to develop smart protection systems, and to predict brain development and disease progression.\n There is a pressing need to characterize the mechanical behavior of human brain tissue under multiple loading conditions, and to identify constitutive models that are able to capture the tissue response under these conditions. We perform a sequence of experimental tests on the same brain specimen to characterize the regional and directional behavior, and we supplement our tests with DTI and histology to explore to which extent the macrostructural response is a result of the underlying microstructure. Results demonstrate that human brain tissue is nonlinear and viscoelastic, with a pronounced compression-tension asymmetry, and we show that the multiaxial data can best be captured by a modified version of the one-term Ogden model.\n Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.\n\nHaybäck, Johannes\n\nLangkammer, Christian\n\n\n"
},
{
"text": "\n4877\nComputerized heart allograft-recipient monitoring: a multicenter study.\n\nGrasser, B\n\nIberer, F\n\nSchreier, G\n\nKastner, P\n\nSchaffellner, S\n\nKniepeiss, D\n\nKleinert, R\n\nMahaux, V\n\nDemoulin, JC\n\nNägele, H\n\nRödiger, W\n\nLaufer, G\n\nGrimm, M\n\nZuckermann, A\n\nWasler, A\n\nPrenner, G\n\nTscheliessnigg, KH\n\nCHARM Multicenter Investigators Group\n\nBeiträge in Fachzeitschriften\nISI:000183161600002\n12730802.0\n10.1007/s00147-002-0530-x\nNone\nComputerized heart allograft recipient monitoring (CHARM) is a unique concept of patient surveillance after heart transplantation (HTx), based on the evaluation of intramyocardial electrograms (IEGMs) recorded non-invasively with telemetric pacemakers. Previous open, single-center studies had indicated a high correlation between CHARM results and clinical findings. The present study was initiated to assess the suitability of CHARM for monitoring the absence of rejection in a blind, multicenter context. During the HTx procedure, telemetric pacemakers and two epimyocardial leads were implanted in 44 patients at four European HTx centers. IEGMs during pacing were recorded and transferred via the Internet to the CHARM computer center, for automatic data processing and extraction of diagnostically relevant information, i.e., the maximum slew rate of the descending part of the repolarization phase of the ventricular evoked response (VER T-slew). The study period comprised the first 6 months after HTx, during which the transplant centers were blind to the CHARM results. A single threshold diagnosis model was prospectively defined to assess the ability of the VER T-slew to indicate clinically significant rejection, which was defined as an endomyocardial biopsy (EMB) grade greater than or equal to 2, according to the grading system of the International Society for Heart and Lung Transplantation. All EMB slides from three centers were reviewed blind by the pathologist of the fourth center in order that agreement among the histological diagnoses at the various centers could be assessed. Totals of 839 follow-ups and 366 EMBs were obtained in 44 patients. Thirty-seven patients were alive at the end of the study period. Age at HTx, EMB grade distribution, and rejection prevalence varied significantly between the centers. Review of the EMB results showed considerable differences with respect to classification of significant rejection. Comparison of average VER T-slew values with and without rejection in the 15 patients who exhibited both states revealed significantly lower values under the influence of rejection (97+/-13% vs 79+/-15%, P<0.0001). Twenty out of the 25 cases with significant rejection were correctly identified by VER T-slew values below a threshold of 98% (sensitivity =80%, specificity =50%, negative predictive value =97%, positive predictive value =11%; P<0.0005). Of the EMBs, 48% could have been saved if the diagnosis model had been used to indicate the need for EMB. A high negative predictive value for the detection of cases with significant rejection has been obtained in a prospective, blind, multicenter study. The presented method can, therefore, be used to supplement patient monitoring after HTx non-invasively, in particular to indicate the need for EMBs. In centers with patient management similar to the ones who participated in the study, this may allow a reduction in the number of surveillance EMBs.\n\nKleinert, Reinhold\n\nKniepeiss, Daniela\n\nPrenner, Günther\n\nSchaffellner, Silvia\n\n\n"
},
{
"text": "\n168249\nClinical, Radiologic, Pathologic, and Molecular Characteristics of Long-Term Survivors of Diffuse Intrinsic Pontine Glioma (DIPG): A Collaborative Report From the International and European Society for Pediatric Oncology DIPG Registries.\n\nHoffman, LM\n\nVeldhuijzen van Zanten, SEM\n\nColditz, N\n\nBaugh, J\n\nChaney, B\n\nHoffmann, M\n\nLane, A\n\nFuller, C\n\nMiles, L\n\nHawkins, C\n\nBartels, U\n\nBouffet, E\n\nGoldman, S\n\nLeary, S\n\nForeman, NK\n\nPacker, R\n\nWarren, KE\n\nBroniscer, A\n\nKieran, MW\n\nMinturn, J\n\nComito, M\n\nBroxson, E\n\nShih, CS\n\nKhatua, S\n\nChintagumpala, M\n\nCarret, AS\n\nEscorza, NY\n\nHassall, T\n\nZiegler, DS\n\nGottardo, N\n\nDholaria, H\n\nDoughman, R\n\nBenesch, M\n\nDrissi, R\n\nNazarian, J\n\nJabado, N\n\nBoddaert, N\n\nVarlet, P\n\nGiraud, G\n\nCastel, D\n\nPuget, S\n\nJones, C\n\nHulleman, E\n\nModena, P\n\nGiagnacovo, M\n\nAntonelli, M\n\nPietsch, T\n\nGielen, GH\n\nJones, DTW\n\nSturm, D\n\nPfister, SM\n\nGerber, NU\n\nGrotzer, MA\n\nPfaff, E\n\nvon Bueren, AO\n\nHargrave, D\n\nSolanki, GA\n\nJadrijevic Cvrlje, F\n\nKaspers, GJL\n\nVandertop, WP\n\nGrill, J\n\nBailey, S\n\nBiassoni, V\n\nMassimino, M\n\nCalmon, R\n\nSanchez, E\n\nBison, B\n\nWarmuth-Metz, M\n\nLeach, J\n\nJones, B\n\nvan Vuurden, DG\n\nKramm, CM\n\nFouladi, M\n\nBeiträge in Fachzeitschriften\nISI:000441233400011\n29746225.0\n10.1200/JCO.2017.75.9308\nPMC6075859\nPurpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1, 30 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1, 08 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials.\n\nBenesch, Martin\n\n\n"
},
{
"text": "\n140051\nA closer look at evolution: Variants (SNPs) of genes involved in skin pigmentation, including EXOC2, TYR, TYRP1, and DCT, are associated with 25(OH)D serum concentration.\n\nSaternus, R\n\nPilz, S\n\nGräber, S\n\nKleber, M\n\nMärz, W\n\nVogt, T\n\nReichrath, J\n\nBeiträge in Fachzeitschriften\nISI:000353126800007\n25396269.0\n10.1210/en.2014-1238\nNone\nVitamin D deficiency is common in the Caucasian population and is associated with increased incidence and unfavorable outcome of many diseases, including various types of cancer, infectious, cardiovascular, and autoimmune diseases. Individual factors that predispose for a person's vitamin D status, such as skin type, have been identified, but limited data exist on genetic determinants of serum 25-hydroxyvitamin D (25[OH]D) concentration. We have tested the hypothesis that variants of genes (single nucleotide polymorphisms [SNPs]) involved in skin pigmentation are predictive of serum 25(OH)D levels. Serum 25(OH)D and SNPs (n = 960) related to genes with relevance for skin pigmentation (tyrosinase [TYR], TYR-related protein 1 [TYRP1], dopachrome tautomerase [DCT], oculocutaneous albinism II [OCA2], two pore segment channel 2 [TPCN2], solute carrier family 24 A4 [SLC24A4], solute carrier family 45 A2 [SLC45A2], agouti signalling peptide [ASIP], cyclic AMP-dependent transcription factor [ATF1], microphthalmia-associated transcription factor [MITF], proopiomelanocortin [POMC], cAMP-dependent protein kinase catalytic subunit beta [PRKACB], cAMP-dependent protein kinase catalytic subunit gamma [PRKACG], cAMP-dependent protein kinase type I-alpha regulatory subunit [PRKAR1A], cAMP-dependent protein kinase type II-alpha regulatory subunit [PRKAR2A], cAMP-dependent protein kinase type II-beta regulatory subunit [PRKAR2B], tubulin beta-3 chain/melanocortin receptor 1 [TUBB3/MC1R], Cadherin-1 [CDH1], catenin beta 1 [CTNNB1], Endothelin 1 [EDN1], endothelin 3 [EDN3], endothelin receptor type B [EDNRB], fibroblast growth factor 2 [FGF2], KIT, KIT ligand [KITLG], nerve growth factor [NGF], interferon regulatory factor 4 [IRF4], exocyst complex component 2 [EXOC2], and tumor protein 53 [TP53]) were analyzed in a cohort of participants of the Ludwigshafen Risk and Cardiovascular Health Study (n = 2970). A total of 46 SNPs were associated (P <.05) with lower or higher serum 25(OH)D levels as compared with the total cohort (median, 15.5 ng/mL). Although 1 SNP in the EXOC2 gene reached the aimed significance level after correction for multiple comparisons (false discovery rate) and was associated with a Δ25(OH)D value more than 5.00 ng/mL, 11 SNPs located in the TYR (n = 4), PRKACG (n = 1), EDN1 (n = 3), TYRP1 (n = 1), and microphthalmia-associated transcription factor (n = 2) genes reached the aimed significance level after false discovery rate correction but were not associated with Δ25(OH)D value more than 5.00 ng/mL. We conclude that variants of genes involved in skin pigmentation are predictive of serum 25(OH)D levels in the Caucasian population. Our data indicate that out of the variants in 29 different genes analyzed, variants of 11 genes, including EXOC2, TYR, and TYRP1, have the highest impact on vitamin D status. Our results have a fundamental importance to understand the role of sunlight, skin pigmentation, and vitamin D for the human evolution.\n\nMärz, Winfried\n\nPilz, Stefan\n\n\n"
},
{
"text": "\n164826\nOncological Outcomes of Laparoscopic Nephroureterectomy Versus Open Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: An European Association of Urology Guidelines Systematic Review.\n\nPeyronnet, B\n\nSeisen, T\n\nDominguez-Escrig, JL\n\nBruins, HM\n\nYuan, CY\n\nLam, T\n\nMaclennan, S\n\nN'dow, J\n\nBabjuk, M\n\nComperat, E\n\nZigeuner, R\n\nSylvester, RJ\n\nBurger, M\n\nMostafid, H\n\nvan Rhijn, BWG\n\nGontero, P\n\nPalou, J\n\nShariat, SF\n\nRoupret, M\n\nBeiträge in Fachzeitschriften\nISI:000486153200022\n29154042.0\n10.1016/j.euf.2017.10.003\nNone\nMost series have suggested better perioperative outcomes of laparoscopic radical nephroureterectomy (RNU) over open RNU. However, the oncological safety of laparoscopic RNU remains controversial.\n To systematically review all relevant literature comparing oncological outcomes of open versus laparoscopic RNU.\n A systematic literature search using the Medline, Embase, and Cochrane databases and clinicaltrial.gov was performed in December 2014 and updated in August 2016. Randomised controlled trials (RCTs) and prospective or retrospective nonrandomised comparative studies comparing the oncological outcomes of any laparoscopic RNU with those of open RNU were included. The primary outcome was cancer-specific survival. The risk of bias (RoB) was assessed using Cochrane RoB tools. A narrative synthesis of the evidence is presented.\n Overall, 42 studies were included, which accounted for 7554 patients: 4925 in the open groups and 2629 in the laparoscopic groups. Most included studies were retrospective comparative series. Only one RCT was found. RoB and confounding were high in most studies. No study compared the oncological outcomes of robotic RNU with those of open RNU. Bladder cuff excision in laparoscopic groups was performed via an open approach in most studies, with only three studies reporting laparoscopic removal of the bladder cuff. Port-site metastasis rates ranged from 0% to 2.8%. No significant difference in oncological outcomes was reported in most series. However, three studies, including the only RCT, reported significantly poorer oncological outcomes in patients who underwent laparoscopic RNU, especially in the subgroups of patients with locally advanced (pT3/pT4) or high-grade upper tract urothelial carcinoma (UTUC), as well as in instances when the bladder cuff was excised laparoscopically.\n The current available evidence suggests that the oncological outcomes of laparoscopic RNU may be poorer than those of open RNU when bladder cuff is excised laparoscopically and in patients with locally advanced high-risk (pT3/pT4 and/or high-grade) UTUC.\n We reviewed the literature comparing the outcomes of two different surgical procedures for the treatment of upper tract urothelial carcinoma. Open radical nephroureterectomy is a surgical procedure in which the kidney is removed through a large incision in the abdomen, while in laparoscopic radical nephroureterectomy, the kidney is removed through a number of small incisions. Our findings suggest that the outcomes of laparoscopic radical nephroureterectomy may be poorer than those of open radical nephroureterectomy, particularly when the bladder cuff is also required to be removed. Laparoscopic radical nephroureterectomy may also be less effective in patients with locally advanced (pT3/pT4) or high-grade upper tract urothelial carcinomas.\n Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n185024\nGuideline on diagnostic procedures for suspected hypersensitivity to beta-lactam antibiotics: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in collaboration with the German Society of Allergology (AeDA), German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Austrian Society for Allergology and Immunology (ÖGAI), and the Paul-Ehrlich Society for Chemotherapy (PEG).\n\nWurpts, G\n\nAberer, W\n\nDickel, H\n\nBrehler, R\n\nJakob, T\n\nKreft, B\n\nMahler, V\n\nMerk, HF\n\nMülleneisen, N\n\nOtt, H\n\nPfützner, W\n\nRöseler, S\n\nRuëff, F\n\nSitter, H\n\nSunderkötter, C\n\nTrautmann, A\n\nTreudler, R\n\nWedi, B\n\nWorm, M\n\nBrockow, K\n\nBeiträge in Fachzeitschriften\nNone\n32568254.0\n10.5414/ALX02104E\nPMC7304290\nThis guideline on diagnostic procedures for suspected beta-lactam antibiotic (BLA) hypersensitivity was written by the German and Austrian professional associations for allergology, and the Paul-Ehrlich Society for Chemotherapy in a consensus procedure according to the criteria of the German Association of Scientific Medical Societies. BLA such as penicillins and cephalosporins represent the drug group that most frequently triggers drug allergies. However, the frequency of reports of suspected allergy in patient histories clearly exceeds the number of confirmed cases. The large number of suspected BLA allergies has a significant impact on, e.g., the quality of treatment received by the individual patient and the costs to society as a whole. Allergies to BLA are based on different immunological mechanisms and often manifest as maculopapular exanthema, as well as anaphylaxis; and there are also a number of less frequent special clinical manifestations of drug allergic reactions. All BLA have a beta-lactam ring. BLA are categorized into different classes: penicillins, cephalosporins, carbapenems, monobactams, and beta-lactamase inhibitors with different chemical structures. Knowledge of possible cross-reactivity is of considerable clinical significance. Whereas allergy to the common beta-lactam ring occurs in only a small percentage of all BLA allergic patients, cross-reactivity due to side chain similarities, such as aminopenicillins and aminocephalosporins, and even methoxyimino cephalosporins, are more common. However, the overall picture is complex and its elucidation may require further research. Diagnostic procedures used in BLA allergy are usually made up of four components: patient history, laboratory diagnostics, skin testing (which is particularly important), and drug provocation testing. The diagnostic approach - even in cases where the need to administer a BLA is acute - is guided by patient history and risk - benefit ratio in the individual case. Here again, further studies are required to extend the present state of knowledge. Performing allergy testing for suspected BLA hypersensitivity is urgently recommended not only in the interests of providing the patient with good medical care, but also due to the immense impact of putative BLA allergies on society as a whole.\n © Dustri-Verlag Dr. K. Feistle.\n\nAberer, Werner\n\n\n"
},
{
"text": "\n117884\nPridopidine for the treatment of motor function in patients with Huntington's disease (MermaiHD): a phase 3, randomised, double-blind, placebo-controlled trial.\n\nde Yebenes, JG\n\nLandwehrmeyer, B\n\nSquitieri, F\n\nReilmann, R\n\nRosser, A\n\nBarker, RA\n\nSaft, C\n\nMagnet, MK\n\nSword, A\n\nRembratt, A\n\nTedroff, J\n\nMermaiHD study investigators\n\nBeiträge in Fachzeitschriften\nISI:000297895600006\n22071279.0\n10.1016/S1474-4422(11)70233-2\nNone\nHuntington's disease is a progressive neurodegenerative disorder, characterised by motor, cognitive, and behavioural deficits. Pridopidine belongs to a new class of compounds known as dopaminergic stabilisers, and results from a small phase 2 study in patients with Huntington's disease suggested that this drug might improve voluntary motor function. We aimed to assess further the effects of pridopidine in patients with Huntington's disease.\n We undertook a 6 month, randomised, double-blind, placebo-controlled trial to assess the efficacy of pridopidine in the treatment of motor deficits in patients with Huntington's disease. Our primary endpoint was change in the modified motor score (mMS; derived from the unified Huntington's disease rating scale) at 26 weeks. We recruited patients with Huntington's disease from 32 European centres; patients were aged 30 years or older and had an mMS of 10 points or greater at baseline. Patients were randomly assigned (1:1:1) to receive placebo, 45 mg per day pridopidine, or 90 mg per day pridopidine by use of centralised computer-generated codes. Patients and investigators were masked to treatment assignment. We also assessed the safety and tolerability profile of pridopidine. For our primary analysis, all patients were eligible for inclusion in our full analysis set, in which we used the last observation carried forward method for missing values. We used an analysis of covariance model and the Bonferroni method to adjust for multiple comparisons. We used a prespecified per-protocol population as our sensitivity analysis. The α level was 0·025 for our primary analysis and 0·05 overall. This trial is registered with ClinicalTrials.gov, number NCT00665223.\n At 26 weeks, in our full analysis set the difference in mean mMS was -0·99 points (97·5% CI -2·08 to 0·10, p=0·042) in patients who received 90 mg per day pridopidine (n=145) versus those who received placebo (n=144), and -0·36 points (-1·44 to 0·72, p=0·456) in those who received 45 mg per day pridopidine (n=148) versus those who received placebo. At the 90 mg per day dose, in our per-protocol population (n=114), the reduction in the mMS was of -1·29 points (-2·47 to -0·12; p=0·014) compared with placebo (n=120). We did not identify any changes in non-motor endpoints at either dose. Pridopidine was well tolerated and had an adverse event profile similar to that of placebo.\n This study did not provide evidence of efficacy as measured by the mMS, but a potential effect of pridopidine on the motor phenotype of Huntington's disease merits further investigation. Pridopidine up to 90 mg per day was well tolerated in patients with Huntington's disease.\n NeuroSearch A/S.\n Copyright © 2011 Elsevier Ltd. All rights reserved.\n\n\n"
},
{
"text": "\n159718\nNon food foreign body injuries.\n\nSlapak, I\n\nPassali, FM\n\nGulati, A\n\nSusy Safe Working Group\n\nBeiträge in Fachzeitschriften\nISI:000303901500006\n22365375.0\n10.1016/j.ijporl.2012.02.006\nNone\nThe aim of the present study is to acquire a better understanding of Non Food Foreign Bodies (NFFB) injuries in children with particular regard to the quantification of the risk of complications and hospitalization associated with patient characteristics, FB features, FB location and circumstances of the accident, as emerging from the SUSY Safe Web-Registry.\n The present study uses data provided by the SUSY Safe Project, a DG SANCO co-funded project which was aimed to collect as many scientific data as possible regarding Foreign Bodies (FB) injuries in children aged 0-14 years and to serve as a basis for a knowledge-based consumer protection activity in the Europe market. FBs were characterized by size, shape and consistency. Descriptive statistics (absolute and relative number or median, I and III quartile according to the categorical or continuous variable, respectively) were calculated for each considered non food item characteristics; FB features distribution by children class age and site of obstruction were assessed. Two different outcomes were considered: hospitalization and complication. FBs which most frequently cause complications were identified. The association between children age, adult presence, object characteristics and outcomes was computed using crude odds ratios and the related 95% confidence intervals.\n 16, 78 FB injuries in children aged 0-14 yrs have been recorded in the Susy Safe databases. FB type was specified in 10, 64 cases; among them 7820 (74%) were due to a non food item. Almost two thirds of injuries occurred in patients 3 years or more old. 53% of patients were males, while 47% were females. When injury happened, the great part of children (86%) was playing. Almost 30% (2339) of injuries happened under adults' supervision. Complications occurred in 299 cases and the most documented was infections (10% of cases) followed by perforation (5%).\n The inhalation/aspiration of a FB, as well as the ingestion and the insertion in the orifices of a FB may result in significant morbidity. Particularly, long-standing or hazardous foreign bodies can cause extensive damage. Some objects, because of their composition, contour, or location, are particularly hazardous: for instance, objects with sharp edges pose a significant risk of laceration and perforation, while fragments of toys have been found only in 2 cases. Parents are frequently unconscious of hazard related with some objects and they are not adequately able to promptly recognize dangerous objects and risky situations. Moreover, also clinicians seem to pay little attention to adult role in the dynamic of the accident: in fact in case series descriptions, data regarding adult presence are often under-reported. On the contrary, since many injuries to children cannot be prevented without some degree of active behavior on the part of parents, the dissemination of information regarding safe behaviors and the implementation of educational strategies aiming to improve parent's attention toward this issue could be fundamental in preventing injuries and need to be promoted by family pediatricians and health practitioners.\n Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.\n\nZaupa, Paola\n\n\n"
},
{
"text": "\n111434\nIn-vitro effects of the antimicrobial peptide Ala8,13,18-magainin II amide on isolated human first trimester villous trophoblast cells.\n\nSengupta, J\n\nKhan, MA\n\nHuppertz, B\n\nGhosh, D\n\nBeiträge in Fachzeitschriften\nISI:000290869800001\n21496281.0\n10.1186/1477-7827-9-49\nPMC3098154\nResearch on antimicrobial cationic peptides (AMPs) has gained pace toward using their potential to replace conventional antibiotics. These peptides preferentially interact with negatively charged membrane lipids typically seen in bacteria and thereby lead to membrane perturbations and membrane dysfunction. However, one possible disadvantage of AMP drugs is their potential for toxicity, especially to those cells which display externalization of negatively charged moieties to the outer leaflet of the plasma membrane during the process of syncytialization. Human placental villous trophoblast is one such cell type. Indeed, intra-vaginal administration of an antimicrobial cationic peptide Ala8, 3, 8-magainin II amide (AMA) which is a synthetic analogue of magainin 2 derived from Xenopus frog has been observed to result in inhibition of pregnancy establishment in monkeys. However, only little is known about the cellular behavior of early placental cytotrophoblasts (CTB) in the presence of cationic antimicrobial peptides. It is believed that suitable cell culture approaches using AMA as a representative alpha-helical AMP may yield tangible knowledge in this regard.\n Immunocytochemical (ICC) analyses using confocal microscopy (n = 6 for each treatment sub-group) and Western blot (WB) method (n = 5 for each treatment sub-group) of CTB differentiation based on synthesis of beta-hCG and hPL, and apoptosis based on apoptosis-associated cytokeratin 18 neo-epitope (CK18f) were performed for CTB isolated from human first trimester placental villi and grown in serum-free primary culture for 24 h, 48 h and 96 h on rat-tail collagen with and without AMA (1000 ng/ml). Moreover, secretion of beta-hCG and hPL into conditioned media from isolated CTB grown in vitro for 24 h, 48 h and 96 h (n = 6/each sub-group) with and without AMA was examined using enzyme immunoassays. Furthermore, TUNEL assay, and cell viability based on LDH leakage into medium (n = 6/each sub-group) were assessed to examine the phenomenon of cell death with time and administration of AMA.\n CTB in serum-free primary culture showed increased (P < 0.05) level of synthesis and secretion of beta-hCG and hPL with time, and higher (P < 0.05) level of cellular cytokeratin 18 neo-epitope and number of TUNEL-positive cells, and LDH activity in conditioned medium at 96 h of culture. Exposure of CTB to AMA resulted in lower (P < 0.05) level of synthesis and secretion of beta-hCG and hPL, as well as, an increase (P < 0.05) of cellular cytokeratin 18 neo-epitope and number of TUNEL-positive cells, and LDH activity in conditioned medium at 96 h as compared to the control treatment.\n Administration of AMA resulted in attenuation of differentiation, enhancement in apoptosis and loss of viability in early placental villi trophoblast cells in primary culture. Thus, it appears that administration of alpha-helical AMP may adversely affect the process of placentation and pregnancy outcome.\n\nHuppertz, Berthold\n\n\n"
},
{
"text": "\n146513\nTreatment with Ca2+ ionophore improves embryo development and outcome in cases with previous developmental problems: a prospective multicenter study.\n\nEbner, T\n\nOppelt, P\n\nWöber, M\n\nStaples, P\n\nMayer, RB\n\nSonnleitner, U\n\nBulfon-Vogl, S\n\nGruber, I\n\nHaid, AE\n\nShebl, O\n\nBeiträge in Fachzeitschriften\nISI:000350146100014\n25376461.0\n10.1093/humrep/deu285\nNone\nDoes calcium ionophore treatment (A23187, calcimycin) improve embryo development and outcome in patients with a history of developmental problems/arrest?\n Application of A23187 leads to increased rates of cleavage to 2-cell stage, blastocyst formation and clinical pregnancy/live birth.\n Studies on lower animals indicate that changes in intracellular free calcium trigger and regulate the events of cell division. In humans, calcium fluctuations were detected with a peak shortly before cell division. Interestingly, these calcium oscillations disappeared in arrested embryos. Mitotic division blocked with a Ca(2+) chelator could be restored by means of ionophores in an animal model.\n This prospective, multicenter (five Austrian centers), uncontrolled intervention study (duration 1 year) includes 57 patients who provided informed consent.\n Inclusion criteria were complete embryo developmental arrest in a previous cycle (no transfer), complete developmental delay (no morula/blastocyst on Day 5), or reduced blastocyst formation on Day 5 (≤15%). Severe male factor patients and patients with <30% fertilization rate after ICSI were excluded because these would be routine indications for ionophore usage. The total of the 57 immediately preceding cycles in the same patients constituted the control cycles/control group. In the treatment cycles, all metaphase II-oocytes were exposed to a commercially available ready-to-use ionophore for 15 min immediately after ICSI. After a three-step washing procedure, in vitro culture was performed as in the control cycles, up to blastocyst stage when achievable.\n Fertilization rate did not differ (75.4 versus 73.2%); however, further cleavage to 2-cell stage was significantly higher (P < 0.001) in the ionophore group (98.5%) when compared with the control cycles (91.9%). In addition, significantly more (P < 0.05) blastocysts formed on Day 5 in the study compared with the control group (47.6 versus 5.5%, respectively) and this was associated with a significant increase (P < 0.01) in the rates of implantation (44.4 versus 12.5%), clinical pregnancy (45.1 versus 12.8%) and live birth (45.1 versus 12.8%). All babies born at the time of writing (22/28) were healthy.\n The frequency of patients showing embryo developmental problems was expected to be low; therefore, a multicenter approach was chosen in order to increase sample size. In one-third of the cycles, the clinician or patient requested a change of stimulation protocol; however, this did not influence the developmental rate of embryos.\n This is the first evidence that developmental incompetence of embryos is an additional indication for ionophore treatment. The present approach is exclusively for overcoming cleavage arrest.\n No funding received. T.E. reports fees from Gynemed, outside the submitted work. All co-authors have no interest to declare.\n © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.\n\nEbner, Thomas\n\n\n"
},
{
"text": "\n4995\nRelationships between plasma leptin levels and body composition parameters measured by different methods in postmenopausal women.\n\nJürimäe, T\n\nSudi, K\n\nJürimäe, J\n\nPayerl, D\n\nRüütel, K\n\nBeiträge in Fachzeitschriften\nISI:000184939800003\n12953174.0\n10.1002/ajhb.10178\nNone\nThe aim of this study was to determine the effects of body composition measured by different methods with different measurement errors on fasting plasma leptin level in normal body mass and obese postmenopausal women. It was hypothesized that the relationship between plasma leptin concentration and body fat is higher using more sophisticated laboratory methods (dual energy X-ray absorptiometry, DXA) in comparison with field methods (bioelectrical impedance analysis, BIA, or skinfold thickness) for body fat measurement because of the greater precision of DXA measurements. Thirty-five postmenopausal (55-83 years of age) healthy Estonian women were divided into two groups: BMI < 27 kg/m(2) as non obese (n = 18) and BMI> 27 kg/m(2) as obese (n = 17). Body composition was determined using DXA (total body, arms, legs, and trunk fat percent, fat mass, and LBM) and BIA methods. Body fat percent was significantly higher using the DXA method. Subcutaneous adipose tissue distribution was determined by measuring nine skinfold thicknesses. Body fat distribution was defined as the ratio of waist-to-hip (WHR) and waist-to-thigh (WTR) circumferences. Leptin was determined by means of radioimmunoassays. Leptin concentration was not significantly different between groups (19.0 +/- 13.3 and 21.5 +/- 21.5 ng/ml in non obese and obese groups, respectively). Body fat percent and fat weight measured by DXA or BIA methods and all measured skinfold thickness values, except biceps and abdominal, were higher in obese women. Body height did not correlate significantly with leptin concentrations. The relationships between leptin concentration were highest with body weight (r = 0.67) and BMI (r = 0.73) values in the obese group. All measured body fat parameters using DXA or BIA methods correlated significantly with plasma leptin concentration in the obese group. LBM did not influence the leptin concentration in postmenopausal women. Stepwise multiple regression analysis indicated that the body fat percent measured using the DXA method was highly related to plasma leptin concentration in the obese group (63.2%; R(2) x 100). When absolute fat mass parameters were considered, leptin concentration was related to the mass of arms fat tissue in the obese group of women (62.3%). Body fat percent measured by BIA was highly related to plasma leptin concentration in the obese group (63.3%). Only biceps skinfold thickness was related to leptin concentration (22.5% and 58.9%, in the nonobese and obese groups, respectively) from the nine measured skinfold thicknesses. WHR and WTR did not reflect leptin concentration in different groups of postmenopausal women. It was concluded that different methods of body composition estimation generate different correlations with plasma leptin concentration. Body fat percent and especially fat mass measured by DXA are the main predictors relating to plasma leptin concentration in obese, but not in nonobese, postmenopausal women. In addition, fat mass in arms measured by DXA and biceps skinfold thickness were also highly related to leptin concentration.\n\nPayerl, Doris\n\n\n"
},
{
"text": "\n142886\nMultiethnic genome-wide association study of cerebral white matter hyperintensities on MRI.\n\nVerhaaren, BF\n\nDebette, S\n\nBis, JC\n\nSmith, JA\n\nIkram, MK\n\nAdams, HH\n\nBeecham, AH\n\nRajan, KB\n\nLopez, LM\n\nBarral, S\n\nvan Buchem, MA\n\nvan der Grond, J\n\nSmith, AV\n\nHegenscheid, K\n\nAggarwal, NT\n\nde Andrade, M\n\nAtkinson, EJ\n\nBeekman, M\n\nBeiser, AS\n\nBlanton, SH\n\nBoerwinkle, E\n\nBrickman, AM\n\nBryan, RN\n\nChauhan, G\n\nChen, CP\n\nChouraki, V\n\nde Craen, AJ\n\nCrivello, F\n\nDeary, IJ\n\nDeelen, J\n\nDe Jager, PL\n\nDufouil, C\n\nElkind, MS\n\nEvans, DA\n\nFreudenberger, P\n\nGottesman, RF\n\nGuðnason, V\n\nHabes, M\n\nHeckbert, SR\n\nHeiss, G\n\nHilal, S\n\nHofer, E\n\nHofman, A\n\nIbrahim-Verbaas, CA\n\nKnopman, DS\n\nLewis, CE\n\nLiao, J\n\nLiewald, DC\n\nLuciano, M\n\nvan der Lugt, A\n\nMartinez, OO\n\nMayeux, R\n\nMazoyer, B\n\nNalls, M\n\nNauck, M\n\nNiessen, WJ\n\nOostra, BA\n\nPsaty, BM\n\nRice, KM\n\nRotter, JI\n\nvon Sarnowski, B\n\nSchmidt, H\n\nSchreiner, PJ\n\nSchuur, M\n\nSidney, SS\n\nSigurdsson, S\n\nSlagboom, PE\n\nStott, DJ\n\nvan Swieten, JC\n\nTeumer, A\n\nTöglhofer, AM\n\nTraylor, M\n\nTrompet, S\n\nTurner, ST\n\nTzourio, C\n\nUh, HW\n\nUitterlinden, AG\n\nVernooij, MW\n\nWang, JJ\n\nWong, TY\n\nWardlaw, JM\n\nWindham, BG\n\nWittfeld, K\n\nWolf, C\n\nWright, CB\n\nYang, Q\n\nZhao, W\n\nZijdenbos, A\n\nJukema, JW\n\nSacco, RL\n\nKardia, SL\n\nAmouyel, P\n\nMosley, TH\n\nLongstreth, WT\n\nDeCarli, CC\n\nvan Duijn, CM\n\nSchmidt, R\n\nLauner, LJ\n\nGrabe, HJ\n\nSeshadri, SS\n\nIkram, MA\n\nFornage, M\n\nBeiträge in Fachzeitschriften\nISI:000353309600020\n25663218.0\n10.1161/CIRCGENETICS.114.000858\nPMC4427240\nThe burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies.\n We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 (P=2.7×10(-19)) and identified novel loci on chr10q24 (P=1.6×10(-9)) and chr2p21 (P=4.4×10(-8)). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 (P=2.0×10(-8)) and chr2p16 (P=1.5×10(-8)). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16).\n We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms.\n © 2015 American Heart Association, Inc.\n\nBirkl-Töglhofer, Anna Maria\n\nHofer, Edith\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n184942\nImpact of the coronavirus disease 2019 (COVID-19) pandemic on the care of patients with acute and chronic aortic conditions.\n\nCzerny, M\n\nGottardi, R\n\nPuiu, P\n\nBernecker, OY\n\nCitro, R\n\nDella Corte, A\n\ndi Marco, L\n\nFink, M\n\nGosslau, Y\n\nHaldenwang, PL\n\nHeijmen, RH\n\nHugas-Mallorqui, M\n\nIesu, S\n\nJacobsen, O\n\nJassar, AS\n\nJuraszek, A\n\nKolowca, M\n\nLepidi, S\n\nMarrocco-Trischitta, MM\n\nMatsuda, H\n\nMeisenbacher, K\n\nMicari, A\n\nMinatoya, K\n\nPark, KH\n\nPeterss, S\n\nPetrich, M\n\nPiffaretti, G\n\nProbst, C\n\nReutersberg, B\n\nRosati, F\n\nSchachner, B\n\nSchachner, T\n\nSorokin, VA\n\nSzeberin, Z\n\nSzopinski, P\n\nDi Tommaso, L\n\nTrimarchi, S\n\nVerhoeven, ELG\n\nVogt, F\n\nVoetsch, A\n\nWalter, T\n\nWeiss, G\n\nYuan, X\n\nBenedetto, F\n\nDe Bellis, A\n\nD Oria, M\n\nDischer, P\n\nZierer, A\n\nRylski, B\n\nvan den Berg, JC\n\nWyss, TR\n\nBossone, E\n\nSchmidli, J\n\nNienaber, C\n\nCollaborators:\n\nAccarino, G\n\nBaldascino, F\n\nBöckler, D\n\nCorazzari, C\n\nD Alessio, I\n\nde Beaufort, H\n\nDe Troia, C\n\nDumfarth, J\n\nGalbiati, D\n\nGorgatti, F\n\nHagl, C\n\nHamiko, M\n\nHuber, F\n\nHyhlik-Duerr, A\n\nIanelli, G\n\nIesu, I\n\nJung, JC\n\nKainz, FM\n\nKatsargyris, A\n\nKoter, S\n\nKusmierczyk, M\n\nKolsut, P\n\nLengyel, B\n\nLomazzi, C\n\nMuneretto, C\n\nNava, G\n\nNolte, T\n\nPacini, D\n\nPleban, E\n\nRychla, M\n\nSakamoto, K\n\nShijo, T\n\nYokawa, K\n\nSiepe, M\n\nSirch, J\n\nStrauch, J\n\nSule, JA\n\nTobler, EL\n\nWalter, C\n\nWeigang, E\n\nBeiträge in Fachzeitschriften\nNone\n33394040.0\n10.1093/ejcts/ezaa452\nPMC7799089\nTo evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on acute and elective thoracic and abdominal aortic procedures.\n Forty departments shared their data on acute and elective thoracic and abdominal aortic procedures between January and May 2020 and January and May 2019 in Europe, Asia and the USA. Admission rates as well as delay from onset of symptoms to referral were compared.\n No differences in the number of acute thoracic and abdominal aortic procedures were observed between 2020 and the reference period in 2019 [incidence rates ratio (IRR): 0.96, confidence interval (CI) 0.89-1.04; P = 0.39]. Also, no difference in the time interval from acute onset of symptoms to referral was recorded (<12 h 32% vs > 12 h 68% in 2020, < 12 h 34% vs > 12 h 66% in 2019 P = 0.29). Conversely, a decline of 35% in elective procedures was seen (IRR: 0.81, CI 0.76-0.87; P < 0.001) with substantial differences between countries and the most pronounced decline in Italy (-40%, P < 0.001). Interestingly, in Switzerland, an increase in the number of elective cases was observed (+35%, P = 0.02).\n There was no change in the number of acute thoracic and abdominal aortic cases and procedures during the initial wave of the COVID-19 pandemic, whereas the case load of elective operations and procedures decreased significantly. Patients with acute aortic syndromes presented despite COVID-19 and were managed according to current guidelines. Further analysis is required to prove that deferral of elective cases had no impact on premature mortality.\n © The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.\n\nKoter, Stephan Herwig\n\n\n"
},
{
"text": "\n6854\nTemozolomide and interferon alpha 2b in metastatic melanoma stage IV.\n\nRichtig, E\n\nHofmann-Wellenhof, R\n\nPehamberger, H\n\nForstinger, Ch\n\nWolff, K\n\nMischer, P\n\nRaml, J\n\nFritsch, P\n\nZelger, B\n\nRatzinger, G\n\nKoller, J\n\nLang, A\n\nKonrad, K\n\nKindermann-Glebowski, E\n\nSeeber, A\n\nSteiner, A\n\nFialla, R\n\nPachinger, W\n\nKos, C\n\nKlein, G\n\nKehrer, H\n\nKerl, H\n\nUlmer, H\n\nSmolle, J\n\nBeiträge in Fachzeitschriften\nISI:000223175000011\n15270876.0\n10.1111/j.1365-2133.2004.06019.x\nNone\nBACKGROUND: A multicentre, centrally randomized, open-labelled study with temozolomide and interferon (IFN)-alpha 2b was carried out to study the therapeutic effect in patients with metastatic melanoma stage IV. OBJECTIVES: The response rate, efficacy, side-effects, reasons for discontinuation of therapy and survival rate of 47 patients treated with temozolomide in combination with two different dosing regimens of IFN-alpha 2b were documented. PATIENTS/METHODS: Twenty-nine male and 18 female patients (mean age 57.6 years, range 34-74) were centrally randomized to two different arms: 20 patients received a treatment schedule with temozolomide 150 mg m(-2) on days 1-5 orally every 28 days in combination with IFN-alpha 2b 10 MIU m(-2) every other day and 27 patients received temozolomide 150 mg m(-2) on days 1-5 every 28 days in combination with IFN-alpha 2b in a fixed dose of 10 MIU every other day. RESULTS: We observed an overall response rate of 27.6% comprising five complete remissions (10.6%: one patient group A, four patients group B), in two of these five patients at the last follow-up in the study (4.3%, both in group B); and eight partial remissions (17%: six patients in group A, two patients in group B), in three of these eight patients at the last follow-up in the study (6.4%, two patients in group A, one patient in group B). Three patients showed stable disease (6.4%: one patient in group A, two patients in group B). Mean survival was 14.5 months [95% confidence interval (CI) 10-19] with no significant differences between treatment groups. However, there was a significant correlation with response after three cycles (log rank test, P < 0.03). Within the 32 patients who completed at least three cycles of therapy, seven patients (three in group A and four in group B) with a partial or complete response showed a significantly better mean survival of 30.6 months (95% CI 19.1-42) compared with 25 patients who did not respond (13.7 months 95% CI 9.2-18.3). In total, patients with at least one complete remission showed the longest survival (37.1 months 95% CI 26.3-47.9), followed by patients with at least one partial response (17.4 95% CI 10.9-23.9). Major side-effects of the treatment were nausea, vomiting, headache, leucopenia, thrombopenia, elevation of liver function parameters and neurological symptoms. In five patients, the side-effects led to a discontinuation of treatment: neurological symptoms (two patients), sepsis (one patient), brain haemorrhage (one patient) and exanthema (one patient). There were no treatment-related deaths. CONCLUSIONS: The combination of temozolomide and IFN-alpha 2b can easily be administered and shows tolerable toxicity. When an objective response occurs after three cycles, it indicates a significant survival advantage.\n\nHofmann-Wellenhof, Rainer\n\nKerl, Helmut\n\nRichtig, Erika\n\nSmolle, Josef\n\n\n"
},
{
"text": "\n171188\nARIA pharmacy 2018 "Allergic rhinitis care pathways for community pharmacy": AIRWAYS ICPs initiative (European Innovation Partnership on Active and Healthy Ageing, DG CONNECT and DG Santé) POLLAR (Impact of Air POLLution on Asthma and Rhinitis) GARD Demonstration project.\n\nBosnic-Anticevich, S\n\nCosta, E\n\nMenditto, E\n\nLourenço, O\n\nNovellino, E\n\nBialek, S\n\nBriedis, V\n\nBuonaiuto, R\n\nChrystyn, H\n\nCvetkovski, B\n\nDi Capua, S\n\nKritikos, V\n\nMair, A\n\nOrlando, V\n\nPaulino, E\n\nSalimäki, J\n\nSöderlund, R\n\nTan, R\n\nWilliams, DM\n\nWroczynski, P\n\nAgache, I\n\nAnsotegui, IJ\n\nAnto, JM\n\nBedbrook, A\n\nBachert, C\n\nBewick, M\n\nBindslev-Jensen, C\n\nBrozek, JL\n\nCanonica, GW\n\nCardona, V\n\nCarr, W\n\nCasale, TB\n\nChavannes, NH\n\nCorreia de Sousa, J\n\nCruz, AA\n\nCzarlewski, W\n\nDe Carlo, G\n\nDemoly, P\n\nDevillier, P\n\nDykewicz, MS\n\nGaga, M\n\nEl-Gamal, Y\n\nFonseca, J\n\nFokkens, WJ\n\nGuzmán, MA\n\nHaahtela, T\n\nHellings, PW\n\nIllario, M\n\nIvancevich, JC\n\nJust, J\n\nKaidashev, I\n\nKhaitov, M\n\nKhaltaev, N\n\nKeil, T\n\nKlimek, L\n\nKowalski, ML\n\nKuna, P\n\nKvedariene, V\n\nLarenas-Linnemann, DE\n\nLaune, D\n\nLe, LTT\n\nLodrup Carlsen, KC\n\nMahboub, B\n\nMaier, D\n\nMalva, J\n\nManning, PJ\n\nMorais-Almeida, M\n\nMösges, R\n\nMullol, J\n\nMünter, L\n\nMurray, R\n\nNaclerio, R\n\nNamazova-Baranova, L\n\nNekam, K\n\nNyembue, TD\n\nOkubo, K\n\nO'Hehir, RE\n\nOhta, K\n\nOkamoto, Y\n\nOnorato, GL\n\nPalkonen, S\n\nPanzner, P\n\nPapadopoulos, NG\n\nPark, HS\n\nPawankar, R\n\nPfaar, O\n\nPhillips, J\n\nPlavec, D\n\nPopov, TA\n\nPotter, PC\n\nProkopakis, EP\n\nRoller-Wirnsberger, RE\n\nRottem, M\n\nRyan, D\n\nSamolinski, B\n\nSanchez-Borges, M\n\nSchunemann, HJ\n\nSheikh, A\n\nSisul, JC\n\nSomekh, D\n\nStellato, C\n\nTo, T\n\nTodo-Bom, AM\n\nTomazic, PV\n\nToppila-Salmi, S\n\nValero, A\n\nValiulis, A\n\nValovirta, E\n\nVentura, MT\n\nWagenmann, M\n\nWallace, D\n\nWaserman, S\n\nWickman, M\n\nYiallouros, PK\n\nYorgancioglu, A\n\nYusuf, OM\n\nZar, HJ\n\nZernotti, ME\n\nZhang, L\n\nZidarn, M\n\nZuberbier, T\n\nBousquet, J\n\nBeiträge in Fachzeitschriften\nISI:000477968800001\n30565275.0\n10.1111/all.13701\nNone\nPharmacists are trusted health care professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact for allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The Allergic Rhinitis and its Impact on Asthma (ARIA)-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses), and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of allergic rhinitis. However, the ARIA-pharmacy ICP should be adapted to local healthcare environments/situations as regional (national) differences exist in pharmacy care.\n © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.\n\nRoller-Wirnsberger, Regina\n\nTomazic, Peter Valentin\n\n\n"
},
{
"text": "\n179123\nThe PROCLIPI international registry of early-stage mycosis fungoides identifies substantial diagnostic delay in most patients.\n\nScarisbrick, JJ\n\nQuaglino, P\n\nPrince, HM\n\nPapadavid, E\n\nHodak, E\n\nBagot, M\n\nServitje, O\n\nBerti, E\n\nOrtiz-Romero, P\n\nStadler, R\n\nPatsatsi, A\n\nKnobler, R\n\nGuenova, E\n\nChild, F\n\nWhittaker, S\n\nNikolaou, V\n\nTomasini, C\n\nAmitay, I\n\nPrag Naveh, H\n\nRam-Wolff, C\n\nBattistella, M\n\nAlberti-Violetti, S\n\nStranzenbach, R\n\nGargallo, V\n\nMuniesa, C\n\nKoletsa, T\n\nJonak, C\n\nPorkert, S\n\nMitteldorf, C\n\nEstrach, T\n\nCombalia, A\n\nMarschalko, M\n\nCsomor, J\n\nSzepesi, A\n\nCozzio, A\n\nDummer, R\n\nPimpinelli, N\n\nGrandi, V\n\nBeylot-Barry, M\n\nPham-Ledard, A\n\nWobser, M\n\nGeissinger, E\n\nWehkamp, U\n\nWeichenthal, M\n\nCowan, R\n\nParry, E\n\nHarris, J\n\nWachsmuth, R\n\nTurner, D\n\nBates, A\n\nHealy, E\n\nTrautinger, F\n\nLatzka, J\n\nYoo, J\n\nVydianath, B\n\nAmel-Kashipaz, R\n\nMarinos, L\n\nOikonomidi, A\n\nStratigos, A\n\nVignon-Pennamen, MD\n\nBattistella, M\n\nCliment, F\n\nGonzalez-Barca, E\n\nGeorgiou, E\n\nSenetta, R\n\nZinzani, P\n\nVakeva, L\n\nRanki, A\n\nBusschots, AM\n\nHauben, E\n\nBervoets, A\n\nWoei-A-Jin, FJSH\n\nMatin, R\n\nCollins, G\n\nWeatherhead, S\n\nFrew, J\n\nBayne, M\n\nDunnill, G\n\nMcKay, P\n\nArumainathan, A\n\nAzurdia, R\n\nBenstead, K\n\nTwigger, R\n\nRieger, K\n\nBrown, R\n\nSanches, JA\n\nMiyashiro, D\n\nAkilov, O\n\nMcCann, S\n\nSahi, H\n\nDamasco, FM\n\nQuerfeld, C\n\nFolkes, A\n\nBur, C\n\nKlemke, CD\n\nEnz, P\n\nPujol, R\n\nQuint, K\n\nGeskin, L\n\nHong, E\n\nEvison, F\n\nVermeer, M\n\nCerroni, L\n\nKempf, W\n\nKim, Y\n\nWillemze, R\n\nBeiträge in Fachzeitschriften\nISI:000478598800036\n30267549.0\n10.1111/bjd.17258\nNone\nSurvival in mycosis fungoides (MF) is varied and may be poor. The PROCLIPI (PROspective Cutaneous Lymphoma International Prognostic Index) study is a web-based data collection system for early-stage MF with legal data-sharing agreements permitting international collaboration in a rare cancer with complex pathology. Clinicopathological data must be 100% complete and in-built intelligence in the database system ensures accurate staging.\n To develop a prognostic index for MF.\n Predefined datasets for clinical, haematological, radiological, immunohistochemical, genotypic, treatment and quality of life are collected at first diagnosis of MF and annually to test against survival. Biobanked tissue samples are recorded within a Federated Biobank for translational studies.\n In total, 430 patients were enrolled from 29 centres in 15 countries spanning five continents. Altogether, 348 were confirmed as having early-stage MF at central review. The majority had classical MF (81·6%) with a CD4 phenotype (88·2%). Folliculotropic MF was diagnosed in 17·8%. Most presented with stage I (IA: 49·4%; IB: 42·8%), but 7·8% presented with enlarged lymph nodes (stage IIA). A diagnostic delay between first symptom development and initial diagnosis was frequent [85·6%; median delay 36 months (interquartile range 12-90)]. This highlights the difficulties in accurate diagnosis, which includes lack of a singular diagnostic test for MF.\n This confirmed early-stage MF cohort is being followed-up to identify prognostic factors, which may allow better management and improve survival by identifying patients at risk of disease progression. This study design is a useful model for collaboration in other rare diseases, especially where pathological diagnosis can be complex.\n © 2018 British Association of Dermatologists.\n\nCerroni, Lorenzo\n\n\n"
},
{
"text": "\n132290\nDeterioration of gait and balance over time: the effects of age-related white matter change--the LADIS study.\n\nKreisel, SH\n\nBlahak, C\n\nBäzner, H\n\nInzitari, D\n\nPantoni, L\n\nPoggesi, A\n\nChabriat, H\n\nErkinjuntti, T\n\nFazekas, F\n\nFerro, JM\n\nLanghorne, P\n\nO'Brien, J\n\nScheltens, P\n\nVisser, MC\n\nWahlund, LO\n\nWaldemar, G\n\nWallin, A\n\nHennerici, MG\n\nBeiträge in Fachzeitschriften\nISI:000326263800008\n23838682.0\n10.1159/000350725\nNone\nCross-sectional studies have shown an association between the severity of age-related white matter change (ARWMC) and lower body motor function. However, the association between prevalent ARWMC and incident deterioration of balance and gait remains insufficiently investigated. This study investigates if the degree of prevalent ARWMC has a differential effect on lower body motor function as it changes over time, hypothesizing that individuals with more severe baseline white matter pathology experience greater clinical deterioration independent of potential confounders. This is of clinical relevance: given the increasing use of neuroimaging, incidental white matter pathology is common; being able to delineate natural trajectories of balance and gait function given ARWMC may improve patient advice and help optimize allocation of care.\n 639 non-disabled elderly individuals with prevalent ARWMC (grading of severity of ARWMC using the Fazekas scale) were followed up yearly for 3 years, as part of the Leukoaraiosis and Disability Study. The primary outcome variable, reflecting the temporal course of gait and balance function, was the change of scores on the Short Physical Performance Battery (SPPB) over time versus the severity of ARWMC. We used linear mixed modelling to analyse change over time. Explorative analysis was carried out investigating the effect of age on potential deterioration of gait and balance function. We used propensity scores to adjust for multiple confounders that affect both the exposure (i.e. ARWMC) and outcome.\n Subjects' lower body motor function deteriorated by 2.6% per year. However, after adjustment for baseline motor impairment and potential confounders, only subjects with moderate [-0.22 points per year on the SPPB (equals -2.3%); 95% CI -0.35 to -0.09, p < 0.001] or severe [-0.46 points per year (equals -4.7%); 95% CI -0.63 to -0.28, p < 0.0001] ARWMC show a loss of function. Age shows differential effects: relatively younger elderly subjects have similar temporal dynamics in SPPB change independent of their individual degree of ARWMC severity; however, subjects with severe ARWMC and who are older than 75.9 years deteriorate significantly more rapidly than their counterparts with only mild or moderate white matter pathology.\n Only moderate and severe ARWMC is independently associated - on average - with a deterioration of gait and balance. Albeit the possibility of unmeasured confounding and other methodological constraints, there is nonetheless evidence of large interindividual variability: some subjects with moderate or severe ARWMC stay stable over time or even show improvement. Furthermore, there is explorative analysis showing that younger elderly subjects may be able to better compensate even severe ARWMC. These individuals' gait and balance function stays relatively stable over time, whereas their older counterparts deteriorate significantly. This may point towards a threshold effect given ARWMC.\n Copyright © 2013 S. Karger AG, Basel.\n\nFazekas, Franz\n\n\n"
},
{
"text": "\n88001\nOpisthonotal glands in the Camisiidae (Acari, Oribatida): evidence for a regressive evolutionary trend\n\nRaspotnig, G\n\nStabentheiner, E\n\nFottinger, P\n\nSchaider, M\n\nKrisper, G\n\nRechberger, G\n\nLeis, HJ\n\nBeiträge in Fachzeitschriften\nISI:000262478600012\nNone\n10.1111/j.1439-0469.2008.00486.x\nNone\nPaired, sac-like and typically large opisthonotal glands (syn. oil glands), mainly considered for chemical protection and communication, characterize the so-called 'glandulate Oribatida' which include the Parhyposomata, Mixonomata, Desmonomata and Brachypylina but also the Astigmata. Among these groups distinct evolutionary trends affect the morphology of glands and their secretion profiles, thereby rendering them highly informative characters with phylogenetic significance. One striking tendency, convergently occurring in a few glandulate groups, leads to the degeneration or even complete regression of opisthonotal glands. In this study, a first example of coherent evolutionary steps towards opisthonotal gland degeneration is described by using desmonomatan Camisiidae as a model: Opisthonotal glands in representatives of genus Platynothrus still show morphologically and chemically ancient conditions with fairly-well developed glandular reservoirs. Secretion patterns mainly consist of a characteristic set of terpenes and aromatics ('astigmatid compounds') as found in outgroups such as desmonomatan Trhypochthoniidae. Progressive states of regression of opisthonotal glands, along with a reduction of component-richness and amounts of secretions, occur in representatives of Heminothrus and, more conspicuously, in species of Camisia, most likely indicating a consistent evolutionary trend. This trend towards opisthonotal gland atrophy may be due to novel alternative and cheap strategies of passive defense in more-derivative camisiids - such as mechanical protection by encrustation of the cuticle - that possibly compensate for the lack of chemical defenses.Paarige, sackformige und typischerweise gro ss e opisthosomatische Drusen (syn. oldrusen), deren Sekrete hauptsAchlich zum chemischen Schutz und zur Kommunikation dienen sollen, kennzeichnen die sogenannten glandulaten Hornmilben. Innerhalb dieser Hornmilbengruppe, die die Parhyposomata, Mixonomata, Desmonomata, Brachypylina, aber auch die astigmaten Milben umfasst, waren die oldrusen offensichtlich in morphologischer und chemischer Hinsicht deutlich unterschiedlichen evolutiven Trends unterworfen; damit sind oldrusen ein phylogenetisch au ss erordentlich wichtiger Merkmalskomplex in der Oribatiden-Systematik geworden. Eine auffAllige Tendenz allerdings, die offensichtlich mehrmals konvergent auftritt, fuhrt zur Ruckbildung der Drusen in bestimmten glandulaten Gruppen. In der vorliegenden Arbeit wird zum ersten Mal eine zusammenhAngende Linie solcher Ruckbildungsstadien am Beispiel der Camisiidae (Desmonomata) beschrieben: die weitgehend noch gut ausgebildeten oldrusen von Vertretern der Gattung Platynothrus zeigen morphologisch und chemisch ursprungliche Merkmale. Sekretprofile bestehen hauptsAchlich aus einem charakteristischen Set von Terpenen und Aromaten ("astigmatid compounds'), das auch in Au ss engruppen wie z.B. bei Trhypochthoniiden auftritt. Fortschreitende Stadien der Ruckbildung von oldrusen, verbunden mit einer Verarmung der Sekretprofile und einer Verringerung an Sekretmengen, treten in Vertretern von Heminothrus und, noch auffAlliger, bei verschiedenen Arten von Camisia auf: dieses PhAnomen, ubereinstimmend mit einem auf morphologischen Daten basierenden Systemvorschlag, wird als evolutiver Trend innerhalb der Camisiidae gedeutet. Dieser Trend zur oldrusenruckbildung ist moglicherweise mit einer alternativen Strategie passiver Verteidigung bei weiter abgeleiteten Camisiiden zu erklAren, die Krustenbildungen aus Cerotegument und Bodenpartikeln auf der KorperoberflAce als mechanischen Schutz gegen PrAdatoren nutzen. Diese moglicherweise energetisch billige Variante konnte den Verlust chemischer Verteidigung uber oldrusensekretion kompensieren.\n\nLeis, Hans-Joerg\n\n\n"
},
{
"text": "\n131465\nDistribution of decidual natural killer cells and macrophages in the neighbourhood of the trophoblast invasion front: a quantitative evaluation.\n\nHelige, C\n\nAhammer, H\n\nMoser, G\n\nHammer, A\n\nDohr, G\n\nHuppertz, B\n\nSedlmayr, P\n\nBeiträge in Fachzeitschriften\nISI:000328417600002\n24140594.0\n10.1093/humrep/det353\nNone\nDo decidual natural killer (dNK) cells and decidual macrophages (dMph) become enriched in the vicinity of the trophoblast invasion front?\n Morphometric image analysis and areal cell density calculations, which excluded observer bias, showed an enrichment of decidual leukocytes in the neighbourhood of the trophoblast invasion front.\n In previous studies, the number of decidual leukocytes was visually counted in medium- or high power fields. These methods, however, cannot reveal the exact spatial relationship between leukocytes and invasive trophoblast cells, and are therefore prone to subjective errors. Thus, a more objective approach is required.\n Applying a new method of morphometric image analysis, leukocyte populations were studied in human tissue fragments derived from first trimester placentation sites (n = 7) as well as in co-cultures of first trimester decidual tissue with placental villi of the same pregnancy representing an appropriate in vitro model of trophoblast invasion (n = 15).\n First trimester decidual tissue was obtained from women undergoing elective terminations of pregnancy at 7-10 weeks of gestational age. Tissue sections were double-stained immunohistochemically for markers of dNK cells or dMph on one hand, and for invasive extravillous trophoblast cells on the other. To analyse the distribution of leukocytes, distinct cell compartments as well as cell neighbourhood areas were defined. Finally, relative areal cell densities were calculated and these data were compared with those of an in vitro model of trophoblast invasion as well as with tissue fragments derived from decidua parietalis without trophoblast cells.\n At first trimester placentation sites, a higher density of dNK cells as well as of dMph was found in close proximity to the invasive trophoblast (P ≤ 0.01), compared with the average areal cell density of decidual leukocytes in the tissue with exclusion of the trophoblast. The highest areal cell density of leukocytes was determined up to a distance of 20 μm from the trophoblast cells, whereas in more distant regions it was even lower than average, indicating a migration of these leukocytes towards the trophoblast invasion front. In the three-dimensional co-culture model, however, we found an enrichment of dMph (P ≤ 0.01) but not of dNK cells (P > 0, 5) in the neighbourhood of the invasive trophoblast.\n The morphometric image analysis depends on intense immunohistochemical staining that is free of background and cross-reactivity.\n The presented method will be useful not only for the investigation of recurrent miscarriage but also in the fields of tumour immunology and inflammation.\n The study was supported by the European Commission (Network of Excellence 'The Control of Embryo Implantation (EMBIC)', FP6-512040, lead researcher: P.S.), and by the Franz Lanyar Foundation of the Medical University of Graz, Austria (Grant #347). None of the authors declared a conflict of interests.\n\nAhammer, Helmut\n\nDohr, Gottfried\n\nHammer, Astrid\n\nHelige, Christine\n\nHuppertz, Berthold\n\nMoser, Gerit\n\nSedlmayr, Peter\n\n\n"
},
{
"text": "\n178252\nSVM recursive feature elimination analyses of structural brain MRI predicts near-term relapses in patients with clinically isolated syndromes suggestive of multiple sclerosis.\n\nWottschel, V\n\nChard, DT\n\nEnzinger, C\n\nFilippi, M\n\nFrederiksen, JL\n\nGasperini, C\n\nGiorgio, A\n\nRocca, MA\n\nRovira, A\n\nDe Stefano, N\n\nTintoré, M\n\nAlexander, DC\n\nBarkhof, F\n\nCiccarelli, O\n\nMAGNIMS study group and the EuroPOND consortium\n\nBeiträge in Fachzeitschriften\nISI:000504663800125\n31734524.0\n10.1016/j.nicl.2019.102011\nPMC6861587\nMachine learning classification is an attractive approach to automatically differentiate patients from healthy subjects, and to predict future disease outcomes. A clinically isolated syndrome (CIS) is often the first presentation of multiple sclerosis (MS), but it is difficult at onset to predict who will have a second relapse and hence convert to clinically definite MS. In this study, we thus aimed to distinguish CIS converters from non-converters at onset of a CIS, using recursive feature elimination and weight averaging with support vector machines. We also sought to assess the influence of cohort size and cross-validation methods on the accuracy estimate of the classification. We retrospectively collected 400 patients with CIS from six European MAGNIMS MS centres. Patients underwent brain MRI at onset of a CIS according to local standard-of-care protocols. The diagnosis of clinically definite MS at one-year follow-up was the standard against which the accuracy of the model was tested. For each patient, we derived MRI-based features, such as grey matter probability, white matter lesion load, cortical thickness, and volume of specific cortical and white matter regions. Features with little contribution to the classification model were removed iteratively through an interleaved sample bootstrapping and feature averaging approach. Classification of CIS outcome at one-year follow-up was performed with 2-fold, 5-fold, 10-fold and leave-one-out cross-validation for each centre cohort independently and in all patients together. The estimated classification accuracy across centres ranged from 64.9% to 88.1% using 2-fold cross-validation and from 73% to 92.9% using leave-one-out cross-validation. The classification accuracy estimate was higher in single-centre, smaller data sets than in combinations of data sets, being the lowest when all patients were merged together. Regional MRI features such as WM lesions, grey matter probability in the thalamus and the precuneus or cortical thickness in the cuneus and inferior temporal gyrus predicted the occurrence of a second relapse in patients at onset of a CIS using support vector machines. The increased accuracy estimate of the classification achieved with smaller and single-centre samples may indicate a model bias (overfitting) when data points were limited, but also more homogeneous. We provide an overview of classifier performance from a range of cross-validation schemes to give insight into the variability across schemes. The proposed recursive feature elimination approach with weight averaging can be used both in single- and multi-centre data sets in order to bridge the gap between group-level comparisons and making predictions for individual patients.\n Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.\n\nEnzinger, Christian\n\n\n"
}
]
}