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PURPOSE To compare readout-segmented echo-planar imaging (EPI) (RESOLVE) to single-shot EPI (ss-EPI) diffusion-weighted imaging (DWI) for the assessment of renal interstitial fibrosis. MATERIALS AND METHODS A phantom, eight healthy volunteers (under 30 years to avoid age-fibrosis related) and 27 chronic kidney disease (CKD) patients (scheduled for kidney biopsy) were scanned (at 3T) with ss-EPI and 5-shot RESOLVE DWI (resolution: 2 × 2 × 5 mm3 , 10 b-values). The cortico-medullary difference for each DW parameter from a monoexponential fit (ΔADC) or, segmented biexponential fit (ΔD, ΔD*, ΔFp ) were compared between both sequences. A fibrosis threshold of 40% was defined to separate all 35 subjects into low and high fibrosis groups. The linear relationship between DW parameters and percentage fibrosis (up to 80%) from Masson trichrome was assessed with the Pearson product-moment correlation coefficient. Fisher Z-transform was used for R2 correlation comparison. RESULTS A coefficient of variation between ADCs of 3% was measured between both sequences in the phantom. In healthy volunteers, no significant difference was measured for all DW parameters. Both sequences separated low to high level of fibrosis with a significant decrease of ΔADC (RESOLVE P = 3.1 × 10-6 , ss-EPI P = 0.003) and ΔD (RESOLVE P = 8.2 × 10-5 , ss-EPI P = 0.02) in the high level of fibrosis. However, RESOLVE ΔADC had a stronger negative correlation (P = 0.04 for R2 comparison) with fibrosis than ss-EPI ΔADC (RESOLVE R2 = 0.65, P = 5.9 × 10-9 , ss-EPI R2 = 0.29, P = 8.9 × 10-4 ). ΔD (RESOLVE) was correlated (moderately) with fibrosis (R2 = 0.29, P = 9.2 × 10-4 ); however, ΔD* and ΔFp did not show, in our population, a significant correlation with interstitial fibrosis (0.01 < R2 < 0.08). CONCLUSION ΔADC derived from both sequences correlated with fibrosis. ΔADC from RESOLVE showed better correlation with fibrosis than ΔADC from ss-EPI and therefore has potential to monitor CKD. LEVEL OF EVIDENCE 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1631-1640.

Calmodulin (CaM) is a ubiquitous Ca2+‐sensing protein regulating many important cellular processes. Several CaM‐associated variants have been identified in a small group of patients with cardiac arrhythmias. The mechanism remains largely unknown, even though a number of ion channels, including the ryanodine receptors and the L‐type calcium channels have been shown to be functionally affected by the presence of mutant CaM. CaM is constitutively bound to the SK channel, which underlies the calcium‐gated ISK contributing to cardiac repolarization. The CaM binding to SK channels is essential for gating, correct assembly, and membrane expression. To elucidate the effect of nine different arrhythmogenic CaM variants on SK3 channel function, HEK293 cells stably expressing SK3 were transiently co‐transfected with CaMWT or variant and whole‐cell patch‐clamp recordings were performed with a calculated free Ca2+ concentration of 400 nmol/L. MDCK cells were transiently transfected with SK3 and/or CaMWT or variant to address SK3 and CaM localization by immunocytochemistry. The LQTS‐associated variants CaMD96V, CaMD130G, and CaMF142L reduced ISK,Ca compared with CaMWT (P < 0.01, P < 0.001, and P < 0.05, respectively). The CPVT associated variant CaMN54I also reduced the ISK,Ca (P < 0.05), which was linked to an accumulation of SK3/CaMN54I channel complexes in intracellular compartments (P < 0.05). The CPVT associated variants, CaMA103V and CaMD132E only revealed a tendency toward reduced current, while the variants CaMF90L and CaMN98S, causing LQTS syndrome, did not have any impact on ISK,Ca. In conclusion, we found that the arrhythmogenic CaM variants CaMN54I, CaMD96V, CaMD130G, and CaMF142L significantly down‐regulate the SK3 channel current, but with distinct mechanism.

Introduction We have comprehensively described the expression profiles of mitochondrial DNA and nuclear DNA genes that encode subunits of the respiratory oxidative phosphorylation (OXPHOS) complexes (I–V) in the hippocampus from young controls, age matched, mild cognitively impaired (MCI), and Alzheimer's disease (AD) subjects. Methods Hippocampal tissues from 44 non-AD controls (NC), 10 amnestic MCI, and 18 AD cases were analyzed on Affymetrix Hg-U133 plus 2.0 arrays. Results The microarray data revealed significant down regulation in OXPHOS genes in AD, particularly those encoded in the nucleus. In contrast, there was up regulation of the same gene(s) in MCI subjects compared to AD and ND cases. No significant differences were observed in mtDNA genes identified in the array between AD, ND, and MCI subjects except one mt-ND6 . Discussion Our findings suggest that restoration of the expression of nuclear-encoded OXPHOS genes in aging could be a viable strategy for blunting AD progression.

Objective To assess differences between parents of adolescents with chronic illness (CI) going through a self-reported easy or difficult transfer. Methods Seventy-two parents of CI youths who had already transferred to adult care were divided according to whether they considered that the transfer had been easy (n = 45) or difficult (n = 27). We performed a bivariate analysis comparing both groups and variables with a significance level

Osteoclast-associated receptor (OSCAR) is an activating receptor expressed by human myeloid cells. Collagen type I (ColI) and collagen type II (ColII) serve as ligands for OSCAR. OSCAR-collagen interaction stimulates RANK-dependent osteoclastogenesis. We have recently reported that OSCAR promotes functional maturation of monocyte-derived dendritic cells. OSCAR is upregulated on monocytes from rheumatoid arthritis (RA) patients with active disease, and these monocytes show an increased proosteoclastogenic potential. In the current study, we have addressed a functional role for an OSCAR-collagen interaction on monocytes. We show that OSCAR-ColII signaling promoted the survival of monocytes. Moreover, ColII stimulated the release of proinflammatory cytokines by monocytes from healthy donors, which could be completely blocked by an anti-OSCAR monoclonal antibody. Mononuclear cells from the synovial fluid of RA patients plated on ColII secreted TNF-α and IL-8 in an OSCAR-dependent manner. Global RNA profiling showed that components of multiple signaling pathways relevant to RA pathogenesis are regulated at the transcriptional level by OSCAR in monocytes. Thus, OSCAR can play a proinflammatory role in monocyte-derived cells and may contribute crucially on multiple levels to RA pathogenesis.

Internationally 3% of the donor hearts are distributed to re-transplant patients. In Eurotransplant, only patients with a primary graft dysfunction (PGD) within 1 week after heart transplantation (HTX) are indicated for high urgency listing. The aim of this study is to provide evidence for the discussion on whether these patients should still be allocated with priority. All consecutive HTX performed in the period 1981-2015 were included. Multivariate Cox' model was built including: donor and recipient age and gender, ischaemia time, recipient diagnose, urgency status and era. The study population included 18 490 HTX, of these 463 (2.6%) were repeat transplants. The major indications for re-HTX were cardiac allograft vasculopathy (CAV) (50%), PGD (26%) and acute rejection (21%). In a multivariate model, compared with first HTX hazards ratio and 95% confidence interval for repeat HTX were 2.27 (1.83-2.82) for PGD, 2.24 (1.76-2.85) for acute rejection and 1.22 (1.00-1.48) for CAV (P < 0.0001). Outcome after cardiac re-HTX strongly depends on the indication for re-HTX with acceptable outcomes for CAV. In contrast, just 47.5% of all hearts transplanted in patients who were re-transplanted for PGD still functioned at 1-month post-transplant. Alternative options like VA-ECMO should be first offered before opting for acute re-transplantation. ispartof: TRANSPLANT INTERNATIONAL vol:31 issue:11 pages:1223-1232 ispartof: location:Switzerland status: published

Evidence-based and reliable measures of addictive disorders are needed in general population-based assessments. One study suggested that heavy use over time (UOT) should be used instead of self-reported addiction scales (AS). This study compared UOT and AS regarding video gaming and internet use empirically, using associations with comorbid factors. Cross-sectional data from the 2011 French Survey on Health and Consumption on Call-up and Preparation for Defence-Day (ESCAPAD), cross-sectional data from the 2012 Swiss ado@internet.ch study and two waves of longitudinal data (2010-13) of the Swiss Longitudinal Cohort Study on Substance Use Risk Factors (C-SURF). Three representative samples from the general population of French and Swiss adolescents and young Swiss men, aged approximately 17, 14 and 20 years, respectively. ESCAPAD: n =22 945 (47.4% men); ado@internet.ch: n =3049 (50% men); C-SURF: n =4813 (baseline + follow-up, 100% men). We assessed video gaming/internet UOT ESCAPAD and ado@internet.ch: number of hours spent online per week, C-SURF: latent score of time spent gaming/using internet] and AS (ESCAPAD: Problematic Internet Use Questionnaire, ado@internet.ch: Internet Addiction Test, C-SURF: Gaming AS). Comorbidities were assessed with health outcomes (ESCAPAD: physical health evaluation with a single item, suicidal thoughts, and appointment with a psychiatrist; ado@internet.ch: WHO-5 and somatic health problems; C-SURF: Short Form 12 (SF-12 Health Survey) and Major Depression Inventory (MDI). UOT and AS were correlated moderately (ESCAPAD: r = 0.40, ado@internet.ch: r = 0.53 and C-SURF: r = 0.51). Associations of AS with comorbidity factors were higher than those of UOT in cross-sectional (AS: .005 ≤ |b| ≤ 2.500, UOT: 0.001 ≤ |b| ≤ 1.000) and longitudinal analyses (AS: 0.093 ≤ |b| ≤ 1.079, UOT: 0.020 ≤ |b| ≤ 0.329). The results were similar across gender in ESCAPAD and ado@internet.ch (men: AS: 0.006 ≤ |b| ≤ 0.211, UOT: 0.001 ≤ |b| ≤ 0.061; women: AS: 0.004 ≤ |b| ≤ 0.155, UOT: 0.001 ≤ |b| ≤ 0.094). The measurement of heavy use over time captures part of addictive video gaming/internet use without overlapping to a large extent with the results of measuring by self-reported addiction scales (AS). Measuring addictive video gaming/internet use via self-reported addiction scales relates more strongly to comorbidity factors than heavy use over time.

Summary Background Suffering from a chronic disease or disability (CDD) during adolescence can be a burden for both the adolescents and their parents. The aim of the present study is to assess how living with a CDD during adolescence, the quality of parent–adolescent relationship (PAR) and the adolescent's psychosocial development interact with each other. Methods Using the Swiss Multicenter Adolescent Survey on Health 2002 (SMASH02) database, we compared adolescents aged 16–20 years with a CDD (n = 760) with their healthy peers (n = 6493) on sociodemographics, adolescents' general and psychosocial health, interparental relationship and PAR. Results Bivariate analyses showed that adolescents with a CDD had a poorer psychosocial health and a more difficult relationship with their parents. The log-linear model indirectly linked CDD and poor PAR through four variables: two of the adolescents' psychosocial health variables (suicide attempt and sensation seeking), the need for help regarding difficulties with parents and a highly educated mother that acted as a protective factor, allowing for a better parent–adolescent with a CDD relationship. Conclusion It is essential for health professionals taking care of adolescents with a CDD to distinguish between issues in relation with the CDD from other psychosocial difficulties, in order to help these adolescents and their parents deal with them appropriately and thus maintain a healthy PAR.

To investigate dynamic behaviors of monocharged particle systems, a direct truncation (DT) method and a hybrid particle-cell (HPC) method are implemented into the discrete element method coupled with computational fluid dynamics (DEM-CFD) with defined cutoff distances. The DT method only considers electrostatic interactions between particles within the cutoff distance while the HPC method computes electrostatic interactions in the entire computational domain. The deposition process of monocharged particles in a container in air was simulated using the developed DEM-CFD. It was found that using the DT method, the macrostructure, evolution of granular temperature, and radial distribution function of the particle system were sensitive to the specified cutoff distance. In contrast, using the HPC method, these results were independent of the specified cutoff distance, as expected. This implies that, although electrostatic interactions between particles with large separation distances are weak, they should be considered in DEM-CFD for accurate modeling of charged particle systems. © 2015 The Authors AIChE Journal published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers AIChE J, 61: 1792–1803, 2015

AIM: This study examined whether problematic Internet use was associated with substance use among young adolescents and assessed whether this association accounted for the use of tobacco, alcohol, cannabis and other drugs. METHODS: Using the Internet Addiction Test we divided a representative sample of 3,067 adolescents in Switzerland (mean age 14 years) into regular and problematic Internet users. We performed a bivariate analysis and two logistic regression models, to analyse substances separately and simultaneously, and developed a log-linear model to define the associations between significant variables. RESULTS: Problematic Internet users were more likely to be female, to use substances, to come from non-intact families, to report poor emotional wellbeing and to be below average students. The first model showed significant associations between problematic users and each substance, with adjusted odds ratios of 2.05 for tobacco, 1.72 for alcohol, 1.94 for cannabis and 2.73 for other drugs. Only smoking remained significant in the second model, with an adjusted odds ratio of 1.71. CONCLUSIONS: Problematic Internet use is associated with other risky behaviours and may be an important early predictor of adolescent substance use. Therefore it should be included in the psychosocial screening of adolescents. This article is protected by copyright. All rights reserved. Language: en

Future individualized patient treatment will need tools to monitor the dose and effects of administrated drugs. Mass spectrometry may become the method of choice to monitor drugs in real time by analyzing exhaled breath. This review describes the monitoring of exhaled drugs in real time by mass spectrometry. The biological background as well as the relevant physical properties of exhaled drugs are delineated. The feasibility of detecting and monitoring exhaled drugs is discussed in several examples. The mass spectrometric tools that are currently available to analyze breath in real time are reviewed. The technical needs and state of the art for on-site measurements by mass spectrometry are also discussed in detail. Off-line methods, which give support and are an important source of information for real-time measurements, are also discussed. Finally, some examples of drugs that have already been successfully detected in exhaled breath, including propofol, fentanyl, methadone, nicotine, and valproic acid are presented. Real-time monitoring of exhaled drugs by mass spectrometry is a relatively new field, which is still in the early stages of development. New technologies promise substantial benefit for future patient monitoring and treatment.

Therapy-induced senescence (TIS) as a permanent growth arrest can be induced by various stimuli, including anticancer compounds. TIS emerged as a promising strategy to overcome resistance phenomena. However, senescent cancer cells might regain proliferation activity in vivo or even secrete tumor-promoting cytokines. Therefore, successful exploitation of TIS in cancer treatment simultaneously requires the development of effective strategies to eliminate senescent cancer cells. Virotherapy aims to selectively hit tumor cells, thus a combination with senescence-inducing drugs was explored. As a model, we chose measles vaccine virus (MeV), which does not interfere with cellular senescence by itself. In different tumor cell types, such as hepatoma, pancreatic and mammary gland carcinoma, we demonstrate efficient viral replication and lysis after TIS by gemcitabine, doxorubicin or taxol. Applying real time imaging, we even found an accelerated lysis of senescent cancer cells, supporting an enhanced viral replication with an increase in cell-associated and released infectious MeV particles. In summary, we show as a proof-of-concept that senescent tumor cells can be efficiently exploited as virus host cells by oncolytic MeV. These observations open up a new field for preclinical and clinical research to further investigate TIS and oncolytic viruses as an attractive combinatorial future treatment approach.

Most pesticides, herbicides and other plant treatment agents are applied to the crop surface. Direct mass spectrometric methods, such as desorption electrospray ionization (DESI), offer new ways to analyze plant samples directly and rapidly. A strategy for the development and optimization of a DESI method for the direct determination of chemicals on complex surfaces is described. Chlorpropham (CP) was applied to potato surfaces as an example for a crop protection agent and analyzed using a self-made DESI source. Aspects such as instrument selectivity, sensitivity and reproducibility were investigated. The MS4 fragmentation pattern of CP was analyzed to achieve the necessary detection selectivity, and is discussed in detail. Similar fragmentation was found in the ESI and DESI mass spectra, indicating that the mechanisms of ESI and DESI are closely related. A DESI method for semi-quantification of CP on potatoes was developed. Detection limits of 6.5 µg/kg were found using MS/MS. The reproducibility, in the range of 12% (signal variation), appears to be sufficient for semi-quantitative measurements. Copyright © 2013 John Wiley & Sons, Ltd.

Objectives/Hypothesis Nicotine, a major constituent of cigarette smoke, can activate the cholinergic anti-inflammatory pathway by binding to α7-nicotinic acetylcholine receptor (α7nAChR) expressed on the surface of certain cells. Here, we ask whether cigarette smoke extract induced different paracrine factors compared to the in vivo regulator of inflammation, tumor necrosis factor-α, in human vocal fold fibroblasts (hVFFs) shown to express low levels of α7nAChR. Study Design In vitro. Methods α7nAChR was detected by nested polymerase chain reaction and immunohistochemistry. γH2AX, a marker for DNA double-stand breaks, was measured by immunofluorescence. Cigarette smoke extract was prepared in accordance with investigators studying effects of cigarette smoke. hVFFs treated for 3 hours had media replaced for an additional 24 hours. Cytokine, chemokine, and growth factor levels in media were assessed by multiplex analysis. Results α7nAChR expression levels decreased with the passage number of fibroblasts. Tumor necrosis factor-α induced a significantly different profile of cytokines, chemokines, and growth factor compared to cigarette smoke extract exposure. Cigarette smoke extract at a concentration not associated with induction of γH2AX nuclear foci significantly increased vascular endothelial growth factor. Conclusions Cigarette smoke extract elicited a response important for regulation of angiogenesis and vascular permeability during inflammation, without evidence of DNA double-stand breaks associated with carcinogenesis. hVFFs are capable of participating in paracrine regulation of pathological blood vessel formation associated with cigarette smoking–related diseases (ie, Reinke edema). These cells express α7nAChR, an essential component of the cholinergic anti-inflammatory pathway regulated by the vagus nerve in certain tissues and a target of therapeutic agents. Laryngoscope, 123:2228–2236, 2013

In this study, we used secondary electrospray ionization mass spectrometry assisted by an ion funnel (IF) operating at ambient pressure to find compounds in the mass range of 100-500 m/z in online breath fingerprinting experiments. In low-resolution experiments conducted on an ion trap instrument, we found that pyridine is present in breath of individuals long after drinking coffee. In high-resolution experiments conducted on a Fourier transform ion cyclotron resonance, we found more than 30 compounds in the mass range of 100-500 m/z in analogous online breath experiments. More than a third of these compounds have molecular weights above 200 Daltons and have not been mentioned in previous studies. In low-resolution experiments as well as experiments without the IF, these compounds could not be detected.

In this study, we use an ion funnel (IF) at ambient pressure to enhance the sensitivity of secondary electrospray ionization (SESI). Atenolol, salbutamol and cocaine as test compounds are delivered to the SESI interface in the gas phase and are charged with three nano electrosprays. In our experiments, we show that the compounds can be detected at concentrations in the low pptv range, which is an increase of two orders of magnitude compared with the results without the IF. With a standard SESI interface, the compounds could not be detected at all. With the use of the SESI IF interface for the headspace analysis of bananas and limes, we can detect many more compounds and at higher intensities than with a standard SESI interface. Copyright © 2012 John Wiley & Sons, Ltd.

r r Abstract: In making decisions, people have to balance between the competing demands of speed and accuracy, a balance generally referred to as the speed-accuracy tradeoff (SAT). In this study, we inves- tigated the role of controlled SAT in a two-choice task in which manual responses were either validly or invalidly cued. Examining electrophysiological measurements of oscillatory brain activity, theta power in the anterior cingulate cortex (ACC), alpha power in the occipital cortex, and beta power in the motor cortex were found to be related to SAT. Because oscillatory effects of SAT were found to em- anate from the SAT baseline interval preceding the two-choice task, the results indicate that SAT is modulated by a change of visuo-motor baseline activities rather than a change of response threshold. Moreover, in the two-choice task, conflict-induced theta power in the ACC was found to be more pro- nounced in speed than in accuracy trials, whereas priming-related beta power dynamics in the motor cortex were unaffected by SAT. These results indicate that conflict processing, but not response pri- ming, depends on SAT. Hum Brain Mapp 33:1834-1849, 2012. V C 2011 Wiley Periodicals, Inc.

Zusammenfassung Um den Einflus einer Salpingitis auf die Befruchtung und die fruhembryonale Entwicklung der befruchteten Eizellen zu untersuchen, wurde in einem Modellversuch bei 29 Kaninchen Aerosil® (SiO2) jeweils in den rechten Eileiter instilliert. In 18 Fallen entstand eine Salpingitis, die histologisch vornehmlich durch eine Infiltration mit Makrophagen gekennzeichnet war. Alle Tiere wiesen zudem eine massive Perisalpingitis auf. Die provozierte Eileiterentzundung hatte folgende Auswirkungen: Senkung der Ovulationsrate von 4,4 auf 2,7 pro Ovar; Beeintrachtigung des Eiabnahmemechanismus (92 % wiedergefundene Eizellen in den unbehandelten Eileitern im Vergleich zu 23 % bei Tieren mit ausgepragter Salpingitis); Senkung der Befruchtungsrate von 100 % der aufgefundenen Eizellen auf 43 %. Zudem wurden in drei Fallen Zygoten gefunden, die offensichtlich im Zweizellstadium einen Entwicklungsstillstand erfahren hatten. Es scheint somit moglich, das eine Endosalpingitis zu einer Beeintrachtigung der Befruchtung und der fruhembryonalen Entwicklung fuhren kann. Summary Influence of an experimental salpingitis on oviduct function in the rabbit To study the effect of salpingitis on fertilization and early embryonic development of the fertilized egg a model experiment with 29 rabbits was carried out by instilling Aerosil® (SiO2) into the right oviduct. In 18 of the rabbits a salpingitis developed which was characterized histologically by an infiltration with macrophages. All the affected animals also showed a massive peri-salpingitis. The induced salpingitis had the following effects: reduction in ovulation rate from 4.4 to 2.7 per ovary; interference with egg attachment mechanism (92 % of eggs recovered in untreated oviduct compared with 23 % in oviducts with marked salpingitis); reduction of fertilization rate from 100 % of eggs found to 43 %. In addition, in three cases zygotes were found which appeared to have stopped at the two-cell stage of development. It seems possible, therefore, that an endosalpingitis can lead to interference with fertilization and early embryo development. Resume Influence d'une salpingite experimentale sur la fonction de l'oviducte chez le lapin Afin d'examiner l'influence d'une salpingite sur la fecondation et le developpement embryonnaire precoce de l'ovule feconde, on a instille de l'Aerosil® (SiO2) par intervalle dans l'oviducte droit dans une recherche sur 29 lapins. Une salpingite est apparue dans 18 cas et fut reconnaissable en histologie principalement par une infiltration avec des macrophages. Tous les animaux ont presente une perisalpingite massive. L'inflammation provoquee de l'oviducte a eu les consequences suivantes: abaissement du taux d'ovulation de 4,4 a 2,7 par ovaire; atteinte du mecanisme de l'expulsion ovulaire (92 % des ovules retrouves dans l'ovuducte non traite en comparaison de 23 % chez des animaux presentant une salpingite etendue); abaissement du taux de fecondation de 100% a 43% des ovules trouves. On a trouve en plus des zygotes dans trois cas qui avaient apparemment eprouve un arret de developpement au stade de deux cellules. Il semble donc possible qu'une endosalpingite conduise a une atteinte de la fecondation et du developpement embryonnaire precoce. Resumen El influjo de una salpingitis experimental sobre la funcion del oviducto en la coneja Para poder estudiar el influjo de una salpingitis sobre la fecundacion y el desarrollo embrionario precoz de los ovulos fecundados, se instilo en un ensayo modelar en 29 conejas Aerosu® (SiO2) cada vez en el oviducto derecho. En 18 casos se origino una salpingitis, la cual histopatologicamente se hallaba caracterizada sobre todo por una infiltracion con macrofagos. Ademas, todos los animales presentaron una perisalpingitis masiva. La salpingitis provocada ejercia los efectos siguientes: disminucion de la tasa de ovulacion de 4,4 a 2,7 por ovario; perjuicio del mecanismo de aceptacion ovular (92 % de ovulos vueltos a encontrar en los oviductos no tratados en comparacion con 23 % en animales con salpingitis pronunciada); disminucion de la tasa de fertilidad de 100 % de los ovulos hallados a 43 %. Ademas se encontraron en tres casos cigotes, los cuales, al parecer, habian sufrido una detencion evolutiva en el estadio bicelular. Por lo tanto, parece ser que resulta posible el que una endosalpingitis puede conducir a un menoscabo de la fecundidad y del desarrollo embrionario precoz.

Zusammenfassung Bei 2 Rindern wurde 3mal im Abstand von 10 Tagen je 5000 I. E. HCG mit Freundschem Adjuvans subkutan verabreicht. Mittels der GEDELISA-Technik konnte gezeigt werden, das das kommerzielle HCG-Praparat aus vier verschiedenen Fraktionen besteht und das die Rinder gegen alle vier Fraktionen mit der Bildung von Antikorpern reagierten. Es bestand eine positive Korrelation zwischen dem Molekulargewicht der einzelnen HCG-Fraktionen und der Menge der induzierten Antikorper. Summary Demonstration of antibodies against HCG in cattle by the GEDELISA test Two cattle were given s. c. 3 doses at intervals of 10 days of 5,000 i. u. of HCG with Freund's adjuvant. By the GEDELISA test it was shown that the commercial HCG preparation consisted of 4 different fractions and that the cattle reacted against all 4 fractions by producing antibodies. There was a positive correlation between the molecular weight of the individual HCG fractions and the amount of induced antibody formed. Resume Mise en evidence d'anticorps anti-HCG chez le bovin a l'aide de la technique GEDELISA 5000 UI HCG ont ete appliquees par voie sous-cutanee avec un adjuvant de Freund 3 fois en I'espace de 10 jours a deux bovins. La technique GEDELISA a pu montrer que la preparation commerciale HCG se composait de quatre fractions differentes et que le bovin formait des anticorps contre ces quatre fonctions. Il existait une correlation positive entre le poids moleculaire de chacune de ces fractions HCG et la quantite d'anticorps induite. Resumen Puesta en evidencia de los anticuerpos anti-HCG en los vacunos con ayuda de la tecnica GEDELISA A dos vacas se le administraron por via subcutanea 3 veces 5.000 UI de HCG con el adyuvante de Freund en el espacio de 10 dias. Mediante la tecnica GEDELISA se pudo demostrar que la especialidad HCG comercial consta de cuatro fracciones diferentes y que las vacas reaccionan frente a todas estas cuatro fracciones con la formacion de anticuerpos. Existia una correlacion positiva entre el peso molecular de las distintas fracciones de la HCG y la cantidad de anticuerpos inducidos.

Zusammenfassung Eine Resistenzuntersuchung ist nur sinnvoll, wenn es gelingt, bei den einzelnen Erregern einen „empfindlichen” und einen „resistenten” Anteil innerhalb der Population objektiv zu unterscheiden. Zur Abklarung dieses Problems wurden Mastitis-Erreger mittels des Agar-Diffusionstestes auf ihre Empfindlichkeit gegenuber verschiedenen Antibiotika gepruft. Durch die Darstellung der Hemmhofgrosen in Form von Haufigkeitsverteilungen war es moglich, einen „empfindlichen” und einen „resistenten” Anteil der Erregerpopulation zu differenzieren und die kritische Ablesegrenze genau festzulegen. Summary Methodical investigations for the determination of the antibiotic resistance of mastitis pathogens In order to differentiate correctly between bacterial strains as either “resistant” or “sensitive” to antibiotics, the agar diffusion test was examined to evaluate the sensitivity of mastitis pathogens to various antibiotics. The frequency distributions of the growth inhibiting zones permitted the separation of a constant number of resistant strains. Critical growth inhibiting zones could be defined objectively. Resume Experiments methodiques sur la determination de la resistance aux antibiotiques des agents de la mammite Experiments methodiques sur la determination de la resistance aux antibiotiques des agents de la mammite. Un traitement antibacterien specifique requiert une connaissance prealable de la sensibilite des agents pathogenes aux differents antibiotiques. Cependant, une analyse de la resistance a l'encontre de tels produits n'est sensee que s'il est possible d'etablir une difference entre une partie «resistante» et une partie «sensible» des agents d'une population bacterienne determinee. Pour repondre a ces questions, nous avons analyse par la methode de diffusion en gelose la sensibilite aux antibiotiques des agents de la mammite. En prenant de diametre des zones d'inhibition comme coefficient de frequence de repartition, il nous a ete possible de differencier une partie «resistante» d'une partie «sensible» de la population. La zone critique pour la separation des souches «sensibles» peut etre definie objectivement. Resumen Estudios metodologicos para poder objetivar la resistencia a los antibioticos de los agentes etiologicos de la mamitis Un examen de resistencia solo tiene sentido si se logra diferenciar objetivamente en los distintos germenes la parte «sensible» y otra «resistente» dentro de la poblacion. Para aclarar este problema se contrastaron agentes de las mastitis mediante la prueba de difusion en agar en cuanto a su sensibilidad frente a diversos antibioticos. Por medio de la representacion de los halos inhibidos en forma de distribuciones por frecuencias, resulto posible diferenciar una parte «sensible» y otra «resistente» en la poblacion de agentes etiologicos y fijar con exactitud el limite critico de lectura.

Zusammenfassung Bei 6 Hundinnen wurde nach beidseitiger Ovarektomie eine Transplantation von autologem Ovargewebe unter die Magenserosa vorgenommen. Histologische Untersuchungen nach Beobachtungszeiten von 2 bis 12 Wochen ergaben, das die Implantate eingewachsen waren und wieder Funktionsstadien bis zu Sekundarfollikeln trugen. Die Hundinnen zeigten wahrend der Versuchsperiode jedoch keinerlei ostrogenbedingte Veranderungen. Aufgrund dieser Ergebnisse erfolgte bei 34 Hundinnen die Ovariohysterektomie nach dieser Methode. Die Besitzer wurden 6 bis 30 Monate spater nach dem Befinden der Tiere und dem Auftreten unerwunschter Kastrationsfolgen befragt. Lediglich zwei Tiere zeigten eine leichte Incontinentia urinae und ein Tier eine geringgradige Gewichtszunahme. Andere Storungen wurden nicht beobachtet. Die protektive Wirkung dieses Verfahrens hinsichtlich unerwunschter Kastrationsfolgen last sich noch nicht endgultig beurteilen, da weder die Anzahl der Tiere noch die Beobachtungszeiten dazu ausreichen. Summary Avoidance of unwanted consequences of castration of the bitch by transplantation of autologous ovarian tissue After bilateral ovariectomy in 6 bitches autologous ovarian tissue was transplanted under the gastric serosa. Histological examination after 2 and 12 weeks showed that the implants had grown and again carried functioning stages up to secondary follicles. During this time the bitches showed no oestrogen — associated changes. As a consequence of these findings 34 bitches were subjected to ovarohysterectomy by this technique. After 6 to 30 months the owners were questioned about the behaviour of the animals and any unwanted effects of the castration. Two bitches showed slight urinary incontinence and one animal showed a small gain in body weight. No other ill effects were found. Resume Inhibition des suites indesirables de la castration chez la chienne par transplantation de tissu ovarien autologue. On a procede a une transplantation de tissu ovarien autologue sous la sereuse stomacale chez 6 chiennes qui avaient subi une ovariectomie bilaterale. Des recherches histologiques apres un temps d'observation de 2 a 12 semaines ont montre que les implantats avaient prolifere et qu'ils portaient a nouveau des stades fonctionnels jusqu'a des follicules secondaires. Les chiennes n'ont cependant aucunement presente des modifications dues aux oestrogenes durant la periode d'essai. Sur la base de ces resultats, 34 chiennes ont subi une ovariohysterectomie selon cette methode. Des questions concernant le comportement des animaux et l'apparition de consequences indesirables dues a la castration ont ete posees aux proprietaires 6 a 30 mois plus tard. Deux animaux presenterent de temps en temps une legere incontinence urinaire et un animal montra une faible augmentation de poids. D'autres troubles n'ont pas ete observes. L'action protectrice de cette methode d'inhibition des suites indesirables de la castration ne peut pas encore etre definitivement interpretee etant donne que le nombre des animaux et les temps d'observation sont insuffisants. Resumen Evitacion de las secuelas indeseables debidas a la castracion en la perra mediante trasplantacion de tejido ovarico autologo En 6 perras se llevo a cabo, tras ovariectomia bilateral, un trasplante de tejido ovarico autologo debajo de la serosa gastrica. Los examenes histologicos, tras tiempos de observacion de 2 hasta 12 semanas, manifestaron que los injertos se habian encarnado y volvian a llevar estadios funcionales hasta foliculos secundarios. Sin embargo, las perras no mostraban durante el periodo de ensayo ninguna modificacion debida a los estrogenos. A la vista de estos resultados, se efectuo en 34 perras la ovariohisterectomia siguiendo la misma tecnica. Los propietarios de los animales fueron preguntados al cabo de 6 hasta 30 meses por el bienestar de las perras y la aparicion de secuelas indeseables de la castracion. Solo dos animales tenian incontinencia de orina y un animal habia aumentado ligeramente de peso. Otras alteraciones no fueron observadas. La accion protectora de este procedimiento respecto a secuelas indeseadas de la castracion no puede ser enjuiciada todavia de manera definitiva, pues para ello no son suficientes ni el numero de animales ni los tiempos de observacion.

We analyze how demographic change affected profits and returns across pharmaceutical industries over the last twenty years. Fluctuations in different age group sizes influence the estimated demand changes for age-sensitive drugs, such as antibacterials for young, antidepressants for middle-aged, and antithrombotics for old people. These demand changes are predictable as soon as a specific age group is born. We use consumption and demographic data to forecast future consumption demand growth for drugs caused by demographic changes in the age structure. We find that long-term forecasted demand changes predict abnormal annual pharmaceutical stock returns for more than 60 firms over the time period from 1986 to 2008. An increase by one percentage point of annual demand growth due to demographic changes predicts an increase in abnormal yearly stock returns in the size of 3-5 percentage points. Short-term forecasted demand changes does predict negative abnormal stock returns for a time horizon below 5 years. A trading strategy taking advantage of the demographic information earns a significant abnormal return between 6 and 8 percentage points per year. Our results are consistent with the model by DellaVigna and Pollet (2007), where investors are inattentive with extrapolation in the distant future and overreact to information in the near future. http://ssrn.com/abstract=1428373

Possible methods have been reviewed for the evaluation of the sexual activity of sterile European cherry fruit flies used in genetic control programs. Mating propensity, or speed (time lapse between meeting and mating of the sexes), and mating frequency (number of matings performed by individual flies within a defined period of time) may be studied in the same test. The analysis and interpretation of mating speed data as well as the experimental parameters influencing the results are discussed. The evaluation of the mating quality of flies treated with oral and topical markers, sterilized by irradiation with 10 krad and receiving a combined marking/irradiation treatment indicated that the sexual activity of released sterile flies matches the corresponding traits of the wild target populations. The mathematical methods and models used in these investigations are described in a statistical appendix. Zusammenfassung Die Qualitatskontrolle bei der Kirschenfliege: Die Beurteilung der sexuellen Aktivitat in Laboratoriums- und Freilandkafigversuchen Die einschlagige Literatur wurde bezuglich der bei Fruchtfliegen angewandten Methodik zur Beurteilung des sexuellen Vigors massenproduzierter Stamme untersucht. Diese Ubersicht fuhrte zur Schlusfolgerung, das fur die Kirschenfliege neue Wege zu beschreiten waren. Als besonders erfolgversprechend wurde die Bearbeitung der Kopulationsgeschwindigkeit erachtet, welche schon seit langerer Zeit in der Drosophila-Forschung Verwendung gefunden hat. Die Kopulationsgeschwindigkeit, ausgedruckt als Zeitspanne zwischen dem Zusammenfuhren von Mannchen und Weibchen in Laboratoriums- oder Freilandkafigen und Kopulation, eroffnet die interessante Moglichkeit, mit einem einzigen Test Hinweise auf die Kopulationsneigung und Kopulationsfrequenz zu beschaffen. Die experimentellen Faktoren, welche die Resultate beeinflussen, die Analyse und Interpretation von Geschwindigkeitsdaten werden diskutiert, wobei die statistischen Uberlegungen in einem separaten statistischen Anhang dargelegt werden. Die Beurteilung der Kopulationstatigkeit von Kirschenfliegen, welche mit oral und topikal applizierten Markiersubstanzen behandelt, welche mit einer Bestrahlungsdosis von 10 krad sterilisiert, oder welche eine in der laufenden genetischen Bekampfungsaktionen verwendete kombinierte Markierung-Sterilisationsbehandlung erhalten haben, zeigte sowohl im Laboratoriumsversuch wie auch im Freiland keine negativen Einflusse im Vergleich mit wildem Freilandsmaterial. Interessant ist die Feststellung, das die Verwendung von fluoreszierenden Farbpigmenten fur die auserliche Markierung die sexuelle Tatigkeit der Fliegen anzuregen scheint. Weitere Untersuchungen werden sich mit der Heritabilitat der gemessenen phanotypischen Qualitatskriterien sowie deren Auswertung fur die Selektion von Kirschenfliegenstammen befassen, welche in einem Autozidverfahren eine erhohte Schlagkraft gegenuber den wilden Zielpopulationen aufweisen.

Every second of non-selected men below the age of 55 years who had survived a myocardial infarction was placed in a group for physical training, while each other constituted a control. The physical training program was selected according to each patient's individual maximal working capacity and lasted for 9 months, beginning 3 months after the myocardial infarction. At the end of the training period the experimental group was subdivided into one group of adequately trained patients and one consisting of drop-outs and patients with poor adherence. The patients who followed the program increased their physical work performance. In this group a decrease was found in plasma insulin values after a glucose tolerance test, a slight increase in glucose tolerance and a decrease in body fat and plasma triglycerides. Body cell mass and plasma cholesterol did not change. The men selected for the training program, but who were not able to follow it sufficiently, as well as the controls, showed a less marked decrease in plasma insulin values at reexamination.

Background. Splenectomy is an effective procedure for children and adults with severe or refractory idiopathic thrombocytopenic purpura (ITP). Data regarding pediatric patients are limited. Procedure. Sixty-eight Intercontinental Childhood ITP Study Group (ICIS) investigators from 57 institutions in 25 countries participated in a splenectomy registry. Data from 153 patients were submitted, of whom 134 had a splenectomy and were analyzed. Results. The median age at splenectomy was 11.8 (2.7-20.7) years. The median postsplenectomy follow-up was 2.0 (0.1-4.5) years. Pre-splenectomy vaccination was not administered in 21 children (15.7%). Open and laparoscopic splenectomy procedures were performed in 67 and 65 evaluable children, respectively. Surgical technique was not reported in two children. Overall immediate platelet response to splenectomy was achieved in 113 patients (86.3%). Eighty percent of responders maintained their status of response during the following 4 years. Older age, longer duration of ITP, and male gender correlated with a complete response. Post-splenectomy sepsis was reported in seven patients without lethal outcome, although sepsis might be differently defined at participating institutions. Conclusions. Splenectomy is effective in children with ITP. Management varies greatly in different institutions. These Registry data may serve as a basis for future clinical trials to assess the indication and timing of splenectomy. Pediatr Blood Cancer 2007;49:829834. (c) 2006 Wiley-Liss, Inc.

Background Acute and chronic idiopathic thrombocytopenic purpura (ITP) is traditionally based on the duration of thrombocytopenia at the cut-off point of 6 months after diagnosis. Registry I evaluated the diagnosis, definition, management, and follow-up of childhood ITP. This report focuses on children with thrombocytopenia persisting more than 6 months. Procedure Data were collected by questionnaires to the physicians caring for children with ITP, at diagnosis, 6, and 12 months later. Data were compared regarding initial features and follow-up with emphasis on children with persistent thrombocytopenia, and those with ITP who recovered their platelet counts between 7 and 12 months from diagnosis. Results At 12 months from diagnosis, 79 of 308 (25.6%) evaluable children recovered from ITP and 229 had ongoing ITP. Children with recovered ITP were younger than children with ongoing ITP (P = 0.043) and exhibited a lower frequency of bleeding symptoms during the first 6 months after diagnosis (P = 0.018). Frequency of hospitalization, bone marrow aspiration, and drug treatment differed regionally. Conclusions The high rate of recovery from ITP between 7 to 12 months demonstrates, that the cut-off point of 6 months for the definition of chronic ITP does not adequately differentiate chronic from acute ITP. The majority of children with ITP have variable time to recovery with gradual improvement of platelet counts and disappearance of bleeding signs. ITP is a heterogeneous disorder with a diverse natural history and diverse pattern of treatment response. © 2005 Wiley-Liss, Inc.

This study analyses two types of information flows in financial markets. The first type represents return information, where informed investors know whether the stock price will increase or decreas ...

A commercial antibody (clone 22) directed against the apoptosis-linked gene 2 (alg2, pdcd6) encoded protein has been used by several groups. Up-regulated expression of the antigen was observed in primary tumours and in metastatic tissue and also during rat brain ischemia. Furthermore, antigen down-regulation was found in human atherosclerotic plaques. Recently, we found that the clone 22 antibody does not recognise ALG-2. In the present study the antigen of the clone 22 antibody was identified as the heat shock protein 90 (HSP90) co-chaperone protein p23, identical to the cytosolic prostaglandin E2 synthase, by immunoprecipitation followed by tryptic in-gel digests and mass spectrometry of the purified peptides. Moreover, the heterogeneous ribonuclear protein A2/B1 was found to be a part of the p23 co-immunoprecipitated protein complex.