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"text": "\n168754\nA longitudinal approach to biological psychiatric research: The PsyCourse study.\n\nBudde, M\n\nAnderson-Schmidt, H\n\nGade, K\n\nReich-Erkelenz, D\n\nAdorjan, K\n\nKalman, JL\n\nSenner, F\n\nPapiol, S\n\nAndlauer, TFM\n\nComes, AL\n\nSchulte, EC\n\nKlöhn-Saghatolislam, F\n\nGryaznova, A\n\nHake, M\n\nBartholdi, K\n\nFlatau, L\n\nReitt, M\n\nQuast, S\n\nStegmaier, S\n\nMeyers, M\n\nEmons, B\n\nHaußleiter, IS\n\nJuckel, G\n\nNieratschker, V\n\nDannlowski, U\n\nSchaupp, SK\n\nSchmauß, M\n\nZimmermann, J\n\nReimer, J\n\nSchulz, S\n\nWiltfang, J\n\nReininghaus, E\n\nAnghelescu, IG\n\nArolt, V\n\nBaune, BT\n\nKonrad, C\n\nThiel, A\n\nFallgatter, AJ\n\nFigge, C\n\nvon Hagen, M\n\nKoller, M\n\nLang, FU\n\nWigand, ME\n\nBecker, T\n\nJäger, M\n\nDietrich, DE\n\nStierl, S\n\nScherk, H\n\nSpitzer, C\n\nFolkerts, H\n\nWitt, SH\n\nDegenhardt, F\n\nForstner, AJ\n\nRietschel, M\n\nNöthen, MM\n\nFalkai, P\n\nSchulze, TG\n\nHeilbronner, U\n\nBeiträge in Fachzeitschriften\nISI:000459452000001\n30070057.0\n10.1002/ajmg.b.32639\nPMC6585634\nIn current diagnostic systems, schizophrenia and bipolar disorder are still conceptualized as distinct categorical entities. Recently, both clinical and genomic evidence have challenged this Kraepelinian dichotomy. There are only few longitudinal studies addressing potential overlaps between these conditions. Here, we present design and first results of the PsyCourse study (N = 891 individuals at baseline), an ongoing transdiagnostic study of the affective-to-psychotic continuum that combines longitudinal deep phenotyping and dimensional assessment of psychopathology with an extensive collection of biomaterial. To provide an initial characterization of the PsyCourse study sample, we compare two broad diagnostic groups defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) classification system, that is, predominantly affective (n = 367 individuals) versus predominantly psychotic disorders (n = 524 individuals). Depressive, manic, and psychotic symptoms as well as global functioning over time were contrasted using linear mixed models. Furthermore, we explored the effects of polygenic risk scores for schizophrenia on diagnostic group membership and addressed their effects on nonparticipation in follow-up visits. While phenotypic results confirmed expected differences in current psychotic symptoms and global functioning, both manic and depressive symptoms did not vary between both groups after correction for multiple testing. Polygenic risk scores for schizophrenia significantly explained part of the variability of diagnostic group. The PsyCourse study presents a unique resource to research the complex relationships of psychopathology and biology in severe mental disorders not confined to traditional diagnostic boundaries and is open for collaborations.\n © 2018 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.\n\nReininghaus, Eva\n\n\n"
},
{
"text": "\n174093\nThe SURV1VE trial-sustained inflation and chest compression versus 3:1 chest compression-to-ventilation ratio during cardiopulmonary resuscitation of asphyxiated newborns: study protocol for a cluster randomized controlled trial.\n\nSchmölzer, GM\n\nPichler, G\n\nSolevåg, AL\n\nFray, C\n\nvan Os, S\n\nCheung, PY\n\nSURV1VE trial collaborators\n\nBeiträge in Fachzeitschriften\nISI:000459476900004\n30782199.0\n10.1186/s13063-019-3240-8\nPMC6381608\nThe need for cardiopulmonary resuscitation (CPR) is often unexpected, and the infrequent use of CPR in the delivery room (DR) limits the opportunity to perform rigorous clinical studies to determine the best method for delivering chest compression (CC) to newborn infants. The current neonatal resuscitation guidelines recommend using a coordinated 3:1 compression-to-ventilation (C:V) ratio (CC at a rate of 90/min and ventilations at a rate of 30/min). In comparison, providing CC during a sustained inflation (SI) (CC + SI) significantly improved hemodynamics, minute ventilation, and time to return of spontaneous circulation (ROSC) compared to 3:1 C:V ratio in asphyxiated piglets. Similarly, a small pilot trial in newborn infants showed similar results. Until now no study has examined different CC techniques during neonatal resuscitation in asphyxiated newborn infants in the DR. To date, no trial has been performed to directly compare CC + SI and 3:1 C:V ratio in the DR during CPR of asphyxiated newborn infants.\n This is a large, international, multi-center, prospective, unblinded, cluster randomized controlled trial in asphyxiated newborn infants at birth. All term and preterm infants > 28+ 0 by best obstetrical estimate who require CPR at birth due to bradycardia (< 60/min) or asystole are eligible. The primary outcome of this study is to compare the time to ROSC in infants born > 28+ 0 weeks' gestational age with bradycardia (< 60/min) or asystole immediately after birth who receive either CC + SI or 3:1 C:V ratio as the CPR strategy.\n Morbidity and mortality rates are extremely high for newborns requiring CC. We believe the combination of simultaneous CC and SI during CPR has the potential to significantly improve ROSC and survival. In addition, we believe that CC + SI might improve respiratory and hemodynamic parameters and potentially minimize morbidity and mortality in newborn infants. In addition, this will be the first randomized controlled trial to examine CC in the newborn period.\n ClinicalTrials.gov, NCT02858583 . Registered on 8 August 2016.\n\nPichler, Gerhard\n\n\n"
},
{
"text": "\n181399\nAbdominal metastases of primary extremity soft tissue sarcoma: A systematic review.\n\nSmolle, MA\n\nLeithner, A\n\nBernhardt, GA\n\nBeiträge in Fachzeitschriften\nISI:000518628500003\n32133276.0\n10.5306/wjco.v11.i2.74\nPMC7046921\nDespite the fact that about one third of patients with primary localized extremity soft tissue sarcoma (eSTS) will develop metastatic disease, abdominal metastases (AM) and retroperitoneal metastases (RM) constitute rare events. There is no clear consensus on how to achieve follow-up on patients with primary localized eSTS following curative resection, especially regarding the surveillance of potential AM/RM.\n To systematically analyse incidence, diagnosis, treatment and outcome of AM/RM in eSTS patients.\n In this systematic review, 899 studies available in PubMed and published between 2000 and 2018 were screened, identifying 17 original articles focused on AM or RM in eSTS. Article selection was based on the PRISMA guidelines, using the search terms (abdominal metastasis AND soft tissue sarcoma) and (soft tissue sarcoma metastasis abdomen). All studies published between January 1, 2000 and December 31, 2018 were screened. Further articles were identified by cross-searching article references, with the final search date being February 18, 2019. Due to limited data and the different reporting techniques used, the present review focused on descriptive analysis of the included studies.\n Of the 17 studies included, six original articles reported on incidence ± diagnosis, therapy and outcome in AM and RM, whilst three original and eight case reports focused on diagnostic pathway, therapeutic procedures or outcomes without allowing conclusions regarding incidence of AM and RM. According to the former six studies, incidence of AM ranged from 0.9%-5.6% in patients with miscellaneous histological subtypes, and up to 12.1% in patients with myxoid liposarcoma. The most common histological subtypes that developed AM or RM were (myxoid) liposarcoma and leiomyosarcoma, but also rare subtypes such as epithelioid sarcoma, myxofibrosarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumour had been reported to develop AM/RM. Surgery for AM/RM was performed in five of eight case-reports (62.5%) and in 20.8%-100.0% of original articles. In particular, patients with hepatic metastases undergoing metastasectomy had a survival benefit compared to patients treated with chemotherapy or best supportive care (> 3 years vs < 6 mo).\n Patients with eSTS should undergo surveillance with abdominal ultrasonography/computed tomography, or even whole-body-magnetic resonance imaging to detect AM/RM at an early stage.\n ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.\n\nBernhardt, Gerwin\n\nLeithner, Andreas\n\nSmolle, Maria Anna\n\n\n"
},
{
"text": "\n118683\nCommon variants at 12q15 and 12q24 are associated with infant head circumference.\n\nTaal, HR\n\nSt Pourcain, B\n\nThiering, E\n\nDas, S\n\nMook-Kanamori, DO\n\nWarrington, NM\n\nKaakinen, M\n\nKreiner-Møller, E\n\nBradfield, JP\n\nFreathy, RM\n\nGeller, F\n\nGuxens, M\n\nCousminer, DL\n\nKerkhof, M\n\nTimpson, NJ\n\nIkram, MA\n\nBeilin, LJ\n\nBønnelykke, K\n\nBuxton, JL\n\nCharoen, P\n\nChawes, BL\n\nEriksson, J\n\nEvans, DM\n\nHofman, A\n\nKemp, JP\n\nKim, CE\n\nKlopp, N\n\nLahti, J\n\nLye, SJ\n\nMcMahon, G\n\nMentch, FD\n\nMüller-Nurasyid, M\n\nO'Reilly, PF\n\nProkopenko, I\n\nRivadeneira, F\n\nSteegers, EA\n\nSunyer, J\n\nTiesler, C\n\nYaghootkar, H\n\nCohorts for Heart and Aging Research in Genetic Epidemiology Consortium\n\nBreteler, MM\n\nDecarli, C\n\nBreteler, MM\n\nDebette, S\n\nFornage, M\n\nGudnason, V\n\nLauner, LJ\n\nvan der Lugt, A\n\nMosley, TH\n\nSeshadri, S\n\nSmith, AV\n\nVernooij, MW\n\nEarly Genetics &\n\nLifecourse Epidemiology Consortium\n\nBlakemore, AI\n\nChiavacci, RM\n\nFeenstra, B\n\nFernandez-Banet, J\n\nGrant, SF\n\nHartikainen, AL\n\nvan der Heijden, AJ\n\nIñiguez, C\n\nLathrop, M\n\nMcArdle, WL\n\nMølgaard, A\n\nNewnham, JP\n\nPalmer, LJ\n\nPalotie, A\n\nPouta, A\n\nRing, SM\n\nSovio, U\n\nStandl, M\n\nUitterlinden, AG\n\nWichmann, HE\n\nVissing, NH\n\nDeCarli, C\n\nvan Duijn, CM\n\nMcCarthy, MI\n\nKoppelman, GH\n\nEstivill, X\n\nHattersley, AT\n\nMelbye, M\n\nBisgaard, H\n\nPennell, CE\n\nWiden, E\n\nHakonarson, H\n\nSmith, GD\n\nHeinrich, J\n\nJarvelin, MR\n\nJaddoe, VW\n\nEarly Growth Genetics Consortium\n\nBeiträge in Fachzeitschriften\nISI:000303416300013\n22504419.0\n10.1038/ng.2238\nPMC3773913\nTo identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10, 68 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19, 89). rs7980687 on chromosome 12q24 (P = 8.1 × 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 × 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height, their effects on infant head circumference were largely independent of height (P = 3.8 × 10(-7) for rs7980687 and P = 1.3 × 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 × 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume, Parkinson's disease and other neurodegenerative diseases, indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.\n\nRopele, Stefan\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n123829\nC-Kit receptor (CD117) in the porcine urinary tract\n\nMetzger, R\n\nNeugebauer, A\n\nRolle, U\n\nBohlig, L\n\nTill, H\n\nBeiträge in Fachzeitschriften\nISI:000252158200009\n18026739.0\n10.1007/s00383-007-2043-2\nNone\nC-Kit positive interstitial cells of Cajal (ICC) play an important role in the regulation of the smooth muscle motility, acting as internal pacemakers to provide the slow wave activity within various luminal organs. Recently c-Kit-(CD117)-positive interstitial cells (IC) have been shown in the genitourinary tract, but systematic studies on the distribution and density of IC within the urinary tract are still lacking. Therefore the aim of the present study was to analyze systematically the localization and distribution of the c-Kit receptor in the urinary tract of the pig using immunohistochemical and molecular methods. Tissue samples were harvested from the porcine urinary tract including renal calices and pelvis, ureteropelvic junction, proximal, middle and distal ureter, ureteral orifice, fundus, and corpus of the bladder and the internal urethral orifice. Small and large intestine specimen served as controls. Immunohistochemistry (APAAP, IF) was applied on serial frozen sections using four monoclonal and polyclonal antibodies recognizing CD117. Whole mounts of the porcine upper urinary tract were prepared and investigated using conventional and confocal fluorescence microscopy followed by three-dimensional reconstruction. UV-laser microdissection and RT-PCR were applied to confirm the immunohistochemical results. CD117-immunoreactivity labeled bipolar IC and round-shaped mast cells (MC) throughout the adventitia, tunica muscularis and submucosa within the whole porcine urinary tract. While MC were found continuously in all investigated segments, a gradient of bipolar IC was evident. The whole mount preparations gave a detailed cytomorphology of IC within the various layers of the porcine urinary tract. Whole mount preparations revealed closed apposition of bi- and tripolar c-Kit positive IC parallel to the smooth muscle bundles and to veins of the tunica muscularis and adventitia. In the urothelium single CD117-positive interepithelial cells were found. The highest density of CD117-positive cells was found at the ureteropelvic junction, however the differences in between the segments were minimal. Microdissection and RT-PCR confirmed the results uncovered by immunohistochemistry. The ubiquitous distribution of IC and their close relationship to smooth muscle provides strong evidence that IC could contribute to the intrinsic pacemaker activity within the porcine (upper and lower) urinary tract. The role of the interepithelial CD117-positive cells as mechanosensors or as a precursor cell in the regeneration of the urothelium, is conceivable.\n\nTill, Holger\n\n\n"
},
{
"text": "\n140160\nAge-related prevalence and morphological appearance of facial skin tumours: a prospective, cross-sectional, observational, multicentre study with special emphasis on melanocytic tumours.\n\nMoscarella, E\n\nKyrgidis, A\n\nSperduti, I\n\nAbramavicus, A\n\nArgenziano, G\n\nCota, C\n\nEibenschutz, L\n\nDe Simone, P\n\nLongo, C\n\nHofmann-Wellenhof, R\n\nZalaudek, I\n\nBeiträge in Fachzeitschriften\nISI:000356813100013\n25399612.0\n10.1111/jdv.12844\nNone\nThe clinical and histopathological diagnosis of skin tumours arising on the face may be challenging.\n An improved knowledge about the age-related patterns of facial skin tumours may aid the correct diagnosis and management.\n We conducted a prospective, cross-sectional morphological study to investigate the age-related frequency and morphological variability in facial skin tumours in a cohort of consecutive subjects attending two skin lesion clinics in Italy between June and September 2011. A total of 454 consecutive subjects (249 women; 55.5%) presenting with a total of 1866 facial tumours were enrolled in the study. Of the entire cohort, 54 (11.9%) subjects had no facial lesion.\n Total body naevus count correlated significantly with the mean number of facial lesions (ρ = 0.289, P < 0.001). The majority of flat lesions were pigmented (1056; 75.70%), compared to palpable (233; 17.40%) and raised lesions (93; 6.90%), the association being statistically significant (Pearson's chi square, P < 0.001. Considering melanocytic tumours only, the frequency of flat lesions significantly decreased with increasing age, while the number of palpable and raised lesions increased with increasing age (chi-square, P < 0.001). This trend was mainly due to naevi, whereby pigmented melanocytic naevi decreased with increasing age. Conversely, the percentage of non- pigmented naevi increased with increasing age (chi-square, P < 0.001).\n The study was conducted in skin lesion clinics in Italy, thus any general conclusions with respect to common traits or features based on the phenotypic and genetic diversity within the European population cannot be stated.\n Our study suggests that a high number of facial naevi could predict a high total naevus count. Moreover, naevi present a different morphological appearance during lifetime being initially flat, small and pigmented and becoming later raised, large and hypopigmented. Instead, lentigo maligna is an intraepidermal proliferation that typically presents as flat, large pigmented macule. A given histopathological diagnosis of a junctional naevus of a flat, facial pigmented macule of an elderly should be critically reviewed and treated with caution.\n © 2014 European Academy of Dermatology and Venereology.\n\nHofmann-Wellenhof, Rainer\n\nZalaudek, Iris\n\n\n"
},
{
"text": "\n173762\nThe Left and Right Ventricles Respond Differently to Variation of Pacing Delays in Cardiac Resynchronization Therapy: A Combined Experimental- Computational Approach.\n\nWillemen, E\n\nSchreurs, R\n\nHuntjens, PR\n\nStrik, M\n\nPlank, G\n\nVigmond, E\n\nWalmsley, J\n\nVernooy, K\n\nDelhaas, T\n\nPrinzen, FW\n\nLumens, J\n\nBeiträge in Fachzeitschriften\nISI:000457396700001\n30774598.0\n10.3389/fphys.2019.00017\nPMC6367498\nIntroduction: Timing of atrial, right (RV), and left ventricular (LV) stimulation in cardiac resynchronization therapy (CRT) is known to affect electrical activation and pump function of the LV. In this study, we used computer simulations, with input from animal experiments, to investigate the effect of varying pacing delays on both LV and RV electrical dyssynchrony and contractile function. Methods: A pacing protocol was performed in dogs with atrioventricular block (N = 6), using 100 different combinations of atrial (A)-LV and A-RV pacing delays. Regional LV and RV electrical activation times were measured using 112 electrodes and LV and RV pressures were measured with catheter-tip micromanometers. Contractile response to a pacing delay was defined as relative change of the maximum rate of LV and RV pressure rise (dP/dtmax) compared to RV pacing with an A-RV delay of 125 ms. The pacing protocol was simulated in the CircAdapt model of cardiovascular system dynamics, using the experimentally acquired electrical mapping data as input. Results: Ventricular electrical activation changed with changes in the amount of LV or RV pre-excitation. The resulting changes in dP/dtmax differed markedly between the LV and RV. Pacing the LV 10-50 ms before the RV led to the largest increases in LV dP/dtmax. In contrast, RV dP/dtmax was highest with RV pre-excitation and decreased up to 33% with LV pre-excitation. These opposite patterns of changes in RV and LV dP/dtmax were reproduced by the simulations. The simulations extended these observations by showing that changes in steady-state biventricular cardiac output differed from changes in both LV and RV dP/dtmax. The model allowed to explain the discrepant changes in dP/dtmax and cardiac output by coupling between atria and ventricles as well as between the ventricles. Conclusion: The LV and the RV respond in a opposite manner to variation in the amount of LV or RV pre-excitation. Computer simulations capture LV and RV behavior during pacing delay variation and may be used in the design of new CRT optimization studies.\n\nPlank, Gernot\n\n\n"
},
{
"text": "\n182142\nTreatment with abiraterone and enzalutamide does not overcome poor outcome from metastatic castration-resistant prostate cancer in men with the germline homozygous HSD3B1 c.1245C genotype.\n\nLu, C\n\nTerbuch, A\n\nDolling, D\n\nYu, J\n\nWang, H\n\nChen, Y\n\nFountain, J\n\nBertan, C\n\nSharp, A\n\nCarreira, S\n\nIsaacs, WB\n\nAntonarakis, ES\n\nDe Bono, JS\n\nLuo, J\n\nBeiträge in Fachzeitschriften\nISI:000562396600013\n32387417.0\n10.1016/j.annonc.2020.04.473\nNone\nIn men with castration-sensitive prostate cancer (CSPC), the HSD3B1 c.1245A>C variant has been reported to be associated with shorter responses to first-line androgen-deprivation therapy (ADT). Here, we evaluated the association between the inherited HSD3B1 c.1245A>C variant and outcomes from metastatic castration-resistant prostate cancer (mCRPC) after first-line treatment with abiraterone (Abi) or enzalutamide (Enza).\n Patients with mCRPC (n = 266) were enrolled from two centers at the time of starting first-line Abi/Enza. Outcomes after Abi/Enza included best prostate-specific antigen (PSA) response, treatment duration, and overall survival (OS). Outcomes after first-line ADT were determined retrospectively, and included treatment duration and OS. As was prespecified, we compared patients with the homozygous variant HSD3B1 genotype (CC genotype) versus the combined group with the heterozygous (AC) and homozygous wild-type (AA) genotypes.\n Among the 266 patients, 22 (8.3%) were homozygous for the HSD3B1 variant (CC). The CC genotype had no association with PSA response rate; the median Abi/Enza treatment duration was 7.1 months for the CC group and 10.3 months for the AA/AC group (log rank P = 0.34). Patients with the CC genotype had significantly worse OS, with median survival at 23.6 months for the CC group and 30.7 months for the AA/AC group (log rank P = 0.02). In multivariable analysis adjusting for age, Gleason score, PSA, prior chemotherapy, and M1 disease, the association between the CC genotype and OS remained significant (hazard ratio 1.78, 95% confidence interval 1.03-3.07, P = 0.04). Poor outcome after first-line ADT in the CC group was also observed when evaluating retrospective ADT duration data for the same combined cohort.\n In this large two-center study evaluating the HSD3B1 c.1245 genotype and outcomes after first-line Abi/Enza, homozygous variant (CC) HSD3B1 genotype was associated with worse outcomes. Novel therapeutic strategies are needed to enable treatment selection based on this genetic marker.\n Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.\n\nTerbuch, Angelika\n\n\n"
},
{
"text": "\n4907\nPenetration of piperacillin and tazobactam into pneumonic human lung tissue measured by in vivo microdialysis.\n\nTomaselli, F\n\nDittrich, P\n\nMaier, A\n\nWoltsche, M\n\nMatzi, V\n\nPinter, J\n\nNuhsbaumer, S\n\nPinter, H\n\nSmolle, J\n\nSmolle-Jüttner, FM\n\nBeiträge in Fachzeitschriften\nISI:000183633700021\n12814459.0\n10.1046%2Fj.1365-2125.2003.01797.x\nPMC1884255\nOBJECTIVES: The pharmacokinetic profile of antibiotics at the site of anti-infective action is one of the most important determinants of drug response, since it correlates with antimicrobial effect. Up to now, only limited information on the lung tissue pharmacokinetics of antibiotic agents has been available. The aim of this study was to measure, using a new microdialysis-based approach, antibiotic penetration into the extracellular space fluid of pneumonic human lung parenchyma. PATIENTS AND METHODS: The lung penetration of a combination of piperacillin and tazobactam, substances with low protein binding, was determined in five patients suffering from pneumonia and metapneumonic pleural empyema. The condition was treated by decortication after lateral thoracotomy. Intra-, or post-operatively, respectively, two microdialysis probes were inserted into pneumonic lung tissue, and into healthy skeletal muscle to obtain reference values. Serum and microdialysis samples were collected at 20-min intervals for at last 8 h following i.v. administration of a single dose of 4 g piperacillin and 500 mg tazobactam. RESULTS: The mean free interstitial concentration profiles of piperacillin in infected lung tissue and serum showed a maximal tissue concentration (Cmax) of 176.0 +/- 105.0 mg l-1 and 326.0 +/- 60.6 mg l-1, respectively. The mean AUC (area under the curve) for infected lung tissue was 288.0 +/- 167.0 mg.h l-1 and for serum 470.0 +/- 142.0 mg.h l-1. There was a statistically significant difference between AUC (lung) and AUC (serum) (P = 0.018) as well as between AUC (lung) and AUC (muscle) (P = 0.043). The intrapulmonary concentrations of piperacillin and tazobactam exceeded the minimum inhibitory concentrations (MIC) for most relevant bacteria for 4-6 h. The procedure was well tolerated by all patients and no adverse events or microdialysis-associated side-effects were observed. CONCLUSION: This microdialysis technique enabled continuous tissue pharmacokinetic measurement of free, unbound anti-infective agents in the lung tissue of patients with pneumonia. The present data corroborate the use of piperacillin and tazobactam in the treatment of lung infections caused by extracellular bacteria and demonstrate the distribution of piperacillin and tazobactam in the interstitial space of pneumonic lung tissue.\n\nMaier, Alfred\n\nMatzi, Veronika\n\nSmolle, Josef\n\nSmolle-Juettner, Freyja-Maria\n\n\n"
},
{
"text": "\n80023\nEffects of zinc on human skeletal alkaline phosphatase activity in vitro.\n\nHall, SL\n\nDimai, HP\n\nFarley, JR\n\nBeiträge in Fachzeitschriften\nISI:000078193900014\n9914326.0\n10.1007/s002239900597\nNone\nInorganic phosphate (Pi) can regulate the level of skeletal alkaline phosphatase (ALP) activity in human osteoblast-like cells by stabilizing the enzyme (without affecting transcription, ALP release from the cell surface, or the amount of ALP protein). These observations suggest that Pi determines the level of ALP activity by modulating a process of irreversible inactivation. The current studies were intended to examine the hypothesis that this inactivation of ALP activity is caused by the dissociation of an active center Zn and that Pi inhibits that dissociation. Initial studies showed that Zn, like Pi, could increase ALP specific activity in human osteosarcoma SaOS-2 cells in a time- and dose-dependent manner (e.g., a 50% increase at 0.2 micromol/liter Zn, P < 0.005). This effect was specific for Zn (i.e., no similar effect was seen with Ca, Fe, Co, Mg, Mn, or Cu), but not for SaOS-2 cells. Zn also increased ALP specific activity in (human osteosarcoma) MG-63 cells and in cells derived from normal human vertebrae (P < 0.001 for each). The effect of Zn to increase ALP activity was not associated with parallel increases in total protein synthesis, collagen production, or tartrate-resistant acid phosphatase activity (no change in any of these indices), net IGF-2 synthesis (a Zn-dependent decrease, P < 0.005), or PTH-dependent synthesis of cAMP (a biphasic increase, P < 0.02). Kinetic studies of Pi and Zn as co-effectors of ALP activity showed that Zn was a mixed-type effector with respect to Pi, whereas Pi was competitive with respect to Zn. Mechanistic studies showed that (1) Zn reversed the effect of Pi withdrawal to decrease ALP activity, but not by reactivating inactive ALP protein (the process required protein synthesis, without increases in ALP mRNA or the level of ALP immunoreactive protein); (2) Zn increased the half-life of ALP activity in intact cells and after a partial purification; and (3) Pi inhibited the process of ALP inactivation by EDTA (which chelates active center Zn). All these findings are consistent with the general hypothesis that Pi increases the half-life of skeletal ALP by preventing the dissociation of active center Zn and with a mechanistic model of skeletal ALP activity in which active center Zn participates in Pi-ester binding and/or hydrolysis.\n\nDimai, Hans\n\n\n"
},
{
"text": "\n113006\nStimulation of natural killer activity in peripheral blood lymphocytes of healthy donors and melanoma patients in vitro: synergism between interleukin (IL)-12 and IL-15 or IL-12 and IL-2.\n\nSeidel, MG\n\nFreissmuth, M\n\nPehamberger, H\n\nMicksche, M\n\nBeiträge in Fachzeitschriften\nISI:000076034400015\n9774227.0\n10.1007/PL00005268\nNone\nInterleukin-2 (IL-2) and IL-12 modify the functional status of T- and natural killer (NK) cells by regulating proliferation, cytolytic activity, cytokine induction, and T-cell subset differentiation. These effects are exploited in immunotherapy of cancer patients with IL-2 or IL-12, which, however, is limited by potentially life-threatening side effects. IL-15 shares many of the biological activities of IL-2 and may therefore represent a therapeutic alternative. Here we have compared the ability of these interleukins to stimulate NK activity in peripheral blood lymphocytes (PBLs) isolated from healthy donors (n = 12) as well as from patients (n = 12) suffering from metastatic disease (melanoma). Target (K562) cell lysis was assessed by determining the release of 51Cr and lactate dehydrogenase (LDH) which gave equivalent results. The NK-resistant DAUDI cell line served as control target. Unstimulated NK activity was significantly lower in PBLs purified from melanoma patients. However, cytolytic activity was readily stimulated by preincubation of PBLs (18 h) with cytokines such that the maximum target cell lysis was comparable to that seen in PBL of healthy donors. Similarly, the potency of IL-2 (EC50 = 20.2+/-1.3 and 22.0+/-1.3 u/ml in healthy donors and patients, respectively), IL-12 (EC50 = 11.0+/-1.1 and 4.3+/-1.6 u/ml) and IL-15 (EC50 = 0.3+/-0.1 and 0.2+/-0.1 u/ml) was comparable. Importantly, if the preincubation was carried out with cytokine concentrations in the EC50 range, the effects of two cytokines (tested in all combinations) were additive. A synergism was evident in PBLs obtained both from healthy donors and melanoma patients if concentration-response curves for IL-12 were determined in the presence of increasing concentrations of IL-2 (enhanced efficacy) or IL-15 (enhanced efficacy and potency). Our observations suggest possible alternatives to the monotherapy with IL-2 (or IL-12) in cancer treatment. Provided that the present findings can be extrapolated to the situation in vivo, the combined administration of IL-12 and IL-15 may be as efficacious as the immunotherapy with IL-2; this approach ought to allow for a marked reduction in cytokine dose and thereby improve the therapeutic index.\n\nSeidel, Markus\n\n\n"
},
{
"text": "\n113655\nInfluence of testing conditions on primary stability of arthroscopic knot tying for rotator cuff repair: slippery when wet?\n\nPietschmann, MF\n\nSadoghi, P\n\nHäuser, E\n\nScharpf, A\n\nGülecyüz, MF\n\nSchröder, C\n\nJansson, V\n\nMüller, PE\n\nBeiträge in Fachzeitschriften\nISI:000297845900010\n21945675.0\n10.1016/j.arthro.2011.06.031\nNone\nPURPOSE: The purpose was to evaluate whether the knot security of sliding and nonsliding knots with different sutures is influenced by dry or wet conditions. METHODS: We tested 5 suture materials, all of them US Pharmacopeia No. 2: PDS (polydioxanone) II (Ethicon, Somerville, NJ), Ethibond (Ethicon), and 3 ultrahigh-molecular weight polyethylene (UHMWPE) sutures-FiberWire (Arthrex, Naples, FL), Orthocord (DePuy Mitek, Raynham, MA), and Herculine (Linvatec, Largo, FL). Testing was performed under dry and wet conditions with sutures soaked in a saline solution. Cyclic loading was performed to simulate physiologic conditions. We started with a tensile load of 25 N. After 100 cycles, the load was increased to 50 N for another 100 cycles. The tensile load was gradually increased by 25 N per 100 cycles until suture rupture or knot slippage, defined as lengthening over 3 mm. RESULTS: Under dry conditions, 170 suture ruptures and 30 knot slippages were reported; and under wet testing conditions, 186 suture ruptures and 14 knot slippages were reported, with P < .044 and P < .027, respectively. Failure by knot slippage (n = 44) was seen under dry and saline solution conditions mainly with UHMWPE sutures, in particular with the Herculine suture using a Roeder knot showing comparable maximum failure loads in dry (274.5 ± 58.2 N) and saline solution (312.5 ± 14.2 N) conditions (P > .056). Knot slippage occurred only with sliding knots. With the Ethibond suture, no knot slippage was found regardless of the testing conditions and knot type. Across all knot types, the UHMWPE sutures were significantly stronger with respect to clinical and maximum failure loads in ultimate load to failure than Ethibond and PDS II under dry and wet testing conditions (P < .001 for both). CONCLUSIONS: We conclude that testing of different suture materials and knot types is different in wet versus dry conditions and believe that biomechanical testing might be more realistic in a wet environment. CLINICAL RELEVANCE: Suture knots behave differently in a wet versus dry environment, and testing of knot mechanics might better be carried out in wet environments. Copyright © 2011 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.\n\nSadoghi, Patrick\n\n\n"
},
{
"text": "\n142542\nAutologous stem cell transplantation for systemic lupus erythematosus.\n\nJayne, D\n\nPassweg, J\n\nMarmont, A\n\nFarge, D\n\nZhao, X\n\nArnold, R\n\nHiepe, F\n\nLisukov, I\n\nMusso, M\n\nOu-Yang, J\n\nMarsh, J\n\nWulffraat, N\n\nBesalduch, J\n\nBingham, SJ\n\nEmery, P\n\nBrune, M\n\nFassas, A\n\nFaulkner, L\n\nFerster, A\n\nFiehn, C\n\nFouillard, L\n\nGeromin, A\n\nGreinix, H\n\nRabusin, M\n\nSaccardi, R\n\nSchneider, P\n\nZintl, F\n\nGratwohl, A\n\nTyndall, A\n\nEuropean Group for Blood and Marrow Transplantation\n\nEuropean League Against Rheumatism Registry\n\nBeiträge in Fachzeitschriften\nISI:000220802300004\n15119545.0\n10.1191/0961203304lu525oa\nNone\nSystemic lupus erythematosus (SLE) is responsive to treatment with immunosuppressives and steroids, but often pursues a relapsing or refractory course resulting in increasing incapacity and reduced survival. Autologous stem cell transplantation (ASCT) following immunoablative chemotherapy is a newer therapy for autoimmune disease of potential use in severe SLE. A retrospective registry survey was carried out by the European Blood and Marrow Transplant and European League Against Rheumatism (EBMT/EULAR) registry. Data was collected from 53 patients with SLE treated by ASCT in 23 centres. Disease duration before ASCT was 59 (2-155) months (median, range), 44 (83%) were female, and median age was 29 (9-52) years. At the time of ASCT a median of seven American College of Rheumatology (ACR) diagnostic criteria for SLE were present (range 2-10) and 33 (62%) had nephritis. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony stimulating factor in 93% of cases. Ex vivo CD34 stem cell selection was performed in 42% of patients. Conditioning regimens employed cyclophosphamide in 84%, anti-thymocyte globulin in 76% and lymphoid irradiation in 22%. The mean duration of follow-up after ASCT was 26 (0-78) months. Remission of disease activity (SLEDAI < 3) was seen in 33/50 (66%; 95%CI 52-80) evaluable patients by six months, of which 10/31 (32%; 95%CI 15-50) subsequently relapsed after six (3-40) months. Relapse was associated with negative anti-double stranded DNA (anti-dsDNA) antibodies before ASCT (P = 0.007). There were 12 deaths after 1.5 (0-48) months, of which seven (12%; 95%CI 3-21) were related to the procedure. Mortality was associated with a longer disease course before ASCT (P = 0.036). In conclusion, this registry study demonstrates the efficacy of ASCT for remission induction of refractory SLE, although mortality appeared high. The safety of this procedure is likely to be improved by patient selection and choice of conditioning regimen. The return of disease activity in one-third of patients might be reduced by long-term immunosuppressive therapy post-ASCT.\n\nGreinix, Hildegard\n\n\n"
},
{
"text": "\n148995\nVariations of treatment in selected proximal femur fractures among surgeons with different surgical experience--A survey at an international AO course.\n\nSciacca, S\n\nLidder, SS\n\nGrechenig, C\n\nGrechenig, S\n\nStaresinic, M\n\nBakota, B\n\nGänsslen, A\n\nBeiträge in Fachzeitschriften\nISI:000366319500014\n26603615.0\n10.1016/j.injury.2015.10.066\nNone\nDifferent modalities of treatment for hip fractures have been discussed in the literature; however, practice may vary between centres. A survey was conducted on participants at an international AO course to assess the current management of pertrochanteric fractures (AO/OTA 31-A2) and displaced, non-impacted, subcapital fractures (AO/OTA 31-B3) in a 35-year-old patient and an 85-year-old patient.\n Surgeons taking part in an international orthopaedic course were invited to participate in a survey and were divided into two groups: inexperienced (one-to-three years since qualification) and experienced (four or more years). A survey was conducted to assess the management modalities used for pertrochanteric fractures (AO/OTA 31-A2) and displaced, non-impacted, subcapital fractures (AO/OTA 31-B3) in a 35-year-old patient and an 85-year-old patient.\n Fifty-two surgeons participated: 18 were inexperienced and 34 were experienced. The method of operative fixation for the pertrochanteric fracture was gamma-nailing for 95% of the surgeons in the inexperienced group; in the experienced group, 56% opted for gamma-nailing and 38% for dynamic hip screw (DHS). For the displaced subcapital fracture in a 35-year-old, screw fixation was the dominant treatment option for both groups. For the displaced subcapital fracture in an 85-year-old, most of the surgeons in both groups preferred hemiarthroplasty: 59% in the inexperienced group chose cemented bipolar hemiarthroplasty and 12% uncemented, whereas 56% of the experienced group suggested cemented bipolar hemiarthroplasty and 25% uncemented.\n This survey shows that a variety of methods are used to treat femoral neck fractures. A prospective randomised trial has shown the DHS to be the implant of choice for pertrochanteric fractures; however, this was not considered an option in the inexperienced group of surgeons and was the treatment of choice in only 13 out of 34 experienced surgeons. There is a general consensus for femoral head-conserving surgery in young patients with displaced subcapital fractures. Replacement arthroplasty was considered in the 85-year-old with a subcapital fracture. In the inexperienced group, 10 of 17 surgeons would cement the prosthesis, as would 27 of 36 in the experienced group.\n Copyright © 2015 Elsevier Ltd. All rights reserved.\n\n\n"
},
{
"text": "\n151261\nSeven years of clinical experience with teleconsultation in craniomaxillofacial surgery.\n\nEwers, R\n\nSchicho, K\n\nWagner, A\n\nUndt, G\n\nSeemann, R\n\nFigl, M\n\nTruppe, M\n\nBeiträge in Fachzeitschriften\nISI:000232289900008\n16182912.0\n10.1016/j.joms.2005.06.020\nNone\nIn this work the experiences from 50 telemedically supported treatments in craniomaxillofacial surgery are summarized and different setups for their technical realization are described. Furthermore, for the first time the innovative UMTS (universal mobile telecommunication system) is applied for the transmission of arthroscopic videos of the temporomandibular joint and other craniomaxillofacial structures.\n The combination of computer-assisted navigation technology in augmented reality environments with telecommunication is used for execution of interactive stereotaxic teleconsultation. Furthermore, treatments without navigation are telemedically supported. This study is composed of 4 technical system configurations: 1) integrated services digital network (ISDN)-based videoconferencing without remote control of the navigation computer; 2) transmission control protocol/internet protocol (TCP/IP)-based interactive teleconsultation via bundled ISDN lines (including remote control of the navigation computer); 3) TCP/IP-based interactive teleconsultation via network; 4) combination of TCP/IP-connection and ISDN-based videoconferencing. The telemedically supported treatments are: orbitozygomatic osteotomies, positioning of the mandibular condyle in orthognathic surgery, insertion of implants, positioning of the maxilla in orthognathic surgery, distraction osteogenesis, arthroscopies of the temporomandibular joint, and operation simulations on stereolithographic models. The surgical interventions are evaluated on a 5-level system performance scale from the technical point of view. In a separate trial 20 videosequences of arthroscopies of the temporomandibular joint are transmitted via UMTS cellular phones and independently evaluated by 3 experts (ie, a total of 60 streamings) to investigate feasibility of this technology in the field of craniomaxillofacial surgery.\n In the years from 1996 to 2002 a total of 50 treatments were telemedically supported. All intraoperative applications were successfully finished; 48 of 60 UMTS transmissions were finished without any interruptions in constant quality, slight interruptions were observed in 8 tests, and a complete breakdown was observed during 4 streamings that required a restart of the transmission. Resolution was sufficient to diagnose even tiny anatomic structures inside the temporomandibular joint, but orientation was hardly recognizable.\n In many applications telecommunication technology can contribute to a quality improvement in cranio- and maxillofacial surgery because of the global availability of specialized knowledge. The required technical expenditure for teleconsultation crucially depends on the infrastructure that is already available at the clinic and the remote site. UMTS is a promising technology with the potential to be valuable in numerous craniomaxillofacial applications.\n\n\n"
},
{
"text": "\n160211\nEffect of Physical Activity and/or Healthy Eating on GDM Risk: The DALI Lifestyle Study.\n\nSimmons, D\n\nDevlieger, R\n\nvan Assche, A\n\nJans, G\n\nGaljaard, S\n\nCorcoy, R\n\nAdelantado, JM\n\nDunne, F\n\nDesoye, G\n\nHarreiter, J\n\nKautzky-Willer, A\n\nDamm, P\n\nMathiesen, ER\n\nJensen, DM\n\nAndersen, L\n\nLapolla, A\n\nDalfrà, MG\n\nBertolotto, A\n\nWender-Ozegowska, E\n\nZawiejska, A\n\nHill, D\n\nSnoek, FJ\n\nJelsma, JG\n\nvan Poppel, MN\n\nBeiträge in Fachzeitschriften\nISI:000398118100018\n27935767.0\n10.1210/jc.2016-3455\nPMC5460688\nLifestyle approaches for preventing gestational diabetes mellitus (GDM) have produced mixed results.\n The aim of the present study was to compare the effectiveness of 3 lifestyle interventions [healthy eating (HE), physical activity (PA), and both HE and PA (HE+PA)] with usual care (UC) in reducing GDM risk.\n The present study was a multicenter randomized controlled trial conducted from 2012 to 2014 [the DALI (vitamin D and lifestyle intervention for GDM prevention) lifestyle study].\n The study occurred at antenatal clinics across 11 centers in 9 European countries.\n Consecutive pregnant women at <20 weeks of gestation with a body mass index (BMI) of ≥29 kg/m2 and without GDM using the International Association of Diabetes and Pregnancy Study Group criteria (n = 436). For the intervention, women were randomized, stratified by site, to UC, HE, PA, or HE+PA. The women received 5 face-to-face and ≤4 telephone coaching sessions using the principles of motivational interviewing. A gestational weight gain (GWG) <5 kg was targeted. The coaches received standardized training and an intervention toolkit tailored to their culture and language.\n The endpoints were the GWG at 35 to 37 weeks and the fasting glucose and insulin sensitivity [homeostasis model assessment insulin resistance (HOMA-IR)] at 24 to 28 weeks.\n We randomized 108 women to HE+PA, 113 to HE, 110 to PA, and 105 to UC. In the HE+PA group, but not HE or PA alone, women achieved substantially less GWG than did the controls (UC) by 35 to 37 weeks (-2.02; 95% confidence interval, -3.58 to -0.46 kg). Despite this reduction, no improvements were seen in fasting or postload glucose levels, insulin concentrations, or HOMA-IR. The birthweights and large and small for gestational age rates were similar.\n The combined HE+PA intervention was able to limit GWG but did not reduce fasting glycemia. Thus, lifestyle changes alone are unlikely to prevent GDM among women with a BMI of ≥29 kg/m2.\n Copyright © 2017 by the Endocrine Society\n\nDesoye, Gernot\n\n\n"
},
{
"text": "\n160395\nMorphological Criteria of Different Class III Manifestations, their Division and Variations in Time\n\nWendl, B\n\nWinsauer, H\n\nWalter, A\n\nMuchitsch, AP\n\nDroschl, H\n\nJakse, N\n\nWendl, M\n\nWendl, T\n\nBeiträge in Fachzeitschriften\nISI:000399027900005\nNone\n10.1055/s-0042-107177\nNone\nAim: of this work was to classify the Class III syndrom according to morphological criteria, to determine their frequency and to identify differences between the various forms in the course of treatment. Materials and methods: In a retrospective analysis 54 patients with a Class III syndrome were examined at 3 time intervals (at the beginning of treatment at the age of 6-9 years, after treatment and at a long-term control in adult patients after about 25 years). For classification by morphological criteria only the initial documents were consulted (before therapy). Results: In 40 % the Class III syndrom was caused due to the lower jaw. The upper jaw was responsible in 11 % of cases for the appearance of the Class III syndrome and in 49% a combination form was evident. In the lower jaw the primary cause for the development of a Class III syndrom is due to a large mandible (86.4%), in 9.1% the prognathic position of the mandible and in 4.5% a combination of both. In the maxilla the retrognathic position of the upper jaw is mainly responsible for the deformity (66, %), followed in 16.7% by a too small maxilla and a combination of micrognathia and retrognathia. In combination cases a large lower jaw and the retrognathic position of the maxilla were dominant, followed by a larger lower and a smaller upper jaw. By classification of the different manifestations of prognathism significant differences with respect to the standard values occured in the course of treatment. At the onset of treatment the smaller SNA value was evident by maxillary retrognathia. During the long term control analysis, the class III combination group presented the largest difference between maxilla and mandible. NSGn and APDI values were closest to the standard values in cases of maxillary retrognathia and showed a larger lower facial height. In comparison, the values APDI in the groups of mandibular prognathism and the combination form had been significantly increased and even rose further on. NSGn increased especially in the group of mandibular prognathism. Conclusion: Manifestations of Class III syndromes vary greatly due to hereditary components. Therapeutic approaches can be modified and used more effectively by an accurate diagnosis.\n\nJakse, Norbert\n\nMuchitsch, Alfred\n\nWendl, Brigitte\n\n\n"
},
{
"text": "\n169424\nHuman germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis.\n\nPlanells-Palop, V\n\nHazazi, A\n\nFeichtinger, J\n\nJezkova, J\n\nThallinger, G\n\nAlsiwiehri, NO\n\nAlmutairi, M\n\nParry, L\n\nWakeman, JA\n\nMcFarlane, RJ\n\nBeiträge in Fachzeitschriften\nISI:000400251600003\n28446200.0\n10.1186/s12943-017-0653-4\nPMC5406905\nCancer/testis (CT) genes have expression normally restricted to the testis, but become activated during oncogenesis, so they have excellent potential as cancer-specific biomarkers. Evidence is starting to emerge to indicate that they also provide function(s) in the oncogenic programme. Human TEX19 is a recently identified CT gene, but a functional role for TEX19 in cancer has not yet been defined.\n siRNA was used to deplete TEX19 levels in various cancer cell lines. This was extended using shRNA to deplete TEX19 in vivo. Western blotting, fluorescence activated cell sorting and immunofluorescence were used to study the effect of TEX19 depletion in cancer cells and to localize TEX19 in normal testis and cancer cells/tissues. RT-qPCR and RNA sequencing were employed to determine the changes to the transcriptome of cancer cells depleted for TEX19 and Kaplan-Meier plots were generated to explore the relationship between TEX19 expression and prognosis for a range of cancer types.\n Depletion of TEX19 levels in a range of cancer cell lines in vitro and in vivo restricts cellular proliferation/self-renewal/reduces tumour volume, indicating TEX19 is required for cancer cell proliferative/self-renewal potential. Analysis of cells depleted for TEX19 indicates they enter a quiescent-like state and have subtle defects in S-phase progression. TEX19 is present in both the nucleus and cytoplasm in both cancerous cells and normal testis. In cancer cells, localization switches in a context-dependent fashion. Transcriptome analysis of TEX19 depleted cells reveals altered transcript levels of a number of cancer-/proliferation-associated genes, suggesting that TEX19 could control oncogenic proliferation via a transcript/transcription regulation pathway. Finally, overall survival analysis of high verses low TEX19 expressing tumours indicates that TEX19 expression is linked to prognostic outcomes in different tumour types.\n TEX19 is required to drive cell proliferation in a range of cancer cell types, possibly mediated via an oncogenic transcript regulation mechanism. TEX19 expression is linked to a poor prognosis for some cancers and collectively these findings indicate that not only can TEX19 expression serve as a novel cancer biomarker, but may also offer a cancer-specific therapeutic target with broad spectrum potential.\n\nFeichtinger, Julia\n\n\n"
},
{
"text": "\n177059\nNational Institutes of Health-Defined Chronic Graft-vs.-Host Disease in Pediatric Hematopoietic Stem Cell Transplantation Patients Correlates With Parameters of Long-Term Immune Reconstitution.\n\nLawitschka, A\n\nGueclue, ED\n\nJanuszko, A\n\nKörmöczi, U\n\nRottal, A\n\nFritsch, G\n\nBauer, D\n\nPeters, C\n\nGreinix, HT\n\nPickl, WF\n\nKuzmina, Z\n\nBeiträge in Fachzeitschriften\nISI:000482814300001\n31507582.0\n10.3389/fimmu.2019.01879\nPMC6718560\nRecent data revealed the importance of immune reconstitution (IR) for the evaluation of possible biomarkers in National Institutes of Health (NIH)-defined chronic graft-vs.-host disease (cGVHD) and its clinical aspects. In this large pediatric study (n = 146), we have analyzed whether cellular and humoral parameters of IR in the long-term follow-up (FU) with a special emphasis on B-cell reconstitution correlate with NIH-defined cGVHD criteria. HYPOTHESIS: we were especially interested in whether meaningful cGVHD biomarkers could be defined in a large pediatric cohort. We here demonstrate for the first time in a highly homogenous pediatric patient cohort that both cGVHD (n = 38) and its activity were associated with the perturbation of the B-cell compartment, including low frequencies of CD19+CD27+ memory B-cells and increased frequencies of circulating CD19+CD21low B-cells, a well-known hyperactivated B-cell subset frequently found elevated in chronic infection and autoimmunity. Notably, resolution of cGVHD correlated with expansion of CD19+CD27+ memory B-cells and normalization of CD19+CD21low B-cell frequencies. Moreover, we found that the severity of cGVHD had an impact on parameters of IR and that severe cGVHD was associated with increased CD19+CD21low B-cell frequencies. When comparing the clinical characteristics of the active and non-active cGVHD patients (in detail at time of analyses), we found a correlation between activity and a higher overall severity of cGVHD, which means that in the active cGVHD patient group were more patients with a higher disease burden of cGVHD-despite similar risk profiles for cGVHD. Our data also provide solid evidence that the time point of analysis regarding both hematopoietic stem cell transplantation (HSCT) FU and cGVHD disease activity may be of critical importance for the detailed investigation of pediatric cohorts. Finally, we have proven that the differences in risk factors and patterns of IR, with cGVHD as its main confounding factor, between malignant and non-malignant diseases, are important to be considered in future studies aiming at identification of novel biomarkers for cGVHD.\n\nGreinix, Hildegard\n\n\n"
},
{
"text": "\n183898\nCOVID-19: Technology, Social Connections, Loneliness & Leisure Activities: An International Study Protocol.\n\nMarston, H\n\nIvan, L\n\nFernández-Ardèvol, M\n\nCliment, AR\n\nGómez-León, M\n\nBlanche, D\n\nEarle, S\n\nKo, P-C\n\nColas, S\n\nBilir, B\n\nÇalıkoğlu, HÖ\n\nArslan, H\n\nKanozia, H\n\nKriebernegg, U\n\nGroßschädl, F\n\nReer, F\n\nQuandt, T\n\nButtigieg, SC\n\nSilva, PA\n\nGallistl, V\n\nRohner, R\n\nBeiträge in Fachzeitschriften\nNone\n33869500.0\n10.3389/fsoc.2020.574811\nPMC8022752\nDrawn from the stress process model, the pandemic has imposed substantial stress to individual economic and mental well-being and has brought unprecedented disruptions to social life. In light of social distancing measures, and in particular physical distancing because of lockdown policies, the use of digital technologies has been regarded as the alternative to maintain economic and social activities. This paper aims to describe the design and implementation of an online survey created as an urgent, international response to the COVID-19 pandemic. The online survey described here responds to the need of understanding the effects of the pandemic on social interactions/relations and to provide findings on the extent to which digital technology is being utilized by citizens across different communities and countries around the world. It also aims to analyze the association of use of digital technologies with psychological well-being and levels of loneliness. The data will be based on the ongoing survey (comprised of several existing and validated instruments on digital use, psychological well-being and loneliness), open for 3 months after roll out (ends September) across 11 countries (Austria, France, Germany, India, Malta, Portugal, Romania, Spain, Turkey, and UK). Participants include residents aged 18 years and older in the countries and snowball sampling is employed via social media platforms. We anticipate that the findings of the survey will provide useful and much needed information on the prevalence of use and intensities of digital technologies among different age groups, gender, socioeconomic groups in a comparative perspective. Moreover, we expect that the future analysis of the data collected will show that different types of digital technologies and intensities of use are associated with psychological well-being and loneliness. To conclude, these findings from the study are expected to bring in our understanding the role of digital technologies in affecting individual social and emotional connections during a crisis.\n Copyright © 2020 Marston, Ivan, Fernández-Ardèvol, Rosales Climent, Gómez-León, Blanche-T, Earle, Ko, Colas, Bilir, Öztürk Çalikoglu, Arslan, Kanozia, Kriebernegg, Großschädl, Reer, Quandt, Buttigieg, Silva, Gallistl and Rohner.\n\nGroßschädl, Franziska\n\n\n"
}
]
}